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Meta-analysis of data from a genome-wide association study (GWAS) identified 7 single nucleotide polymorphisms (SNPs) as strong predictors of IgA nephropathy (IgAN). To replicate the association of these 7 SNPs and understand whether they influence the clinical characteristics of IgAN, a case-control study including 521 IgAN patients and 535 controls was conducted in a Western Han cohort.
Data were analyzed using logistic regression and multifactor dimensionality reduction (MDR). Clinical data collected from 459 IgAN patients were investigated to estimate the relationship between the genotype and phenotype of IgAN. A retrospective cohort study of 315 IgAN patients was conducted to investigate the relationship between genotype and progression of renal disease over a mean period of 44.49 ± 19.94 months.
Upon Bonferroni correction, none of the 7 SNPs were associated with IgAN (corrected pvalue [Pc], >0.05). A combination of the rs2856717T/C, rs9275596C/T, and rs2412971A/G had effects on the susceptibility of IgAN (p = 0.001). Marginally significant association of rs2856717 T/C recessive model for the T allele was significantly associated with estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) in IgAN patients (p = 0.008, Pc = 0.056, odds ratio [OR] = 1.527). The T allele at rs9275596 was significantly associated with macroscopic hematuria of IgAN patients under the dominant and additive models of inheritance, (p < 0.001, Pc = 0.007, OR = 2.983) and (p < 0.001, Pc = 0.007, OR = 2.17), respectively. Kaplan–Meier survival analysis showed that patients carrying the TT + TC genotype for rs2856717 had reduced renal survival rate than those carrying the CC genotype (85.1% vs. 92.7%, p = 0.046).
rs2856717 may influence the clinical characteristics and poor outcome of IgAN. Further studies are warranted to explore the mechanisms for such genotype-disease phenotype association.
This study aimed to examine the roles of fibroblast growth factor 23 (FGF23) and soluble Klotho in phosphate metabolism in autosomal-dominant polycystic kidney disease (ADPKD) patients.
We measured these two factors and phosphate metabolism parameters in 80 patients with ADPKD and 53 patients with non-diabetic chronic kidney disease (CKD).
The mean serum FGF23 level in the ADPKD group was significantly (2-fold) higher than in the non-diabetic CKD patients, but the mean soluble Klotho level in the ADPKD group was significantly lower in the non-diabetic CKD group. The mean serum phosphate levels of the two groups were similar. The estimated glomerular filtration rate (eGFR) was approximately 45 ml/min per 1.73 m2 in both groups, and their serum vitamin D metabolite levels were in the normal range.
The serum FGF23 levels were significantly higher and soluble Klotho levels significantly lower in the ADPKD group than in the non-diabetic CKD group matched for eGFR, and these findings may be associated with resistance of renal phosphate excretion.
Serum adipokines have a role in the development of arterial stiffness. We aim to investigate the risk factors of developing arterial stiffness and the association of leptin and arterial stiffness in hypertensive (HTN) patients.
There were 101 HTN patients enrolled. Fasting blood samples and baseline characteristics were obtained and carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor system. A cfPWV > 10 m/s was defined as high arterial stiffness, and ≤ 10 m/s as low arterial stiffness.
Forty-seven patients (46.5 %) had high arterial stiffness, and had a higher percentage of diabetes (P = 0.044), , older age (P < 0.001), higher pulse pressure (P = 0.049), and higher serum blood urea nitrogen (P = 0.029), creatinine (P = 0.027), intact parathyroid hormone (P = 0.004), serum leptin level (P = 0.002), C-reactive protein (P < 0.001), but lower estimated glomerular filtration rate (P = 0.006) compared to patients with low arterial stiffness. After adjusting for factors significantly associated with arterial stiffness by multivariate logistic regression analysis, it revealed that leptin (aOR = 1.037, 95% C.I. = 1.007-1.067, P = 0.014), having DM (aOR = 4.885, 95% C.I. = 1.590-15.006, P = 0.006), and elevated CRP (aOR = 1.503, 95% C.I. = 1.110-2.0371,P = 0.009) were significant independent predictors of arterial stiffness in HTN patients.
Serum leptin level could be a predictor for arterial stiffness in HTN patients. This article is protected by copyright. All rights reserved.
Renal hyperfiltration (RHF) is a marker of early kidney injury that was recently shown to be a novel marker of mortality. However, it has no clear definition. In this study, we suggested an age- and sex-adjusted RHF definition and explored the association between RHF and mortality by sex.
We analyzed data from individuals receiving routine health examinations from 1995 to 2009. RHF was defined as an estimated glomerular filtration rate over the 95th percentile matched for age and sex.
A total of 114,966 individuals were included. During the 75-month of observation period, 2,559 (2.2%) participants died. Among those, 71.4% were men. Because sex and RHF had a significant interaction for mortality (P for interaction < 0.001), we performed survival analysis according to sex. RHF was related to lower body weight and a higher proportion of cigarette smoking in men, whereas these relationships were not found in women. In the Kaplan-Meier curve, RHF was associated with higher mortality rate than non-RHF in both sexes, but this relationship was more prominent in men. In the multivariate analysis, RHF remained as an independent risk factor for all-cause mortality even after adjustment for confounding in men (hazard ratio, 1.34; 95% confidence interval, 1.12–1.59; P = 0.001). In women, RHF was not associated with increased mortality.
We demonstrated that RHF was a significant risk factor for mortality in men but not in women. The mechanisms and clinical implications of these different associations according to sex require a further clarification.
Opportunistic screening in general practice (GP) is a cost-effective and viable approach to the early identification of chronic kidney disease (CKD). This study sought to identify the barriers and facilitators to CKD screening practices of GP nurses working in a regional area of New South Wales, Australia.
An eight item elicitation questionnaire informed by the Theory of Planned Behaviour was administered to a convenience sample of 26 GP nurses.
Participants identified that the advantages of CKD screening were its early detection and treatment, the reduction of disease burden, and the opportunity to increase awareness and provide disease prevention education. These positive attitudinal beliefs were offset by negative beliefs about the impost of opportunistic screening on nursing time, particularly when there were other competing clinical priorities. Participants reported that practice doctors were wary of the financial costs associated with additional non-claimable services and believed that unfunded services, regardless of patient benefit, were difficult to justify in a private business environment. Screening was enabled in GP settings with existing screening protocols or initiatives, and when patients presented with known risk factors. Barriers to screening were more frequently described and illustrated a strong focus on financial aspects of GP. Without reimbursement through the Medicare Benefits Scheme, screening was not considered an economical use of nursing time. Other competing and billable clinical services took precedence.
The findings of this study can be used to inform the development and evaluation of interventions that target opportunistic CKD screening in the GP setting.
Carbon disulfide (CS2) is widely used as an organic solvent. However, there is little information available regarding the clinical manifestations and the pathological features of kidney injury caused by CS2. The current study aimed to describe the renal manifestations of a group of patients with long-term occupational exposure to CS2.
10 patients with long-term exposure to CS2 and visiting a single center were enrolled, with their clinical features recorded. Renal biopsies were taken from all patients and their pathological findings were documented.
All patients came from the same chemical fiber factory. Their mean age at enrollment was 36.9 ± 2.4 years, and each patient had a CS2 exposure duration exceeding 10 years. 8 patients (80%) presented with proteinuria and none had hematuria. 2 patients (20%) had underlying hypertension and 5 (50%) had increased serum creatinine levels. Light microscopic examination of their renal biopsy specimens revealed diffuse mesangial cell proliferation and mesangial hyperplasia in all patients. Moreover, 3 patients (30%) had nodular hyperplasia, resembling the lesions of diabetic nephropathy. Variable degrees of tubular atrophy and interstitial infiltrations of lymphocytes and monocytes were observed in all patients. Similarly, Electron microscopic examination showed glomerular mesangial cell proliferation and mesangial hyperplasia. Immunopathological staining for IgA and IgG, complements, or hepatitis B markers (hepatitis B surface antigen and e antigen-antibody) are negative in all patients.
Long-term occupational exposure to CS2 may be associated with renal injury, although the renal pathological features are often nonspecific.
Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. The lncRNA activated by transforming growth factor β (TGF-β) (lncRNA-ATB) was discovered as a prognostic factor in hepatocellular carcinoma, gastric cancer, and colorectal cancer. However, little is known about the role of lncRNA-ATB in renal transplantation. This study aimed to assess lncRNA-ATB expression in renal transplant patients with acute kidney injury and explore its role in postoperative pharmaceutical immunosuppression therapy. Methods: We detected lncRNA-ATB expression in the kidney biopsies of a cohort of 72 patients with renal allograft rejection and 36 control transplant patients. lncRNA-ATB were overexpressed from lentiviral vectors in renal cells. Results: We found that lncRNA-ATB was remarkably upregulated in patients with acute rejection compared with controls. Meanwhile, lncRNA-ATB could influence the kidney cell phenotypes and impact the nephrotoxicity of immunosuppressive drug. Conclusion: In conclusion, lncRNA-ATB are strongly altered in patients with acute rejection and may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function. This article is protected by copyright. All rights reserved.
IgA nephropathy (IgAN) is one of the leading causes of glomerulonephritis characterized by the findings of IgA and IgG immune deposits in the mesangium of kidney biopsies from patients with persistent microscopic hematuria. IgAN is frequently detected among adolescents and young adults. IgAN presents a highly variable course that includes a spectrum from a very mild disease to end-stage renal disease (ESRD). There are several clinical and histological factors that strongly determined the final outcome of patients with IgAN. Pathological variables associated with unfavorable outcomes are mesangial hypercellularity, segmental glomerulosclerosis, endocapillary hypercellularity and interstitial fibrosis/tubular atrophy, according to the Oxford classification. Moreover, some studies also suggest a role for complement activation in the pathogenesis of IgAN. In this regard, staining for C4d may be an independent risk factor for the development of ESRD in IgAN. Despite the growing number of studies assessing IgAN risk factors, this kind of investigation in pediatric patients is still very limited. The aim of this article is to revise pathological markers related to deterioration of renal function in pediatric patients with IgAN, particularly those that can independently affect renal survival. This article is protected by copyright. All rights reserved.
To evaluate the incidence of and risk factors for subclinical hypothyroidism (SCH) in patients with type 2 diabetes mellitus (T2D), and determine the association of SCH with renal function.
T2D patients hospitalized between June 2007 and July 2008 were cross-sectionally assessed. Clinical indicators and renal function were compared between the SCH and normal thyroid function groups. Risk factors for SCH and diabetic renal injury (albuminuria) were evaluated by univariate and multivariate analyses.
SCH prevalence was significantly higher in women, with a male to female ratio of 1:2.7. Age (62.56 ± 10.79 vs. 59.09 ± 10.82 years, p = 0.008), systolic blood pressure (138.80 ± 18.85 vs. 131.29 ± 16.97, p = 0.000), TC (5.22 ± 1.20 vs. 4.83 ± 1.03 mmol/L; p = 0.008), LDL-C (3.35 ± 0.96 vs. 3.06 ± 0.87 mmol/L; p = 0.007), creatinine (84.54 ± 47.05 vs. 74.49 ± 29.96 µmol/L; p = 0.01), urinary albumin excretion rate [18.6 (7.58-326.78) vs. 10.69 (5.79-40.8) µg/min; p = 0.001], and thyrotropin [4.92 (4.37-6.27) vs. 1.4 (0.92-2.09) μIU/ml; p = 0.000] were significantly higher in the SCH group; meanwhile, TBIL (12.05 ± 5.20 vs. 13.98 ± 5.32 µmol/L; p = 0.008), DBIL (2.54 ± 1.20 vs. 2.88 ± 1.17 µmol/L; p = 0.033), IDBIL (9.51 ± 4.62 vs. 11.10 ± 4.72 µmol/L; p = 0.013), and total glomerular filtration rate [46.96 (35-68.26) vs. 71.74 (50.13-83.36) ml/min; p = 0.000] were significantly lower in SCH patients. Macroalbuminuria prevalence was significantly higher in the SCH group (18.2 vs. 11.4%; P < 0.001). Interestingly, SBP (OR = 1.050; 95%CI 1.034–1.066; p = 0.000), DR (OR = 5.248; 95%CI 2.816–9.777; p = 0.000), SCH (OR = 2.256; 95%CI 1.184–4.299; p = 0.013), and TC (OR = 1.389; 95%CI 1.108–1.742; p = 0.004) were found to be independent risk factors for macroalbuminuria.
These findings demonstrate an association of SCH with renal injury in diabetic patients. This article is protected by copyright. All rights reserved.
Inflammation is one of the major challenges in the management of ischaemia/reperfusion (I/R) induced acute kidney injury (AKI). Our aim was to assess the anti-inflammatory and protective effects of saffron extract against I/R-induced renal disturbances.
A total of 35 male Wistar rats were randomly divided into five groups (n = 7) as sham, I/R and three groups of I/R that were pretreated with different doses of saffron extract (5 mg/kg, 10 mg/kg, or 20 mg/kg) intraperitoneally (i.p.). The I/R-induced renal inflammation was assessed by measuring leukocyte infiltration and mRNA expression levels of intercellular adhesion molecule-1 (ICAM-1) and tumour necrotic factor-alpha (TNF-α). For the assessment of oxidative stress, thiobarbituric acid reactive species and antioxidant capacity of kidneys were measured in the right kidneys. In addition, plasma creatinine and urea-nitrogen concentrations were determined for renal functional disturbances. Statistical analysis was performed using one way ANOVA using the Duncan-post hoc test.
The I/R increased all of the measured parameters, except for the tissue level of FRAP, which decreased. Pretreatment with saffron extract in all doses significantly reduced the severity of these disturbances in such a way that there were no significant differences between the FRAP level and urea-nitrogen concentrations between the sham and all three saffron extract-treated groups. However, the saffron extract could decrease the plasma creatinine concentration, malondialdehyde level, TNF-α and ICAM-1expression and leukocyte infiltration in a dose-dependent manner.
The present study showed anti-inflammatory, anti-oxidative and protective effects for the hydro-ethanolic extract of saffron in I/R induced AKI.
Post-donation kidney function has not been well characterized in the Southeast Asian population. We studied a retrospective cohort of 174 living kidney donors at Singapore General Hospital between 1976 and 2012, evaluated patterns of change in kidney function using quantile regression analysis and investigated for predictors of low estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Median follow-up time (range) was 7.8 (0.1–33.8) years following donor nephrectomy.
Of the donors, 43.1% regained 75% or more of pre-nephrectomy eGFR after five years post-donation; 9.8% exhibited 100% recovery to pre-nephrectomy eGFR. High pre-nephrectomy eGFR was protective for risk of low post-donation eGFR, with a 6% risk reduction for each unit increase in pre-nephrectomy eGFR (odds ratio, 0.94; 95% confidence interval, 0.91–0.97; P = 0.002). This relationship was stronger in the short term (>6 months to < 5 years) than medium to long term (5 years or longer) (interaction P = 0.052).
In general, kidney function is well preserved following kidney donation in Southeast Asian donors. Pre-nephrectomy eGFR is a good predictor of post-donation eGFR, especially in the short-term.
Primary membranous nephropathy (PMN) accounts for only 1–2% of nephrotic syndrome in children. Antibodies to m-type phospholipase A2 receptor (aPLA2R) is seen in 70% of adult PMN cases. The present study was undertaken to study m-type phospholipase A2 receptor (PLA2R) status and clinical behavior in adolescent PMN cases.
The present prospective observational study included adolescent (10-19 years) onset biopsy proved PMN. Patients were followed on a monthly basis with urine protein, serum albumin and creatinine. Serum aPLA2R was done at baseline and at 6 and 12 months of starting treatment. Patients were treated as per unit's protocol.
During the study period a total of 18 patients were enrolled. The mean age of the cases was 16.27 ± 2.39 (11-19) years. Seventeen (94.44%) patients presented with nephrotic syndrome. The mean proteinuria and serum albumin was 4.52 ± 1.93 (2.43-9.20) g/day and 2.1 ± 0.6 (1.1-3.4) g/dL respectively. PMN was PLA2R related in 83%. aPLA2R and enhanced staining for PLA2R in glomeruli was seen in 14 (77.78%) and 13 (72.22%) respectively. Clinical remission at the end of 6 and 12 months of therapy was seen in 11 (61.11%) and 09 (50%) subjects respectively. There was a significant association of aPLA2R to clinical remission/ resistance.
PMN in adolescent population is aPLA2R related in over three-fourth of the cases and the response to therapy is seen in only one half of them. aPLA2R monitoring is clinically relevant and should be incorporated in the management of adolescent onset PMN.
The association between responsiveness to continuous erythropoietin-receptor activator (C.E.R.A.) and renal survival in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) is uncertain.
We performed a pooled analysis of individual patient-level data drawn from five clinical trials involving C.E.R.A. administration. Based on the responsiveness to C.E.R.A., patients were classified into poor- or good-response groups. Primary endpoints were defined as the initiation of dialysis or a 30% decrease in the estimated glomerular filtration rate (eGFR) from baseline. We set the landmark time point at 12 weeks after the start of C.E.R.A., from which we evaluated the time to the first renal event. The cumulative renal survival rates were calculated for each group using the Kaplan-Meier method. The adjusted hazard ratio was calculated using a stratified Cox regression model.
Of 408 patients, 226 were analyzed. Hemoglobin levels and eGFRs were significantly lower in the poor-response group (n = 113) than in the good-response group (n = 113). Renal events occurred in 36.3% of the poor-response group and in 23.0% of the good-response group. The intergroup difference in renal survival rates was significant (log-rank test, P = 0.03) and the adjusted hazard ratio was 1.71 (95% confidence interval, 1.03–2.83), indicating an unfavorable outcome in the poor-response group.
Hyporesponsiveness to C.E.R.A. was associated with poor renal survival, consistent with the results of the conventional erythropoiesis-stimulating agent (ESA). It is recommended that a randomized controlled trial on C.E.R.A. use be performed in patients with NDD-CKD with ESA-hyporesponsive anemia.
Indigenous Australians are significantly burdened by chronic kidney disease (CKD). Elevated levels of C-reactive protein (CRP) have been associated with diabetes and cardiovascular incidence in previous studies. Elevated CRP has been associated with albuminuria and reduced eGFR in cross-section, this study investigated the long term predictive association between CRP measured at a baseline exam and the incidence of a CKD-related hospitalisation.
Health screening examinations were conducted for individuals of a remote indigenous Australian community between 1992 and 1998. Using Northern Territory hospital records up to 2010, Cox proportional hazard models estimated the risk of CKD hospitalisations.
546 participants were included in the analysis and represented 80% of the age-eligible population. The baseline characteristics showed increased levels of traditional cardiovascular risk factors in individuals of the highest CRP tertile. Participants in the highest CRP tertile had almost 4 times the risk for a CKD-related hospitalisation compared with participants in the lowest tertile (HR = 3.91, 95%CI 1.01-15.20, p = 0.049) after adjustment for potential confounding factors. Participants with CRP concentrations greater than 3 mg/L had almost 3 times the risk of CKD hospitalisations than those ≤3 mg/L (HR = 2.84, 95%CI 1.00-8.00, p = 0.049). Furthermore, risk for CKD increased 34% per doubled increase in CRP (HR = 1.34, 95%CI 1.04-1.74, p = 0.024).
Elevated C-reactive protein levels can predict the risk for CKD almost a decade prior to an incident CKD-related hospitalisation in individuals of this remote indigenous community. Further research is needed to understand the role CRP and systemic inflammation plays in CKD risk.
Hyperchloremic acidosis may have an important role as a precursor of acute kidney injury (AKI) in the hyperchloremic environment induced by chloride-rich fluids, but this remains unclear. We tested the hypothesis that hyperchloremic acidosis assessed by the Stewart approach is associated with postoperative AKI.
A historical cohort study was conducted in adult patients who had normal renal function preoperatively and required admission to the intensive care unit after elective abdominal surgery. The RIFLE classification was used for definition of AKI.
Of 206 patients (144 male, 69.9%) included in the study, 42 (20.4%) had postoperative AKI (AKI group) and 164 (79.6%) did not (non-AKI group). Base excess-chloride (BE-Cl) and strong ion difference (SID, approximated as Na-Cl) decreased and the chloride level on postoperative day 1 increased compared to preoperative values in both groups (p < 0.05). In the AKI group, BE-Cl and SID were lower and chloride was higher than in the non-AKI group (p < 0.05). The intraoperative load of chloride ions in fluids increased the risk of postoperative AKI (p < 0.01). In multivariate logistic regression analysis, postoperative BE-Cl < -7 mEq L-1 (i.e., SID <31 mEq L-1) was an independent risk factor for AKI (odds ratio; 2.8, 95% CI; 1.2-6.4, p = 0.01). In the AKI group, stays in the intensive care unit and in hospital were longer than those in the non-AKI group (p < 0.05).
Hyperchloremic acidosis is associated with postoperative AKI, and this may be attenuated by reducing the intraoperative chloride load.
Treatment of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is difficult. Addition of ribavirin to pegylated-interferon (Peg-IFN) may help to improve the treatment response. Further, treatment duration could be shortened using a response-guided treatment (RGT) approach.
We retrospectively reviewed records of treatment-naïve adult patients with ESRD and chronic HCV infection treated with Peg-IFN and low-dose ribavirin using a RGT approach. Rapid responders (undetectable HCV-RNA at 4 weeks) received treatment for 12 weeks, and slow responders (HCV-RNA detectable at 4 weeks, but undetectable or with >2.0 log10 reduction at week 12) for 24 (genotype 3; GT3) or 48 (genotype 1; GT1) weeks. In those without such reduction (null responders), treatment was discontinued.
Of 26 non-cirrhotic patients (GT1 15, GT3 11) treated, four (15%; GT1 3, GT3 1) were null responders. Twenty-two (85%) patients had either rapid (n = 14 [54%]; GT1 10, GT3 4) or slow response (n = 8 [31%]; GT1 2, GT3 6), and had undetectable RNA at end of treatment. One patient could not complete the treatment and was lost thereafter. There were no deaths during treatment. Three patients relapsed and three others died in 6 months after stopping treatment. Overall, 15/26 (58%) patients attained SVR24. Fourteen patients underwent transplantation beginning one month after treatment completion, and all were relapse-free after 17 (14-24) months of follow-up.
RGT using Peg-IFN and ribavirin was effective ESRD patients on maintenance dialysis. Renal transplant was safely done within one month of completing such treatment.
The main cause of malnutrition in hemodialysis patients is a spontaneous decline in energy and protein intakes. This study aims to report the dietary energy intake (DEI), dietary protein intake (DPI), and dietary micronutrient intake in a French HD population, to report factors associated with a low DPI and DEI, and to analyze if nutritional intake was correlated with nutritional status.
We conducted an observational cross-sectional study in a hemodialysis population of 87 adult patients in July 2014. Daily nutritional oral intake, handgrip strength, body composition measured by bioimpedancemetry, and biological and dialysis parameters were obtained from medical records. Statistical analyses of parameters associated with DEI and DPI were performed.
The median age (interquartile range) of the population was 77.3[71.1; 84.8] years, 57.5% were men, and 52.9% had diabetes mellitus. Median weight-adjusted DEI was 18.4[15.7;22.3]kcal/kg/day (1308 [1078; 1569] kcal/day), and median weight-adjusted DPI was 0.80[0.66; 0.96] g/kg/day (57.5[47.1; 66.8] g/day).
In multivariate analysis, weight-adjusted DEI was statistically lower in patients with diabetes (coefficient [95%CI] -3.81[-5.21;-2.41] kcal/kg/day; p = 0.01) but was not associated with the others parameters. When DEI was not adjusted for weight, diabetes was no longer associated with DEI, but female gender (-178[-259;-961] kcal/day; p = 0.03) and a higher Charlson comorbidity index (-30[-44;-15]; p = 0.04) were associated with a lower calorie intake. Results for DPI were similar except that the Charlson comorbidity index did not reach significance.
Diabetes is an important factor associated with low dietary intake in hemodialysis patients. Restrictive regimens should be prescribed cautiously in hemodialysis patients, especially in those with diabetes.
This study was designed to evaluate the relationship between sleep quality and hypertension and to determine if there was an association between nondipper blood pressure (BP) and sleep quality in chronic kidney disease (CKD) patients.
A total of 775 pre-dialysis CKD patients (314 normal BP patients, 461 hypertension patients) defined as dippers or nondippers by ambulatory BP monitoring were recruited for this study. Demographics and clinical correlates were collected, including body mass index, estimated glomerular filtration rate (eGFR) and other measures. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI).
A total of 185 (58.9%) patients with normal BP and 341 (74.0%) hypertensive patients had a nondipper BP pattern. The hypertension group had a higher prevalence of the nondipper BP pattern, smoking, alcohol intake and diabetes mellitus (DM), and lower eGFR levels and poorer sleep quality than the normal BP group. Patients with the nondipper BP pattern had lower hemoglobin, worse renal function and poorer sleep quality when compared to hypertensive CKD patients with the dipping BP pattern. PSQI scores were significantly associated with the rate of nocturnal BP decline (p < 0.05) in the hypertension group but not in the normal BP group. Poor sleep quality was an independent factor affecting BP pattern in hypertensive CKD patients using multivariate linear and logistic regression analyses. There was no association between sleep quality and hypertension in CKD patients after multivariate logistic regression analyses.
Poor sleep quality, which is commonly observed in pre-dialysis CKD patients, is an independent associated factor of the nondipper BP pattern in hypertensive CKD patients. No association was found between poor sleep and nondipper BP in normotensive patients.
Furosemide is a loop diuretic. Different authors demonstrated that continuous administration of furosemide modulates the expression of organic anion transporters. This study was undertaken to simultaneously evaluate the effects of furosemide pretreatment on organic anion transporter 1 (Oat1) and multidrug resistance protein 2 (Mrp2) renal expressions, on p-aminohippurate (PAH) pharmacokinetics and on renal and urinary PAH levels in rats.
Male Wistar rats were treated with furosemide (6 mg/100 g b.w./day, s.c, 4 days) (Treated group) or saline (Control group). On the 5th day, PAH was administered as a bolus infusion in the femoral vein and plasma samples were obtained from femoral artery at different time points. PAH levels in renal tissue and urine were also assessed. Renal Oat1 and Mrp2 expressions were evaluated by Western blotting.
Furosemide pretreatment increased both the expression of Oat1 and Mrp2. PAH plasma concentrations decreased following a biexponential function. Furosemide-treated group showed higher PAH plasma levels, a lower systemic clearance and elimination rate constant from the peripheral compartment, indicating that PAH renal elimination was decreased. PAH levels in renal tissue were significantly elevated and in urine appeared to be significantly lower as compared with control animals.
Furosemide pretreatment caused a significant decrease of PAH renal elimination, despite Oat1 and Mrp2 augmented renal expression.
The goal of the present study is the addition of important information in the wide gap of knowledge that exists about drug-drug interactions. Due to furosemide worldwide use, the data obtained are interesting and useful in terms of translation to clinical practice.
Risk profile for incident chronic kidney disease (CKD) in Japanese subjects has not been established.
Consecutive 171536 health examinees (median age 49 yrs and estimated glomerular filtration rate (eGFR) 78.2 mL/min/1.73 m2) without CKD were re-examined after a median period of 6.2 yrs. Results of Cox proportional hazards models in randomly assigned two thirds (Derivation cohort) were verified in the rest (Validation cohort). CKD was defined as eGFR <60 mL/min/1.73 m2 or positive dipstick proteinuria.
n Derivation cohort, CKD developed in 1,002 (5.8%) subjects. Seven variables such as lower eGFR, male gender, higher uric acid concentration, lower red cell count and higher age, BMI and systolic blood pressure were identified as significant risks for CKD, with lowered eGFR being an overwhelmingly strong risk: adjusted odds ratio for those with the baseline eGFR <70 ml/min/1.73 m2 was as high as 90.1. Performance of prediction of CKD by the probability on the basis of the seven risk factors combined was only marginally preferable to eGFR alone. Namely, the area under the receiver operating characteristic curve (95% CI) for the prediction was 0.846 (0.826-0.864) and 0.822 (0.802-0.840) (P <0.01), the kappa statistic was 0.263 and 0.250 (n.s.), and the mean absolute difference between "predicted probability" and "observed" CKD was 1.4% and 1.9% (P =0.14) by the combined model and eGFR alone, respectively.
Seven risk factors for incident CKD were identified in Japanese health examinees. However, lowered baseline eGFR outweighed other risks to the degree that eGFR alone was suffice for CKD prediction.
To determine the concordance among the Cockcroft-Gault, the Modification of Diet in Renal Disease (MDRD) and the CKD-Epidemiology Collaboration (CKD-EPI) equations in hypothetical dosing of renally cleared medications.
A total of 2163 patients prescribed at least one of the 31 renally cleared drugs under review were included in the study. Kidney function was estimated using the three equations. We compared actual prescribed dosages of the same drug to recommended dosages based on the kidney function as calculated by each of the equations and applying dosing recommendations in the Australian Medicines Handbook.
There was a significant difference in the kidney function values estimated from the three equations (P < 0.001). Despite the good overall agreement in renal drug dosing, we found selected but potentially important discrepancies among the doses rendered from the equations. The CKD-EPI equation non-normalised for body surface area had a greater rate of concordance with the Cockcroft-Gault equation than the MDRD equation for renal drug dosing.
There is need for a long-term multi-centre study in a diverse population to define the clinical effects of the discrepancies among the equations for drug dosing. Given the greater concordance of the non-normalised CKD-EPI equation with the Cockcroft-Gault equation for dosing, the recommendation by Kidney Health Australia and the United States National Kidney Disease Education Program that "dosing based on either eCrCl or an eGFR with body surface area normalisation removed are acceptable" seems suitable and practicable for the purpose of dosing of non-critical drugs in the primary care setting.
Haemodiafiltration has been widely studied for evidence of superior outcomes in comparison to conventional haemodialysis and there is increasing interest in determining if haemodiafiltration confers any benefit in relation to quality of life. Studies have been conducted with randomized incident patients however little is known regarding haemodiafiltration and quality of life for prevalent patients. This study examined and compared self–reported quality of life at two time points twelve months apart in a cohort of satellite haemodialysis and haemodiafiltration patients using a disease specific questionnaire to determine if HDF conferred an advantage.
A longitudinal study with a linear mixed effect model measuring quality of life in a cohort of 171 patients (HD n 85, HDF n 86) in seven South Australian satellite dialysis centres.
Factors associated with significant reduction across the Kidney Disease Quality Of Life ™ domains measured were younger age (- 20 to 29.4) and comorbid diabetes (- 4.8 to 11.1). Haemodiafiltration was not associated with moderation of this reduction at either time point (p > 0.05). Baseline physical functioning was reported as very low (median 33.9) and further reduced at time point two. In addition dialysing for more than twelve hours per week in a satellite dialysis unit was associated with reduced quality of life in relation to the burden of kidney disease(- 13.69).
This study has demonstrated that younger age and comorbid diabetes were responsible for a statistically significant reduction in quality of life and haemodiafiltration did not confer any advantage.
This study aims to describe patients' perspectives on the transition to home haemodialysis.
Up to three sequential semi-structured interviews were conducted with 20 patients during the transition to home haemodialysis at an Australian renal unit. Transcripts were analysed thematically. Participants completed a satisfaction questionnaire after commencing home haemodialysis.
We identified six themes: persevering despite trepidations (diminishing intimidation of
machinery, acquiescing to fatal risks, reconciling fears of cannulation, dispelling concerns of neglect, tolerating necessary concessions); optimising the learning pathway (practising problem solving, learning from mistakes, grasping technical complexity, minimising cognitive overload, progressing at own pace); developing confidence (believing in own abilities, adapting to independence, depending on caregiver partnership, faith in crisis support); interrupted transition momentum (lacking individual attention, language barriers, installation delays, interfering illness and complications, acclimatising to new conditions); noticing immediate gains (reclaiming lifestyle normality, satisfying self-sufficiency, personalising treatment regime, thriving in a positive environment); depleting resources and energy (exhaustion with gruelling routine, confronting medicalization of the home, draining financial reserves, imposing family burden). Fewer than 30% of respondents indicated low satisfaction with staff availability domains, staff interpersonal domains or technical domains.
Home haemodialysis training fosters confidence in patients; however many patients experience stress due to medical isolation, treatment responsibilities, family impositions and financial difficulties. .Addressing patient's on-going psychosocial concerns may alleviate burdens on patients and their families during the transition to home haemodialysis.
Diabetes, hypertension and smoking may contribute to the development and progression of chronic kidney disease (CKD) and its complications. The aim of this study was to assess patients' awareness and beliefs about these and other risk factors associated with CKD.
Participants with CKD Stages 1-5 were purposively sampled for participation in a mixed methods study. Focus group participants completed a survey on CKD risk factors and discussed the reasons for their choices. Thematic analysis was used to analyse the qualitative data.
Of the 38 participants, the proportion who identified hypertension, family history, diabetes and obesity as risk factors for CKD were 89%, 87%, 87% and 70% respectively. Only 54% and 38% recognised that smoking and Aboriginal or Torres Strait Islander status were risk factors. Participants considered the risks of heart attack, stroke and premature mortality to be 20-40% lower in people with CKD than those with diabetes or pre-existing CVD. Five themes were identified: invisibility (lack of signs and symptoms of CKD), invincibility (participants did not feel they were at risk), lacking awareness (identified not knowing much about their disease), cumulative comorbidities (concerned about the increased risks of associated diseases) and inevitability of death (there is no cure for CKD).
Participants had good understanding of some risk factors for CKD (hypertension and diabetes) but limited understanding of others. Awareness of comorbidities was also less than for other chronic conditions. Compared to diabetes and CVD, CKD was perceived to pose less of a threat to life. Patient education that addresses CKD risk factors, comorbidities and outcomes may increase awareness and foster better self-management for people with CKD.
We aimed to estimate the burden of end-stage renal disease (ESRD) among patients admitted to intensive care units (ICUs), by comparing hospital outcomes between patients with and without ESRD.
Using the Japanese Diagnosis Procedure Combination database, we identified patients aged 20 years or older who were admitted to ICUs for ≥3 days (2 nights) in 2011. We created a matched cohort of patients with and without ESRD for hospital, age, sex, main diagnosis category, and ICU admission type (medical or surgical) at a maximum ratio of 1:3. For these matched patients, we compared patient characteristics, treatment regimens at ICU admission, and hospital outcomes. We also performed a multivariable logistic regression analysis for the associations between ESRD and 28-day (counting from ICU admission) and in-hospital mortality.
Among the 164,423 eligible patients, 7,998 (4.9%) had ESRD, from which 5,228 ESRD and 12,274 non-ESRD patients were matched for the aforementioned factors. Compared to non-ESRD patients, ESRD patients were on more intensive treatment regimens, including mechanical ventilation, vasoactive drugs, and blood transfusion. Patients with ESRD showed significantly higher ICU, 28-day, and in-hospital mortality and longer lengths of stay in the ICU and hospital (28-day mortality: 11.7% vs. 8.3%; P < 0.001, in-hospital mortality: 21.1% vs. 12.0%; P < 0.001). After adjusting for confounding factors, ESRD was independently associated with 28-day mortality (adjusted odds ratio: 1.36, 95% confidence interval [CI]: 1.22–1.52) and in-hospital mortality (adjusted odds ratio: 1.85, 95% CI: 1.69–2.02).
This study involving the Japanese national inpatient database, with a matched-pair cohort design, suggested that ESRD is an important burden in the critical care setting.
Recent studies indicate that pirfenidone (PFD) may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. The purpose of this study is to investigate the potential effects of PFD on epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a unilateral ureteral obstruction (UUO) rat model and the involved molecular mechanism related to cultured human renal proximal tubular epithelial cells (HK-2).
Sixty rats were randomly divided into three groups: sham-operated, vehicle-treated UUO, and PFD-treated UUO. Kidney specimens were collected at day 7 or 14 after UUO. PFD treatment was also performed for human HK-2. The tubulointerstitial injury, interstitial collagen deposition, and expression of type I and III collagen, α-SMA, S100A4, fibronection and E-cadherin were assessed. In addition, extracellular signal regulated kinase (ERK1/2), p38 MAPK (p38), and c-Jun N-terminal kinase/stress-activated protein kinase (JNK) were also detected.
In vitro, PFD significantly attenuated TGF-β1-induced EMT and extracellular matrix (ECM) synthesis, as determined by reducing expression of α-SMA, type I and III collagen, S100A4, fibronection, and increased expression of E-cadherin. PFD treatment attenuated TGF-β1-induced up-regulation of phosphorylation of ERK1/2, p38 and JNK. In vivo, PFD reduced the degree of tubulointerstitial injury and renal fibrosis, which was associated with reduced expression of TGF-β1, type III collagen, α-SMA, S100A4, fibronection, and increased expression of E-cadherin.
These results suggest that pirfenidone is able to attenuate EMT and fibrosis in vivo and in vitro through antagonizing the MAPK pathway, providing a potential treatment to alleviate renal tubulointerstitial fibrosis.
The aim of this study was to investigate the association of an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) gene with serum ACE level in relation to the type and severity of malformations from congenital anomalies of the kidney and urinary tract (CAKUT) spectrum.
Group of 134 Bulgarian children with CAKUT divided into four subgroups according to the leading malformation and 109 controls were genotyped by classical polymerase chain reaction. The quantitative determination of serum ACE was performed by ELISA method.
A significant elevation of DD-genotype was observed in high-grade hydronephrosis compared to low-grade (43% vs. 9%). The carrying of DD-genotype was associated with higher risk for severe hydronephrosis with OR = 7.5 (95% CI: 1.242÷45.278; p = 0.028). Also, elevated serum ACE concentrations in patients with high-grade compared to low-grade hydronephrosis (237.4 ± 45 ng/ml vs 180.5 ± 64 ng/ml; p = 0.0065) were found. ACE level was significantly lower in patients with unilateral renal agenesis; hypo/dysplasia and multicystic dysplastic kidney (156.6 ± 54 ng/ml) than controls (200.6 ± 56.7 ng/ml; p = 0.005) and the rest CAKUT subgroups.
The DD genotype of I/D ACE polymorphism encodes the highest serum ACE level may be an additional genetic risk factor contributing to the severe hydronephrosis in Bulgarian patients with obstructive uropathies in contrast to other investigated categories of CAKUT malformations.
Palliative care is seldom proposed to patients with end-stage renal disease despite a mortality rate and disease burden as high as among cancer patients. The aim of this study is to analyse the access of palliative care-related hospitalization in the management of patients on dialysis in France, by describing the characteristics of these hospitalizations, the clinical status of the concerned patients, and the use of palliative care in those stopping dialysis.
The French REIN registry includes data about 51,834 patients aged 20 years and older who began dialysis from January 1, 2008, to December 31, 2013, and were followed longitudinally until that date. Linkage to the anonymized national hospital discharge database allowed us to analyse hospitalizations associated with palliative care.
During the follow-up period, 1865 patients (3.6%) had a palliative care-related hospitalization corresponding to a total of 3382 hospitalizations. Lower levels of serum albumin, active cancer, and impaired mobility were each independently associated with the probability of at least one such hospitalization. During the same period 4540 patients withdrew from dialysis (9% of the patients), 10% of them had a palliative care-related hospitalization.
This study suggests that among ESRD patients, only a few resorted to palliative care-related hospitalization, even those withdrawing from dialysis. Cooperation between nephrologists and physicians trained in palliative care should be improved at least to the extent necessary to identify patients who should be referred to palliative care. Our study also highlights the need of more information on the current access to any kind of supportive care for dialysis patients.
The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the prognostic implications and treatment patterns in Asian region. We have established the Asian Renal Collaboration (ARC) with the goal of consolidating region-wide data regarding CKD.
This collaborative project will synthesize data and perform meta-analyses of observational studies conducted in Asia. Studies will be identified through a systematic literature search including abstracts, proceedings of meetings, electronic databases such as MEDLINE and EMBASE. Personal enquiry among collaborators and experts in the region will identify additional studies, or other data sources such as registries. Both cross-sectional and longitudinal studies that describe the prevalence of CKD and its complications will be included, as will longitudinal studies that describe important clinical outcomes for people with CKD. Individual participant data will be sought, where possible, from each of the studies included in the collaboration for baseline parameters and subsequent outcomes, in order to maximize flexibility and consistency of data analyses.
This study is an initiative offering a unique opportunity to obtain information about the prevalence and manifestations of CKD in Asia, as well as its risk factors. The ARC will also provide insights into important outcomes including progression of CKD, CKD complications, cardiovascular disease and death. These findings will improve our understanding of kidney disease in Asia, and thus help inform service provision, preventive care and further research across the region.
Complement-mediated atypical hemolytic uremic syndrome (aHUS) is a rare disease with high mortality and morbidity if left untreated. The diagnostic work-up is complicated and the manifestations overlap with other conditions. Therefore, we hypothesize that complement-mediated aHUS is an underdiagnosed disease.
A cohort of 768 referrals referred to the Coagulation Unit in Malmo, Sweden, for analysis of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), 2007-2012, were retrospectively reviewed. Subjects were included on the basis of presence of hemolytic anemia, thrombocytopenia, renal failure and ADAMTS13 > 0.05. They were excluded if tested positive for Escherica Coli. Included subjects were categorized as "suspected HUS" with and without potential causes and triggers. Levels of C3 and C4, presence of complement factor H (CFH)-specific antibodies and associated deficiency in complement factor H related protein 1 (CFHR1) were analyzed on frozen samples.
In total, 134/316 (42%) unique subjects fulfilled inclusion criteria; 103 were categorized as "suspected HUS associated with potential causes/triggers" and 31 subjects categorized as "suspected HUS" without such association. One case of complement-mediated aHUS had been confirmed during the treatment period. Laboratory analyses performed showed that in total 78 cases had findings consistent with complement-mediated aHUS: twenty-four cases indicated presence of CFH-specific antibodies whereof five cases had isolated low C3 titers and six cases had deficiency of CFHR1. Additionally 54 cases indicated isolated alternative pathway consumption.
The results suggest that the presence of complement-mediated aHUS was underdiagnosed in this cohort calling for improvement of diagnostic availability.
Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline (HERO) multi-centre double-blind, randomized controlled trial. The present sub-study evaluated the effects of pentoxifylline on the iron-regulatory hormone hepcidin in ESA-hyporesponsive CKD patients.
This sub-study included 13 patients in the pentoxifylline arm (400 mg daily) and 13 in the matched placebo arm. Hepcidin-25 was measured by Ultra Performance Liquid Chromatography/Quadrupole time-of-flight mass spectrometry following isolation from patient serum. Serum hepcidin-25, serum iron biomarkers, haemoglobin and ESA dosage were compared within and between the two groups.
Hepcidin-25 concentration at 4 months adjusted for baseline did not differ significantly in pentoxifylline vs. placebo treated patients (adjusted mean difference (MD) -7.9 nmol, P = 0.114), although the difference between the groups mean translated into a >25% reduction of circulating hepcidin-25 due to pentoxifylline compared to the placebo baseline. In paired analysis serum hepcidin-25 levels were significantly decreased at 4 months compared to baseline in the pentoxifylline group (-5.47 ± 2.27 nmol/l, P < 0.05), but not in the placebo group (2.82 ± 4.29 nmol/l, P = 0.24). Pentoxifylline did not significantly alter serum ferritin (MD 55.4mcg/l), transferrin saturation (MD 4.04%), the dosage of ESA (MD -9.93 U/kg/week), or haemoglobin concentration (MD 5.75 g/l).
The reduction of circulating hepcidin-25 due to pentoxifylline did not reach statistical significance, however, the magnitude of the difference suggests that pentoxifylline may be a clinically and biologically meaningful modulator of hepcidin-25 in dialysis patients with ESA-hyporesponsive anaemia.
To describe the clinical features, treatment and outcomes in Australian adults with focal segmental glomerulosclerosis and identify predictors of disease progression and all-cause mortality.
The study included all patients with biopsy confirmed focal segmental glomerulosclerosis between January 1997 and June 2014 at participating hospitals. Clinical factors, histopathological findings, biochemical markers and treatments were analysed and potential predictors of doubling serum creatinine, end stage kidney disease or death identified.
98 patients were included with a median follow-up of 4.3 years. 34 (35%) patients were Aboriginal or Torres Strait Islander. Focal segmental glomerulosclerosis not-otherwise-specified was the most common variant. 17 (59%) patients initially treated with immunosuppression experienced an improvement in renal function. At the end of follow-up 43 (44%) patients had progressed to the composite outcome. Baseline tubulointerstitial scarring and lower haemoglobin predicted shorter time to doubling serum creatinine. Dual diagnosis, higher serum creatinine, lower estimated glomerular filtration rate and doubling creatinine were associated with shorter time to end stage kidney disease with remission the only protective factor. Age was the only variable associated with all-cause mortality.
Focal segmental glomerulosclerosis holds serious implications for patients. Concomitant diabetic nephropathy, higher serum creatinine and lower estimated glomerular filtration rate at renal biopsy were associated with poorer renal prognosis. Indigenous people had a female predominance and are over-represented in relation to their population size, however were not associated with poorer prognosis. Remission was the only modifiable variable and thus should be at the forefront of patient management goals and future studies.
The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed the diagnostic criteria for protein-energy wasting (PEW). We studied Japanese haemodialysis (HD) patients to verify the diagnostic method, especially with respect to the body mass index (BMI) criterion, as well as the prevalence of PEW and its association with mortality.
Japanese patients receiving maintenance HD at three outpatient clinics in Tokyo (n = 210) were enrolled, and prospectively followed-up for 3 years. PEW was diagnosed at baseline, according to the four categories (serum chemistry, body mass, muscle mass and dietary intake) recommended by the ISRNM. For the category of body mass, we select a body mass index (BMI) and set up three thresholds, <18.5, <20.0 and <23.0 kg/m2, as the diagnostic criterion. The patients who satisfied at least three out of the four categories were diagnosed as PEW.
PEW, when the threshold of a BMI among the diagnostic criteria was defined as <18.5 kg/m2, was recognized as an independent risk factor for mortality. However, PEW was not recognized as a risk factor when the BMI diagnostic criterion was set at <20.0 or <23.0 kg/m2. Overall, 14.8% of the patients had PEW. The survival rate of PEW patients was significantly lower than that of non-PEW patients (log rank, p < 0.001).
The diagnosis algorithm of PEW proposed by an expert panel of the ISRNM strongly associates with mortality. However, given differences in body size in Japan, we suggest to revise the BMI criterion from <23.0 kg/m2 to <18.5 kg/m2.
The purpose of this study was to investigate the possible association of circulating concentrations of sclerostin with abdominal aortic calcification (AAC) and cardiovascular outcomes in patients with chronic kidney disease stage 3-5.
One hundred and sixty-one patients with CKD3-5D were enrolled. The patients were divided into two groups according to the presence of AAC: an AAC group (n = 99) and a non-AAC group (n = 62). The concentration of serum sclerostin was measured using an enzyme-linked immunosorbent assay (ELISA). AAC was evaluated using abdominal lateral X-ray examination. The follow-up intervals ranged from 7 to 29 months (median 16 months), and cardiovascular events(CVEs) were recorded.
The prevalence of vascular calcification (VC) was 61.5% (99/161). Serum sclerostin was significantly higher in an AAC group than in a non-AAC group (P < 0.001), but the concentration in the moderate-to-severe AAC group was lower than in the mild AAC group (P < 0.001). Binary logistic regression analysis revealed that high serum sclerostin, high serum calcium, diabetes, and old age were independently correlated with AAC. Patients with higher sclerostin values had a reduced risk of major cardiovascular events (log-rank test, P = 0.001).
Serum sclerostin values are associated with the presence of AAC, but are lower when AAC is moderate to severe. Higher values are predictive of reduced short-term cardiovascular events. Taken together, these results suggest that sclerostin may have a role in the development of or the response to vascular calcification.
The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair.
Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor β (TGF-β), cystatin C (CysC) and urinary N-Acetyl-ß-D–Glucosaminidase (UNAG), and histopathological investigation of of kidney tissue sections were performed.
The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decrease serum creatinine, urea, TGF-β and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules.
The current data provided distinct evidence about the favorable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation.
Physical performance in chronic kidney disease affects morbidity and mortality. The aim was to find out which measures of physical performance are important in CKD and if there are associations with declining measured GFR.
Endurance was assessed by 6-minute walk test (6-MWT) and stair climbing, muscular endurance by 30-seconds sit to stand, heel rises and toe lifts, strength by quadriceps- and handgrip strength, balance by functional reach and Berg´s balance scale, and fine motor skills by Moberg´s picking-up test. GFR was measured by Iohexol clearance.
The study comprised 101 patients with CKD 3b-5 not started dialysis, 40 women and 61 men, with a mean age of 67 ± 13 (range: 22 – 87) years. All measures of physical performance were impaired. A decrease in GFR of 10 ml/min/1.73 m2 corresponded to a 35 metre shorter walking distance in the 6-MWT. Multivariable linear regression analysis showed significant relationships between decline in GFR and the 6-MWT (p = 0.04), isometric quadriceps strength left (p = 0.04), balance measured as functional reach (p = 0.02) and fine motor skills in the left hand as measured by Moberg´s picking-up test (p = 0.01), respectively, after sex, age, comorbidity and the interaction between sex and age had been taken into account.
Endurance, muscular endurance, strength, balance and fine motor skills were impaired in patients with CKD 3b-5. Walking capacity, isometric quadriceps strength, balance, and fine motor skills were associated with declining GFR. The left extremities were more susceptible to GFR, ageing and comorbidities and seem thus to be more sensitive
People with end-stage kidney disease receiving haemodialysis are restricted to holidays where dialysis services are readily available. Holiday dialysis in regional, rural and remote areas is particularly challenging. The aims of this study were to (1) evaluate the wellbeing of those who received dialysis in a holiday haemodialysis bus, and (2) to measure patient wellbeing with that of a comparable cohort of haemodialysis patients.
A three machine haemodialysis bus, the Big Red Kidney Bus, was built to enable people, their families and carers to take holidays across a range of tourist destinations in Victoria, Australia. Measures included pre-post subjective wellbeing, dialysis symptoms and mood questionnaires complemented by post semi-structured telephone interviews.
Participating holidaymakers were positive about the haemodialysis bus service and the standard of care experienced. They reported decreased dialysis side effects of fatigue, muscle cramp, and dry skin. The overall number of reported symptoms decreased and the perceived level of bother associated with symptoms also decreased. No changes in subjective wellbeing and mood were detected. Mean Personal Wellbeing Index scores were significantly higher than in a comparative haemodialysis sample.
The Big Red Kidney Bus provided a safe and feasible holiday dialysis service. Holidaymakers' wellbeing was reflected by the decreased dialysis patient side effects.
Lupus nephritis (LN) is associated with significant morbidity and mortality and hence usually treated aggressively with immunosuppressants. This predisposes LN patients to increased infections, yet few studies have evaluated LN patients for infective complications. We aimed to describe the epidemiology and identify risk factors for infections requiring hospitalisation among patients with biopsy-proven LN.
This was a single-centre retrospective cohort study of patients with biopsy-proven LN between 1st January 2000 and 31st May 2009. Patients were excluded if they were <16 years old at time of biopsy, had previous kidney transplant or if pharmacotherapy data were incomplete. Hospitalisations for infections, bacteremia and polymicrobial infections were recorded until patients' last visit or when they received immunosuppression for non-glomerulonephritis indications, such as solid organ transplant or chemotherapy.
We studied 189 patients who had biopsy-proven lupus nephritis. Median age at diagnosis was 36.9 (IQR: 27.4, 47.5) years and 82% were female. Most patients received at least 1 immunosuppressant after LN diagnosis, including glucocorticosteroids in 94.2%. One hundred and four patients (60.3%) had at least 1 hospitalisation for infection at 11 (1, 53) months from diagnosis. Bacteraemia occurred in 26 patients (13.8%) and 32 patients (16.9%) had polymicrobial infections. On multi-variate analysis, LN relapse was associated with hospitalisation for infection [OR 2.33 (1.18, 4.60), p = 0.01] and bacteraemia [OR 3.47 (1.05, 11.45), p = 0.04]. Infection-related mortality occurred in 10 patients (5.3%).
Serious infections are common among patients with LN and are associated with mortality.
Prolonged QT interval is related to changes of electrolytes in hemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients.
The QT intervals were measured in 2003 and all patients were followed to Dec 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis.
Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 [95% confidence interval (CI): 1.06-2.39, p = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, p = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (p = 0.03, log-rank test) and cardiac mortality free survival (p = 0.05, log-rank test).
Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.
A single center retrospective cohort study was designed to investigate the estimated glomerular filtration rate (eGFR) in school-age children born with extremely low birth weight (ELBW) and to determine risk factors predictive of decreased eGFR.
We compared eGFR based on cystatin C (CysC-eGFR) between school-age children born with ELBW (ELBW group, n = 48; median gestational age: 26.9 weeks; median birth weight: 792 g) and children born at term (control group, n = 48). The ELBW group was then further divided into a decreased CysC-eGFR subgroup (eGFR <90 ml/min/1.73 m2, n = 20) and a normal CysC-eGFR subgroup (n = 28), and perinatal background factors were compared.
The ELBW group showed a significantly lower CysC-eGFR compared with the control group (p < 0.001). Comparison between the decreased and normal CysC-eGFR subgroups in the ELBW group showed that children with lower birth weight, shorter gestational age, lower 5-min Apgar score, longer length of mechanical ventilation, lower weight gain in the first 11 weeks, chronic lung disease, and postnatal corticosteroid administration had significantly decreased CysC-eGFR. Multivariate logistic regression showed that a lower 5-min Apgar score was the only independent risk factor for decreased CysC-eGFR.
CysC-eGFR might already be decreased at school age in children born with ELBW. Renal assessment in regular follow-up examinations is recommended.
Tumor lysis syndrome (TLS) is a life threatening emergency due to destruction and massive release of intracellular metabolites from cancer cells often resulting in acute kidney injury (AKI), sometimes severe enough to require dialysis (AKI-D). The impact of dialysis requirement in AKI has not been explored. We utilized data from the Nationwide Inpatient Sample and using International Classification of Diseases, 9th Revision, diagnoses codes for TLS, AKI and dialysis, evaluated the incidence, risk factors and impact of AKI-D on mortality, adverse discharge and length of stay (LOS). Survey multivariable logistic regression was used to compute adjusted Odds Ratios (aOR and 95% confidence intervals (CI). An estimated 12% (2,919) of all TLS hospitalizations (N = 22,875) develop AK-D. After adjustment for confounders, AKI-D was associated with greater odds of mortality (aOR 1.98; 95% CI 1.60-2.45]), adverse discharge (aOR 1.63 [95% CI 1.19-2.24]) and longer LOS (19 vs. 14.6 days; p < 0.01) compared to those without AKI-D. Further studies to evaluate the association of AKI-D on long-term outcomes in patients with TLS are needed.
Total parathyroidectomy with autotransplantation(TPTX+AT) and subtotal parathyroidectomy(SPTX) have been recommended to patients with renal hyperparathyroidism(RHPT).But which one is the best surgical method remains controversial. The aim of the present study was to compare the two surgical procedures with respect to long-term outcomes.
A literature search was undertaken using Medline, EMBASE, CNKI and CBM from inception to May 2015. Study quality was assessed using the Newcastle-Ottawa Scale. Data were analyzed using Review Manager version 5.1.0.
A total of 13 studies comprising 1589 patients with renal failure were identified. There was no statistically significant difference in the rate of symptomatic improvement(OR 0.77; 95%CI 0.22 to 2.69; P = 0.68), radiological success (OR 0.17; 95%CI 0.02 to 1.56; P = 0.90), hyperparathyroidism recurrence or persistence(OR 1.31; 95%CI 0.65 to 2.65; P = 0.45) and reoperation(OR 1.55; 95%CI 0.62 to 3.86;P = 0.35) between TPTX + AT and SPTX. The effects on serum calcium and parathyroid hormone(PTH) were similar between two surgical protocols.
Both the TPTX + AT and SPTX were effective in treating RHPT and preventing recurrence. The difference between the two surgeries in recurrence or persistence and reoperation rate was insignificant. Further prospective, randomized controlled trials with high statistic power are necessary to comparative the two surgeries on the long term safety.
The study evaluated the risk of sudden sensorineural hearing loss (SSHR) in patients with end-stage renal disease (ESRD) undergoing dialysis
We identified 18,905 patients newly diagnosed with ESRD, comprising 6,382 patients on peritoneal dialysis (PD) and 12,523 patients on hemodialysis (HD) using Taiwan's National Health Insurance claims data from 2000 to 2010. A total of 76,520 controls without kidney disease were randomly selected with frequency matched with the ESRD group by age and sex. We further established additional cohorts with 6,375 patients on PD and 6,375 patients on HD matched by their propensity scores. Cox proportional hazards models were used to examine the effect of ESRD and dialysis modality on the risk of SSHL by the end of 2011.
The incidences for SSHR were 0.49, 2.37, 2.95, and 2.12 per 1,000 person-years in the control, ESRD (PD and HD), PD, and HD cohorts, respectively. The adjusted HRs of SSHR was 2.71, 3.60, and 2.33 for ESRD, PD, and HD groups (95% CI = 2.17-3.38, 2.71-4.78 and 1.81-2.99, respectively) compared with the control cohort. Patients on PD exhibited 1.53-fold (95% CI = 1.14-2.04) and 1.64-fold (95% CI = 1.19-2.27) higher SSHL risk than their age- and sex-matched and propensity score-matched patients on HD, respectively.
Patients with ESRD exhibit a higher risk of SSHL than people without kidney disease. The SSHL risk is greater for patients on PD than on HD.
The incidence of acute kidney injury (AKI) is a frequent and serious complication of cardiac surgery. In 2013, 95% of cardiac surgical procedures performed in Australia and New Zealand utilised cardiopulmonary bypass (CPB). Acute kidney injury following CPB is well known yet the perioperative factors contributing to its development are incompletely understood. Acute kidney injury following CPB has significant implications on both short and long term outcomes. The techniques for conducting CPB have evolved moving towards evidence-based practice however there is still no generally accepted definition of optimal perfusion and its conduct. This review examines the current incidence of AKI following cardiac surgery and the short and longer-term effects of AKI on morbidity and mortality. The purpose of this review is to discuss the perioperative risk factors related to CPB and their contribution to the development of AKI. Outcomes in regards to off pump cardiac surgery, the role of remote ischaemic preconditioning on AKI and outcomes in patients with chronic renal failure undergoing cardiac surgery will also be discussed. This article is protected by copyright. All rights reserved.
We summarise new knowledge that has accrued in recent years on CKD in Indigenous Australians. CKD refers to all stages of pre-terminal kidney disease, as well as to end-stage kidney failure (ESKF), whether or not a person receives renal replacement therapy (RRT)). Recently recorded rates of ESKF, RRT, non-dialysis CKD hospitalisations and CKD attributed deaths were, respectively, more than 6-fold, 8-fold, 8-fold and 3-fold those of non-Indigenous Australians, with age adjustment, although all except the RRT rates are still under-enumerated. However, the nationwide average Indigenous incidence rate of RRT appears to have stabilised. The median age of Indigenous people with ESKF was about 30 years less than for non-Indigenous people, and 84% of them received RTT, while only half of non-Indigenous people with ESKF did so. The first-ever (2012) nationwide health survey data showed elevated levels of CKD markers in Indigenous people at the community level. For all CKD parameters, rates among Indigenous people themselves were strikingly correlated with increasing remoteness of residence and socioeconomic disadvantage, and there was a female predominance in remote areas. The burden of renal disease in Australian Indigenous people is seriously understated by Global Burden of Disease Mortality methodology, because it employs underlying cause of death only, and because deaths of people on RRT are frequently attributed to non-renal causes.
These data give a much expanded view of CKD in Aboriginal people. Methodologic approaches must be remedied for a full appreciation of the burden, costs and outcomes of the disease, to direct appropriate policy development. This article is protected by copyright. All rights reserved.
Acute post infectious glomerulonephritis is common in Indigenous communities in the Northern Territory, Australia. It is a major risk factor for the high prevalence of chronic kidney disease. We aimed to analyse the clinical presentation, pathological spectra, treatment and outcomes of biopsy-proven acute post infectious glomerulonephritis in the Northern Territory.
We performed a retrospective cohort analysis of all adult patients (≥18 years) who were diagnosed with acute post infectious glomerulonephritis on native renal biopsies from 01/01/2004 to 31/05/2014. The outcome measure was end stage renal disease requiring long-term dialysis.
Forty-three of 340 patients who had renal biopsies had acute post infectious glomerulonephritis. Most were Aboriginals (88.4%). They had comorbidities; diabetes mellitus (60.5%), hypertension (60.5%) and smoking (56.4%). 49% had multiple pathologies on biopsy. Predominant histological pattern was diffuse proliferative glomerulonephritis (72%). Main sites of infections were skin (47.6%) and upper respiratory tract infection (26.2%) with streptococcus and staphylococcus as predominant organisms. Fifty percent of patients developed end stage renal disease. On multivariable logistic regression analysis, those on dialysis had higher baseline creatinine (p = 0.003), higher albumin/creatinine ratio at presentation (p = 0.023), higher serum creatinine at presentation (p = 0.02), and lower estimated glomerular filtration rate at presentation (p = 0.012).
Overall, most patients had pre-existing pathology with superimposed acute post infectious glomerulonephritis that led to poor outcomes in our cohort.
Sepsis is the leading cause of ICU admission. Plasma NGAL is a promising biomarker for AKI detection, however it is also increased with inflammation and few studies have been conducted in non-caucasion populations and/or in developing economies. Therefore, we evaluated plasma NGAL's diagnostic performance in the presence of sepsis and systemic inflammatory response syndrome (SIRS) in a Malaysian ICU cohort.
This is a prospective observational study on patients with SIRS. Plasma creatinine (pCr) and NGAL were measured on ICU admission. Patients were classified according to the occurrence of AKI and sepsis.
Of 225 patients recruited, 129 (57%) had sepsis of whom 67 (52%) also had AKI. 96 patients (43%) had non-infectious SIRS, of whom 36 (21%) also had AKI. NGAL concentrations were higher in AKI patients within both the sepsis and non-infectious SIRS cohorts (both p < 0.0001). The diagnostic area under curve for AKI was 0.81 (95%CI: 0.74 to 0.87). The optimal cut-off was higher in sepsis compared to non-infectious SIRS patients (454 versus 176 ng/ml). Addition of NGAL to a clinical model comprising age, pCr, medical admission category and SAPS II score increased the mean risk of those with AKI by 4% and reduced the mean risk of those without AKI by 3%.
AKI is more common with sepsis than non-infectious SIRS. Plasma NGAL was diagnostic of AKI in both subgroups. The optimal cut-off for diagnosing AKI was higher in sepsis than in non-infectious SIRS. Addition of plasma NGAL improved the clinical model used to diagnose AKI.
Cryoglobulinemic glomerulonephritis related to hepatitis B virus (HBV) infection has been rarely reported. The aim of this study was to investigate the clinical features, renal biopsy findings in patients with HBV-associated cryoglobulinemia.
Twelve patients with HBV-associated cryoglobulinemia were identified in this study. The demographic, clinical, pathological characteristics, treatment and follow-up data were analyzed.
Renal involvement was characterized by nephrotic range proteinuria with microscopic hematuria in all patients, and impaired renal function in 9 patients (75%). Purpuric rash was the main extrarenal manifestation (58.3%). Type II cryoglobulinemia was presented in 3 patients and type III in 9 patients. Hypocomplementemia and positive of rheumatoid factors were present in all patients. Membranoproliferative glomerulonephritis (MPGN) was observed in all kidney specimens. Seven patients also had evidence of prominent cryoglobulins thrombi on renal biopsy, but only three patients had HBV antigen deposits in renal tissues. Antiviral and steroids or immunosuppressive agents have been used in most of patients. During follow-up, 2 patients died, and 4 reaching end-stage renal disease; 3 patients had complete remission, and 3 patients had renal function improved after therapy.
Nephrotic syndrome with hematuria and renal insufficiency are the main clinical manifestation; cryoglobulinemic glomerulonephritis are the main renal lesion in patients with HBV-Associated cryoglobulinemia; a half of patients have poor outcome even with antiviral and immunosuppressive therapy. The results of this study indicate that cryoglobulins should be detected in hepatitis B virus-Associated nephropathy in endemic area.
The preservation of kidney function after kidney donation depends on the kidney reserve-the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 centimeter increase in ear length, it was associated with 5.7 percent less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, p =0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associated with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation. This article is protected by copyright. All rights reserved.
The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps.
The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centers that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points.
This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors.
In this prospective observational cohort study we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors one year post donation. Body mass index (BMI), systolic/diastolic blood pressure, kidney function (51 Cr-EDTA eGFR), and lipid parameters were measured at baseline and one year. Data on 87 live kidney donors was collected. BMI increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m2 post donation (p < 0.0001). 51 Cr-EDTA eGFR decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 ml/min/1.73 m2 post donation (p < 0.0001). Serum triglyceride levels increased from 0.8 (IQR 0.6-1.3) pre to 1.0 mmol/l (IQR 0.7–1.6) post donation (p = 0.0004). Statin use increased from 11.5% pre to 21% post donation (p < 0.005). LDL remained stable and other lipids (HDL, Apo B, Lp(a)) did not change post donation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Vascular access in hemodialysis is critical for effective therapy. We aim to evaluate the outcomes of AVF creation in incident hemodialysis patients, impact of preoperative vein mapping and predictors of successful AVF maturation in our center.
Data of End-stage Renal Disease (ESRD) patients initiated on hemodialysis from January 2010 to December 2012 in our center were retrospectively obtained from electronic medical records and clinical notes. Demographic characteristics, medical comorbidities, perioperative details were collected, and patients were followed up till 1st January 2014.
A total of 708 patients (median age 64, IQR 55-72) were included with mean duration of follow up of 2.3 ± 1.2 years, with access of AVF and arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight patients were lost to follow-up. Successful AVF maturation was achieved in 542 patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis revealed male gender, upper arm AVF and good post-operative thrill and pulse as predictors of successful AVF maturation. Preoperative vein mapping was performed in 42.5% (295/694) of patients, with mean vein diameter of 2.44 ± 0.82 mm. Maturation rates with and without vein mapping were 72.2% and 82.4% respectively (p = 0.001). In patients with vein diameters of <2 mm and ≥2 mm, there was no statistically significant difference in maturation rates (71.3% vs. 72.6%; p = 0.887) and median maturation time (66 vs. 78 days; p = 0.73).
AVF can be successfully created in majority of incident hemodialysis patients. Routine vein mapping is not necessary if veins are suitable on physical examination alone, and vein sizes of <2 mm on ultrasound is not associated with lower AVF maturation rate.
The term renal osteodystrophy (ROD) refers to changes in bone morphology induced by chronic kidney disease (CKD) and represents the skeletal component of the entity 'Chronic Kidney Disease – Mineral Bone Disorder' (CKD-MBD). Changes in turnover, mineralisation, mass and microarchitecture impair bone quality, compromising strength and increasing susceptibility to fractures. Fractures are more common in CKD compared to the general population and result in increased morbidity and mortality. Screening for fracture risk and management of ROD is hindered by the complex, and still only partially understood, pathophysiology and the inadequacy of currently available diagnostic methods. Bone densitometry and bone turnover markers, though potentially helpful, have significant limitations in patients with CKD and the "gold standard" test of bone biopsy is infrequently performed in routine clinical practice. However, recent advances in high resolution bone microarchitecture imaging may offer greater potential for quantification and assessment of bone structure and strength and, when used in conjunction with serum biomarkers, may allow non-invasive testing for a diagnostic virtual bone biopsy.
Up-regulation of miR-21 in renal ischemic preconditioning (IPC) was associated with increased hypoxia inducible factor (HIF)-1α expression. Hypoxic induction of HIF-1α is mediated by inhibition of prolyl hydroxylase domain protein 2 (PHD2) .We hypothesized that miR-21 regulated HIF-1α by targeting PHD2 in the renal IPC.
Luciferase reporter assay examined if miR-21 target the 3'-untranslated region of PHD2. In vitro, human proximal tubular cell line (HK-2) was incubated in hypoxia or hypoxia/ reoxygenation condition. Kidneys of Mice were respectively subjected to ischemia/reperfusion injury (IRI) and IPC. Locked nucleic acid (LNA) modified anti-miR-21 was used to knockdown miR-21. Serum creatinine and histological changes estimated the renal injury. Levels of HIF-1α, PHD2, VEGF and miR-21 were examined by western blot or real-time PCR.
miR-21 targeting of PHD2 was confirmed by 3'-untranslated region reporter assay. miR-21 was significantly up-regulated by hypoxia/reoxygenation in HK-2 cell, while PHD2 protein level decreased significantly. LNA anti-miR-21 significantly repressed miR-21 levels and increased the abundance of PHD2. In vivo, IPC up-regulated miR-21 expression 24 h after the second ischemia, while PHD2 expression decreased significantly with up-regulation of HIF-1α protein and VEGF mRNA. MiR-21 induced by delayed IPC was effectively inhibited by the LNA anti-miR-21. With down-regulation of miR-21, the protection of delayed IPC was attenuated and PHD2 protein was increased. Furthermore, up-regulation of HIF-1α and VEGF were abolished after the LNA anti-miR-21 treatment.
miR-21 could protect kidney against IRI via HIF-1α by inhibiting its target PHD2.The study suggested a new relationship between miR-21 and HIF-1α. This article is protected by copyright. All rights reserved.
The NLRP3 inflammasome is an intracellular platform that converts the pro-inflammatory cytokines IL-1β and IL-18 to their active forms in response to 'danger' signals, which can be either host or pathogen derived, and mediates a form of inflammatory cell death called 'pyroptosis.' This component of the innate immune system was initially discovered due to its role in rare autoinflammatory syndromes called cryopyrinopathies, but it has since been shown to mediate injurious inflammation in a broad range of diseases. Inflammasome activation occurs in both immune cells, primarily macrophages and dendritic cells, and in some intrinsic kidney cells such as renal tubular epithelium. The NLRP3 inflammasome has been implicated in the pathogenesis of a number of renal conditions, including acute kidney injury, chronic kidney disease, diabetic nephropathy and crystal related nephropathy. The inflammasome also plays a role in autoimmune kidney disease, as IL-1β and IL-18 influence adaptive immunity through modulation of T helper cell subsets, skewing development in favour of Th17 and Th1 cells which are important in the development of autoimmunity. Both IL-1 blockade and two recently identified specific NLRP3 inflammasome blockers, MCC950 and β-hydroxybutyrate have shown promise in the treatment of inflammasome mediated conditions. These targeted therapies have the potential to be of benefit in the growing number of kidney diseases in which the NLRP3 inflammasome has been implicated.
Several studies have demonstrated that levels of circulating inflammatory markers such as TNFα, are associated with early progression of diabetic nephropathy (DN). The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria.
Between 2006 and 2011, we measured levels of circulating soluble TNFα receptor 1 (TNFR1) and soluble TNFα receptor 2 (TNFR2) at baseline and 4 and 12 months in 101 patients included in a multicenter randomized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination (dual blockade) to slow progression of established type 2 DN. The primary composite endpoint was a >50% increase in baseline serum creatinine, end-stage renal disease, or death.
The median follow-up was 32 months (IQR, 18-48), during which time 28 patients (22.7%) achieved the primary endpoint. The TNFR1 level, but not the TNFR2 level, was correlated with other inflammatory markers. Cox regression analysis showed that the highest TNFR1 levels (HR, 2.60; 95%CI, 1.11-86.34) and baseline proteinuria (HR 1.32; 95%CI 1.15-1.52) were associated with the primary endpoint. The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers.
Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN. The renin angiotensin blockers have no effect on these inflammatory markers
As one of the most popular social networking sites in the world, Facebook has strong potential to enable peer support and the user-driven sharing of health information. We carried out a qualitative thematic analysis of the wall posts of a public Facebook group focused on dialysis to identify some of the major themes discussed.
We searched Facebook using the word "dialysis". A Facebook group (Dialysis Discussion Uncensored) with the highest number of members was selected among publicly available forums related to dialysis and operated in English (http://www.facebook.com/groups/DialysisUncensored). Two researchers independently extracted information on features of the group including purpose, group members, and the user-generated posts on the group wall. Posts were further analyzed to develop major themes.
Characteristics of a Facebook group based on its participants and activities are presented. Three themes are described with representative quotations. In a period of two weeks, we found 1257 wall posts with total of 31,636 likes and 15,972 comments. All messages were in English and the majority of the participants were dialysis patients. However, we observed the participation of family members and care providers as well. Posts were categorized into three major themes: sharing information, seeking and providing emotional and social support, and sharing experience.
Findings of this study provide an example of how a social networking platform can enable patients and their families to share information and to encourage peer-based support for managing dialysis-related experiences.
No abstract is available for this article.]]>
Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored ≥14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate–major depression. The treatment effect should be re-evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients.
BK virus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients and can result in graft loss. The reactivation of BK virus in renal transplant recipients is largely asymptomatic, and routine surveillance especially in the first 12–24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and anti-viral treatment in the early stages may be effective in stopping BK virus replication. Urinary decoy cells, although highly specific, lack sensitivity to diagnose BKVN. Transplant biopsy remains the gold standard to diagnose BKVN, good surrogate markers for surveillance using quantitative urinary decoy cells, urinary SV40 T immunochemical staining or polyoma virus-Haufen bodies are offered by recent studies. Advanced BKVN results in severe tubulo-interstitial damage and graft failure. Retransplantation after BKVN is associated with good outcomes. Newer treatment modalities are emerging.
The risk of bradykinin B2 receptor (BDKRB2)-58T/C gene polymorphism on hypertension remains controversial. The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. The significant association between BDKRB2 -58T/C gene polymorphism and risk of hypertension were found under C-allele comparison (odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05–1.42), recessive model (OR: 1.32, 95% CI: 1.07–1.64), dominant model (OR: 0.74, 95% CI: 0.58–0.94), homozygote model (OR: 1.66, 95% CI: 1.11–2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06–1.43). The magnitude of the association between the BDKRB2-58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C-allele comparison (OR: 1.24, 95% CI: 1.04–1.49), recessive model (OR: 1.39, 95% CI: 1.04–1.86), dominant model (OR: 0.72, 95% CI: 0.56–0.93), homozygote model (OR: 1.78, 95% CI: 1.09–2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07–1.49). No publication bias was found in the meta-analysis. The meta-analysis suggested -58C allele and -58CC genotype increase the risk of hypertension in Asians and African-Americans. Inversely, -58TT genotype decreases the risk of hypertension in Asians and African-Americans.
The objective of the study is to compare the anti-factor Xa (AXa) level in the blood, after arterial and venous line administration of equivalent doses of enoxaparin for prevention of thrombosis in the extracorporeal blood circuit.
The design of the study is a dual centre, prospective, open-labelled randomized crossover, 7 weeks trial.
The setting of the study is on a patient on long-term haemodialysis (HD) or haemodiafiltration (HDF) using high-flux membrane.
There were eight patients on HD and eight on HDF.
Participants were randomly assigned to receive enoxaparin either through the arterial line or venous line of extracorporeal blood circuit for an initial study interval of 2 weeks, followed by 2 weeks of alternate route administration. During the run-in period of 1 week and the follow-up period of 2 weeks, enoxaparin was administered through the arterial line.
The primary outcome measure was to compare AXa blood level 4 h after enoxaparin administration. The secondary outcome measures were manual compression time to stop bleeding from arteriovenous fistula, extracorporeal circuit clotting and systemic bleeding episodes.
The mean AXa blood level, 4 h after venous circuit administration (0.58 ± 0.21 (HD), 0.82 ± 0.29 (HDF)) of enoxaparin, was significantly greater than that after arterial administration of enoxaparin (0.39 ± 0.25 (HD), 0.39 ± 0.14 (HDF) U/mL), (P < 0.001).
In patients on HD or HDF, venous line administration of enoxaparin achieves greater 4 h blood AXa level compared with arterial line administration of equivalent dose. Based on this, we suggest a 25% or 50% reduction in the dose of venous line enoxaparin, compared with the dose administered through arterial line in patients receiving either HD or HDF, respectively.
This study aimed to evaluate the cost-effectiveness of haemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) for patients with end-stage renal disease (ESRD) in Singapore.
A Markov model was developed to examine the incremental cost-effectiveness ratios (ICERs) of HD, CAPD and APD over the 10-year time horizon from the societal perspective, using clinical data from an observational study and the national renal registry, utilities from published studies and costs from dialysis services providers. The base-case analysis was for a hypothetical cohort of 60-year-old non-diabetic ESRD patients. A high-risk group of 60-year-old diabetic ESRD patients was also studied.
In the base-case analysis, the quality-adjusted life-years (QALYs) were 3.27 with CAPD, 3.48 with APD and 4.69 with HD. The total costs were Singapore dollar $169 872 for CAPD, $201 509 for APD and $306 827 for HD. CAPD and HD had extended dominance over APD. The ICER of HD versus CAPD was $96 447 (US$69 121) per QALY. One-way sensitivity analyses indicated that the results were most sensitive to the utility of HD. Probabilistic sensitivity analyses demonstrated that CAPD had the maximum probability of being cost-effective among treatments under evaluation at a willingness-to-pay (WTP) threshold of $60 000 (US$43 000) per QALY. The high-risk group analyses showed similar results. The ICER of HD versus CAPD was $106 281 (US$76 168) per QALY and the probability of CAPD being optimal was the highest using the same WTP threshold.
Our analysis suggested that starting dialysis with CAPD is most cost-effective for ESRD patients in Singapore.
There are limited data on the risks of chronic kidney disease (CKD) in Southeast Asian populations. Several GFR estimating equations have been developed in diverse Asian populations, but they produce markedly discrepant results. We investigated the impact of Asian equations on the mortality risk of CKD in a Thai cohort during long term follow-up, and explored the differences between equations grouped according to the reference GFR methods used to develop them.
Employees of the Electricity Generating Authority of Thailand (n = 3430) were enrolled in a health survey and followed up for 22 years. The risks for all-cause mortality for each GFR stage classified by CKD-EPI or different Asian equations were assessed by using Cox proportional hazard models.
Equations derived from DTPA clearance (Chinese MDRD, Thai GFR, Singapore CKD-EPI) produced higher GFR, whereas equations from inulin clearance (Japanese CKD-EPI, Taiwan MDRD or Taiwan CKD-EPI) produced lower GFR compared to CKD-EPI. (Average ΔGFR: inulin, –14.9 vs. DTPA +5.80 mL/min per 1.73 m2, P < 0.001). CKD prevalence varied widely (0.7 to 24 %) with inulin-based equations being higher than DTPA-based. GFR stage concordance was over 80% for equations using similar reference method compared to less than 40% between inulin and DTPA-based equations. Low GFR (<45) was an independent mortality risk factor when DTPA-based equations were used, but not when inulin-based equations were used.
Chronic kidney disease prevalence and prognosis in Thais varied widely depending on the equation used. Differences in the reference GFR methods could be an important cause for the discrepancies between Asian equations.
Little is known about the association between renal cyst and renal dysfunction. We evaluated the deterioration of renal function in patients with unilateral, large, simple renal cysts.
Fifty patients with unilateral, simple renal cysts measuring ≥ 4 cm (cyst group) and 50 kidney donors (control group) were enrolled. Dimercaptosuccinic acid (DMSA) renal scans were performed to calculate split renal function. The differences between split renal function were calculated and compared. Clinical factors affecting decreased renal function in the cyst group were assessed.
The mean age of the patients in the cyst group was higher than the control group (59.1 vs 39.2 years; P = 0.001). Patients with renal cysts tended to be diagnosed with hypertension (P = 0.001), However, the two groups did not significantly differ in terms of the other characteristics. The median cyst size was 7.2 cm (range, 4.5–14.2), and 31 of the 50 patients (60.2%) in the cyst group demonstrated decreased renal function in the cystic kidney units (median: 5.8%; range, 0.2–33). Although there were no differences in split renal function (50.1% vs 49.9%; P = 0.629) in the control group, the relative renal function of the cystic kidney units were significantly lower than the contralateral kidney units in the cyst group (48.3% vs 51.7%; P = 0.001). The decrease in relative renal function (>8%) in the cystic kidney units was associated with a higher serum uric acid levels and higher RENAL complexity (P = 0.035 and P = 0.007, respectively).
A significant proportion of unilateral, large, simple renal cysts are associated with decreased relative renal function on DMSA renal scans.
Erythropoietin (EPO) production is stimulated by hypoxia in the kidney. Ischaemic injury plays a crucial role in the pathogenesis of acute kidney injury (AKI). However, EPO concentrations in critically ill patients complicated with AKI have not been evaluated sufficiently. This study was conducted to clarify the factors associated with plasma EPO concentrations in AKI.
This study prospectively enrolled 98 critically ill adult patients treated at the adult mixed ICU. Plasma EPO, insulin-like growth factor-binding protein-1 (IGFBP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and urinary N-acetyl-β-D-glucosaminidase (NAG) were measured on ICU admission.
Acute kidney injury occurred in 42 (42.9%) patients. Significantly higher plasma EPO in the AKI group was detected than in the non-AKI group (16.13 (9.87–28.47) mIU/mL versus 27.81 (10.16–106.02) mIU/mL, P < 0.05). Plasma IGFBP-1 in the AKI group was also significantly higher than in the non-AKI group (19 208 (8820–50 780) pg/mL versus 63 199 (25 289–147 489) pg/mL, P < 0.05). Plasma EPO concentration was negatively correlated with haemoglobin in the non-AKI group with statistical significance, but not in the AKI group. Multiple logistic regression analysis revealed that plasma EPO in the AKI group was associated significantly with plasma IGFBP-1 and complication of diabetes mellitus, but not the haemoglobin concentration, partial pressure of arterial oxygen (PaO2), and IL-6.
Not low arterial oxygen tension, haemoglobin concentration, and inflammation evaluated by IL-6 but plasma IGFBP-1 was significantly associated with plasma EPO concentration in AKI, suggesting an unknown mechanism related to systemic stress conditions for EPO regulation in AKI.
Acute antibody-mediated rejection (ABMR) after kidney transplantation (KT) is associated with poor allograft survival. Current therapies for ABMR are able to deplete B-lymphocytes but do not target plasma cells. Bortezomib is a proteasome inhibitor that can eliminate plasma cells and has demonstrated utility in the treatment of ABMR.
A retrospective study was carried out from 2010 to 2014, including all patients with ABMR refractory to conventional treatment who received bortezomib. Bortezomib (1.3 mg/m2) was administered intravenously on days 1, 4, 8, and 11. Renal function, graft survival, follow-up biopsies, and donor-specific antibodies (DSA) were recorded.
We identified seven patients. Of these, high immunological risk was found in 6 of 7, preformed DSA were found in 5 of 7, flow cytometry crossmatch was positive in 4 of 7, and desensitization before KTx was provided in 6 of 7 patients. ABMR was diagnosed at a median of 90 days (8-167) post-KT. After bortezomib therapy, renal function improved or stabilized in 5 of 7 patients and progressively deteriorated in 2 of 7, leading to haemodialysis after 7 and 11 months, respectively. Follow-up kidney biopsies showed persistence of ABMR in 2 of 7, chronic active ABMR 3 of 7 and inactive chronic lesions in 2 of 7. DSA titres significantly decreased after treatment (P = 0.028). All patients experienced mild adverse events. After a follow-up of 22 ± 18 months, three grafts were lost (42%) and four remained functioning.
Bortezomib could be useful as an adjuvant therapy for ABMR refractory to conventional treatment with acceptable mid-term outcomes in these severe cases. More research is needed to develop strategies to better preserve graft function after refractory ABMR.
There is limited knowledge on the relationship between kidney function and incidence of atrial fibrillation. Thus, this prospective study was designed to evaluate whether various biomarkers of kidney function are associated to the risk of atrial fibrillation. The study population consisted of 1840 subjects (615 women and 1225 men) aged 61–82 years. Cystatin C- and creatinine-based estimation of glomerular filtration rate (eGFRcys and eGRFcreat, respectively) and urinary albumin/creatinine ratio (ACR) were assessed to investigate their relationship with the risk of atrial fibrillation. During a median follow-up of 3.7 years, a total of 159 incident atrial fibrillation cases occurred. After adjustment for potential confounders, the risk of atrial fibrillation was increased (hazard ratio 2.74, 95% confidence interval (CI) 1.56–4.81, P < 0.001) in subjects with reduced kidney function (eGFRcys, 15–59 mL/min per 1.73 m2) compared to subjects with normal kidney function (≥90 mL/min per 1.73 m2). Similar results were also found when comparing the respective groups of subjects defined by their eGRFcreat levels (hazard ratio 2.41, CI 1.09–5.30, P = 0.029). Consistently, subjects with ACR ≥300 mg/g had an increased risk of incident atrial fibrillation (hazard ratio 2.16, CI 1.35–2.82, P < 0.001) compared to those with ACR <30 mg/g. Reduced eGFR and albuminuria were associated with an increased risk of atrial fibrillation.