malaria is one of the most common parasitic infection in tropical areas , and 243 million cases were reported worldwide in 2008 ( 1 ) . renal involvement is particularly common in plasmodium malariae and plasmodium falciparum infections and is generally manifested as chronic progressive glomerulopathy in the former and acute kidney injury ( aki ) in the latter ( 2 ) . in endemic areas , aki occurs as a complication of falciparum malaria , mostly caused by acute tubular necrosis ( atn ) and/or interstitial nephritis , in 1% to 4.8% of native patients , and its incidence increases up to 25% to 30% in european patients . another less common form of renal involvement in falciparum malaria is acute glomerulonephritis , which is characterized by mesangial proliferation and matrix expansion ( 3 ) . to date , only igm , igg , and c3 deposits within the mesangium have been detected , and immunoglobulin a ( iga ) nephropathy associated with falciparum malaria has not yet been reported . herein , we present a case of falciparum malaria - associated iga nephropathy accompanied by aki that was resolved after recovery from the malaria infection . a 49-yr - old korean male visited our hospital on february 22 , 2010 because of persistent fever for three days despite repeated use of antipyretics . the patient had a 6-yr history of diabetes and had been receiving treatment at our hospital . clinical evaluations performed 2 months earlier showed serum creatinine level of 0.9 mg / dl [ corresponding to estimated glomerular filtration rate ( egfr ) of 95.3 ml / min/1.73 m , calculated using the 4-variable modification of diet in renal disease ( mdrd ) study equation ] and random urine albumin - creatinine ratio ( acr ) of 42.5 mg / g without microhematuria . serial urine analyses two weeks before the illness , he traveled uganda in east africa . upon admission , blood pressure , pulse rate and body temperature were 110/60 mmhg , 98 beats / min and 38.3 , respectively . initial laboratory tests showed the following values : hemoglobin , 9.0 g / dl ; platelets , 57  10/l ; serum creatinine , 1.8 mg / dl ; aspartate / alanine aminotransferase , 101/90 u / l ; total bilirubin , 6.0 mg / dl ; prothrombin time international normalized ratio , 1.03 . the patient tested negative for hepatitis b surface antigen , and anti - hepatitis c virus antibody . urine dipstick examination showed microhematuria ( 2 + ) and proteinuria ( 2 + ) . spot urine protein - creatinine ratio ( upcr ) and acr were 2.92 g / g and 1,064 mg / g , respectively , and 24-hr urinary protein and creatinine excretion was 953 and 1,158 mg / day , respectively , with mixed glomerular and tubular proteinuria on urine electrophoresis . serum iga was elevated to 606 mg / dl , but other serologic tests for antinuclear antibody and antineutrophil cytoplasmic antibodies were negative . c3 and c4 were 95 and 32 mg / dl , respectively . based on his travel history and clinical features , malaria was suspected , and a peripheral blood smear revealed 6% hyperparasitemia with plasmodium falciparum . the patient was immediately prescribed intravenous quinine dihydrochloride with oral doxycycline on the second day of admission . however , he became anuric with increase in serum creatinine up to 4.7 mg / dl on the third day of admission , and was started on hemodialysis . to further ascertain the cause of aki and proteinuria , in addition , some tubular lumens were packed with hemosiderin casts , and the interstitium was infiltrated with many inflammatory cells . seven glomeruli processed for immunofluorescence analysis showed mesangial staining for iga ( 1 + to 2 + ) and c3 ( 1 + ) . in addition , 3 glomeruli examined by electron microscopy showed multifocal electron - dense deposits within the mesangium and thickened glomerular basement membrane ranging from 800 nm to 1,200 nm in thickness ( fig . , he became negative for p. falciparum and his kidney function recovered with increased urine output . serum creatinine and upcr decreased to 2.2 mg / dl and 0.47 mg / g on the 33rd day after admission , and the patient was discharged in good condition . two months later , his serum creatinine level had decreased to 1.2 mg / dl with upcr of 0.07 mg / g . three consecutive urinalyses revealed no microhematuria ( fig . it is characterized by mesangial cell proliferation , expansion of the extracellular matrix , and predominant iga deposition within the mesangium ( 4 ) . although the etiology of the disease has not been clearly elucidated , these include haemophilus parainfluenzae , staphylococcus species , mycoplasma pneumoniae , and the hepatitis b and dengue viruses , but no individual bacterial or viral organism has been specifically associated with the development of iga nephropathy ( 5 - 9 ) . meanwhile , in an previous experimental study , mesangial iga deposits were rarely noted in mouse malaria nephropathy caused by plasmodium berghei ( 10 ) . however , similar findings were not reported among human malaria nephropathy to date . to our best knowledge , this is the first case suggesting a possible link between iga nephropathy and plasmodium falciparum infection . in line with the previous studies , aki due to atn and interstitial nephritis was clearly evident , which clearly explains our patient 's clinical features . one might question whether the patient had glomerulonephritis or latent iga nephropathy before the infection . however , the patient had been followed for 6 yr at our clinic for diabetes management , and previous blood and urine tests consistently had revealed no evidence of glomerulopathy . in addition , his urine analysis from 2 months before the illness showed no microscopic hematuria but only microalbuminuria suggesting that glomerulonephritis such as iga nephropathy was less likely . in fact , he might have diabetic nephropathy , as evidenced by the biopsy finding showing a thickened glomerular basement membrane and history of coexisting mild non - proliferative diabetic retinopathy . moreover , subsequent blood and urine tests after recovery from malaria showed a disappearance of urine abnormalities along with normalization of both kidney function and serum iga level . these findings taken together suggest that plasmodium falciparum may have been associated with iga nephropathy in this patient . it is uncertain how malaria infection is involved in the development of iga nephropathy . in general , undergalactosylated iga1 is reported to play a role in the pathogenesis of idiopathic iga nephropathy ( 11 ) . such aberrantly glycosylated polymeric iga1 are prone to form circulating immune complexes , leading to mesangial deposition and proliferation ( 12 , 13 ) . however , it is possible that anti--galactosyl ( anti - gal ) antibodies may contribute to the development of immune complexes with aberrantly glycosylated iga1 . anti - gal antibodies are originally natural human polyclonal antibodies that specifically bind to the mammalian carbohydrate structure gal1 , 3gal1,4glcnac - r ( -galactosyl epitope ) on glycoproteins and glycolipids ( 14 ) . some investigators showed that anti - gal was associated with iga nephropathy and henoch - schonlein purpura ( 15 ) . interestingly , the titers of these antibodies were also found to be elevated in many of the sera collected from subjects living in malaria endemic areas or patients with falciparum malaria ( 16 ) . it was reported that terminal -linked galactosyl residues in some of the carbohydrate side chains of glycoproteins of the asexual blood stages of plasmodium falciparum could provoke increased anti - gal production ( 17 , 18 ) . therefore , in the present case , it can be surmised that plasmodium falciparum might have induced augmented production of anti - gal , and in turn , might have caused formation of aberrantly glycosylated polymeric iga1 . unfortunately , we could not perform any pertinent study to confirm the presence of abnormal iga1 because the patient 's serum was not available by the time the biopsy revealed iga nephropathy . another possible explanation for iga nephropathy in our report is that clearance of iga and immune complexes were reduced due to liver and/or renal dysfunction . however , such assumptions can not fully explain why iga deposits were more prominent than other immune - complexes within the mesangium in our patient because only igg , igm , and c3 deposits have been reported in malarial nephropathies to date although most reported cases involved both renal failure and hepatitis . as in some previous reports on iga nephropathy associated with infection ( 9 , 19 ) , the glomerulopathy in our patient appeared to be transient . it is possible that removal of the causative organism from circulation and improvements in renal and hepatic dysfunction might result in increased clearance of immune - complexes , thus leading to the resolution of iga nephropathy . unfortunately , a second biopsy to prove the complete resolution of iga nephropathy was not feasible because the patient did not agree to a repeated test . however , based on the results from consecutive blood and urine tests after recovery from malaria infection , it is likely that such glomerulopathy was resolved . in addition , although it is not easy to discriminate between true igan and iga - dominant postinfectious glomerulonephritis , the latter was less likely because hypocomplementemia , diffuse glomerular endocapillary hypercellularity , and subepithelial humps ( 20 ) were not found in our case ( fig . , our findings suggest that plasmodium falciparum may be involved in the development of iga nephropathy . however , this report is limited to a single case and the mechanism responsible for this remains speculative .
glomerulonephritis occurs as a rare form of renal manifestation in plasmodium falciparum malaria . 
 herein , we report a case of falciparum malaria - associated iga nephropathy for the first time . 
 a 49-yr old male who had been to east africa was diagnosed with plasmodium falciparum malaria . 
 microhematuria and proteinuria along with acute kidney injury developed during the course of the disease . 
 kidney biopsy showed mesangial proliferation and iga deposits with tubulointerstitial inflammation . 
 laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function . 
 our findings suggest that malaria infection might be associated with iga nephropathy .