the term  kaliopenic nephropathy  was introduced by conn and johnson   in 1956 to describe a distinct clinical entity characterized by the pathologic lesions of vacuolar tubulopathy and functional disorders such as impaired urine concentration in patients resulting from long - term potassium depletion . since then , chronic laxative or diuretic abuse in patients of anorexia nervosa of purging type ( an - p ) has been reported as a cause of chronic tubulointerstitial nephropathy due to hypokalemic nephropathy , sometimes leading to end - stage renal disease ( esrd ) requiring renal replacement therapy including dialysis or renal transplantation [ 24 ] . there have been some reports of acute kidney injury ( aki ) from unidentified causes in preexisting chronic kidney disease ( ckd ) due to hypokalemic nephropathy in the presence of chronic hypokalemia in an - p . through the present case , we wish to advance a postulate that hypokalemia plays an important role in precipitating renal ischemia - induced aki in the presence of other contributors of aki . a 42-year - old woman presented at the emergency department ( ed ) with chief complaints of anergy and progressive weakness of lower extremities for the past 10 days . she was emaciated with a body mass index of 14  kg / m ( weight 34  kg , height 155  cm ) . on further questioning , she confessed to having taken large amounts of three types of nonprescription laxatives ( up to 50 tablets daily ) for at least 10 years after the birth of her second child . the laxative dosage was increased to almost 70 tablets a day over the previous month , and during this period she developed progressive loss of appetite . the laxatives contained bisacodyl , docusate sodium , sennoside calcium , lactobacillus acidophilus , and carbenoxolone ( glycyrrhetinic acid ) . vital signs in the supine position showed blood pressure 80/64  mmhg , heart rate 84/min , respiratory rate 24/min , and body temperature 37  c . she appeared severely volume depleted with poor skin turgor , dry oral mucosa , and shiny skin on both legs . complete blood examination : white blood cell count 12.110/mm , hemoglobin 9.0  g / dl , platelets 30710/mm ; serum chemistry : sodium 127  mmol / l , potassium 1.2  mmol / l , chloride 94  mmol / l , urea nitrogen 117  mg / dl , creatinine 11.7  mg / dl , calcium 6.3  mg / dl phosphate 8.5  mg / dl magnesium 2.2  mg / dl intact parathyroid hormone 80  pg / ml , creatine phosphokinase 3,371  units / l ( 30180  units / l ) . arterial blood gas on 4  l oxygen per minute showed ph 7.19 , po2 163  mmhg , pco2 10.8  mmhg , hco3 4.2 urinalysis yielded the following results : albumin ( 2 + ) , occult blood ( 2 + ) with no red blood cells / high power field ( hpf ) , pyuria 510/hpf with no bacteria . a renal ultrasonogram on day 3 showed 9.5  cm bilaterally with prominent medulla and nephrolithiasis in the left renal pelvis without hydronephrosis . in the supine position , the plasma renin activity and aldosterone level was 15.29  ng / ml / h ( 0.681.36  ng / ml / h ) and 98.6  ng / dl ( 1.016  ng / dl ) , respectively . the serologic markers for glomerulonephritis were negative . in the ed and the intensive care unit , 3  l of a half - normal saline mixed with kcl ( 60  mmol / l ) and bicarbonate ( 100 however , the patient remained anuric ( < 5  ml / h ) with serum potassium of 1.7  mmol / l , and the electrocardiogram showed u waves , arterial ph 7.23 , and blood bicarbonate 8.4  mmol / l . subsequently , hemodialysis with 4  mmol / l of potassium in the dialysate was initiated and continued at a frequency of three times a week for 10 days until the patient passed urine ( > 700800  ml / d ) . on day 15 , a kidney biopsy showed advanced chronic tubulointerstitial nephritis with some evidence of acute tubular necrosis ( atn ) . the predominant light microscopic lesions were moderate to severe residual atrophy or loss of tubules and scattered interstitial mononuclear cell infiltration ( fig . also , focal tubular degenerative change and mild regenerative proximal tubules suggested atn in the recovery phase , and a few nonatrophic tubular epithelial cells in the proximal tubule were focally enlarged and vacuolated . the glomeruli displayed ischemic changes such as wrinkling and thickening of the glomerular capillary walls but without advanced glomerular lesions ( fig . ultrastructurally , diffuse thickening of the glomerular basement membrane was noted with no electron dense deposits . on the day of discharge , the patient weighed 38  kg with serum potassium of 4.3  mmol / l and creatinine of 1.8  mg / dl . after intensive counseling from renal , psychiatric , social , and dietary consultants , she understood the seriousness of her condition , and agreed to refrain from laxative abuse . however , on the second monthly follow - up at the outpatient renal clinic , her serum creatinine was increased to 2.7  mg / dl , which was also accompanied by decreased serum potassium to 2.7  mmol / l and body weight to 36  kg . on careful questioning , the patient admitted to resuming the intake of laxatives ( about 5070  tablets / d ) . she was again counseled about the serious renocardiac consequences of continued laxative abuse and the necessity of regular psychiatric follow - up for body image disorder . at the last follow - up 3 weeks later , her serum creatinine , serum potassium , and body weight had improved to 1.9  mg / dl , 4.1  mmol / l , and 38  kg , respectively . the present case , based on clinical presentation and pathological findings , describes two episodes of aki due to severe renal ischemia from severe hypokalemia , volume depletion , and mild rhabdomyolysis , superimposed on preexisting ckd with hypokalemic nephropathy . our patient had two major potential contributing factors for aki : severe volume depletion and rhabdomyolysis . the degree of rhabdomyolysis in our patient on the basis of creatine phosphokinase levels was quite mild and is unlikely to have caused aki , whereas volume depletion was quite severe and could have precipitated aki . by contrast , worsening hypokalemia and profound volume depletion as the predisposing factors for ischemic aki appear to coexist in most an - p cases . however , only one report of an - p has considered the cause of aki in detail ; in that case , it was attributed to renal ischemia from profound volume depletion in the setting of hypokalemia ( 1.83.1  mmol / l ) , requiring transient hemodialysis with no response to initial intravenous volume replacement , as in the present case . in a clinical study , 13 out of 40 patients with an - p with severe to moderate hypokalemia ( 1.92.8  mmol / l ) developed aki , and cremer and bock   reported five episodes of aki in three patients with an - p , and did not note any apparent cause for aki such as volume depletion or rhabdomyolysis , except for moderate hypokalemia ( 2.653.0  mm / l ) . in an animal study it is unlikely that hypovolemia in an - p is the only underlying cause for the pathogenesis of ischemic aki . other factors such as severe to moderate hypokalemia and/or rhabdomyolysis appear to lead to severe renal ischemia from intense intrarenal vasoconstriction and decreased activation of the neurohumoral system responsible for intrarenal vasodilation , a recognized factor in the pathophysiology of ischemic aki . in fact , one case report in a laxative abuser has suggested volume depletion and hypokalemia - related tubular lesions as causes of the anuric aki , and termed it patients with long - term an - p who are diuretic or laxative abusers are constantly at a risk of chronic potassium deficiency , either owing to direct loss of potassium by the renal and/or extrarenal route or to high levels of angiotensin ii and aldosterone as a result of activation of the renin  angiotensin aldosterone system secondary to hypovolemia following the loss of water and salt induced by purging combined with restricted food intake . therefore , the hypokalemic nephropathy and aki in chronic laxative abusers with an - p appear to involve two major factors  hypokalemia and hypovolemia . these result in renal ischemia as follows : ( 1 ) the hypokalemia stimulates increased ammoniagenesis , which in turn activates the alternative complement pathway releasing proinflammatory cytokines and profibrotic molecules . ( 2 ) the hypokalemia also stimulates the production of vasoactive mediators , resulting in increased vasoconstrictor stimuli ( endothelin-1 , thromboxane b2 , angiotensin - converting enzyme , angiotensin ii ) and reduced vasodilatory mediators such as prostaglandin e2 and endothelium - derived relaxing factor . ( 3 ) the hypovolemia causes renal ischemia directly , with activation of the renin the most likely cause of the intermittent or recurrent aki was renal ischemia due to intrarenal vasoconstriction caused by the worsening of hypokalemia and hypovolemia . however , the preexisting ckd due to long - standing hypokalemic nephropathy was also an important factor in the patient s recurrent episodes of aki . the histological findings from the kidney biopsy performed on day 15 showed atn with focal tubular degenerative change including mild regenerative and vacuolar proximal tubules , and prominent chronic tubulointerstitial nephritis combined with diffuse ischemic glomerular changes such as wrinkling and thickening of the glomerular basement membrane ( figs . 1a1c ) . the clinicopathological findings compatible with hypokalemic nephropathy showed that tubulopathy alone may lead to ckd as a result of tubulointerstitial fibrosis , as in the renal fibrosis in ckd due to glomerulopathy . our findings also support a contributory role of aki in the progression of ckd in patients with an - p involving a vicious cycle of the preexisting ckd and repeated episodes of aki . underlying ckd is a major predisposing factor for aki , and recurrent aki superimposed on ckd may increase the rate of loss of the remaining nephron mass . in conclusion , episodes of worsening hypokalemia in an - p could play an important role in the progression of the preexisting ckd with hypokalemic nephropathy , as suggested in a recent study that shows hypokalemia in ckd to be a risk factor for progression to esrd . health providers involved in the care of patients with hypokalemic nephropathy , particularly patients with an - p , should address potassium depletion and hypovolemia as well as offer intensive counseling to encourage the patients to abstain from purgative drug abuse .
prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease , known as 
 hypokalemic nephropathy ,  but it is not clear whether it contributes to acute kidney injury ( aki ) . a 42-year - old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa ( an - p ) , developed an anuric aki requiring hemodialysis and a mild aki 2 months later . both episodes of aki involved severe to moderate hypokalemia ( 1.2 and 2.7  mmol / l , respectively ) , volume depletion , and mild rhabdomyolysis . 
 the histologic findings of the first aki revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury . along with these observations , the intertwined relationship among precipitants of recurrent aki in an - p is discussed , and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia - induced aki .