- Email: [email protected]
Laxative Abuse, Eating Disorders, and Kidney Stones: A Case Report and Review of the Literature
Case Report Laxative Abuse, Eating Disorders, and Kidney Stones: A Case Report and Review of the Literature David E. Leaf, MD,1 Phillip R. Bukberg, MD,2 and David S. Goldfarb, MD3,4 Kidney stones are listed among the complications of eating disorders; however, very few cases have been reported. We present an additional case of nephrolithiasis associated with laxative abuse, including detailed results of the patient’s urine metabolic profiles, in a patient with idiopathic hypercalciuria. We review the literature and provide an explanation for the paucity of cases of nephrolithiasis associated with these disorders. Despite low urine volumes resulting from extracellular fluid volume depletion and hypocitraturia resulting from hypokalemia, both of which would tend to favor the formation of kidney stones, most patients with eating disorders are likely to be protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion and increased proximal tubular sodium reabsorption. However, patients with underlying idiopathic hypercalciuria who develop eating disorders may be at increased risk of stone formation in the setting of low urine volume and therefore high supersaturation of calcium oxalate and phosphate. Am J Kidney Dis. 60(2):295-298. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. INDEX WORDS: Anorexia nervosa; bulimia; citrate; hypercalciuria; nephrolithiasis; urolithiasis.
E
ating disorders, such as anorexia nervosa, bulimia, and laxative abuse, are associated with extracellular fluid volume depletion and electrolyte and acid-base disturbances, including hypokalemia, metabolic alkalosis, and hyper-reninemic hyperaldosteronism.1,2 Extracellular fluid volume depletion is associated with decreased urine volume and hypokalemia is associated with hypocitraturia, effects that would favor the formation of kidney stones. Although kidney stones are listed among the complications of eating disorders,3 we have identified only 4 case reports4-7 and a small case series8 describing this connection. In most cases, urine chemistry results were not reported. We present an additional case of nephrolithiasis associated with laxative abuse, including urine metabolic profiles, a review of the literature, and an explanation for the paucity of cases of nephrolithiasis associated with these disorders.
CASE REPORT
sionally for constipation. There was no relevant family history. She was married and denied alcohol, tobacco, or drug use. On physical examination, the patient was 160 cm tall, weighed 46.7 kg (body mass index, 18.2 kg/m2), and appeared thin but well nourished. Pulse rate was 84 beats/min and blood pressure was 96/66 mm Hg. She was not orthostatic and had no pedal edema. Laboratory evaluation showed serum creatinine level of 0.7 mg/dL (61.9 mol/L; corresponding to estimated glomerular filtration rate of 100 mL/min/1.73 m2 [1.67 mL/s/1.73 m2] by the MDRD [Modification of Diet in Renal Disease] Study equation), and serum urea nitrogen level was 15 mg/dL (5.4 mmol/L). Serum sodium concentration was 141 mEq/L, potassium level was 3.4 mEq/L, bicarbonate level was 31 mEq/L, and calcium level was 9.3 mg/dL (2.3 mmol/L). She was euthyroid, and 25-hydroxyvitamin D level was 54 ng/mL (134.8 nmol/L). Results of 2 consecutive baseline 24-hour urine collections were averaged (Table 1). The patient had very low urine volume at 0.6 L/d and mild hypercalciuria (calcium excretion, 260 mg/d). She had hypocitraturia and low oxalate excretion. Urine sodium excretion was extremely low, and potassium, ammonium, and phosphorus excretion also were low. Urine magnesium excretion was high. The results also suggested low animal protein intake, with a protein catabolic rate of 0.8 g/d, and low urine urea nitrogen, phosphorus, and sulfate excretion.
A 37-year-old Hispanic woman presented to the Kidney Stone Prevention Program, referred by her endocrinologist, who noted a serum potassium concentration of 3.4 mEq/L. She had undergone a recent thyroidectomy for Graves disease. Blood pressure was 100/74 mm Hg. Plasma renin activity was elevated at 24 ng/mL/h (307.2 pmol/L/min; reference range, 1-4 ng/mL/h [12.8-51.2 pmol/L/min]) with a simultaneous serum aldosterone level of 42 ng/dL (1,163.4 pmol/L; reference range, 5-30 ng/dL [138.5-831 pmol/L]). The patient spontaneously passed her first kidney stone 10 years earlier. A second stone, shown on computed tomography, was passed and recovered 4 years later. Its composition was calcium, but whether it was calcium phosphate or oxalate was not known. Other stones led to bilateral shock wave lithotripsies. Medical history was otherwise unremarkable. The patient’s medications were levothyroxine, liothyronine, and bisacodyl occa-
From the 1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA, 2Beth Israel Medical Center; 3New York University School of Medicine; and 4Nephrology Section, New York Harbor VA Medical Center, New York, NY. Received January 5, 2012. Accepted in revised form February 23, 2012. Originally published online May 7, 2012. Address correspondence to David S. Goldfarb, MD, Nephrology Section/111G, New York DVAMC, 423 E 23 St, New York, NY 10010. E-mail: [email protected] Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. 0272-6386/$0.00 http://dx.doi.org/10.1053/j.ajkd.2012.02.337
Am J Kidney Dis. 2012;60(2):295-298
295
Leaf, Bukberg, and Goldfarb Table 1. The 24-Hour Urine Metabolic Profile at Baseline and Follow-up
Stone risk factors Volume (L/d) Calcium (mg/d) Oxalate (mg/d) Citrate (mg/d) Uric acid (mg/d) Supersaturation Calcium oxalate Calcium phosphate Uric acid pH Dietary factors Sodium (mmol/d) Potassium (mmol/d) Phosphorus (g/d) Sulfate (mEq/d) Urea nitrogen (g/d) Protein catabolic rate (g/kg) Creatinine/body weight (mg/kg)
Reference Range (female adult)
Baseline Collectiona
Follow-up Collectionb
0.5-4 ⬍200 20-40 ⬎550 ⬍750
0.6 260 13 306 419
0.7 322 24 446 432
6-10 0.5-2 0-1 5.8-6.2
10.7 2.7 2.5 5.8
17.6 2.4 2.7 5.5
50-150 20-100 0.6-1.2 20-80 6-14 0.8-1.4
9 15 0.3 13.5 4.7 0.8
59 43 0.7 23 8.9 1.4
15-20
17.8
17.3
Note: Conversion factors for units: calcium in mg/d to mmol/d, ⫻0.025; oxalate in mg/d to mol/d, ⫻11.1; citrate in mg/d to mol/d, ⫻5.2; uric acid in mg/d to mol/d, ⫻5.9; phosphorus in g/d to mol/d, ⫻0.032; urea nitrogen in g/d to mol/d, ⫻0.036. a Baseline collection represents the mean of two 24-hour urine studies collected on consecutive days. b Follow-up collection was obtained 1 year after baseline.
The overall picture of secondary hyper-reninemic hyperaldosteronism with normal or low blood pressure, very low urine volume, and very low sodium excretion suggested an eating disorder or laxative abuse, and the patient was questioned. On further discussion, she revealed that she had been surreptitiously abusing laxatives for at least 20 years. The diagnosis explained the patient’s secondary hyper-reninemic hyperaldosteronism. Her kidney stones were due to extremely low urine volume with moderate calcium excretion, leading to elevated supersaturation values of calcium oxalate and calcium phosphate. The patient was referred to a program for eating disorders. One year later, she said that she had been somewhat successful at reducing her laxative abuse. A follow-up 24-hour urine collection (Table 1) showed an increase in urine sodium excretion, suggesting that she had been at least partially successful
in moderating her behavior. Urine volume remained low. The increase in sodium excretion was accompanied by more severe hypercalciuria, so that the net effect was an increase in supersaturation of calcium oxalate.
DISCUSSION Reported cases of nephrolithiasis associated with eating disorders, which we obtained by searching MEDLINE with the key words nephrolithiasis, urolithiasis, kidney stones, eating disorders, anorexia, bulimia, and laxative abuse, are summarized in Table 2. The first case involved a 17-year-old girl with anorexia nervosa who had severe body image distortion, self-induced vomiting, and laxative abuse, ingesting a “semistarvation” diet.4 She had calcium oxalate stones. She did not have hypokalemia but had anion gap metabolic acidosis with a serum bicarbonate level of 16 mEq/L and anion gap of 20 mEq/L, which were attributed to starvation ketoacidosis. No urine chemistry results were reported. The second reported case described a 17-year-old girl who presented with calcium oxalate stones after treatment of minimal change disease with corticosteroids.5 The patient’s urinary calcium to creatinine ratio was “normal,” but the urine was highly concentrated, which was attributed to anorexia, which in turn was induced by her concern about steroid-associated weight gain. The authors concluded that low urine volume resulted in elevated supersaturation of calcium oxalate, leading to stone formation. A third case of recurrent calcium oxalate stones was reported in a 41-year-old woman with anorexia nervosa.6 She exercised excessively, restricted her food intake, and at times had a body mass index as low as 11 kg/m2. Serum electrolyte levels were normal, and no urine metabolic parameters were reported. In addition to these cases of calcium oxalate stones, a fourth case report describes ammonium acid urate stones in a 27-year-old Japanese woman with bulimia, habitual vomiting, hypokalemia, and hypochloremic metabolic alkalosis.7 Other cases of laxative abuse and ammonium acid urate stones were reported in a case series of 9 women.8 The 24-hour urine chemistry tests showed decreased urine volume (902 mL) and sodium (28 mEq), citrate (116 mg), and potassium (21
Table 2. Reported Cases of Eating Disorders Associated With Kidney Stones Reference
Age (y)
Sex
Eating Disorder
Stone Composition
Urine Chemistry
Silber & Kass4 Cachat & Guignard5 Jonat & Birmingham6 Komori et al7 Dick et al8
17 17 41 27 33-52
F F F F F
Anorexia nervosa Anorexia nervosa Anorexia nervosa Bulimia Laxative abuse
Calcium oxalate Calcium oxalate Calcium oxalate Ammonium urate Ammonium urate
Not reported Highly concentrated Not reported Not reported 2 Volume, 1 ammonium urate supersaturation
296
Am J Kidney Dis. 2012;60(2):295-298
Eating Disorders and Kidney Stones
Eating Disorders Laxatives, vomiting, anorexia nervosa
ECFV Depletion
↑Renin
↑ADH*
↑Angiotensin II
↑Proximal Renal Na reabsorption
Metabolic Alkalosis
Figure 1. Stone-inhibiting and stonepromoting effects of eating disorders. *The effect of antidiuretic hormone (ADH) on urine volume may be blunted by coexisting hypokalemia because of both resistance9 and decreased secretion of the hormone.10 Abbreviations: Ca, calcium; ECFV, extracellular fluid volume; K, potassium; U, urinary.
↑U Citrate
Am J Kidney Dis. 2012;60(2):295-298
↓U Calcium
Stone-inhibiting
mEq) excretion, with elevated ammonium urate supersaturation. The authors hypothesized that the elevated supersaturation originated from gastrointestinal loss of water and electrolytes, resulting in extracellular fluid volume depletion, hypokalemia, intracellular acidosis, and enhanced ammoniagenesis. The paucity of cases of nephrolithiasis associated with eating disorders suggests that eating disorders alone generally are insufficient to precipitate stones. The effect of eating disorders on stone-promoting and stone-inhibiting factors is summarized in Fig 1. Whereas low urine volumes result in supersaturation of stone-forming salts, thereby favoring stone formation, extracellular fluid volume depletion results in low urine sodium excretion and consequently low urine calcium excretion, an effect that inhibits stone formation. Hyper-reninemia stimulates increased levels of circulating angiotensin II, stimulating proximal tubular sodium-hydrogen exchange. Increased proximal sodium reabsorption leads to increases in proximal calcium reabsorption as well.11 Hyper-reninemia and enhanced sodium reabsorption thus are associated with reductions in urine calcium excretion. The dramatic hypocalciuric effect of thiazide diuretics was attributed to their effect on the sodium/ chloride cotransporter in the distal convoluted tubule. However, their effect instead seems to be attributable to enhanced proximal calcium reabsorption, stimulated in turn by enhanced paracellular sodium reabsorption.12 To the extent that laxative abuse and other
↓Serum K
↑Aldosterone
↓U Volume
↓U Citrate
Stone-promoting
eating disorders result in extracellular fluid volume depletion and sodium avidity, they mirror the physiology of thiazides. Our patient’s hypercalciuria was not explained. Her thyroid disease was treated appropriately. Serum calcium and vitamin D levels were normal. Her high urine calcium excretion, worse when urine sodium excretion increased, thus was considered idiopathic. Idiopathic hypercalciuria is considered the most common disorder associated with calcium stone formation.13 Our patient’s hypermagnesuria is a curious finding in the context of laxative abuse, which typically is associated with gastrointestinal magnesium loss and consequently renal conservation of magnesium. Hypermagnesemia has been reported with ingestion of magnesium-containing laxatives.14 However, our patient explicitly denied taking such agents. Hypokalemia inhibits renal magnesium reabsorption15 and provides a plausible explanation for her elevated urinary magnesium excretion. A multiple-hit model may provide a link between eating disorders and kidney stones. Patients with predisposing risk factors for nephrolithiasis, such as idiopathic hypercalciuria, are likely to be at highest risk of stone formation when they have low urine volume and therefore high supersaturation of calcium oxalate and phosphate. Similarly, such patients frequently are hypokalemic from vomiting, laxatives, and hyperaldosteronism, as was our patient. Hypokalemia causes intracellular acidosis, which in the proxi297
Leaf, Bukberg, and Goldfarb
mal tubule stimulates sodium/citrate reabsorption through the sodium/dicarboxylate transporter.16 Hypokalemia thereby results in hypocitraturia and adds to the risk of kidney stone formation. In summary, our patient, having baseline idiopathic hypercalciuria, was at risk of kidney stone formation when she developed secondary hyper-reninemic hyperaldosteronism, low urine volume, hypokalemia, and hypocitraturia, all as a consequence of laxative abuse. Whether other reported patients with eating disorders and kidney stones also had underlying hypercalciuria as an additional risk factor is unknown because our case, to our knowledge, is the first to report detailed 24-hour urine collection results. Despite low urine volume, most patients with eating disorders probably are protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion caused by extrarenal sodium loss.
ACKNOWLEDGEMENTS The authors appreciate the counsel of Dr Joanna Steinglass. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.
REFERENCES 1. Wolff HP, Vecsei P, Kruck F, et al. Psychiatric disturbance leading to potassium depletion, sodium depletion, raised plasmarenin concentration, and secondary hyperaldosteronism. Lancet. 1968;1(7537):257-261. 2. Baker EH, Sandle GI. Complications of laxative abuse. Annu Rev Med. 1996;47:127-134.
298
3. Rodman JS, Sosa RE, Seidman C, Jones R. No More Kidney Stones. Hoboken, NJ: John Wiley & Sons Inc; 2007. 4. Silber TJ, Kass EJ. Anorexia nervosa and nephrolithiasis. J Adolesc Health Care. 1984;5(1):50-52. 5. Cachat F, Guignard JP. Too little water intake causing nephrolithiasis, revealed by too much water! Pediatrics. 1999;104(3, pt 1):578-579. 6. Jonat LM, Birmingham CL. Kidney stones in anorexia nervosa: a case report and review of the literature. Eat Weight Disord. 2003;8(4):332-335. 7. Komori K, Arai H, Gotoh T, et al. A case of ammonium urate urinary stones with anorexia nervosa. Acta Urologica Japonica. 2000;46(9):627-629. 8. Dick WH, Lingeman JE, Preminger GM, Smith LH, Wilson DM, Shirrell WL. Laxative abuse as a cause for ammonium urate renal calculi. J Urol. 1990;143(2):244-247. 9. Relman AS, Schwartz WB. The kidney in potassium depletion. Am J Med. 1958;24(5):764-773. 10. Rutecki GW, Cox JW, Robertson GW, Francisco LL, Ferris TF. Urinary concentrating ability and antidiuretic hormone responsiveness in the potassium-depleted dog. J Lab Clin Med. 1982; 100(1):53-60. 11. Bindels RJ. 2009 Homer W. Smith Award: minerals in motion: from new ion transporters to new concepts. J Am Soc Nephrol. 2010;21(8):1263-1269. 12. Nijenhuis T, Vallon V, van der Kemp AW, Loffing J, Hoenderop JG, Bindels RJ. Enhanced passive Ca2⫹ reabsorption and reduced Mg2⫹ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest. 2005;115(6): 1651-1658. 13. Worcester EM, Coe FL. New insights into the pathogenesis of idiopathic hypercalciuria. Semin Nephrol. 2008;28(2):120-132. 14. Fine KD, Santa Ana CA, Fordtran JS. Diagnosis of magnesium-induced diarrhea. N Engl J Med. 1991;324(15):1012-1017. 15. Quamme GA. Renal magnesium handling: new insights in understanding old problems. Kidney Int. 1997;52(5):1180-1195. 16. Zacchia M, Preisig P. Low urinary citrate: an overview. J Nephrol. 2010;23(suppl 16):S49-S56.
Am J Kidney Dis. 2012;60(2):295-298
E
ating disorders, such as anorexia nervosa, bulimia, and laxative abuse, are associated with extracellular fluid volume depletion and electrolyte and acid-base disturbances, including hypokalemia, metabolic alkalosis, and hyper-reninemic hyperaldosteronism.1,2 Extracellular fluid volume depletion is associated with decreased urine volume and hypokalemia is associated with hypocitraturia, effects that would favor the formation of kidney stones. Although kidney stones are listed among the complications of eating disorders,3 we have identified only 4 case reports4-7 and a small case series8 describing this connection. In most cases, urine chemistry results were not reported. We present an additional case of nephrolithiasis associated with laxative abuse, including urine metabolic profiles, a review of the literature, and an explanation for the paucity of cases of nephrolithiasis associated with these disorders.
CASE REPORT
sionally for constipation. There was no relevant family history. She was married and denied alcohol, tobacco, or drug use. On physical examination, the patient was 160 cm tall, weighed 46.7 kg (body mass index, 18.2 kg/m2), and appeared thin but well nourished. Pulse rate was 84 beats/min and blood pressure was 96/66 mm Hg. She was not orthostatic and had no pedal edema. Laboratory evaluation showed serum creatinine level of 0.7 mg/dL (61.9 mol/L; corresponding to estimated glomerular filtration rate of 100 mL/min/1.73 m2 [1.67 mL/s/1.73 m2] by the MDRD [Modification of Diet in Renal Disease] Study equation), and serum urea nitrogen level was 15 mg/dL (5.4 mmol/L). Serum sodium concentration was 141 mEq/L, potassium level was 3.4 mEq/L, bicarbonate level was 31 mEq/L, and calcium level was 9.3 mg/dL (2.3 mmol/L). She was euthyroid, and 25-hydroxyvitamin D level was 54 ng/mL (134.8 nmol/L). Results of 2 consecutive baseline 24-hour urine collections were averaged (Table 1). The patient had very low urine volume at 0.6 L/d and mild hypercalciuria (calcium excretion, 260 mg/d). She had hypocitraturia and low oxalate excretion. Urine sodium excretion was extremely low, and potassium, ammonium, and phosphorus excretion also were low. Urine magnesium excretion was high. The results also suggested low animal protein intake, with a protein catabolic rate of 0.8 g/d, and low urine urea nitrogen, phosphorus, and sulfate excretion.
A 37-year-old Hispanic woman presented to the Kidney Stone Prevention Program, referred by her endocrinologist, who noted a serum potassium concentration of 3.4 mEq/L. She had undergone a recent thyroidectomy for Graves disease. Blood pressure was 100/74 mm Hg. Plasma renin activity was elevated at 24 ng/mL/h (307.2 pmol/L/min; reference range, 1-4 ng/mL/h [12.8-51.2 pmol/L/min]) with a simultaneous serum aldosterone level of 42 ng/dL (1,163.4 pmol/L; reference range, 5-30 ng/dL [138.5-831 pmol/L]). The patient spontaneously passed her first kidney stone 10 years earlier. A second stone, shown on computed tomography, was passed and recovered 4 years later. Its composition was calcium, but whether it was calcium phosphate or oxalate was not known. Other stones led to bilateral shock wave lithotripsies. Medical history was otherwise unremarkable. The patient’s medications were levothyroxine, liothyronine, and bisacodyl occa-
From the 1Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA, 2Beth Israel Medical Center; 3New York University School of Medicine; and 4Nephrology Section, New York Harbor VA Medical Center, New York, NY. Received January 5, 2012. Accepted in revised form February 23, 2012. Originally published online May 7, 2012. Address correspondence to David S. Goldfarb, MD, Nephrology Section/111G, New York DVAMC, 423 E 23 St, New York, NY 10010. E-mail: [email protected] Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. 0272-6386/$0.00 http://dx.doi.org/10.1053/j.ajkd.2012.02.337
Am J Kidney Dis. 2012;60(2):295-298
295
Leaf, Bukberg, and Goldfarb Table 1. The 24-Hour Urine Metabolic Profile at Baseline and Follow-up
Stone risk factors Volume (L/d) Calcium (mg/d) Oxalate (mg/d) Citrate (mg/d) Uric acid (mg/d) Supersaturation Calcium oxalate Calcium phosphate Uric acid pH Dietary factors Sodium (mmol/d) Potassium (mmol/d) Phosphorus (g/d) Sulfate (mEq/d) Urea nitrogen (g/d) Protein catabolic rate (g/kg) Creatinine/body weight (mg/kg)
Reference Range (female adult)
Baseline Collectiona
Follow-up Collectionb
0.5-4 ⬍200 20-40 ⬎550 ⬍750
0.6 260 13 306 419
0.7 322 24 446 432
6-10 0.5-2 0-1 5.8-6.2
10.7 2.7 2.5 5.8
17.6 2.4 2.7 5.5
50-150 20-100 0.6-1.2 20-80 6-14 0.8-1.4
9 15 0.3 13.5 4.7 0.8
59 43 0.7 23 8.9 1.4
15-20
17.8
17.3
Note: Conversion factors for units: calcium in mg/d to mmol/d, ⫻0.025; oxalate in mg/d to mol/d, ⫻11.1; citrate in mg/d to mol/d, ⫻5.2; uric acid in mg/d to mol/d, ⫻5.9; phosphorus in g/d to mol/d, ⫻0.032; urea nitrogen in g/d to mol/d, ⫻0.036. a Baseline collection represents the mean of two 24-hour urine studies collected on consecutive days. b Follow-up collection was obtained 1 year after baseline.
The overall picture of secondary hyper-reninemic hyperaldosteronism with normal or low blood pressure, very low urine volume, and very low sodium excretion suggested an eating disorder or laxative abuse, and the patient was questioned. On further discussion, she revealed that she had been surreptitiously abusing laxatives for at least 20 years. The diagnosis explained the patient’s secondary hyper-reninemic hyperaldosteronism. Her kidney stones were due to extremely low urine volume with moderate calcium excretion, leading to elevated supersaturation values of calcium oxalate and calcium phosphate. The patient was referred to a program for eating disorders. One year later, she said that she had been somewhat successful at reducing her laxative abuse. A follow-up 24-hour urine collection (Table 1) showed an increase in urine sodium excretion, suggesting that she had been at least partially successful
in moderating her behavior. Urine volume remained low. The increase in sodium excretion was accompanied by more severe hypercalciuria, so that the net effect was an increase in supersaturation of calcium oxalate.
DISCUSSION Reported cases of nephrolithiasis associated with eating disorders, which we obtained by searching MEDLINE with the key words nephrolithiasis, urolithiasis, kidney stones, eating disorders, anorexia, bulimia, and laxative abuse, are summarized in Table 2. The first case involved a 17-year-old girl with anorexia nervosa who had severe body image distortion, self-induced vomiting, and laxative abuse, ingesting a “semistarvation” diet.4 She had calcium oxalate stones. She did not have hypokalemia but had anion gap metabolic acidosis with a serum bicarbonate level of 16 mEq/L and anion gap of 20 mEq/L, which were attributed to starvation ketoacidosis. No urine chemistry results were reported. The second reported case described a 17-year-old girl who presented with calcium oxalate stones after treatment of minimal change disease with corticosteroids.5 The patient’s urinary calcium to creatinine ratio was “normal,” but the urine was highly concentrated, which was attributed to anorexia, which in turn was induced by her concern about steroid-associated weight gain. The authors concluded that low urine volume resulted in elevated supersaturation of calcium oxalate, leading to stone formation. A third case of recurrent calcium oxalate stones was reported in a 41-year-old woman with anorexia nervosa.6 She exercised excessively, restricted her food intake, and at times had a body mass index as low as 11 kg/m2. Serum electrolyte levels were normal, and no urine metabolic parameters were reported. In addition to these cases of calcium oxalate stones, a fourth case report describes ammonium acid urate stones in a 27-year-old Japanese woman with bulimia, habitual vomiting, hypokalemia, and hypochloremic metabolic alkalosis.7 Other cases of laxative abuse and ammonium acid urate stones were reported in a case series of 9 women.8 The 24-hour urine chemistry tests showed decreased urine volume (902 mL) and sodium (28 mEq), citrate (116 mg), and potassium (21
Table 2. Reported Cases of Eating Disorders Associated With Kidney Stones Reference
Age (y)
Sex
Eating Disorder
Stone Composition
Urine Chemistry
Silber & Kass4 Cachat & Guignard5 Jonat & Birmingham6 Komori et al7 Dick et al8
17 17 41 27 33-52
F F F F F
Anorexia nervosa Anorexia nervosa Anorexia nervosa Bulimia Laxative abuse
Calcium oxalate Calcium oxalate Calcium oxalate Ammonium urate Ammonium urate
Not reported Highly concentrated Not reported Not reported 2 Volume, 1 ammonium urate supersaturation
296
Am J Kidney Dis. 2012;60(2):295-298
Eating Disorders and Kidney Stones
Eating Disorders Laxatives, vomiting, anorexia nervosa
ECFV Depletion
↑Renin
↑ADH*
↑Angiotensin II
↑Proximal Renal Na reabsorption
Metabolic Alkalosis
Figure 1. Stone-inhibiting and stonepromoting effects of eating disorders. *The effect of antidiuretic hormone (ADH) on urine volume may be blunted by coexisting hypokalemia because of both resistance9 and decreased secretion of the hormone.10 Abbreviations: Ca, calcium; ECFV, extracellular fluid volume; K, potassium; U, urinary.
↑U Citrate
Am J Kidney Dis. 2012;60(2):295-298
↓U Calcium
Stone-inhibiting
mEq) excretion, with elevated ammonium urate supersaturation. The authors hypothesized that the elevated supersaturation originated from gastrointestinal loss of water and electrolytes, resulting in extracellular fluid volume depletion, hypokalemia, intracellular acidosis, and enhanced ammoniagenesis. The paucity of cases of nephrolithiasis associated with eating disorders suggests that eating disorders alone generally are insufficient to precipitate stones. The effect of eating disorders on stone-promoting and stone-inhibiting factors is summarized in Fig 1. Whereas low urine volumes result in supersaturation of stone-forming salts, thereby favoring stone formation, extracellular fluid volume depletion results in low urine sodium excretion and consequently low urine calcium excretion, an effect that inhibits stone formation. Hyper-reninemia stimulates increased levels of circulating angiotensin II, stimulating proximal tubular sodium-hydrogen exchange. Increased proximal sodium reabsorption leads to increases in proximal calcium reabsorption as well.11 Hyper-reninemia and enhanced sodium reabsorption thus are associated with reductions in urine calcium excretion. The dramatic hypocalciuric effect of thiazide diuretics was attributed to their effect on the sodium/ chloride cotransporter in the distal convoluted tubule. However, their effect instead seems to be attributable to enhanced proximal calcium reabsorption, stimulated in turn by enhanced paracellular sodium reabsorption.12 To the extent that laxative abuse and other
↓Serum K
↑Aldosterone
↓U Volume
↓U Citrate
Stone-promoting
eating disorders result in extracellular fluid volume depletion and sodium avidity, they mirror the physiology of thiazides. Our patient’s hypercalciuria was not explained. Her thyroid disease was treated appropriately. Serum calcium and vitamin D levels were normal. Her high urine calcium excretion, worse when urine sodium excretion increased, thus was considered idiopathic. Idiopathic hypercalciuria is considered the most common disorder associated with calcium stone formation.13 Our patient’s hypermagnesuria is a curious finding in the context of laxative abuse, which typically is associated with gastrointestinal magnesium loss and consequently renal conservation of magnesium. Hypermagnesemia has been reported with ingestion of magnesium-containing laxatives.14 However, our patient explicitly denied taking such agents. Hypokalemia inhibits renal magnesium reabsorption15 and provides a plausible explanation for her elevated urinary magnesium excretion. A multiple-hit model may provide a link between eating disorders and kidney stones. Patients with predisposing risk factors for nephrolithiasis, such as idiopathic hypercalciuria, are likely to be at highest risk of stone formation when they have low urine volume and therefore high supersaturation of calcium oxalate and phosphate. Similarly, such patients frequently are hypokalemic from vomiting, laxatives, and hyperaldosteronism, as was our patient. Hypokalemia causes intracellular acidosis, which in the proxi297
Leaf, Bukberg, and Goldfarb
mal tubule stimulates sodium/citrate reabsorption through the sodium/dicarboxylate transporter.16 Hypokalemia thereby results in hypocitraturia and adds to the risk of kidney stone formation. In summary, our patient, having baseline idiopathic hypercalciuria, was at risk of kidney stone formation when she developed secondary hyper-reninemic hyperaldosteronism, low urine volume, hypokalemia, and hypocitraturia, all as a consequence of laxative abuse. Whether other reported patients with eating disorders and kidney stones also had underlying hypercalciuria as an additional risk factor is unknown because our case, to our knowledge, is the first to report detailed 24-hour urine collection results. Despite low urine volume, most patients with eating disorders probably are protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion caused by extrarenal sodium loss.
ACKNOWLEDGEMENTS The authors appreciate the counsel of Dr Joanna Steinglass. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.
REFERENCES 1. Wolff HP, Vecsei P, Kruck F, et al. Psychiatric disturbance leading to potassium depletion, sodium depletion, raised plasmarenin concentration, and secondary hyperaldosteronism. Lancet. 1968;1(7537):257-261. 2. Baker EH, Sandle GI. Complications of laxative abuse. Annu Rev Med. 1996;47:127-134.
298
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