ESRD Caused by Nephrolithiasis: Prevalence, Mechanisms, and Prevention Paul Jungers, MD, Dominique Joly, MD, Frédéric Barbey, MD, Gabriel Choukroun, MD, and Michel Daudon, PhD ● Background: The contribution of nephrolithiasis-related end-stage renal disease (ESRD) to patients requiring renal replacement therapy has never been specifically evaluated. Methods: Of the entire cohort of 1,391 consecutive patients who started maintenance dialysis therapy at our nephrology department between January 1989 and December 2000, a total of 45 patients (21 men) had renal stone disease as the cause of ESRD and constitute the study material. Type and cause of renal stone disease was determined in the 45 patients, as well as the change in prevalence of nephrolithiasis-related ESRD with time during this 12-year period. Results: The overall proportion of nephrolithiasis-related ESRD was 3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%; uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant among patients with infection and calcium stones, whereas men were predominant among patients with uric acid or hereditary stone disease. The proportion of patients with nephrolithia- sis-related ESRD decreased from 4.7% in the triennial period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 (P  0.07). This tendency to a decreasing prevalence mainly was caused by a rarefaction of infection and calcium stones with time, whereas frequencies of uric acid and hereditary stone disease remained essentially unchanged. Conclusion: Severe forms of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD and need for renal replacement therapy. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and proper therapy for conditions that may lead to ESRD through recurrent stone formation and/or parenchymal crystal infiltration. Am J Kidney Dis 44:799-805. © 2004 by the National Kidney Foundation, Inc. INDEX WORDS: End-stage renal disease (ESRD); nephrolithiasis; infection stones; parenchymal crystal deposits; hereditary renal stone diseases. I N THE GREAT majority of cases, urolithia- sis is a painful, but otherwise benign, con- dition, infrequently leading to loss of renal function, at least in common forms of calcium or uric acid stone disease. However, severe forms of urolithiasis also exist. Although very infrequent, they should not be overlooked be- cause they may lead to progressive loss of renal function and, ultimately, end-stage renal disease (ESRD) requiring renal replacement therapy. 1 Infection stones, especially when bi- lateral and growing to a staghorn development, are universally considered the most frequent cause of urolithiasis-associated ESRD. 2-4 Ex- tensive stone development also has been ob- served with calcium-oxalate, uric acid, or cys- tine stones and in patients with anatomic abnormalities of the urinary tract. 1 Urological procedures themselves, mainly classic surgery, may injure the renal parenchyma, especially if interventions are repeated and if applied in a solitary or remnant kidney. 1,4 In addition to the well-known obstructive and infectious mecha- nisms of kidney injury, crystal deposition in tubules and interstitium of both kidneys consti- tutes another, often underappreciated, mecha- nism of progressive renal failure, mainly ob- served in patients with genetically transmitted metabolic diseases. 1 Studies specifically devoted to assessing the incidence of chronic renal failure in patients with urinary stone disease are scarce. 5,6 The incidence of ESRD caused by urolithiasis is even more difficult to assess in the absence of specific studies. Some indications are provided from an- nual reports of the United States Renal Data System. In incident patients who started renal replacement therapy in the United States be- tween 1993 and 1997, a total of 1.2% had neph- rolithiasis as the cause of ESRD, but no precision was given to the type of stone disease. 5 In the From the Departments of Nephrology and Biochemistry, Necker Hospital, Paris; Nephrology Department, University Hospital, Amiens, France; and Nephrology Department, CHU Vaudois, Lausanne, Suisse. Received April 19, 2004; accepted in revised form July 22, 2004. Address reprint requests to Michel Daudon, PhD, Labora- toire de Biochimie A, Necker Hospital, 149 Rue de Sèvres, 75743 Paris Cedex 15, France. E-mail: michel.daudon@ nck.ap-hop-paris.fr © 2004 by the National Kidney Foundation, Inc. 0272-6386/04/4405-0004$30.00/0 doi:10.1053/j.ajkd.2004.08.014 American Journal of Kidney Diseases, Vol 44, No 5 (November), 2004: pp 799-805 799