0022-5347 /79/1214-0506$02. 00/0 THE JOURNAL OF UROLOGY Copyright © 1979 by The Williams & Wilkins Co.

Vol. 121, April

Printed in U.S.A.

RENAL FAILURE OWING TO OXALATE NEPHROSIS AFTER JEJUNOILEAL BYPASS SAKTI DAS,* BRUCE JOSEPH

AND

ARTHUR L. DICK

From the Department of Surgery, Division of Urology, UCLA Medical Center and White Memorial Medical Center, Los Angeles, California

ABSTRACT

Oxalate nephrosis resulted in progressive renal failure in 4 patients after jejunoileal bypass for morbid obesity. In general, increased levels of oxalates in the blood and urine of such patients result from enhanced absorption of exogenous oxalates. Urinary calculous formation is determined further by concomitant deficiency of inhibitor substances, whereas oxalate nephrosis probably occurs as a result of oxalate deposition in renal interstitium via the blood stream. Clinical manifestations of oxalate nephrosis include pain, infection, hematuria and renal failure. Routine postoperative renal function studies and early renal biopsy in suspicious cases are urged to establish early diagnosis. Continued deterioration of renal function, despite therapy with oxalate restriction and oxalate binding agents, indicates a reversal of the bypass to preserve unaffected renal substance. In a significant number of patients jejunoileal bypass performed for morbid obesity causes hyperoxaluria. Insoluble oxalate salts precipitate in the urinary tract as clinically evident urinary calculi in 2 to 32 per cent1 of the patients. High levels of oxalates in the blood and urine of these patients could also deposit in the nephrons and renal interstitium, leading to oxalate nephrosis. Cryer and associates,2 and Vainder and Kelly3 have each reported 1 such occurrence but, generally, oxalate nephrosis has not been a recognized complication of small bowel bypass.'· 4--7 Herein we report our experience with 4 patients who had progressive renal failure owing to histologically proved oxalate nephrosis after jejunoileal bypass. It seems that, despite recent interest in the subject of the post-bypass urinary lithiasis, oxalate nephrosis has not received the attention it warrants in the pathological spectrum of intestinal hyperoxaluria. CASE REPORTS

Case 1. A 48-year-old man who weighed 350 pounds underwent ajejunoileal bypass in February 1966. Preoperative blood urea nitrogen and creatinine levels were within normal limits. In August 1967 the patient passed a left renal calculus. Excretory urography (IVP) at that time revealed a hypoplastic right kidney, with a hypertrophied left kidney. The patient was hospitalized 2 years later with mild congestive heart failure, hyperchloremic acidosis and renal failure with a creatinine of 3.5 mg. per cent. He improved on medical management with fluid and electrolyte regulation. In August 1970 he was referred to us for consideration of hemodialysis for progressive renal failure. Creatinine was 11.9 mg. per cent with a clearance of 6 ml. per minute. The patient did reasonably well on regular hemodialysis for 7 months and in March 1971 he underwent elective splenectomy as recommended by the hematologist to manage the refractory anemia. The patient died 2 days postoperatively of a massive pulmonary embolism. Autopsy revealed extensive oxalate nephrosis. Case 2. A 50-year-old man who weighed 375 pounds underwent a jejunoileal bypass in April 1973. He was hospitalized 18 months later with nausea, vomiting and malaise. Creatinine was 4.7 mg. per cent and the clearance was 22 ml. per minute. Although an IVP showed no radiopaque calculus generalized poor excretion was evident. The 24-hour urinary Accepted for publication July 21, 1978. * Requests for reprints: c/o Editor's Office, Department of Surgery, UCLA School of Medicine, Los Angeles, California 90024.

oxalate was 87 mg. The patient improved on a regimen of fluid and electrolyte replacements and was discharged from the hospital. However, 4 months later he returned in severe renal failure with a creatinine of 13.8 mg. per cent and a clearance of 5.4 ml. per minute. On this occasion the 24-hour urinary oxalate measured 56 mg. Percutaneous renal biopsy revealed oxalate nephrosis. He was started on hemodialysis and the bypass was taken down in April 1975. The patient is still on maintenance dialysis with no significant return of creatinine clearance. Case 3. A 35-year-old female diabetic who weighed 340 pounds had a jejunoileal bypass in May 1975. Preoperative creatinine was 0.9 mg. per cent. She was rehospitalized in July 1976 with complaints of malaise, weakness and backache. Creatinine at this time was 3.3 mg. per cent with a clearance of 16 ml. per minute. The patient was having 6 to 8 loose movements everyday. The bypass was modified by adding 6 more inches of ileum to the functioning loop. Renal biopsy done at the same time showed oxalate nephrosis. The 24-hour urinary oxalate was 63 mg. Although low oxalate diet and cholestyramine were started, the creatinine steadily increased to 10.6 mg. per cent and the clearance decreased to 5 ml. per minute. The patient refused to have the bypass taken down and presently she is on regular hemodialysis. Case 4. A 37-year-old women underwent ajejunoileal bypass for morbid obesity in June 1974. She was rehospitalized 8 months later with complaints of nausea and anorexia. Creatinine at that time was 2.8 mg. per cent. She improved on electrolyte replacements but progressive weakness, lethargy and dyspnea on exertion developed and the creatinine increased to 31.5 mg. per cent. Renal biopsy revealed oxalate nephrosis. The intestinal bypass was taken down and regular hemodialysis was started. During the next 8 months the patient became completely anuric and peripheral neuropathies developed. In June 1976 a cadaveric renal transplantation was done and 3 months later she underwent a transplant nephrectomy because of chronic rejection with fever. Currently, the patient is on maintenance hemodialysis. Light microscopy of the biopsies in all of the patients revealed widespread deposits of oxalate crystals in the tubules, intrarenal vessels and renal interstitium with varying degrees of atrophy and inflammatory reaction (fig. 1, A). The oxalate crystals appeared brilliantly fluorescent when viewed through polarized light (fig. 1, B). Electron microscopy performed on biopsies from cases 3 and 4 showed similar changes

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RENAL FAILURE OWING TO OXALATE NEPHROSIS AFTER JEJUNOILEAL BYPASS

FIG. l. A, light microscopy study demonstrates intratubular and intravascular deposits of oxalate crystals. B, light microscopy study under polarized light shows fluorescent deposits of oxalate crystals.

of clear intracellular defects of angular or spiculed configuration, presumed to be owing to deposits of oxalate crystals (fig. 2).

caused increased permeability of colonic mucosa in rats leading to increased oxalate absorption. 12 DISCUSSION

MECHANISM OF INTESTINAL HYPEROXALURIA

Chadwick and associates have conclusively proved with their isotope studies that urinary oxalates in these patients are derived from the exogenous dietary sources. 8 When C14 labeled oxalate was used they showed that the patients with ileal resection absorbed and excreted in the urine up to 5 times as much oxalate as the control subjects when the isotope was given ·with food. Moreover, treatment of these patients with low oxalate diets promptly abolished the hyperoxaluria. The exact mechanism of this enhanced absorption of exogenous oxalates after ileal resection or bypass has not yet been established. Steatorrhea in these instances may cause loss of calcium in the form of calcium soap, allowing less calcium available to form insoluble calcium oxalates and, thereby, leaving behind more free oxalates to be absorbed easily. 9 Morphological and functional changes observed in the small bowel after lengthy resections, such as increased villus height and increased glucose absorption per unit area, also have been conjectured to have a possible role in the hyperabsorption of oxalates. 10 However, Dobbins and Binder found that hyperoxaluria was extremely rare in patients with ileostomy, thus proving that the colon is the essential site of enhanced oxalate absorptiono 11 also showed that fatty acids and bile salts

Urinary calculi and oxalate nephrosis culminating in renal failure are seen classically in primary hyperoxaluria owing to congenital enzymatic deficiencies. Jejunoileal bypass provides a similar iatrogenic model when all the causal mechanisms of colonic hyperoxaluria would be operative. However, despite a high incidence of calculous disease, other authors have not reported the occurrence of oxalate nephrosis subsequent to this operation. It is probable that such occurrences have been overlooked because renal function studies were not mentioned in these postoperative followup protocols. Moreover, on critical analysis reports of diminished renal function in some of the bypass patients with calculous disease (especially in the absence of obstruction) suggest the possibility of underlying oxalate nephrosis. The most important clinical manifestation of oxalate nephrosis is progressive renal failure. Other clinical features include hematuria, infection and renal pain. Concomitant urinary calculi were present in 1 of our patients. Renal failure further increases oxalate levels in blood and tissues, thus maintaining a vicious cycle. Early diagnosis depends on a critical followup of renal function in these patientso Renal should be done at the earliest sign of compromised

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Fm. 2. Electron microscopy shows areas of intracellular oxalate deposits in tubule cells

Although urinary oxalate studies are helpful in the initial postoperative period in regulating the prophylactic therapy they lose their significance in established oxalate nephrosis because, with the loss of nephrons, the oxalate clearance also decreases as noted in 2 of our patients. The exact mechanism of calculogenesis or oxalate nephrosis after small intestinal bypass is still obscure. In the United States Gregory and associates 1 and in Sweden Backman and Hallberg13 reported simultaneously large series in which hyperoxaluria was an almost constant finding after this operation. The incidence or severity ofhyperoxaluria, however, was similar in the stone formers and the non-stone formers, suggesting that other factors besides increased urinary oxalates are responsible for the ultimate precipitation of insoluble oxalate crystals. Gregory and associates also observed an increased crystallization rate in the urine of stone formers. 1 Various other factors, such as dehydration, low urinary citrates and magnesium, and vitamin B6 deficiency, 14 have been incriminated but their dietary substitution has failed to provide any significant prophylaxis against oxalate precipitation. We also have been unable to determine why certain postbypass patients had oxalate nephrosis and others had stone disease. Renal biopsy on 2 different patients in our institution who had multiple stone operations after jejunoileal bypass revealed no oxalate nephrosis. We considered 2 possible mechanisms for the appearance of oxalate crystals in the renal interstitium: 1) high urinary oxalates might deposit in the tubules, causing blockage, pressure atrophy and subsequent extrusion from the lumen into the surrounding peritubular interstitium or 2) high serum oxalate levels might cause deposition of oxalate crystals in the renal interstitium as well as in other tissues of the body. The latter is probably the main mechanism of oxalate nephrosis development, whereas hyperoxaluria along with deficiency of inhibitor substances cause calculous disease. Light microscopy and ultrastructural studies revealed changes that were too extensive to isolate peritubular localization from that of perivascular deposits of oxalates. Further studies on biopsies at earlier stages of the disease will probably lend more credence to our conjecture and help determine cases that are more prone to oxalate nephrosis. Management of hyperoxaluria and hyperoxalemia in these cases with dietary restrictions, oxalate binding agents, such as calcium salts and cholestyramine, magnesium and citrates has been recommended by various authors. The only uniformly effective therapy is the restriction of exogenous oxa-

lates, although patients often fail to comply with such regimens because they usually are addicted to eating and oxalaterestricted diets are rather unpalatable. Whether bypassing the colon (which is the main site of enhanced oxalate absorption) and performing an ileoproctostomy would eliminate the problem of oxalate hyperabsorption without adding further elements ofmalabsorption is a matter for continuing research. If an operation is contemplated in patients with stone disease subsequent to intestinal bypass we advocate a renal biopsy to diagnose any underlying oxalate nephrosis. The presence of oxalate nephrosis would indicate more vigorous therapy and vigilant followup. Routine postoperative renal function studies and prompt renal biopsy in cases of suspicion are urged for post-bypass patients in an endeavor to establish an early diagnosis. The gravity and rapid progression of this sinister complication cannot be overemphasized. If renal function continues to deteriorate, despite dietary restrictions, the patient should be advised to have the bypass taken down to preserve the unaffected nephrons. REFERENCES 1. Gregory, J. G., Park, K. Y. and Schoenberg, H. W.: Oxalate stone disease after intestinal resection. J. Urol., 117: 631,

1977. 2. Cryer, P. E., Garber, A. J., Hoffsten, P., Lucas, B. and Wise, L.: Renal failure after small intestinal bypass for obesity. Arch. Intern. Med., 135: 1610, 1975. 3. Vainder, M. and Kelly, J.: Renal tubular dysfunction secondary tojejunoileal bypass. J.A.M.A., 235: 1257, 1976. 4. Payne, J. H., DeWind, L., Schwab, C. E. and Kern, W. H.: Surgical treatment of morbid obesity. Arch. Surg., 106: 432, 1973. 5. Weisman, R. E.: Surgical palliation of massive and severe obesity. Amer. J. Surg., 125: 437, 1973. 6. Scott, H. W., Dean, R., Shull, H.J., Abram, H. S., Webb, W., Younger, R. K. and Brill, A. B.: Considerations in use of jejunoileal bypass in patients with morbid obesity. Ann. Surg., 177: 723, 1973. 7. Corso, P. J. and Joseph, W. L.: Intestinal bypass in morbid obesity. Surg., Gynec. & Obst., 138: 1, 1974. 8. Chadwick, V. S., Modha, J. and Dowling, R. H.: Mechanism of hyperoxaluria in patients with ileal dysfunction. New Engl. J. Med., 289: 172, 1973. 9. Andersson, H. and Jagenburg, R.: Fat reduced diet in the treatment of hyperoxaluria in patients with ileopathy. Gut, 15: 360, 1974. 10. Stauffer, J. Q., Humphreys, M. H. and Weir, G. J.: Acquired

RENAL FAILURE OWING TO OXALATE NEPHROSIS AFTER JEJUNOILEAL BYPASS

hyperoxaluria with regional enteritis after ileal resection. Role of dietary oxalate. Ann. Intern. Med., 79: 383, 1973. 11. Dobbins, J. W. and Binder, H. J.: Importance of the colon in enteric hyperoxaluria. New Engl. J. Med., 296: 298, 1977. 12. Dobbins, J. W. and Binder, H. J.: Effect of bile salts and fatty acids on the colonic absorption of oxalate. Gastroenterology, 70: 1096, 1976.

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13. Backman, L. and Hallberg, D.: The incidence of kidney stones after small intestinal bypass operations for treatment of obesity. In: Urolithiasis Research. Edited by H. Fleisch, W. G. Robertson, L. H. Smith and W. Vahlensiech. New York: Plenum Press, p. 401, 1976. 14. Salyer, W. R. and Salyer, D. C.: Thiamine deficiency and oxalosis. J. Clin. Path., 27: 558, 1974.

Renal failure owing to oxalate nephrosis after jejunoileal bypass.

0022-5347 /79/1214-0506$02. 00/0 THE JOURNAL OF UROLOGY Copyright © 1979 by The Williams & Wilkins Co. Vol. 121, April Printed in U.S.A. RENAL FAIL...
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