Hyperoxaluria and Urinary Tract Calculi after Jejunoileal Bypass Erden Fikri, MD, Pittsburgh, Pennsylvania R. R. Casella, MD, PhD, Pittsburgh, Pennsylvania
Smith, Fromm, and Hoffman [I] have recently described a syndrome of acquired hyperoxaluria and calcium oxalate urolithiasis in seven patients with resection of the distal ileum. None of these patients had other known causes of secondary hyperoxaluria such as excessive intake of ascorbic acid or rhubarb. The cause of hyperoxaluria in these patients was not clear but was partly thought to result from the disturbance in bile acidglycine metabolism known to be present in patients with distal small bowel resection. Although urinary tract calculi have been mentioned in patients with jejunoileal shunt, they have not been associated with this syndrome. We are presenting five cases of hyperoxaluria and recurrent calcium oxalate urolithiasis among fifty-two patients with intestinal shunts for morbid obesity. The shunt was an end to end jejunoileostomy in which 14 inches of jejenum, measured from the ligament of Treitz, was anastomosed to 4 inches of distal ileum. The proximal end of the ileum was anastomosed end to side to the cecum. The twenty-four hour urine oxalic acid excretion was measured in twenty-six patients who had had jejunoileal shunt for six months or longer. Twenty had urinary excretion of oxalate greater than 40 mg per twenty-four hours (normal, 15 to 40 mg). The highest value, 179 mg per hour, occurred in a patient who had had the bypass for two years and showed no clinical or x-ray evidence of urinary tract calculi. All five patients to be presented had
From the Division of Surgery, The Western Pennsylvania Hospital, Pittsburgh, Pennsylvania. Reprint requests shoukl be addressed to Erden Fikri, MD, 353 Market Street, Johnstown, Pennsylvania 15901.
334
hyperoxaluria; however, there was no correlation between urolithiasis and the degree of urinary oxalic acid excretion. Case Reports
Case 1. A thirty-eight year old white man weighing 290 pounds for longer than five years, who could not lose weight on medical and psychiatric therapy and who had no endocrinopathy, underwent jejunoileal bypass in May 1969. Fourteen inches of jejunum, measured along the mesenteric border from the ligament of Treitz, was anastomosed end to end to 4 inches of distal ileum. During the first three months after surgery he was maintained on antidiarrheal agents (LomotiF) and was having four to eight semiliquid bowel movements a day. After this period he did not require antidiarrheal agents and was having two to four semiformed bowel movements a day. In March 1970 left flank pain and hematuria developed. An intravenous urogram showed a radiopaque stone in the left middle ureter. He was treated conservatively and two days later he passed the stone. Examination of the calculus showed that it was composed of calcium oxalate. In August 1971 left renal colic developed and he was admitted to the hospital. An intravenous urogram showed a stone in the right pelvis and one in the left upper ureter. Both stones were radiopaque. He underwent uneventful left ureterolithotomy. In February 1972, because of symptoms caused by the calculus seen in the right renal pelvis on the previous admission, he underwent right pyelolithotomy. In September 1972 left renal colic developed again and an intravenous urogram showed a radiopaque calculus in the left upper ureter. Because of persistent severe pain, left upper ureterolithotomy was performed. All the stones were composed of calcium oxalate. During these admissions he was having two to four semiformed bowel movements a day. Urine volume
The Amerkan
Journal 01 Surgery
Hyperoxaluria
ranged from 1,100 to 1,700 cc per twenty-four hours. Routine laboratory studies gave normal results. Serum protein electrophoresis, and calcium, phosphorus, and uric acid levels were in the normal range. During the last admission the twenty-four hour urinary excretion of calcium was 38 mg and the twenty-four hour oxalic acid level was 88 per cent. The urinary pH was 6.1 and abundant calcium oxalate crystals were present in the urinary sediment. No calcium oxalate crystals were present in the urine before bypass. The urine oxalic acid level was not measured before bypass. Case II. A twenty-nine year old white woman weighing 260 pounds underwent a shunt in November 1970 similar to the one in case I. She had been receiving Lomotil for two months because of diarrhea. After this period she did not require antidiarrheal agents and was having two to five semiformed bowel movements a day. Five months after bypass, in March 1971, she was admitted to our hospital because of left renal colic. Plain film of the abdomen and the intravenous urogram revealed two radiopaque calculi in the left pelvis. Within three days she had passed both stones, and analysis showed these to be made of calcium oxalate. In May 1971 left renal colic developed and she was readmitted. An intravenous urogram showed a large pelvic stone, and left pyelolithotomy was performed. This stone too was composed of calcium oxalate. In October 1972 she was readmitted because of right renal colic. She had passed several small stones at home and eight in the hospital during a one week period. These stones were also composed of calcium oxalate. Routine laboratory studies, serum protein electrophoresis, and calcium phosphorus and uric acid levels were within normal limits. The urinary pH was 5.8 and the urine sediment contained abundant calcium oxalate crystals. No calcium oxalate crystals were present in the urine before the intestinal shunt. The twenty-four hour urine oxalic acid level was 112 mg. This was not measured before bypass. Case III. A thirty-three year old white woman weighing 276 pounds underwent end to end jejunoileal bypass in February 1970, with anastomosis of 14 inches of jejunum to 4 inches of distal ileum. She was on antidiarrheal therapy for three months, after which it was discontinued and the patient was having one to three semiformed bowel movements a day. Six months after bypass she underwent right ureterolithotomy because of a ureteral calculus. The stone consisted of calcium oxalate. Four months later she was readmitted because of a symptomatic radiopaque stone in the left ureter. This was passed two days later and analysis showed it to be made of calcium oxalate. In May 1972 a right ureteral calculus developed and she underwent right ureterolithotomy. The stone again was composed of calcium oxalate. The urinary sediment contained abundant calcium oxalate crystals present on all admissions after bypass but not before. The twenty-four hour urine oxalic acid
Volume 129, March 1975
and Calculi after Jejunoileal Bypass
was elevated,
it being 121 mg. Routine laboratory studies, protein electrophoresis, and twenty-four hour urinary excretion of calcium gave normal results. Case IV. A forty-five year old white woman weighing 268 pounds underwent end to end jejunoileal bypass in May 1968, with anastomosis of 14 inches of jejunum to 4 inches of distal ileum. She was on antidiarrheal therapy for three months, after which it was discontinued, and the patient was having two to four semiformed bowel movements a day. Eleven months after bypass a large 2 by 3 cm radiopaque calculus developed in the bladder. She underwent suprapubic cystotomy with removal of the calculus. Analysis of the stone revealed that it consisted of calcium oxalate. In July 1970 she was readmitted because of right ureterolithiasis. A day after admission a calcium oxalate stone was removed during cystoscopy by right ureteral catheterization with stone manipulation. Routine laboratory studies, protein electrophoresis, and twenty-four hour urinary calcium excretion were within normal limits. The urine sediment contained abundant calcium oxalate crystals as seen on both admissions after bypass whereas none was present before the shunt. The twenty-four hour urinary oxalic acid was slightly elevated, it being 54 mg. Case V. A forty-four year old white woman weighing 282 pounds had a jejunoileal shunt in October 1971, with anastomosis of 14 inches of jejunum from the ligament of Treitz end to end to 4 inches of terminal ileum. Her postoperative course was uneventful and she was discharged on Lomotil therapy for diarrhea. Two months later the Lomotil was discontinued and the patient was having two to five semiformed bowel movements a day. On November 16, 1972, she was admitted to the hospital because of right renal colic. She had lost approximately 100 pounds and weighed 180 pounds. Plain films of the abdomen and an intravenous urogram showed an opaque calculus of the right ureter, with right hydronephrosis. The stone was removed by ureteral catheterization and stone manipulation. However, this resulted in upper ureteral perforation demonstrated by extravasation of dye on retrograde pyelogram. The patient then became febrile and severe pain in the right flank developed. An infusion pyelogram performed one week later showed evidence of right perinephric abscess. Incision and drainage of the abscess were performed on November 28. Culture of the abscess grew Proteus mirubilk She was treated with Garamycine and was finally discharged afebrile on December 18, 1972. The stone was composed of calcium oxalate. During her admission, routine laboratory studies, protein electrophoresis, and twenty-four hour urinary calcium excretion were within normal limits. The twentyfour hour urinary oxalic acid excretion was 94 mg. The urine sediment revealed calcium oxalate crystals. The urinalysis before bypass did not indicate calcium crystals.
335
Fikri and Casella
Comments
The incidence of urinary tract calculi in hospitalized patients in the United States is approximately 0.1 per cent [2]. The incidence in patients with inflammatory bowel disease is about 7 per cent [3]. In patients with ileostomy the incidence of urolithiasis is somewhat higher. Jacob, Pace, and Thomford [4] reported an incidence of 12.5 per cent and ascribed stone formation to the decreased absorptive surface of the bowel and electrolyte loss. Hyperoxaluria and calcium oxalate urolithiasis in patients with distal ileal resection have recently been recognized as a new clinical syndrome [2,4]. The five cases we have described presented this entity of hyperoxaluria and calcium oxalate urolithiasis after jejunoileal bypass. The cause of hyperoxaluria is unclear. It could be related to deranged bile acid-glycine metabolism [1,4]. Real resection or bypass results in decreased bile absorption with secondary increase in synthesis of glycine-conjugated bile salts. It was speculated that bile acid glycine is converted by intestinal bacteria to glyoxylate or oxalate [5]. However, this is disproved by experiments carried out by Hoffman and associates [6]. Archer et al [7] have also noted that glycine loading does not cause hyperoxaluria. Earnest, Williams, and Admirand [B] have shown more recently that it is the excessive absorption of oxalate that contributes to hyperoxaluria in patients with ileal disease. Smith, Fromm, and Hoffman [1] have had some success, in reducing the elevated urinary oxalate levels to normal by the administration of cholestyramine, 4 gm four times a day for one month. Reduction of hyperoxaluria to normal by the admin-
336
istration of taurine has also been reported [5]. Taurine is believed to compete with glycine for conjugation with bile salts. However, further evaluation of cholestyramine and taurine therapy is needed.
Summary
Five patients with jejunoileal shunt for morbid obesity in whom postshunt hyperoxaluria and recurrent urinary tract calculi developed are presented. All the stones were composed of calcium oxalate. The twenty-four hour urinary oxalic acid levels were also elevated in twenty of twenty-six patients who had had jejunoileal shunt for six months or longer. No correlation was present between urolithiasis and the degree of hyperoxaluria.
References 1. Smith LH, Fromm H, Hoffman AF: Acquired hyperoxaluria nephroltthiisis and intestinal disease. N Engl J Mad 288: 1371,1972. 2. Boyce WH, Garvey FK, Strawcutter HE: Incidence of urinary calculi among patients in general hospitals, 1948-1952. JAMA 181: 1437, 1958. 3. Gelzatyd EA, Breuer RI, Kirsaer JB: Nephroliii@s in inflarnmatory bowel disease. Am J Dig Dis 13: 1027, 1988. 4. Jacob RH, Pace WG, Thomford NR: The hazards of perrnanent ileostomy. Arch Swg 99: 549, 1969. 5. Admirand WV, Earnest D, Williams H: ljyperoxalurta and bowel disease. C/in /?es 19: 562, 1971. 6. Hoffman AF, Tacker M, Fromm H, et al: Acquired hyperoxaluria and intestinal disease. Mayo C/in Proc 48: 35, 1973. 7. Archer HE, Dormer AE, Scowen EF, et al: The aettologv of primary hyperoxaluria. Br w J 1: 175, 1958. 8. Earnest DL, Williams HE, Admirand WH: Excessive absorption of oxalate contributes to hyperoxaluria in patients with iteal disease. Gastroenterobgy 64: 723, 1973.
The Amerkan Journalof Surfjory
Smith, Fromm, and Hoffman [I] have recently described a syndrome of acquired hyperoxaluria and calcium oxalate urolithiasis in seven patients with resection of the distal ileum. None of these patients had other known causes of secondary hyperoxaluria such as excessive intake of ascorbic acid or rhubarb. The cause of hyperoxaluria in these patients was not clear but was partly thought to result from the disturbance in bile acidglycine metabolism known to be present in patients with distal small bowel resection. Although urinary tract calculi have been mentioned in patients with jejunoileal shunt, they have not been associated with this syndrome. We are presenting five cases of hyperoxaluria and recurrent calcium oxalate urolithiasis among fifty-two patients with intestinal shunts for morbid obesity. The shunt was an end to end jejunoileostomy in which 14 inches of jejenum, measured from the ligament of Treitz, was anastomosed to 4 inches of distal ileum. The proximal end of the ileum was anastomosed end to side to the cecum. The twenty-four hour urine oxalic acid excretion was measured in twenty-six patients who had had jejunoileal shunt for six months or longer. Twenty had urinary excretion of oxalate greater than 40 mg per twenty-four hours (normal, 15 to 40 mg). The highest value, 179 mg per hour, occurred in a patient who had had the bypass for two years and showed no clinical or x-ray evidence of urinary tract calculi. All five patients to be presented had
From the Division of Surgery, The Western Pennsylvania Hospital, Pittsburgh, Pennsylvania. Reprint requests shoukl be addressed to Erden Fikri, MD, 353 Market Street, Johnstown, Pennsylvania 15901.
334
hyperoxaluria; however, there was no correlation between urolithiasis and the degree of urinary oxalic acid excretion. Case Reports
Case 1. A thirty-eight year old white man weighing 290 pounds for longer than five years, who could not lose weight on medical and psychiatric therapy and who had no endocrinopathy, underwent jejunoileal bypass in May 1969. Fourteen inches of jejunum, measured along the mesenteric border from the ligament of Treitz, was anastomosed end to end to 4 inches of distal ileum. During the first three months after surgery he was maintained on antidiarrheal agents (LomotiF) and was having four to eight semiliquid bowel movements a day. After this period he did not require antidiarrheal agents and was having two to four semiformed bowel movements a day. In March 1970 left flank pain and hematuria developed. An intravenous urogram showed a radiopaque stone in the left middle ureter. He was treated conservatively and two days later he passed the stone. Examination of the calculus showed that it was composed of calcium oxalate. In August 1971 left renal colic developed and he was admitted to the hospital. An intravenous urogram showed a stone in the right pelvis and one in the left upper ureter. Both stones were radiopaque. He underwent uneventful left ureterolithotomy. In February 1972, because of symptoms caused by the calculus seen in the right renal pelvis on the previous admission, he underwent right pyelolithotomy. In September 1972 left renal colic developed again and an intravenous urogram showed a radiopaque calculus in the left upper ureter. Because of persistent severe pain, left upper ureterolithotomy was performed. All the stones were composed of calcium oxalate. During these admissions he was having two to four semiformed bowel movements a day. Urine volume
The Amerkan
Journal 01 Surgery
Hyperoxaluria
ranged from 1,100 to 1,700 cc per twenty-four hours. Routine laboratory studies gave normal results. Serum protein electrophoresis, and calcium, phosphorus, and uric acid levels were in the normal range. During the last admission the twenty-four hour urinary excretion of calcium was 38 mg and the twenty-four hour oxalic acid level was 88 per cent. The urinary pH was 6.1 and abundant calcium oxalate crystals were present in the urinary sediment. No calcium oxalate crystals were present in the urine before bypass. The urine oxalic acid level was not measured before bypass. Case II. A twenty-nine year old white woman weighing 260 pounds underwent a shunt in November 1970 similar to the one in case I. She had been receiving Lomotil for two months because of diarrhea. After this period she did not require antidiarrheal agents and was having two to five semiformed bowel movements a day. Five months after bypass, in March 1971, she was admitted to our hospital because of left renal colic. Plain film of the abdomen and the intravenous urogram revealed two radiopaque calculi in the left pelvis. Within three days she had passed both stones, and analysis showed these to be made of calcium oxalate. In May 1971 left renal colic developed and she was readmitted. An intravenous urogram showed a large pelvic stone, and left pyelolithotomy was performed. This stone too was composed of calcium oxalate. In October 1972 she was readmitted because of right renal colic. She had passed several small stones at home and eight in the hospital during a one week period. These stones were also composed of calcium oxalate. Routine laboratory studies, serum protein electrophoresis, and calcium phosphorus and uric acid levels were within normal limits. The urinary pH was 5.8 and the urine sediment contained abundant calcium oxalate crystals. No calcium oxalate crystals were present in the urine before the intestinal shunt. The twenty-four hour urine oxalic acid level was 112 mg. This was not measured before bypass. Case III. A thirty-three year old white woman weighing 276 pounds underwent end to end jejunoileal bypass in February 1970, with anastomosis of 14 inches of jejunum to 4 inches of distal ileum. She was on antidiarrheal therapy for three months, after which it was discontinued and the patient was having one to three semiformed bowel movements a day. Six months after bypass she underwent right ureterolithotomy because of a ureteral calculus. The stone consisted of calcium oxalate. Four months later she was readmitted because of a symptomatic radiopaque stone in the left ureter. This was passed two days later and analysis showed it to be made of calcium oxalate. In May 1972 a right ureteral calculus developed and she underwent right ureterolithotomy. The stone again was composed of calcium oxalate. The urinary sediment contained abundant calcium oxalate crystals present on all admissions after bypass but not before. The twenty-four hour urine oxalic acid
Volume 129, March 1975
and Calculi after Jejunoileal Bypass
was elevated,
it being 121 mg. Routine laboratory studies, protein electrophoresis, and twenty-four hour urinary excretion of calcium gave normal results. Case IV. A forty-five year old white woman weighing 268 pounds underwent end to end jejunoileal bypass in May 1968, with anastomosis of 14 inches of jejunum to 4 inches of distal ileum. She was on antidiarrheal therapy for three months, after which it was discontinued, and the patient was having two to four semiformed bowel movements a day. Eleven months after bypass a large 2 by 3 cm radiopaque calculus developed in the bladder. She underwent suprapubic cystotomy with removal of the calculus. Analysis of the stone revealed that it consisted of calcium oxalate. In July 1970 she was readmitted because of right ureterolithiasis. A day after admission a calcium oxalate stone was removed during cystoscopy by right ureteral catheterization with stone manipulation. Routine laboratory studies, protein electrophoresis, and twenty-four hour urinary calcium excretion were within normal limits. The urine sediment contained abundant calcium oxalate crystals as seen on both admissions after bypass whereas none was present before the shunt. The twenty-four hour urinary oxalic acid was slightly elevated, it being 54 mg. Case V. A forty-four year old white woman weighing 282 pounds had a jejunoileal shunt in October 1971, with anastomosis of 14 inches of jejunum from the ligament of Treitz end to end to 4 inches of terminal ileum. Her postoperative course was uneventful and she was discharged on Lomotil therapy for diarrhea. Two months later the Lomotil was discontinued and the patient was having two to five semiformed bowel movements a day. On November 16, 1972, she was admitted to the hospital because of right renal colic. She had lost approximately 100 pounds and weighed 180 pounds. Plain films of the abdomen and an intravenous urogram showed an opaque calculus of the right ureter, with right hydronephrosis. The stone was removed by ureteral catheterization and stone manipulation. However, this resulted in upper ureteral perforation demonstrated by extravasation of dye on retrograde pyelogram. The patient then became febrile and severe pain in the right flank developed. An infusion pyelogram performed one week later showed evidence of right perinephric abscess. Incision and drainage of the abscess were performed on November 28. Culture of the abscess grew Proteus mirubilk She was treated with Garamycine and was finally discharged afebrile on December 18, 1972. The stone was composed of calcium oxalate. During her admission, routine laboratory studies, protein electrophoresis, and twenty-four hour urinary calcium excretion were within normal limits. The twentyfour hour urinary oxalic acid excretion was 94 mg. The urine sediment revealed calcium oxalate crystals. The urinalysis before bypass did not indicate calcium crystals.
335
Fikri and Casella
Comments
The incidence of urinary tract calculi in hospitalized patients in the United States is approximately 0.1 per cent [2]. The incidence in patients with inflammatory bowel disease is about 7 per cent [3]. In patients with ileostomy the incidence of urolithiasis is somewhat higher. Jacob, Pace, and Thomford [4] reported an incidence of 12.5 per cent and ascribed stone formation to the decreased absorptive surface of the bowel and electrolyte loss. Hyperoxaluria and calcium oxalate urolithiasis in patients with distal ileal resection have recently been recognized as a new clinical syndrome [2,4]. The five cases we have described presented this entity of hyperoxaluria and calcium oxalate urolithiasis after jejunoileal bypass. The cause of hyperoxaluria is unclear. It could be related to deranged bile acid-glycine metabolism [1,4]. Real resection or bypass results in decreased bile absorption with secondary increase in synthesis of glycine-conjugated bile salts. It was speculated that bile acid glycine is converted by intestinal bacteria to glyoxylate or oxalate [5]. However, this is disproved by experiments carried out by Hoffman and associates [6]. Archer et al [7] have also noted that glycine loading does not cause hyperoxaluria. Earnest, Williams, and Admirand [B] have shown more recently that it is the excessive absorption of oxalate that contributes to hyperoxaluria in patients with ileal disease. Smith, Fromm, and Hoffman [1] have had some success, in reducing the elevated urinary oxalate levels to normal by the administration of cholestyramine, 4 gm four times a day for one month. Reduction of hyperoxaluria to normal by the admin-
336
istration of taurine has also been reported [5]. Taurine is believed to compete with glycine for conjugation with bile salts. However, further evaluation of cholestyramine and taurine therapy is needed.
Summary
Five patients with jejunoileal shunt for morbid obesity in whom postshunt hyperoxaluria and recurrent urinary tract calculi developed are presented. All the stones were composed of calcium oxalate. The twenty-four hour urinary oxalic acid levels were also elevated in twenty of twenty-six patients who had had jejunoileal shunt for six months or longer. No correlation was present between urolithiasis and the degree of hyperoxaluria.
References 1. Smith LH, Fromm H, Hoffman AF: Acquired hyperoxaluria nephroltthiisis and intestinal disease. N Engl J Mad 288: 1371,1972. 2. Boyce WH, Garvey FK, Strawcutter HE: Incidence of urinary calculi among patients in general hospitals, 1948-1952. JAMA 181: 1437, 1958. 3. Gelzatyd EA, Breuer RI, Kirsaer JB: Nephroliii@s in inflarnmatory bowel disease. Am J Dig Dis 13: 1027, 1988. 4. Jacob RH, Pace WG, Thomford NR: The hazards of perrnanent ileostomy. Arch Swg 99: 549, 1969. 5. Admirand WV, Earnest D, Williams H: ljyperoxalurta and bowel disease. C/in /?es 19: 562, 1971. 6. Hoffman AF, Tacker M, Fromm H, et al: Acquired hyperoxaluria and intestinal disease. Mayo C/in Proc 48: 35, 1973. 7. Archer HE, Dormer AE, Scowen EF, et al: The aettologv of primary hyperoxaluria. Br w J 1: 175, 1958. 8. Earnest DL, Williams HE, Admirand WH: Excessive absorption of oxalate contributes to hyperoxaluria in patients with iteal disease. Gastroenterobgy 64: 723, 1973.
The Amerkan Journalof Surfjory
