Brunner, F. P.

Kistler, H.

Peter, J.

Thiel, G.

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Nephrol Dial Transplant (1995) 10: 1466-1469Case ReportNephrologyDialysisTransplantationSeven-year survival of renal transplant for oxalate nephropathy due toshort-bowel syndromeH. Kistler, J. Peter, G. Thiel and F. P. BrunnerMedizinische Abteilung, Spital Limmattal Schlieren, Zurich and Abteilung fur Nephrologie, Departement fur InnereMedizin, Universitatsklinik in Basel, SwitzerlandIntroductionPatients with ileal resection or extensive jejunal resec-tion resulting in malabsorption are likely to developrenal hyperoxaluria [1-3]. Deficiencies due to malab-sorption can be avoided if supplementation therapy isinstituted as early as possible, but in patients withextensive bowel resection steatorrhoea cannot be cor-rected completely. Hyperoxaluria due to hyperabsorp-tion of oxalic acid or its precursors is a well-establishedphenomenon, leading to renal complications such asrecurrent urolithiasis, oxalate nephropathy, and ulti-mately end-stage renal failure [4-6]. In this report wedescribe a female patient with a severe malabsorptionsyndrome and hyperoxaluria after extensive small-bowel resection. Five years after the initial operationthe patient suffered from recurrent stone formationand occasional urinary tract infections. The renalfunction deteriorated continuously and 25 years afterthe small-bowel resection the patient was in severeuraemia. Six months after starting maintenance haemo-dialysis the patient received a cadaveric kidney trans-plant. Despite persisting hyperoxaluria during the first5 years after transplantation the transplant has con-tinued to function normally over a period of 7 yearswith normalization of urinary oxalate excretion andno further stone formation occurred. To our knowledgethis is the first reported case of a long-term successfulkidney transplantation in a patient with a short-bowelsyndrome and enteric hyperoxaluria.Case reportIn 1958 at the age of 33 years this female patientunderwent surgery for myoma and appendectomywithout appendicitis. Three years later, in 1961, anextensive resection of necrotic small bowel was neces-sary because of unrecognized bowel obstruction.Approximately 90 cm of small bowel and most ofthe large bowel remained. Barium passage fromCorrespondence and offprint requests to: Prof. Dr H. Kistler, SpitalLimmattal, 8952 Schlieren, Switzerland.stomach to caecum was found to take only 15 min.Consequently the patient developed a severe globalmalabsorption syndrome and a weight loss of 20 kg inless than 2 years. When the patient was first seen byus she weighed 42 kg, had a height of 162 cm, andsuffered from hypocalcaemic tetany, hypokalaemia,and hypomagnesaemia.The following laboratory results were obtained(with normal values in brackets): Faecal fat 50 g/24 h(<7g/24h), faecal nitrogen 4.7 g/day (<2g/day),xylose absorption 15% (20-35%), vitamin B12 absorp-tion 0.08% (>4%), lactose absorption was highlyabnormal, with severe diarrhoea. Blood serumvalues: albumin 22 g/1 (>36g/l), calcium 1.8mmol/l(>2.2 mmol/1), potassium 3.2mmol/l (>3.7mmol/l)and magnesium 0.6 mmol/1 (>0.8 mmol/1). Serum cre-atinine was at the upper limit of normal with 80 umol/1.The patient received dietary counselling with the intro-duction of a low-fat diet with the addition of medium-chain triglycerides, vitamin supplementation, and oralcalcium 1-2 g/day. On this regime the patient gained10 kg in weight, but suffered persistently from anabnormal frequency and consistency of bowel move-ments despite different drug trials.Five years after the small-bowel resection the patientpassed a first kidney stone. Starting in 1973 the patientsuffered from recurrent stone formation on both sideswith or without obstruction or infection and Gram-negative septicaemia. At least six times she underwentoperations to remove renal calculi. At one time shepassed 20 small renal stones within 1 month. Thechemical analyses of the stones always revealed acalcium oxalate composition. Urinary excretion ofoxalic acid was regularly highly abnormal, above500 umol/day. Dietary restriction of oxalic acid orvarious drug trials had no permanent effect on oxalateexcretion (Figure 1); the normal values for oxalateexcretion in 1977 and 1978 were obtained duringhospitalization of the patient. Figure 2 illustrates theprogressive deterioration of the kidney function. In1986 the patient became obliguric, probably followingingestion of a small dose of indomethacin, anddeveloped uraemia, with a serum creatinine of© 1995 European Dialysis and Transplant Association-European Renal AssociationTransplant survival in oxalate nephropathyumol/d12001000800 '6001467400200• mH 1 1 1——I 1 1 1-year 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94Fig. 1. Renal oxalate excretion (normal value <500 umol/day).mVmin ptnol/l1401201008060402001400-120010008006004002000 I I I I 1 1 I I 1 I I I Iyear 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94• Creatinine Clearance (ml/min) o Plasma Creatinine (urnd/l)Fig. 2. Plasma creatinine and creatinine clearance before and after kidney transplantation in 1987.1300umol/l and acidosis with a pH of 7.06. Noobstruction was seen on ultrasound, but both kidneyswere small. Consequently the patient was treated withhaemodialysis. Bleeding from the gastrointestinal tractand a decreased left ventricular ejection fraction prob-ably due to oxalate cardiomyopathy were additionalsevere complications.Six months later, in February 1987, a cadaverickidney transplant was performed. Initially the patientwas oliguric and a transplant biopsy on day 9 showedischaemic damage as well as oxalate crystal depositionin the proximal tubular lumina. Despite oxalate crystaldeposition, the kidney resumed function on day 12,when daily haemodialysis was instituted for another 5days. Thereafter the renal course was uneventful. Therewas never a sign of rejection despite a HLA-mismatchof five antigens out of a total of six. Seven years aftertransplantation the plasma creatinine is 70 umol/1 andthe creatinine clearance between 60 and 70 ml/min.(Figure 2).Before transplantation the patient had been testedfor her enteral absorption of cyclosporin and prednis-one. While prednisone was absorbed normally, whole-blood cyclosporin levels varied between undetectableand barely immunosuppressive concentrations, afteroral administration of both twice 100 mg per day ofcyclosporin in olive oil as well as 100 mg or 200 mgtwice per day dissolved in medium-chain triglycerides.Initial immunosuppression therefore consisted of intra-venous cyclosporin 100-200 mg/day for the first 30days combined with oral azathioprine 100 mg/day andprednisone 20 mg/day. After discontinuing cyclospo-rin, prednisone was increased to 40 mg/day for 10 daysfollowed by tapering to 10 mg/day over the next 6months. For the last 6 years the patient has beentaking 7.5 mg prednisone and 150 mg azathioprinedaily. Complications of immunosuppressive ther-apy included a localized pulmonary lesion withCryptococcus neoformans, requiring surgical resectionin 1989, and recurrent small skin tumours on the handsand the face.Regarding oxalate hyperabsorption the patient's1468posttransplant course has been remarkably uneventful.Attempts to reduce oxaluria with dietary restrictionsto levels below the upper range of normal(0.5 mmol/day) were only partially successful. Duringthe first 5 years after transplantation the majority ofurinary analyses showed oxalate excretion ratesbetween 0.6 and 0.8 mmol/day with only occasionalvalues below 0.5 mmol/day. The decrease of oxalateexcretion rates to normal values with only occasionalresults slightly above normal during years 6 and 7 aftertransplantation is difficult to explain. Oral calciumsupplementation was increased to the point whereurinary calcium excretion ranged between 3 and5 mmol/day. Magnesium was supplemented at a doseof 400 mg/day. A trial with organic marine hydrocol-loid charged with calcium, although effective regardingcontrol of oxaluria, had to be abandoned because ofabdominal distension and constipation. Despite per-sisting hyperoxaluria during the first few years aftertransplantation, the patient was rather fortunate notto form a single kidney stone after transplantation.Despite persisting gastrointestinal problems withabdominal distension, fullness, and occasional cramp-ing pains when constipated, this patient has resumeda fully active life as housewife, travelling around theworld and enjoying extensive and strenuous walks inthe mountains.CommentsThis is the first report of a long-term survival of acadaveric renal transplant over a period of 6 yearswithout renal complications in a patient with enterichyperoxaluria. In the literature we found only oneother similar case-report [7]. The patient mentioned inthat report developed end-stage renal failure due torenal oxalosis 9 years after extensive bowel resection.Because of difficulties with dialysis procedures heunderwent successful renal transplantation with goodrenal function. The follow-up covered only 10 monthsand it is not known whether complications developedlater in the course. The patient of the present reporthad a course of 25 years before developing end-stagerenal insufficiency. After the transplantation persistenthyperoxaluria with a few exceptions was observeddespite various modifications of diet and drugs. Nonew stone formation or signs of oxalate nephropathyoccurred in the graft. The kidney function has remainednormal, as reflected by serum creatinine levels below80 umol/1. Kidney biopsy was not performed to estab-lish potential interstitial oxalate deposits. During thelast 2 years urinary oxalate excretion was mostly withinthe normal range and the risk of recurrence of oxalatelithiasis or oxalate nephropathy is therefore reduced.Despite this uneventful course in our patient we thinkthat the recurrence of oxalosis or stone formation in arenal transplant has to be watched closely.According to our experience enteric hyperoxaluriashould not be a contraindication for renal transplanta-tion [5,6]. There are several reports of patients withH. Kistler et al.primary oxalosis and kidney transplantation and goodrenal function when certain conditions are observed[8-10]. We believe that in secondary hyperoxaluriakidney transplantation should also be considered forpatients with end-stage kidney disease in preference tomaintenance dialysis. Enteric hyperoxaluria is causedby intestinal hyperabsorption of exogenous oxalic acidand correlates well to the degree of steatorrhoea [11].The reduction of dietary intake of oxalic acid necessaryto lower oxaluria into the normal range is nearlyimpossible to achieve outside the hospital, as othershave also observed [12,13]. Dietary counseling isdifficult because of great differences in the analyticalmethods regarding content of oxalic acid in variousfoods. It is important to reduce the fat content in thediet with the addition of medium-chain triglyceridesand to supply oral calcium and magnesium salts inlarge amounts. Recommended are also oral applicationof citrate, resin exchange, and aluminium hydroxide[14]. As in all patients with kidney stones a large urinevolume to avoid a supersaturated urine is of primaryimportance.Good results were recently reported with anorganic marine hydrocolloid charged with calcium(Ox-absorb), a potent binding substance for oxalate[15]. Because of gastrointestinal side-effects we werenot able to treat our patient over a longer period inthis way.Another problem in a patient with global malabsorp-tion is the correct dosage of immunosuppressive drugs.As the absorption and bioavailability of oral cyclospo-rin in a malabsorption syndrome is unpredictable,cyclosporin has to be administered intravenously withcareful monitoring of serum concentrations [7]. Inorder to achieve immunosuppression with oral medica-tion our patient was put on prednisone and azathio-prine because cyclosporin administered orally waspoorly absorbed. With a small dosage of 7.5 mg pred-nisone and 150 mg azathioprine the renal function isnormal and no sign of rejection has occurred over theyears. In the early phase of transplantation oxalatedeposition in the new kidney has to be prevented.Therefore intensive haemodialysis is mandatory,should oliguria occur. In this way serum oxalate levelscan be lowered and damage to the kidney transplantavoided. More extensive experience with transplanta-tion has been reported in patients with primary oxalosis[9,10]. Good results have been achieved when thepatients had a period of intensive dialyses beforetransplantation. In order to avoid further oxalateaccumulation, forced diuresis after transplantation andearly haemodialysis is recommended, whenever thecadaver kidney shows a reduced function. We thinkthat the same procedure can be applied for patientswith secondary hyperoxaluria. Our good experiencewith this patient should encourage others to considerkidney transplantation in patients with end-stage renalfailure due to enteric hyperoxaluria.References1. Barilla DE, Notz C, Kennedy D, Pak CYC. Renal oxalateexcretion following oral oxalate loads in patients with ilealTransplant survival in oxalate nephropathydisease and with renal and absorptive hypercalciurias: effect ofcalcium and magnesium. Am J Med 1978; 64: 579-5852. Chadwick VS, Modha K, Dowling RH. Mechanism for hyperox-aluria in patients with ileal dysfunction. N EngI J Med 1973;289: 172-1763. Earnest DL, Johnson G, Williams HE, Admirand WH.Hyperoxaluria in patients with ileal resection: an abnormalityin dietary oxalate absorption. Gastroenterology 1974; 66:1114-11224. Canos HJ, Hogg GA, Jeffery JR. Oxalate nephropathy due togastrointestinal disorders. Can Med Assoc J 1981; 124: 729-7335. Das S, Joseph B, Dick AL. Renal failure owing to oxalatenephrosis after jejunoileal bypass. J Vrol 1979; 121: 506-5096. Gelbart DR, Brewer LL, Fajardo LF, Weinstein AB. Oxalosisand chronic renal failure after intestinal bypass. Arch InternMed 1977; 137: 239-2437. Roberts RA, Sketris IS, MacDonald AS, Belitsky P. Renaltransplantation in secondary oxalosis. Transplantation 1988;45: 985-9868. Morgan JM, Hartley MW, Miller AC, Diethelm AG. Successfulrenal transplantation in hyperoxaluria. Arch Surg 1974; 109:430-43314699. Scheinman JI, Najarian JS, Mauer SM. Successful strategies forrenal transplantation in primary oxalosis. Kidney Int 1984;25: 804-81110. Whelchel JD, Alison DV, Luke RG, Curtis J, Diethelm AG.Successful renal transplantation in hyperoxaluria.Transplantation 1983; 35: 161-16411. McDonald GB, Earnest DL, Admirand WH. Hyperoxaluriacorrelates with fat malabsorption in patients with sprue. Gut1977; 18: 561-56612. Earnest DL. Perspectives on incidence, etiology and treatmentof enteric hyperoxaluria. Am J Clin Nutr 1977; 30: 72-7513. Andersson H, Filipsson S, Hulten L. Urinary oxalate excretionrelated to ileocolic surgery in patients with Crohn's disease.Scand J Gastroenterol 1978; 13: 465-46914. Laker MF, Hofmann AF. Effective therapy of enteric hyper-oxaluria: In vitro binding of oxalate by anion-exchange resinsand aluminium hydroxide. J Pharm Sci 1981; 70: 1065-106715. Lindsjo M, Fellstrom B, Ljunghall S, Wikstrom B, DanielsonBG. Treatment of enteric hyperoxaluria with calcium-containingorganic marine hydrocolloid. Lancet 1989; 2: 701-704Received for publication: 3 April 1995Accepted in revised form: 12 April 1995

Seven-year survival of renal transplant for oxalate nephropathy due to short-bowel syndrome

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