Combined Kidney and Intestinal Transplantation in Patients With Enteric Hyperoxaluria Secondary to Short Bowel Syndrome



Kidney transplantation is the treatment of choice for end-stage renal disease whereas indications for intestinal transplantation are currently restricted to patients with irreversible small bowel failure and severe complications of total parenteral nutrition (mostly shortage and infection of venous accesses, major electrolyte disturbances and liver failure). Enteric hyperoxaluria is secondary to certain intestinal diseases like intestinal resections, chronic inflammatory bowel disease and other malabsorption syndromes and can lead to end-stage renal disease requiring kidney transplantation. We report two patients suffering from renal failure due to enteric hyperoxaluria (secondary to extensive intestinal resection) in whom we elected to replace not only the kidney but also the intestine to prevent recurrence of hyperoxaluria in the transplanted kidney.


end-stage renal disease


intestinal transplantation


kidney transplantation


short bowel syndrome


superior mesenteric artery


superior mesenteric vein


total parenteral nutrition.


Intestinal transplantation (ITx) is indicated in patients with short bowel syndrome (SBS) and severe complications of total parenteral nutrition (TPN) and bowel failure [1]. ITx has also been performed as part of multivisceral grafts including the liver and other splanchnic organs [2-4]. Albeit sporadically, inclusion of the kidney in these multivisceral grafts has been described [4, 5]. In contrast, reports on simultaneous kidney transplantation (KTx) and ITx—not as part of a multivisceral graft—are extremely scarce. We found only one case report in man and one experimental study in rodents [6, 7]. Given the lack of information on this rarely performed transplant procedure, its indications and technical aspects, we report two cases of dual renal and small bowel replacement. Both were performed in patients primarily referred for KTx because of end-stage renal disease (ESRD) as a consequence of enteric hyperoxaluria.

Case Reports

Case 1

A 41-year-old Caucasian female (weight: 50 kg, length: 161 cm, blood group: AB+) became TPN-dependent at the age of 28 years after a complete small bowel resection due to volvulus. In order to maintain the gastrointestinal transit, a duodenotransversostomy was performed. Renal function at that time was normal (serum creatinine: 0.64 mg/dL; estimated glomerular filtration rate (eGFR): 117 mL/min). She then gradually developed ESRD caused by recurrent nephrolithiasis and interstitial nephritis. The diagnosis of hyperoxaluria was confirmed by an elevated 24 h urinary oxalate excretion of 112 mg (normal: 10–41 mg/24 h) and kidney stone analysis revealed oxalate composition. Despite administration of 6 g of calcium carbonate and restricted oxalate diet she evolved toward renal failure and required hemodialysis (serum creatinine: 9.32 mg/dL; eGFR: 5.0 mL/min). To prevent disease recurrence in the transplanted kidney we listed her for a combined kidney and ITx. An entire small bowel and left kidney were procured from a 7-year-old blood group identical deceased male donor (weight: 26 kg, length: 124 cm). The intestine was transplanted first by anastomosing the superior mesenteric artery (SMA) to the aorta and the superior mesenteric vein (SMV) to the inferior vena cava. Thereafter, the donor kidney was transplanted in the left iliac fossa with conventional anastomoses of the renal vessels to the left iliac vessels, followed by a standard uretero-neocystostomy (Figure 1). The intestinal continuity was restored by an end-to-side gastro-jejunostomy, a side-to-side duodeno-jejunostomy and an ileo-transversostomy. Finally, a double loop ileostomy was constructed. Both native kidneys were removed and histological examination revealed massive glomerular scarring and tubular necrosis. Many intraluminal crystals (black arrows) had a slightly yellowish tinge and formed a radial pattern (Figure 2). They were confirmed as calcium oxalate crystals by their characteristic birefringence with polarized light (Figure 3). An immunomodulatory/immunosuppressive regimen, which is standard at our center, including donor specific blood transfusion and low dose immunosuppression with prednisolone, tacrolimus and azathioprine was administered [8]. The postoperative course was uneventful, the ileostomy was closed and the patient was discharged at day 60. She developed one episode of acute cellular rejection 3 years and 10 months posttransplant due to noncompliance, but fully recovered after steroids therapy and reinstitution of maintenance immunosuppression. Currently—5 years and 7 months posttransplant—she is TPN- and dialysis-free and doing well. Oxalate urinary excretion has returned to normal (32 mg/24 h) and renal function remains stable (serum creatinine: 0.9 mg/dL; eGFR: 71.3 mL/min).

Figure 1.

Anatomical sketch to illustrate the combined intestinal and kidney transplantation. The donor mesenteric vessels (SMA, superior mesenteric artery; SMV, superior mesenteric vein) are anastomosed to the recipient aorta (AO) and inferior vena cava (IVC), respectively. The kidney is transplanted in the left iliac fossa by connecting the renal vessels (RA, renal artery; RV, renal vein) to the iliac vessels (IA, iliac artery; IV, iliac vein), followed by a standard uretero-neocystostomy (black star). Depending on the type of intestinal graft, at the proximal side a gastro-, duodeno- or jejuno-jejunostomy (white arrow) is performed and distally an ileostomy (black arrow) is constructed.

Figure 2.

Histological examination of the cortex of the native kidney. There is glomerular scarring, tubular necrosis and interstitial fibrosis. Massive oxalate depositions, formed in a radial pattern with a slightly yellowish tinge (black arrows), can be seen in the surviving tubules. Hematoxylin and eosin 100×.

Figure 3.

Same microscopic field as in Figure 2, examined with polarized light. Birefringent crystals, characteristic of calcium oxalate, can be seen in the tubules. Hematoxylin and eosin 100×.

Case 2

A 56-year-old Caucasian female (weight: 50.3 kg, length: 160 cm, blood group: A+) was diagnosed with Crohn's disease at the age of 14 years. After multiple small bowel resections, she became TPN-dependent. At that time renal function was normal (serum creatinine: 0.64 mg/dL; eGFR: 117 mL/min). Progressively, she developed bilateral nephrolithiasis secondary to hyperoxaluria, diagnosed on the basis of increased plasma oxalate levels {62 µmol/L (normal: <3.0 µmol/L)}. A left nephro-ureterectomy was performed at the age of 31 years because of renal abscesses and pyelocutaneous fistula. Eventually, despite oral administration of 3 g calcium carbonate, low-oxalate intake and increased fluid uptake, she progressed toward ESRD (serum creatinine: 7.7 mg/dL; eGFR: 6 mL/min), became dialysis-dependent at the age of 47 years and was referred for KTx in combination with ITx. An entire small bowel and a left kidney graft were procured from a 9-year-old blood group identical deceased male donor (weight: 30 kg, length: 145 cm). The intestine was transplanted by anastomosing the donor SMV to the recipient inferior vena cava and the donor SMA to the recipient right common iliac artery. Then, the kidney was implanted in the left iliac fossa with construction of a standard uretero-neocystostomy. Finally, a proximal jejuno-jejunostomy and a terminal ileostomy were performed. Because of the preexisting reduced abdominal cavity, the fascia could not be closed and the defect was bridged with a vicryl mesh. The aforementioned immunomodulatory/immunosuppressive regimen was administered [8]. The postoperative course was marked by an episode of wound dehiscence that required replacement of the vicryl mesh. At day 56, the patient was discharged with normal intestinal and renal function. Nine months after transplantation, she presented with an episode of hydronephrosis due to ureteral calculi. This was resolved by placement of a double-J stent. Currently, the patient is 11 months posttransplant and TPN- and dialysis-free. Recurrence of enteric hyperoxaluria was excluded by a urine analysis showing normal oxalate urinary excretion (20 mg/24 h) and despite previous hydronephrosis, renal function remains stable (serum creatinine: 0.85 mg/dL; eGFR: 71.5 mL/min).


ITx—albeit still a higher risk procedure compared to other abdominal organ transplantations—represents a life-saving option in patients with SBS and TPN-related complications [1]. The intestine is frequently transplanted in combination with the liver in case of associated liver failure [2] and sometimes as part of a complex multivisceral graft including the stomach, the duodenum, the pancreas and the colon [3-5]. Multivisceral transplantation has been performed for complex diseases affecting the entire abdominal cavity like diffuse splanchnic thrombosis, major vascular abdominal trauma or benign but progressive tumors [3, 4] and the kidney has occasionally been included in these multivisceral grafts [4, 5]. Here, we report two patients who underwent combined KTx and ITx (not as part of a multivisceral transplant), a procedure apparently rarely performed.

These two patients were primarily referred for KTx because of enteric hyperoxaluria and ESRD secondary to extensive intestinal resection. Unlike primary hyperoxaluria—that is due to hepatic enzyme deficiencies (alanine/glyoxylate aminotransferase, reductase/hydroxypyruvate reductase and 4-hydroxy-2-oxoglutarate aldolase in types I–III primary hyperoxaluria, respectively) causing an excessive endogenous production of oxalate [9]—the enteric form of hyperoxaluria is secondary to various gastrointestinal diseases (jejunoileal resection, small bowel bypass, chronic inflammatory bowel disease) that lead to an excessive absorption of calcium oxalate [10].

Calcium normally binds to oxalate in the intestinal lumen and is eliminated in the feces. Less than 10% of the oxalate is absorbed enterally. In case of gastrointestinal malabsorption, the excess of intraluminal free fatty acids inhibits the complexing of oxalate and calcium by binding to the available calcium ions. This allows soluble uncomplexed oxalate to be absorbed in the large bowel. Additionally, bile salts and free fatty acids, toxic to the colonic mucosa, may increase permeability of the bowel wall and increase oxalate absorption [11]. These calcium oxalate complexes precipitate in the renal tubules where they damage tubular epithelial cells, facilitating tubular injury and necrosis, leading to progressive tubular atrophy and interstitial fibrosis. Other contributing factors for calcium oxalate precipitation include volume depletion—as a consequence of chronic diarrhea in case of SBS—metabolic acidosis, reduced urinary citrate excretion and hypomagnesaemia [12, 13].

Several strategies are available to reduce oxalate absorption. First, the amount of oxalate available for absorption should be reduced. Reduction of dietary oxalate intake is recommended but can be difficult to tolerate for the patients. Administration of oral calcium and magnesium salts to complex free oxalate and limit its absorption is usually recommended, but remained ineffective in our two cases. Furthermore, excess of calcium salts may enhance formation of calcium oxalate kidney stones and magnesium salts could worsen diarrhea. Cholestyramine has been shown to bind oxalate or bile acids effectively but is often tolerated poorly. Oxalobacter formigenes, a gram-negative, anaerobic bacterium, has been shown promising in patients with primary hyperoxaluria in reducing urinary oxalate by degrading intestinal oxalate and limiting its absorption [12, 14]. Second, calcium oxalate precipitation should be minimized. Therefore, increased fluid administration should be maintained to ensure good hydration and high urine flow. Metabolic acidosis and urinary magnesium levels should be corrected. And third, it seems logical not only to treat the nephrolithiasis and associated kidney disease but more importantly the underlying bowel disease. In primary hyperoxaluria, liver transplantation is usually recommended in addition to KTx to avoid disease recurrence in the transplanted kidney and in certain cases, “preemptive” isolated liver transplantation has even been advocated to avoid the need for KTx [9, 15]. In contrast, data on KTx for secondary hyperoxaluria are scarce [12, 16, 17] and to our knowledge no case of combined KTx and ITx for this indication has been reported. To prevent recurrence of enteric hyperoxaluria in the transplanted kidney, performing an ITx simultaneously with a KTx—like in our two patients—may represent the only curative treatment. In support of this, Lim et al. reported a patient with enteric hyperoxaluria secondary to Crohn's disease and who only received a kidney graft. Biopsies at 7 months posttransplant showed intraglomerular and interstitial calcifications consistent with recurrence of oxalate deposition [16]. Also Bernhardt et al. [17] described relapse of hyperoxaluria after an isolated KTx in a patient with Crohn's disease. Another argument to replace the bowel in addition to the kidney, in these patients, is the possibility to render them not only dialysis-free but also nutritionally independent, thereby avoiding the TPN-related complications, improving their quality of life and prolonging their life expectancy [1, 2, 4]. Moreover, resorption of immunosuppressive drugs may reveal problematic in KTx recipients who are left with SBS [18].

In the literature, we found only one report of a dual kidney and intestine replacement performed in a 36-year-old female. She had been referred for a second KTx and was suffering from chronic small bowel obstructions, secondary to encapsulating peritoneal sclerosis [6]. This lack of information may reflect that—in similar situations—preference was given to isolated KTx in order to avoid the additional morbidity and mortality, generally associated with ITx. In support of this, we found one report of a KTx candidate with SBS in whom the possibility of combined ITx was evoked, but who eventually received an isolated KTx [19]. However, it is also possible that cases of dual intestine and renal replacement have been performed but not reported. Indeed, data from the Intestinal Transplant Registry between 2005 and 2012 indicate that of 534 isolated ITx, 19 (3.5%) were combined with KTx (Personal communication, M. Marquez and D. Grant, Intestinal Transplant Registry, Toronto General Hospital, September 2012).

The surgical aspects of combined KTx and ITx are not different from isolated KTx and ITx. One particular problem, however, may be the difficulty to close the abdomen due to the small abdominal cavity, resulting from the lack of intestinal content, abdominal wall fibrosis or intra-abdominal scarring due to multiple bowel resections [1]. For this reason—whenever possible—donors who are smaller than recipients should be selected. If primary closure of the fascia is not possible—like in our second patient—alternative surgical strategies such as mesh-repair, musculocutaneous flaps or skin expansion by subcutaneous prosthesis should be considered [20].

In conclusion, replacing the intestine in addition to the kidney is a valuable treatment option in KTx candidates with enteric hyperoxaluria secondary to SBS. In contrast to kidney replacement alone, combined ITx will resolve the underlying bowel disease and prevent recurrence of enteric hyperoxaluria and associated nephrolithiasis in the transplanted kidney.


No funding was provided for this study. J. Pirenne and D. Monbaliu are recipients of a CAF chair for abdominal transplant surgery. The department of abdominal transplant surgery has received unrestricted grants from Astellas and Roche.


The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.