Enteric Oxalate Nephropathy in the Renal Allograft: An Underrecognized Complication of Bariatric Surgery


Corresponding author: Megan L. Troxell, troxellm@ohsu.edu


Enteric hyperoxalosis is a recognized complication of bariatric surgery, with consequent oxalate nephropathy leading to chronic kidney disease and occasionally end-stage renal failure. In patients with prior gastrointestinal bypass surgery, renal allografts are also at risk of oxalate nephropathy. Further, transplant recipients may be exposed to additional causes of hyperoxalosis. We report two cases of renal allograft oxalate nephropathy in patients with remote histories of bariatric surgery. Conservative management led to improvement of graft function in one patient, while the other patient returned to dialysis. Interpretation of serologic, urine and biopsy studies is complicated by oxalate accumulation in chronic renal failure, and heightened excretion in the early posttransplant period. A high index of suspicion and careful clinicopathologic correlation on the part of transplant nephrologists and renal pathologists are required to recognize and treat allograft oxalate nephropathy. As the incidence of obesity and pretransplant bariatric surgery increases in the transplant population, allograft oxalate nephropathy is likely to be an increasing cause of allograft dysfunction.


mycophenolate mofetil


postoperative day


Oxalate nephropathy is a rare cause of acute and chronic renal failure [1-4]. Oxalate accumulation in renal allografts may arise de novo, or as “recurrence” of native kidney disease if underlying hyperoxalosis remains uncorrected. Causes of renal oxalosis have been fairly well characterized, yet new associations continue to emerge. Primary hyperoxaluria is a hereditary condition with at least three different genetic enzymatic defects (Table 1) [1]. Currently, liver or combined liver–kidney transplantation is recommended for patients with primary hyperoxaluria, with liver transplantation serving to correct the enzymatic deficiency [1]. Secondary hyperoxaluria can arise from a variety of different processes (Table 1), including iatrogenic causes. Gastrointestinal surgery is a known cause of hyperoxaluria, most notably in situations of fat malabsorption and diarrhea [1-4].

Table 1. Causes of renal oxalate accumulation1
  1. 1Table 1 compiled from references 1–4, 22, 30–31, 33, 36.

  2. 2With fat malabsorption, hyperoxaluria is thought to result when excess free fatty acids complex with calcium in the gut, making calcium unavailable to bind oxalate, such that free oxalate is absorbed. The presence of high levels of free fatty acids and bile are also said to increase colonic mucosal permeability to oxalate.[1, 2] Cystic fibrosis patients with lung transplants are at particular risk of oxalate (native) nephropathy due to fat malabsorption, diabetes, antibiotic exposure which alters bowel flora including Oxalobacter formigenes, and a role for CTFR in reciprocal regulation of oxalate transporters in renal tubular epithelial cells [1, 21, 22].

Type I: deficiency of alanine-glyoxylate aminotransferase 
Type II: deficiency of glyoxylate reductase/hydroxypyruvate reductase 
Type III: deficiency of 4-hydroxy-2-oxoglutarate aldolase (remains to be fully characterized) 
 Foods high in oxalic acid, (carambola (star fruit), beans, spinach, rhubarb, beer, cocoa, lemons, tomatoes, tofu, nuts, parsley, gelatin, etc) 
 Xylitol sweetner 
 Excessive vitamin C ingestion (elevated precursors) 
 Ethylene glycol poisoning (elevated precursors) 
 Deficiency of pyridoxine (vitamin B6) and thiamine 
 Low oral calcium intake 
 Gastrointestinal surgery2 (gastric bypass surgery (both jejunal-ileal bypass and Roux-en-Y), surgery for gastric cancer, and intestinal surgery for Crohn's disease) 
 Cystic fibrosis, other causes of chronic pancreatitis2 
 Diabetic gastroenteropathy 
 Altered bowel flora (Oxalobacter formigenes metabolizes oxalate to formate and creates a transepithelial gradient favorable to oxalate secretion) 
 Mycophenolate mofetil associated fat malabsorption syndrome (1 case report (37))2 
 Orlistat (Xenical) and other lipid lowering drugs inhibiting gastric and pancreatic lipases2 
 Naftidrofuryl oxalate (Praxilene) antihypertensive 
 Methoxyflurane anesthetic 

The jejunoileal bypass bariatric procedure was discontinued in the United States in 1979 due to a high rate of nephrolithiasis (over 25%) among other serious complications [5]. However, recent data suggest that modern bariatric procedures, such as Roux-en-Y bypass, may also impart a twofold increased risk of nephrolithiasis, while 20–75% may have hyperoxaluria, including 20% with very high urine oxalate levels, also putting them at considerable risk of oxalate nephropathy (Table 2) [2, 5-12]. Purely restrictive bariatric procedures, such as gastric banding, may not increase oxalate excretion, yet more data are needed (Table 2) [13-16]. Morbidly obese patients are increasingly encouraged to consider bariatric surgery in order to meet body mass index thresholds for renal or other solid-organ transplantation. Some recipients have a more remote history of bariatric surgery, and others may undergo surgery after transplantation [6, 17, 18]. Registry data report that the prevalence of obesity among kidney transplant recipients increased from 23% to 33% over the last decade [18]. Given these trends, oxalate nephropathy in the renal allograft is likely to increase in prevalence. We present two cases of renal allograft oxalate nephropathy, one that improved with conservative management, and one that was initially unrecognized on biopsy.

Case Reports

Patient 1

The patient is a 70-year-old woman with end-stage renal disease of indeterminate etiology. Her past medical history included hypertension, and dilated cardiomyopathy. Her prior surgical history included remote hysterectomy for uterine cancer, cholecystectomy and gastric bypass surgery 27 years earlier, resulting in an 80-pound weight loss. There was no evidence of nephrocalcinosis on pretransplant ultrasound. She received a deceased donor renal allograft and had an unremarkable postoperative course with near-immediate graft function. She received thymoglobulin induction (3 mg/kg), followed by immunosuppression with tacrolimus, mycophenolate mofetil (MMF) and steroids. Her posttransplant nadir creatinine was 1.0 mg/dL on postoperative day 5 (POD 5), and remained at 1.1–1.2 mg/dL during the first year, with oxalate crystals noted on surveillance urinalysis once at 8 months posttransplantation. She was briefly hospitalized for pneumonia 1 month later. Creatinine rose to 1.8 mg/dL 1 year posttransplantation. A biopsy was performed, and based on suspicion of rejection a steroid pulse was initiated on the day of biopsy (5 mg/kg × 3 days with rapid taper).

The allograft biopsy contained 12 histologically normal glomeruli. There was a scant predominantly lymphocytic inflammatory cell infiltrate that did not meet criteria for acute cellular rejection. Translucent crystals were seen in many tubules, and rarely within proximal tubular epithelial cells; polarization revealed bright birefringence and fan-shaped morphology (Figure 1). Acute tubular injury was diffuse; additionally interstitial fibrosis was estimated to involve 30% of the biopsy sample, with a lesser degree of tubular atrophy. Upon re-review, the native kidney biopsy from 4.5 year prior contained no crystalline material, but was limited by its small size.

Figure 1.

Histopathologic features of renal oxalate deposition. (A) Translucent crystals are seen in cortical tubules on H&E stained section; inset shows intracellular crystals (case 1). Crystals are inapparent on PAS, Jones, and trichrome histochemical stains (not shown). Oxalate was semiquantitated at 7.3 crystals/cm of cortical biopsy length, or 0.9 crystals/glomerulus for case 1. Case 2 had 11 crystals/cm cortex, or 2.2 crystals/glomerulus 2 (not shown). (B) Crystals are brightly birefringent in polarized light; inset shows intracellular crystals (case 1, same microscopic field as A).

After biopsy, her 24-h urine oxalate was found to be 81 mg (normal range 4–31 mg), with a urine oxalate:creatinine ratio of 0.123 mg/mg (normal range 0.003–0.062). Review of other risk factors associated with oxalosis revealed 1 g/day vitamin C supplementation; however, there were no clinical symptoms of fat malabsorption. Upon discontinuation of vitamin C, addition of calcium carbonate (1 g of elemental calcium/day) and initiation of a low oxalate diet, renal allograft function improved, with a creatinine of 1.4 mg/dL 2 months postbiopsy. A subsequent urine oxalate study showed improved, though still elevated oxalate excretion (70 mg/day; urine oxalate:creatinine of 0.101 mg/mg).

Patient 2

The patient is a 67-year-old man who underwent renal transplantation for end-stage renal disease attributed to diabetes mellitus type II. Other past medical history included gastrointestinal bleed secondary to nonsteroidal anti-inflammatory drugs, with past surgical history of bilateral knee replacements that were complicated by reoperations and a staphylococcal knee infection requiring prolonged vancomycin treatment. He had Roux en-Y gastric bypass surgery 7 years prior to transplantation resulting in 100 pound weight loss, though he maintained a body mass index of 35. The patient received a deceased donor renal allograft with thymoglobulin induction (3 mg/kg), followed by maintenance immunosuppression with tacrolimus, MMF and steroids. He experienced delayed graft function; a biopsy on POD 20, while the patient remained on dialysis, revealed acute cellular rejection, which was treated with pulse steroids (500 mg/kg × 3 days with rapid taper). Dialysis was discontinued one month posttransplant, with nadir creatinines of 1.5–2.2 mg/dL. After an episode of hypertension with creatinine increase to 2.9 mg/dL, a diagnosis of renal artery stenosis was made and a transplant artery stent placed, with creatinine return to 1.5 mg/dL. Despite this transient improvement in allograft function, the creatinine again rose to 2.7 mg/dL in the fifth posttransplant month. Several interval allograft biopsies were reviewed at outside hospitals; none were reported to show acute rejection. MMF was changed to azathioprine because of persistent diarrhea and upper gastrointestinal symptoms. The patient was treated for several intercurrent urinary tract infections with various antibiotic regimens; he was

Table 2. Literature summary of enteric hyperoxaluria and oxalate nephropathy in the modern era. Panel A Studies of urine oxalate and nephrolithiasis after modern bariatric surgery. Panel B Studies of enteric oxalate nephropathy, native kidneys. Panel C Prior cases of enteric oxalate nephropathy in renal allografts
Panel A
StudyType of surgeryOxalate levels/nephrolithiasisComments
  1. *Includes gastric bypass and banding.

  2. hyperoxaluria defined as >45mg/24hr.

  3. BD-DS, Biliopancreatic diversion with duodenal switch.

  4. AKI, acute kidney injury; ESRD, end-stage renal disease; DGF, delayed graft function; FSGS, focal segmental glomerulosclerosis.

Oxalate levels
 Nelson, 2005 and Sinha 2007 retrospective [37, 38]15 Roux-en-Y stone formers16 Roux-en-Y very very long limb stone formersOxalate excretion 0.61 mmol/day; supersaturation 2.02 Delta GOxalate excretion 0.71 mmol/day; supersaturation 2.34 mmol/dayFirst stone mean 2.1 years post-opFirst stone mean 1.9 years post-op. 27% of 168 surveyed patients report nephrolithiasis
 Sinha 2007 Prospective cohort [38]Roux-en-YUrine oxalate in mmol/24 h (supersaturation, Delta G)Different patients at each time point, not longitudinal study (see Kumar 2011)
  Pre-op (N = 20): 0.35 (1.51) 
  Post-op 6 mo (N = 8): 0.32 (1.49) 
  Post-op 12 mo (N = 13): 0.74 (2.38) 
 Asplin, 2007 [39]Patient groupsOxalate excretion in mg/24 hStudy population derived from kidney stone clinic/database
 Modern bariatric stone formers* (N = 132)83 
 JI bypass stone formers (N = 27)102 
 Nonoperated stone formers (N = 2048)39 
 Normal (N = 168)34 
 Duffey, 2008 and Duffey 2010 [40, 41]Roux-en-Y bypass surgery (75–150 cm limb, N = 21)Oxalate excretion mg/24 h (supersaturation) 
  Pre-op: 33 (1.73) 
  Post-op 90 days: 41 (3.47) N = 24 
  Post-op 1 year: 64 (2.51) 
  Post-op 2 years: 63 (2.20) 
 Park, 2009 [42]Roux-en-Y bypass surgery (N = 45)Urinary oxalate: mg/24 h (supersaturation)Patients with pre-op stones excluded.
  Pre-op: 32 (1.27)Post-op, 6 patients had >60 mg and 2 patients >100 mg urinary oxalate
  Post-op, mean 9.6 months: 40 (2.23) 
 Patel, 2009 [7]Patient groupsUrine oxalate mg/24 h (supersaturation)Patients with pre-op stones excluded
 Bariatric surgery (Roux-en-Y N = 52; duodenal switch N = 6)67.2 (7.78); 52–74% hyperoxaluricMean 427 days postsurgery, most bariatric patients tested twice
 Stone former database (N = 1303)37.0 (7.34)Corrected for serum creatinine, etc
 Normal controls34.1 (7.41) 
 Penniston, 2009 [13]Patient groupsUrine oxalate mg/24 h (supersaturation)Mean 2.06 years postgastric banding and 3.35 years post-Roux-en-Y surgery
 Gastric banding surgery (N = 12)40.8 (2.78) 
 Roux-en-Y bypass (N = 27)48.1 (1.89) 
 Semins 2010 [15]Gastric restrictive (Band N = 14; sleeve gastrectomy N = 4)Urine oxalate: 35.44 mg/hr (supersaturation 5.22)Mean 12.4 months after surgery
 Maalouf 2010 [9]Patient groupsUrine oxalate mg/24 h (% hyperoxaluric)Mean 3.5 year after surgery
 Roux-en-Y (limb 50–100 cm; N = 19)45 (47%) 
 Morbidly obese controls (N = 19)30 (10.5%) 
 Kumar, 2011 [11]Roux-en-Y (N = 9); BPD-DS (N = 2)Plasma oxalate, umol/LUrine oxalate after an oral oxalate challenge was also tested at each time point, with significant increases at 6 and 12 months. No patients developed stones in the 12-month study period by CT scan
  Pre-op: 1.2 
  Post-op 6 months: 2.2 
  Post-op 12 months: 1.9 
  Urine oxalate, mg/24 h (supersaturation, Delta G) 
  Pre-op: 26.4 (1.0) 
  Post-op 6 months: 27.2 (2.3) 
  Post-op 12 months: 32.6 (1.8) 
 Wu, 2011 [10]Roux-en Y (75–100 cm limb, N = 38)Oxalate excretion mg/24 h (supersaturation) 
  Pre-op: 38 (4.9) 
  Post-op 6 months: 48 (10.5) 
 Froeder 2012 [12]Bariatric SurgeryUrine oxalate: 26 mg/24 hCalcium supplements stopped
 Roux-en-Y (N = 58); BD-DS (N = 3)Hyperoxaluric: 20%In response to oral oxalate challenge, surgery patients (N = 22) had a significantly higher uOx:uCr ratio than pre-surgery patients (N = 21) at all time points
  O. formigenes colonization: 4/10 
 Morbidly obese (pre surgery; N = 30)Urine oxalate: 29 mg/24 h 
  Hyperoxaluric: 13% 
  O. formigenes colonization: 2/13 
Nephrolithiasis studies
 Durrani 2006 [43]972 Roux-en-Y85 nephrolithiasis pre-op 
   26 with recurrent stones post-op 
  32 de novo nephrolithiasis post-op 
 Matlaga, 2009 [8]Patient groups% nephrolithiasisInsurance databases, only 3 years post-op follow-up
 Roux-en-Y surgery (N = 4639)7.65% 
 Morbidly obese controls (N = 4639)4.63% 
 Semins 2009 [14]Patient groups% nephrolithiasisInsurance databases, only 2 years post-op follow-up
 Gastric banding surgery (N = 201)1.49% 
 Morbidly obese controls (N = 201)5.97% 
 Chen 2012 [16]Patient groups (chart review)Stone diagnosis per 1000 person yearsPrior nephrolithiasis excluded
 Adjustable gastric banding (N = 332)3.4Calculates from Matlaga (stones per 1000
 Sleeve gastrectomy (N = 85, shorter follow-up)5.25person years): Roux-en-Y = 16.62; obese = 11.2
Panel B
 Type of surgery orRenal 
Studygastrointestinal conditionoutcomeComments
Modern bariatric surgery
 Nasr, 2008 [2]11-Roux-en-Y8- ESRD6 with diarrhea
  3-elevated creatinine9 diabetic
 Moutzouris, 2011 [23]1- Roux-en-YESRDDiabetic; case report
Other gastrointestinal conditions
 Wharton 1990 [44]1-extensive small bowl resection TB2-ESRDDiarrhea
 1- alcoholic pancreatitis, diabetes  
 Fakhouri 2002 [45]1-alcoholic pancreatitisESRDDiarrhea with cessation of pancreatic enzyme replacement; antibiotic course immediately prior to presentation
 Lefaucheur, 2006 [22]2-cystic fibrosis, lung transplant2-ESRDFat malabsorption in cystic fibrosis, extensive
 1-dilated alcoholic cardiomyopathy, heart transplant1-died (sepsis) antibiotic treatment
 Cartery, 2011 [4]8-chronic pancreatitis3-ESRD9 diabetic
 4-occult pancreatitis9-functioning kidneys (creatinine 1.1–4.6 mg/dL)5 with diarrhea
   1 with massive vitamin C
   4 with recent antibiotics
 Dheda, 2012 [46]1-ileal resection, cystic fibrosis, lung transplantAKI from 10 days postlung transplant progressing to ESRDSubsequent renal transplant with normal function at 8 months (creatinine 1.4 mg/dL)
 Pancreatic dysfunction, extensive antibiotic treatment  
Panel C
AuthorPredisposing factorsRenal outcomecomments
Case reports of oxalate nephropathy diagnosed in allograft
 Cuvelier, 2002 [47]Occult chronic pancreatitisFirst graft lostNative-bilateral renal dysplasia
  Second graft recovered function afterBoth grafts essentially primary nonfunction
  11 months 
 Jahromi, 2008 [36]DiabetesDiarrhea, possibly MMF associatedElevated creatinine (4.6 mg/dL)Simultaneous pancreas kidney transplant recipient
 Rankin, 2008 [48]Chronic pancreatitis with diarrheaGraft function for 15 months, then ESRD atDiabetes; antibiotics for recurrent UTI
   episode of sepsisDiarrhea attributed to pancreatic replacement non-compliance
 Capolongo, 2012 [49]Occult celiac diseaseNormal creatinine (1.2 mg/dL)FSGS and oxalate in native kidney
 Present case 1Gastric bypassCreatinine 1.4 mg/dLVitamin C, antibiotic exposure
 Present case 2Gastric bypassESRDMultiple prolonged antibiotic courses; diabetes
Case reports of renal transplantation in known enteric hyperoxaluria
 Roberts, 1988 [50]Bowel resection for mesenteric artery thrombosisNormal renal function at 10 months (1.4 mg/dL)Native renal failure due to enteric hyperoxaluria. Graft biopsies at 1 and 10 months with no oxalate
 Kistler, 1995 [32]Extensive small bowel resection for bowel necrosisGraft function for >7 yearsMalabsorption and known enteric hyperoxaluria at transplant. DGF; oxalate and “ischemia” on day 9 biopsy. Graft functions at day 12, no further biopsies
 Bernhardt, 2006 [33]Crohns, bowel resections, malabsorptionCreatinine 4.9 mg/dL at 18 monthsKnown enteric hyperoxaluria at transplant; native ESRD due to nephrolithiasis. Severe anemia due to oxalosis resolved with transplant. DGF; graft biopsy at day 11 with borderline rejection and sporadic proximal tubule oxalate crystals; subsequent biopsies show increasing oxalate
 Rifkin, 2007 [24]Crohns, bowel resectionsGraft function for >3 yearsKnown hyperoxaluria, native kidney ESRD due to stone disease. One allograft biopsy with Banff 1B rejection, no oxalate

hospitalized 8 months posttransplant for pneumonia with sepsis complicated by a myocardial infarction with peak creatinine of 3.9 mg/dL. Subsequently, creatinine fluctuated but continued to rise to 6.0 mg/dL 11 months posttransplantation; after a 3-day course of steroids an allograft biopsy was performed and referred to our laboratory for special studies.

The renal biopsy specimen contained five glomeruli, some enlarged with increased mesangial matrix suggestive of early diabetic glomerulopathy. Large birefringent crystals were seen within tubules, with regional variation. Rare crystals were present within tubular epithelial cells, and acute tubular injury was noted. There was sparse inflammation, though chronic interstitial fibrosis and tubular atrophy involved at least half of the small cortical sample. Prior allograft biopsies were obtained for retrospective review. Oxalate crystals were rare to absent in the first two allograft biopsies; however, biopsies at 3 and 4 months posttransplantation contained numerous oxalate crystals.

The patient returned to hemodialysis, with allograft failure attributed primarily to oxalate nephropathy, although he did experience other posttransplantation complications. Unfortunately, oxalate studies are not available. In retrospect, there was no evidence of nephrolithiasis by ultrasound or CT scan on several exams prior to transplantation; interestingly, a CT scan 5 months posttransplantation showed stones in the native kidneys. Factors likely contributing to oxalate nephropathy in this patient included gastric bypass surgery, multiple antibiotic regimens and potentially MMF associated diarrhea and/or diabetic gastroenteropathy, as the patient had progressive complaints of gastrointestinal reflux disease.


Both of these patients presented with allograft dysfunction and mild nonspecific inflammation in the allograft biopsy. Oxalate nephropathy was not suspected clinically, but tubular oxalate crystalline precipitates, intracellular crystals, and evidence of acute tubular injury were seen on allograft biopsy. Both patients had history of gastric bypass surgery along with other risk factors, likely contributing to multifactorial hyperoxaluria.

Patient 1 had a high intake of vitamin C intake, which may be metabolized to oxalate. Oral vitamin C (ascorbate) has been shown to increase both urinary total and endogenous oxalate levels, and 1–2 g/day ascorbate ingestion has been associated with a 10–19 mg/day increase in 24 h urinary oxalate levels in stone formers (with a lesser change in non-stone formers) [20]. One case of oxalate nephropathy has been reported with oral ingestion of 4 g vitamin C/day [19]. Although the contribution of vitamin C to hyperoxaluria in patient 1 is not entirely clear, it is interesting to note that the incremental change in urinary oxalate was on the order of 11 mg/day with discontinuation of vitamin C and dietary modifications.

Patient 2 had received several courses of antibiotics, and had other gastrointestinal complaints (Table 1). Prolonged antibiotic therapy is well known to alter gut flora, including reduction or elimination of Oxalobacter formineges, an oxalate-metabolizing bacterium which also induces a transepithelial gradient favoring oxalate secretion [1, 21, 22].

Screening and clinical monitoring for oxalosis remain challenging as urinary oxalate levels in patients with renal failure may be deceptively high or low [1, 23-25]. Serum oxalate concentration is inversely correlated with glomerular filtration rate, and oxalate accumulates in serum and tissue in the setting of chronic renal failure [1, 25, 26] Thus, pretransplant screening is impractical. Further, although dialysis does remove oxalate to a varying degree dependent upon method and duration, dialysis does not normalize oxalate levels in end stage renal disease [27, 28]. In the immediate posttransplant period, the allograft clears excess plasma oxalate, which results in transient hyperoxaluria usually lasting from 3 days to 3 weeks [25, 26, 29, 30]. Several studies have characterized the typical plasma and urine oxalate profile in transplant recipients. In one small study, mean pretransplant serum oxalate concentration was 55 μmol/L, which decreased to 21 μmol/L on day 1, and varied between 9–16 μmol/L on days 2–5 (normal range 7–11 μmol/L) [25]. Urine oxalate was very high on day 1 (mean 1244 μmol/day) and remained elevated through day 5 (417–584 μmol/day, normal range 325–379 μmol/day) [25]. A larger study reported median pretransplant plasma oxalate of 35.0 μmol/L (normal range 2.6–11.0) [26]. At 10 weeks posttransplantation, median oxalate concentration had significantly decreased to 9.0 μmol/L, yet 37% of patients still had oxalate levels above the normal range [26].

Oxalate crystals in renal biopsy specimens have characteristic morphology, as described in the cases above, yet may be difficult to recognize (Figure 1). Oxalate crystals are translucent on standard hematoxylin and eosin stained sections, but show strong birefringence under polarized light. These crystals dissolve and disappear during preparation of the other histochemical stains commonly used in renal pathology (PAS, Jones silver, trichome), and are negative on calcium stains von Kossa and Alizarin red [31]. However, Pizzolato's stain is reported to highlight calcium oxalate [31]. Oxalate crystals are deposited preferentially but unevenly in the cortex, often associated with acute tubular injury/necrosis, with fewer crystals in the medulla [30].

Several groups have characterized oxalate deposition in renal allograft biopsy series. Truong et al. reported a 4% frequency of calcium oxalate crystals in biopsies (13/315) either within 1 month of transplantation with acute tubular necrosis or rejection, in grafts with chronic renal failure, or in an allograft from a previously undiagnosed primary hyperoxaluria patient [31]. Subsequently Bagnasco et al. identified oxalate in nearly 5% of allograft biopsies (76 of 1621 biopsies; 63 of 680 patients), with about half of those from the 1-month posttransplant time period when the renal allograft is typically clearing an accumulated oxalate load [30]. No oxalate crystals were seen in 26 implantation biopsies [30]. Pinheiro et al. reported oxalate crystals in 52% of early allograft biopsies, especially in patients with higher creatinine or within 3 weeks of transplantation [29]. In each of these studies, oxalate crystals were associated with acute tubular injury/necrosis, and may rarely be associated with delayed graft function (Table 2) [29-33]. Thus, it appears that oxalate crystals in allograft biopsies are quite common in the immediate posttransplant period, but distinctly rare thereafter, except in the setting of chronic renal (allograft) failure. Although several studies have quantitated oxalate crystals in renal biopsies (normalized as crystals per cm length, per glomerulus, per 20× microscopic field, etc.) [2, 19-31], there is no established deleterious threshold level of oxalate crystal deposition in the native or allograft renal biopsy. Nevertheless, the finding of oxalate on biopsy three or more months posttransplantation should prompt clinicopathologic investigation.

As illustrated by these cases, allograft oxalate nephropathy may be treatable if chronic tubulointerstitial damage has not occurred, and the renal oxalate burden can be successfully reduced. However, oxalate nephropathy leads to end-stage renal or allograft failure in a high proportion of cases. In a series of 11 native renal biopsies with oxalate nephropathy, Nasr et al. reported end stage renal failure in 8 patients (72%) [2]; however, in a recent series of 11 native and 1 allograft biopsies in patients with oxalate nephropathy attributed to chronic pancreatitis, only 3/12 (25%) of patients had end stage renal failure at 7 months [4]. Individual case reports of secondary allograft oxalate nephropathy have also documented mixed outcomes (Table 2).

In a patient with suspected oxalosis, biopsy findings should be correlated with serum and urine oxalate studies, keeping in mind the expected profile of oxalate excretion posttransplantation. Careful review of patient history, including discussion of diet and supplement use, is necessary to elucidate potential causes of hyperoxaluria, which may be multifactorial. Treatment of allograft oxalate nephropathy will necessarily depend on the likely etiology, but typical management includes oral calcium supplementation as emphasized by Lightner, in addition to a low-oxalate and low-fat diet, increased fluids, and possibly vitamin B6 [1, 24, 34]. Recent studies have explored administration of Oxalobacter formigenes or lactic acid bacteria to alter gut flora, with mixed results [1, 35].

In summary, the incidence of allograft oxalate nephropathy is likely to rise, given trends in obesity and bariatric surgery among transplant recipients and those on the waitlist [6, 17, 18]. A high index of suspicion is warranted in bariatric surgery patients with unexplained allograft dysfunction. However, careful clinicopathologic correlation is needed, as oxalate crystals in allograft biopsies may not always be pathologic, especially early after transplantation. Additionally, oxalate serum and urine oxalate levels may vary widely in chronic renal failure, end stage renal disease, and immediately posttransplantation.


The authors thank Dr. Eric Kerns for critical reading of the manuscript.


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