Search

A 73-year-old Caucasian female with a history of obesity status post Roux-en-Y gastric bypass (RYGB) surgery presented with generalized weakness and was found to have acute kidney injury (AKI) with a creatinine peak of 9.1 mg/dL above her baseline of 1.2 mg/dL, and anemia with hemoglobin 5.7 g/dl. Kidney biopsy revealed oxalate nephropathy likely related to gastric bypass surgery four years prior. RYGB is a strong risk factor for hyperoxaluria, nephrolithiasis, and oxalate nephropathy which often progresses to end-stage renal disease (ESRD). Meaningful treatment strategies for this disease entity are lacking. We present a case in which dietary and pharmacological management without the use of renal replacement therapy resulted in stabilization of chronic kidney disease (CKD) stage 5 for seven years at the time of this writing.

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

Introduction: Current knowledge of risk factors and renal histologic patterns of oxalate nephropathy (ON) not due to primary hyperoxaluria (PH) has been limited to small case series and case reports. Thus, we analyzed and compared clinical risk factors, histologic characteristics, and renal outcomes of patients with biopsy-confirmed ON among a cohort of patients with enteric and nonenteric risk factors. Methods: A clinical data repository of native kidney pathology reports from 2009 to 2020 at all Mayo Clinic sites was used to identify 421 ON cases. Results: After excluding cases in transplanted kidneys or due to PH, 64 cases remained. Enteric risk factors were present in 30 and nonenteric in 34. Roux-en-Y gastric bypass (17) and pancreatic insufficiency (6) were most common in the enteric hyperoxaluria group. In the nonenteric group, vitamin C (7) and dietary oxalate (7) were common, while no apparent risk was noted in 16. Acute kidney injury (AKI) stage III at the time of diagnosis was present in 60%, and 40.6% required dialysis. Patients in the nonenteric group had more interstitial inflammation (p = 0.01), and a greater number of tubules contained intratubular calcium oxalate (CaOx) crystals (p = 0.001) than the nonenteric group. Patients in the enteric group were more likely to have baseline chronic kidney disease (CKD) (p = 0.02) and moderate-to-severe tubulointerstitial fibrosis and atrophy (IFTA) (OR 3.49, p = 0.02). After a median follow-up of 10 months, 39% were dialysis dependent, 11% received a kidney transplant, and 32% died. On univariate analysis, >10 tubules with CaOx crystals, baseline CKD, and AKI requiring dialysis correlated with the risk of dialysis, transplant, or death. On multivariate analysis, only AKI requiring dialysis correlated with adverse renal outcomes. Conclusion: This is the largest cohort study of ON not due to PH. Histologic features differ in patients with enteric versus nonenteric risks. Patients in the enteric group are more likely to have baseline CKD and significant IFTA, while patients in the nonenteric group were more likely to have a greater number of tubules with CaOx crystals and corresponding interstitial inflammation. AKI requiring dialysis at the time of diagnosis was the single most significant predictor of adverse renal outcome.

Calcium oxalate (CaOx) crystal deposition within the tubules is often a perplexing finding on renal biopsy of both native and transplanted kidneys. Understanding the underlying causes may help diagnosis and future management. The most frequent cause of CaOx crystal deposition within the kidney is hyperoxaluria. When this is seen in native kidney biopsy, primary hyperoxaluria must be considered and investigated further with biochemical and genetic tests. Secondary hyperoxaluria, for example due to enteric hyperoxaluria following bariatric surgery, ingested ethylene glycol or vitamin C overdose may also cause CaOx deposition in native kidneys. CaOx deposition is a frequent finding in renal transplant biopsy, often as a consequence of acute tubular necrosis and is associated with poorer long-term graft outcomes. CaOx crystal deposition in the renal transplant may also be secondary to any of the causes associated with this phenotype in the native kidney. The pathophysiology underlying CaOx deposition is complex but this histological phenotype may indicate serious underlying pathology and should always warrant further investigation.

Purpose of review The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. Recent findings Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation. Summary The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.

INTRODUCTION AND OBJECTIVE:High urinary oxalate levels (UOx) in patients with enteric hyperoxaluria (EH) can lead to recurrent kidney stones, nephrocalcinosis and chronic kidney disease (CKD). Ther...

To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI − 23.71, − 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (− 2.8; 95% CI − 4.9, − 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria. Trial registration: Clinicaltrials.gov NCT02289755.

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Purpose of review Enteric hyperoxaluria is commonly observed in malabsorptive conditions including Roux en Y gastric bypass (RYGB) and inflammatory bowel diseases (IBD). Its incidence is increasing secondary to an increased prevalence of both disorders. In this review, we summarize the evidence linking the gut microbiota to the risk of enteric hyperoxaluria. Recent findings In enteric hyperoxaluria, fat malabsorption leads to increased binding of calcium to free fatty acids resulting in more soluble oxalate in the intestinal lumen. Bile acids and free fatty acids in the lumen also cause increased gut permeability allowing more passive absorption of oxalate. In recent years, there is more interest in the role of the gut microbiota in modulating urinary oxalate excretion in enteric hyperoxaluria, stemming from our knowledge that microbiota in the intestines can degrade oxalate. Oxalobacter formigenes reduced urinary oxalate in animal models of RYGB. The contribution of other oxalate-degrading organisms and the microbiota community to the pathophysiology of enteric hyperoxaluria are also currently under investigation. Summary Gut microbiota might play a role in modulating the risk of enteric hyperoxaluria through oxalate degradation and bile acid metabolism. O. formigenes is a promising therapeutic target in this population; however, further studies in humans are needed to test its effectiveness.

Patients with malabsorptive gastrointestinal disorders are at higher risk of kidney stones than those without. These disorders include inflammatory bowel diseases, with or without bowel resection, chronic pancreatitis, and celiac disease. The malabsorption of water, sodium, oxalate, bicarbonate, and fat leads to increased urinary concentration of stone-forming factors. The most common stones seen in gastrointestinal disorders contain calcium oxalate or uric acid. Major risk factors for stone formation are decreased urinary volume, hyperuricosuria, and hypocitraturia from high gastrointestinal output, and enteric hyperoxaluria from fat malabsorption. Prevention of kidney stones in such patients requires modifying standard stone-forming risk factors, but special consideration should be paid to metabolic abnormalities specific to this patient population. Treatment of the underlying gastrointestinal disorders also results in decreased incidence of kidney stones in this group.

Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer.

Enteric hyperoxaluria is a common occurrence in the setting of fat malabsorption, usually due to intestinal resection or intestinal bypass surgery. Enhanced intestinal absorption of dietary oxalate leads to elevated renal oxalate excretion, frequently in excess of 100 mg/d (1.14 mmol/d). Patients are at increased risk of urolithiasis and loss of kidney function from oxalate nephropathy. Fat malabsorption causes increased binding of diet calcium by free fatty acids, reducing the calcium available to precipitate diet oxalate. Delivery of unabsorbed bile salts and fatty acids to the colon increases colonic permeability, the site of oxalate hyper-absorption in enteric hyperoxaluria. The combination of soluble oxalate in the intestinal lumen and increased permeability of the colonic mucosa leads to hyperoxaluria. Dietary therapy consists of limiting oxalate and fat intake. The primary medical intervention is the use of oral oxalate binding agents such as calcium salts to reduce free intestinal oxalate levels. Bile acid sequestrants can be useful in patients with ileal resection and bile acid malabsorption. Oxalate degrading bacteria provided as probiotics are being investigated but as of yet, no definite benefit has been shown with currently available preparations. The current state of medical therapy and potential future directions will be summarized in this article.

Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD).The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing.In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis.New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced.

Oxalat ist ein schwer wasserlösliches Stoffwechselprodukt, das durch die Nieren ausgeschieden wird. Störungen des Oxalatstoffwechsels treten in Form von intestinaler Hyperoxalurie (sekundär infolge Malabsorption, Magen-Bypass oder bei ungenügender Oxalobacter-Kolonisation), hereditärer Hyperoxalurie und als Intoxikationen (Ethylenglykol, Vitamin C) auf. Hyperoxalurie verursacht ein breites Spektrum von Krankheiten von isolierter Hyperoxalurie bis zu Nierensteinen und Nephrokalzinosebildung, was schliesslich zu Nierenversagen und systemischer Oxalose mit lebensbedrohlichen Ablagerungen in wichtigen Organen führen kann. Eine neue Ursache der Hyperoxalurie entstand mit der Magenbypass-Operation, die eine regelmässige und präemptive Überwachung erfordert. Die Behandlung einer Hyperoxalurie besteht in der Reduktion der Oxalataufnahme und in der Erhöhung der Kalziumzufuhr. Eine optimale Urinverdünnung und Supplementierung mit Inhibitoren der Nierensteinbildung (Zitrat) sind erforderlich. Spezifische Fälle können eine Vitamin-B6-Supplementierung und Zugabe von Probiotika erforderlich machen. Hausärzte sollten Fälle von rezidivierenden Kalziumoxalatsteinen und schwerer Hyperoxalurie erkennen und an spezialisierte Zentren weiterleiten.

Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and nephrocalcinosis. The associated prevalence of chronic kidney disease and end-stage kidney disease (ESKD) is less clear but may be more consequential than recognized. In this review, we highlight three cases of ESKD due to enteric hyperoxaluria following small bowel resections. We review current information on the pathophysiology, complications and treatment of this complex disease.

The relationship between calcium oxalate kidney stone formation and inflammatory bowel disease (IBD) was first noted in two large retrospective case series from the 1960s. In over 1,400 patients with inflammatory bowel disease, 92 of 1,468 patients (6%) were identified to have developed renal stones, an occurrence that appeared as frequent as other systemic complications of this disease process [1, 2]. The mechanisms behind this high stone incidence were confirmed in the 1970s to be a complication of fat malabsorption and chronic diarrhea, which resulted in enteric hyperoxaluria, decreased urine citrate concentration and pH, and decreased urine volumes [3, 4]. Since those early descriptions, other malabsorptive intestinal disease states have also been added to the IBD/stone- associated list, including jejunoileal bypass (historical) and Roux-en-Y gastric bypass for obesity, chronic mesenteric ischemia, and small bowel ostomies [5, 6]. In general, patients with ileocolonic disease (9–17%) tend to be more commonly affected than those with ileal (6–8%) or colonic disease (3–5%) alone, and stone composition varies between calcium oxalate (malabsorptive diseases, ileocolonic Crohn’s disease) and uric acid (copious diarrhea, small bowel ostomies) depending on the disease state and amount of volume loss/diarrhea. This chapter will highlight the urinary abnormalities seen in modern bariatric surgical patients and in patients with the two most common forms of IBD (Crohn’s, ulcerative colitis) with a focus on the nutritional aspects that can be improved in these stone-forming populations.

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m2) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function.

This perspective focuses on how the gut microbiota can impact urinary oxalate excretion in the context of hyperoxaluria, a major risk factor in kidney stone disease. In the genetic disease of Primary Hyperoxaluria Type 1 (PH1), an increased endogenous production of oxalate, due to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT), results in hyperoxaluria and oxalate kidney stones. The constant elevation in urinary oxalate in PH1 patients ultimately leads to tissue deposition of oxalate, renal failure and death and the only known cure for PH1 is a liver or liver-kidney transplant. The potential impact of a probiotic/therapeutic approach may be clinically significant in PH1 and could also extend to a much larger population of idiopathic oxalate stone formers who comprise ~12% of Americans, individuals with enteric hyperoxaluria, and an emerging population of hyperoxaluric patients who have undergone bariatric surgery and develop kidney stone disease as a consequence.

Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated. We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria. A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 μg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline. Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further studies will need to investigate the mechanisms of renal damage in chronic pancreatitis and the potential benefits of therapies reducing oxaluria.

Roux-en-Y gastric bypass (RYGB) is a popular weight loss surgery for adults with morbid obesity. This chapter reviews potential renal complications caused by abnormalities in oxalate handling after RYGB—i.e., enteric hyperoxaluria, calcium oxalate (CaO x ) nephrolithiasis, and oxalate nephropathy. Hyperoxaluria is an adverse effect of RYGB that occurs due to fat malabsorption and contributes to CaO x nephrolithiasis and oxalate nephropathy. Risk factors for CaO x kidney stones after RYGB include low urine volume, high urine oxalate, and low urine citrate. Oxalate nephropathy is diagnosed by the characteristic kidney biopsy finding of acute tubular injury with oxalate crystals in renal tubules. Therapies to lower urine oxalate include lowering fat and oxalate intake, using calcium supplements to bind oxalate, bile acid sequestrants, or probiotics that degrade intraluminal oxalate. Physicians need to be aware of the possibility of oxalate-mediated renal complications after RYGB, and promptly treat hyperoxaluria to stop kidney damage.

Nephrolithiasis: Metabolic defects and terapeutic implications Over the past 10 years, major progress has been made in the knowledge of urinary lithogenesis, including the potential pathogenetic role of Randall's plaques and renal tubular crystal retention. Urine supersaturation is the driving force of this process and can be induced by some risk factors, including low urine volume, high urinary excretion of calcium oxalate and uric acid and low urinary excretion of citrate. Primary hypercalciuria can be due to intestinal overabsorption renal leak and bone reabsorption of calcium. Prophilaxis is mainly conducted with thiazides and low calcium diet which is indicated only in the intestinal form. Primary hyperoxaluria is treated with pyridoxine and may require in the severe forms simultaneous renal and liver transplantation. Enteric hyperoxaluria is secondary to fatty acids malabsorption and requires diet, oral calcium and cholestiramine. Hyperuricosuria is caused by diet endogenous overproduction, mainly due to enzymatic defects or high renal excretion of uric acid. Urine alkalinization with K or K and Mg citrate can prevent stone formation even in idiopathic uric acid nephrolithiasis, in which a defect of urine acidification is supposed to be the main abnormality, and in hypocitraturic patients. Cystinuria is a rare inherited defect with an intense clinical impact. It can be classified in three forms and urinary stone formation is the role. Increased solubility and conversion of cystine in a more soluble form are the main goals of the prophylaxis which includes K citrate and thiol agents administration. Tiopronin is preferred to D-penicillamine due to its lower side effects.

Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD).To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure.This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018.Twenty-four-hour urinary oxalate excretion.A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD).This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P .001) and positively with 24-hour proteinuria (r = 0.22, P .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion,11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event.Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.

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.

Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis, and progressive renal failure. It has long been known that as the glomerular filtration rate becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary cause.The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the NOD-like receptor family, pyrin domain containing 3 inflammasome (also known as NALP3, NLRP3, or cryopyrin), resulting in release of IL-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure.The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.

Background: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. Methods: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. Results: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. Conclusions: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use.

Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis.The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function.All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004).In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones.

Background Hyperoxaluria and increased calcium oxalate stone formation occur after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity. The etiology of this hyperoxaluria is unknown. We hypothesized that after bariatric surgery, intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation. Methods We prospectively examined oxalate metabolism in 11 morbidly obese subjects before and 6 and 12 months after RYGB ( n = 9) and biliopancreatic diversion-duodenal switch (BPD-DS) ( n = 2). We measured 24-hour urinary supersaturations for calcium oxalate, apatite, brushite, uric acid, and sodium urate; fasting plasma oxalate; 72-hour fecal fat; and increases in urine oxalate following an oral oxalate load. Results Six and 12 months after RYGB, plasma oxalate and urine calcium oxalate supersaturation increased significantly compared with similar measurements obtained before surgery (all P ≤ .02). Fecal fat excretion at 6 and 12 months was increased ( P = .026 and .055, 0 vs 6 and 12 months). An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months (all P ≤ .02). Therefore, after bariatric surgery, increases in fecal fat excretion, urinary oxalate excretion after an oral oxalate load, plasma oxalate, and urinary calcium oxalate supersaturation values were observed. Conclusion Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss.

Background and objectives: The most common bariatric surgery is Roux-en-Y gastric bypass (RYGB), which has been associated with hyperoxaluria and nephrolithiasis. We report a novel association of RYGB with renal insufficiency as a result of oxalate nephropathy. Design, setting, participants, & measurements: Eleven cases of oxalate nephropathy after RYGB were identified from the Renal Pathology Laboratory of Columbia University. The clinical features, pathologic findings, and outcomes are described. Results: Patients were predominantly white (72.7%) with a mean age of 61.3 yr. Indications for RYGB included morbid obesity (eight patients) and reconstruction after total gastrectomy for gastric cancer (three patients). All 11 patients had a history of hypertension, and 9 were diabetic. Patients presented with acute renal failure, often superimposed on mild chronic renal insufficiency (n = 7), at a median of 12 mo after RYGB. The mean creatinine at baseline, at discovery of acute renal failure, and at biopsy was 1.5, 5.0, and 6.5 mg/dl, respectively. Renal biopsies revealed diffuse tubular degenerative changes, abundant tubular calcium oxalate deposits, and varying degrees of tubulointerstitial scarring. In addition, seven biopsies had underlying diabetic glomerulosclerosis and two had glomerulosclerosis attributable to obesity and hypertension. Eight of 11 patients rapidly progressed to ESRD and required hemodialysis at a mean of 3.2 wk after renal biopsy. The remaining three patients were left with significant chronic kidney disease. Conclusions: Oxalate nephropathy is an underrecognized complication of RYGB and typically results in rapid progression to ESRD. Patients with pre-existing renal disease may be at higher risk for this complication.

Calcium oxalate (CaOx) deposition in the renal allograft is an under recognized and important cause of acute tubular injury and early allograft dysfunction. We present a case of late transplant dysfunction due to acute oxalate nephropathy. The patient presented with diarrhea and deteriorating graft function, and a diagnosis of enteric hyperoxaluria secondary to pancreatic insufficiency was made. This had occurred, as the patient had been noncompliant with his pancreatic enzyme replacement therapy. Treatment to reduce his circulating oxalate load was initiated, including twice-daily hemodialysis, low fat and oxalate diet and appropriate administration of pancreatic enzyme supplements. Graft function subsequently recovered. The possibility of fat malabsorption leading to enteric hyperoxaluria should be considered in renal graft recipients presenting with loose stools and graft dysfunction.

Aim This report describes a case of kidney failure secondary to orlistat, a lipase inhibitor commonly used in the treatment of obesity. Case report An 80-year-old man with type 2 diabetes who was being treated with orlistat developed rapidly progressive kidney failure. Low-grade albuminuria argued against diabetic nephropathy. Renal biopsy showed tubulointerstitial nephritis associated with numerous calcium oxalate crystals. Enteric hyperoxaluria was attributed to the orlistat treatment. The latter was stopped and the patient received calcium supplements. Six months after orlistat withdrawal, oxaluria was normalized and kidney function stabilized. Conclusion Oxalate nephropathy may result from hyperoxaluria secondary to orlistat treatment. This suggests that kidney function and oxaluria be closely monitored in patients taking orlistat.

Acute renal insufficiency (ARI) is a frequent complication of nonrenal solid organ transplantation and may be responsible for an unfavorable outcome, particularly if dialysis is required. The etiology of post-transplantation ARI is poorly understood, with only isolated clinical cases being reported, most imputed to drug toxicity. We report here, the first three observations of irreversible ARI associated with acute oxalate nephropathy (AON) in the course of nonrenal organ transplants: a lung transplant and a lung-liver transplant in two patients with mucoviscidosis, and a cardiac transplant. The diagnosis of AON was made histologically. In all three cases, the ARI supervened after prolonged consumption of antibiotics capable of interfering with the colonic flora, and leading to enteric hyperoxaluria. The recognition of AON as a cause of post-transplantation, ARI underlines hyperoxaluria and digestive hyperabsorption of oxalate as specific risk factors for AON and should permit better posttransplant care of these patients.

Studies dealing with the increased tendency to stone formation noted in cystic fibrosis, focus on enteric hyperoxaluria. It is well recognized, however, that low urine volume, hypocitraturia and perhaps even hypercalciuria are further risk factors for stone formation.Nineteen patients with cystic fibrosis (14 boys and 5 girls, aged 10-23, median 15 years) underwent a standard protocol for metabolic evaluation of the lithogenic tendency. In 10 patients, the study was repeated after treatment with recombinant human growth hormone 43 microgram/kg body weight daily for 12 months.The metabolic evaluation disclosed low urine output in 12, hyperoxaluria in 8 and hypocitraturia in 9 of the 19 cystic fibrosis patients. The mentioned parameters were not influenced by treatment with recombinant human growth hormone.The report indicates that in cystic fibrosis low urine volume, hypocitraturia and hyperoxaluria act in concert and contribute to the likelihood of stone formation. This tendency is not modified by treatment with recombinant human growth hormone.

Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB.Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and 1 year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat7 g/day and urine oxalate40 mg/day. Differences were evaluated using paired 2-tailed t tests.Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r = 0.71, P.001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day.Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration.BackgroundHyperoxaluria is a major risk factor for renal stones, and in most cases, it appears to be sustained by increased dietary load or increased intestinal absorption. Previous studies have shown that components of the endogenous digestive microflora, in particular Oxalobacter formigenes, utilize oxalate in the gut, thus limiting its absorption. We tested the hypothesis of whether oxaluria can be reduced by means of reducing intestinal absorption through feeding a mixture of freeze-dried lactic acid bacteria.MethodsSix patients with idiopathic calcium-oxalate urolithiasis and mild hyperoxaluria (>40 mg/24 h) received daily a mixture containing 8 × 1011 freeze-dried lactic acid bacteria (L. acidophilus, L. plantarum, L. brevis, S. thermophilus, B. infantis) for four weeks. The 24-hour urinary excretion of oxalate was determined at the end of the study period and then one month after ending the treatment. The ability of bacteria to degrade oxalate and grow in oxalate-containing media, and the gene expression of Ox1T, an enzyme that catalyzes the transmembrane exchange of oxalate, also were investigated.ResultsThe treatment resulted in a great reduction of the 24-hour excretion of oxalate in all six patients enrolled. Mean levels ± SD were 33.5 ± 15.9 mg/24 h at the end of the study period and 28.3 ± 14.6 mg/24 h one month after treatment was interrupted compared with baseline values of 55.5 ± 19.6 mg/24 h (P < 0.05). The treatment was associated with a strong reduction of the fecal excretion of oxalate in the two patients tested. Two bacterial strains among those used for the treatment (L. acidophilus and S. thermophilus) proved in vitro to degrade oxalate effectively, but their growth was somewhat inhibited by oxalate. One strain (B. infantis) showed a quite good degrading activity and grew rapidly in the oxalate-containing medium. L. plantarum and L. brevis showed a modest ability to degrade oxalate even though they grew significantly in oxalate-containing medium. No strain expressed the Ox1T gene.ConclusionsThe urinary excretion of oxalate, a major risk factor for renal stone formation and growth in patients with idiopathic calcium-oxalate urolithiasis, can be greatly reduced with treatment using a high concentration of freeze-dried lactic acid bacteria. We postulate that the biological manipulation of the endogenous digestive microflora can be a novel approach for the prevention of urinary stone formation.

Contribution of dietary oxalate to urinary oxalate excretion. Background The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. Methods We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. Results Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 ± 15.5% on the 10 mg/2500 kcal/day diet to 41.5 ± 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 ± 4.8%, and the mean dietary contribution increased to 52.6 ± 8.6%. Conclusions These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

We studied the effect of oral calcium supplementation in patients with enteric hyperoxaluria. Three patients with renal stone events following ileal resection were given oral calcium supplement. One of the three patients was put on a low-fat diet. The treatment reduced urinary oxalate excretion to the normal range. Subsequently, 2 patients reduced the dose of calcium supplementation at their own discretion and consequently developed renal stones again together with hyperoxaluria. Based on these observations, we believe that an adequate dose of calcium can normalize urinary oxalate excretion.

Orlistat is a gastrointestinal lipase inhibitor used for weight reduction in obese individuals. Enteric hyperoxaluria caused by orlistat leads to oxalate absorption. Acute oxalate nephropathy is a rare complication of treatment with orlistat. Herein we report a patient presenting with acute renal failure which improved minimal with intravenous hydration. She was found to have oxalate crystals on renal biopsy. Patient admitted orlistat use over the counter for weight reduction on further questioning. The purpose of this case review is to increase awareness among patients since they are more focused on losing weight. This case also calls for the provider attention to educate patients regarding side effects of orlistat because of easy availability of orlistat over the counter.

Oxalate nephropathy with renal failure is caused by multiple disorders leading to hyperoxaluria due to either overproduction of oxalate (primary hyperoxaluria) or excessive absorption of dietary oxalate (enteric hyperoxaluria). To study the etiology of renal failure in crystal-induced kidney disease, we created a model of progressive oxalate nephropathy by feeding mice a diet high in soluble oxalate (high oxalate in the absence of dietary calcium). Renal histology was characterized by intratubular calcium-oxalate crystal deposition with an inflammatory response in the surrounding interstitium. Oxalate nephropathy was not found in mice fed a high oxalate diet that also contained calcium. NALP3, also known as cryopyrin, has been implicated in crystal-associated diseases such as gout and silicosis. Mice fed the diet high in soluble oxalate demonstrated increased NALP3 expression in the kidney. Nalp3-null mice were completely protected from the progressive renal failure and death that occurred in wild-type mice fed the diet high in soluble oxalate. NALP3 deficiency did not affect oxalate homeostasis, thereby excluding differences in intestinal oxalate handling to explain the observed phenotype. Thus, progressive renal failure in oxalate nephropathy results primarily from NALP3-mediated inflammation.

To identify the effect of a controlled metabolic diet on reducing urinary calcium oxalate (CaOx) supersaturation in subjects with hyperoxaluric nephrolithiasis after potentially malabsorptive forms of bariatric surgery.Subjects with a history of CaOx kidney stones and mild hyperoxaluria after bariatric surgery (n = 9) collected baseline 24-hour urine samples while consuming a free choice diet. They were then instructed to consume a controlled diet low in oxalate (70-80 mg/d), normal in calcium (1000 mg/d), and moderate in protein before 2 final 24-hour urine collections.Overall, the urinary CaOx supersaturation decreased from 1.97 ± 0.49 delta Gibbs (DG) with the free choice diet to 1.13 ± 0.75 DG with the controlled diet (P.01). This occurred in the absence of a significant change in urinary oxalate excretion (0.69 ± 0.29 mmol/d with the free choice diet compared with 0.66 ± 0.38 mmol/d with the controlled diet). Urinary volume, citrate, and pH all increased, although not significantly (P.05), contributing to the significant CaOx supersaturation change.A controlled metabolic diet normal in calcium, moderate in protein, and reduced in oxalate can positively affect urinary CaOx supersaturation after bariatric surgery. However, this diet did not appear to decrease urinary oxalate excretion. Therefore, restriction of dietary oxalate alone might not be enough to reduce urinary oxalate excretion to normal levels in this group of patients with known enteric hyperoxaluria. Additional strategies could be necessary, such as the use of oral calcium supplements as oxalate binders and a lower fat diet.

Urinary excretion of calcium and oxalate are two of the critical determinants of urine supersaturation of calcium oxalate salts and the risk of calcium oxalate stone formation. Therefore, treatment to reduce stone recurrence is focused on lowering the excretion of these lithogenic factors. Both diet and medication can lower urine calcium. Thiazide diuretics have been shown to reduce stone recurrence in randomized controlled trials and have the added benefit of improving bone mineral density. Citrate and bisphosphonates can lower urine calcium modestly but have not been well studied in hypercalciuric stone disease. Treatments to lower oxalate are not as well documented as are those for hypercalciuria. For idiopathic hyperoxaluria, pyridoxine and magnesium have been proposed as therapies, but there is conflicting data regarding their effectiveness. In enteric hyperoxaluria, low-oxalate diets and calcium supplements to bind dietary oxalate are the standard therapy. There is great interest in the use of oxalate-degrading bacteria as probiotics to treat hyperoxaluria, but human data is limited at this time.

Calcium oxalate is the major component of 70–80 % of renal calculi. Both of these components have both dietary and endogenous sources. Oxalate is found in many plant foods but is particularly rich in certain foods such as spinach, certain nuts, green leafy vegetables, and fruits. Hyperoxaluria occurs in 18 % of kidney stone patients, and treatment has been to reduce intake of oxalate-containing foods or co-ingesting calcium-containing foods or supplements in an attempt to have calcium and oxalate bind together to stay in the gastrointestinal tract. Oxalate absorption occurs all along the intestinal tract and recently shown to be transported from the bloodstream into the lumen of the gastrointestinal tract (i.e., secreted). Small intestine and proximal colon are thought to be the secretory portion, and the distal colon is thought to absorb oxalate into the body. This may prove to be an important mechanism to reduce systemic levels of oxalate in future studies. The intestinal bacterium,Oxalobacter formigenes, has been shown to degrade oxalate from dietary foodstuffs and is found less commonly in stone-forming patients. There are any other oxalate-degrading bacteria, but many of these do not rely solely on oxalate as their main food source. There is much room for investigation in this area as only a small amount of the complete intestinal flora can be identified using traditional microbiologic techniques. Probiotic preparations involving many different types of bacteria have met with limited success in clinical trials to reduce hyperoxaluria. There are many subtypes ofO. formigenesand it is unknown which would be the best to recolonize kidney stone patients. Enteric hyperoxaluria increases the bioavailability of oxalate in patients with extensive small-bowel resection or enteric bypass surgery for obesity. Primary hyperoxaluria is a rare genetic disorder whereby the defective liver enzyme peroxisomal AGT1 results in a failure to convert glyoxylate to glycine or glycolate resulting in an increased conversion to oxalate. Treatment is challenging and typically requires a combined hepatic and renal transplantation.

Prevalence of recurrent calcium-oxalate (CaOx) urolithiasis (UL) is up to fivefold higher in Crohn's disease than in the general population. Treatment options are scarce and the risk of recurrent UL or progressive renal CaOx deposition, (oxalosis) based early end-stage renal failure (ESRF), subsequent systemic oxalosis, and recurrence in the kidney graft is pronounced. We aimed to find proof that secondary hyperoxaluria is the main risk factor for the devastating course and correlates with intestinal oxalate absorption.24-h urines were collected and analyzed for urinary oxalate (Uox) in 27 pediatric (6-18 years) and 19 adult patients (20-62 years). In the 21 patients (8 adults and 13 children) with hyperoxaluria a [(13)C(2)]oxalate absorption test was performed under standardized dietary conditions.Mean Uox was significantly higher in patients with UL or oxalosis (0.92 ± 0.57) compared with those without (0.53 ± 0.13 mmol/1.73 m(2)/24 h, p0.05, normal0.5). Hyperoxaluria then significantly correlated with intestinal oxalate absorption (p0.05).As UL/oxalosis has major implications for the general health in patients with Crohn's disease (ESRF and systemic oxalosis), new medication, e.g. to reduce intestinal oxalate absorption, is definitely needed.

The formation of renal calculi secondary to enteric hyperoxaluria is rare in the paediatric population. We present the case of an 8-year-old boy who had short bowel syndrome resulting in enteric hyperoxaluria which led to the development of urolithiasis and bilateral ureteric strictures, both of which resolved with medical management. We also review the literature on enteric hyperoxaluria.

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat. Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

Background: Urinary oxalate excretion is an important contributor to calcium oxalate stone formation. Methods of reducing oxalate excretion are not wholly satisfactory, and no controlled trials using them have been performed to prevent stone recurrence. Some lactic acid bacteria can degrade oxalate in vitro. This study sought to reduce urinary oxalate excretion in calcium stone formers with idiopathic hyperoxaluria. Design, setting, participants, and measurements: A randomized, double-blind, placebo-controlled trial was performed of Oxadrop, a mix of four lactic acid bacterium species. This preparation previously reduced oxalate excretion in stone formers with idiopathic and enteric hyperoxaluria. Patients were selected from two stone prevention clinics. Twenty people with calcium stones and idiopathic hyperoxaluria (>40 mg/d) were enrolled and randomly assigned 1:1 in placebo and active preparation arms. Both groups took 3.6 g of granulate each day: Either placebo or the experimental preparation. Participants performed two consecutive 24-h urine collections at baseline, at 28 d of therapy, and at 56 d, after being off the preparation for 4 wk. Diet was replicated at each point. Results: There was no effect of the study preparation: Mean 24-h urinary oxalate excretion in placebo-treated patients was 73.9 mg at baseline and 72.7 mg after treatment, whereas the Oxadrop-treated patients had 59.1 mg at baseline and 55.4 mg after treatment. The preparation was well tolerated; three participants on active treatment experienced mild constipation. Conclusions: In this randomized, placebo-controlled trial, Oxadrop did not reduce urinary oxalate excretion in participants with idiopathic hyperoxaluria.

Enteric hyperoxaluria can lead to renal failure. There have only been a few reports of renal transplantation as treatment of endstage renal disease secondary to enteric hyperoxaluria and results have been mixed. This report describes a patient with Crohn's disease who developed chronic renal failure from enteric hyperoxaluria. He subsequently had a successful renal transplant without any post-operative oxalate related complications and has satisfactory renal function almost three years later. Aggressive pre-transplant hemodialysis was not done. The literature associated with renal transplantation for enteric hyperoxaluria is reviewed.