Enteric Hyperoxaluria Research Articles

Pathophysiology and Treatment of Enteric Hyperoxaluria.

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.

Enteric Hyperoxaluria and Kidney Stone Management in Inflammatory Bowel Disease

Enteric hyperoxaluria is frequently seen in patients with inflammatory bowel disease (IBD). IBD patients are therefore at higher risk of nephrolithiasis, particularly calcium oxalate stones. We reviewed the recent medical literature to elucidate the mechanisms and risk factors behind nephrolithiasis in IBD patients, as well as therapies to treat and prevent the formation of kidney stones. At present, there are no specific guidelines for screening and monitoring the progression of nephrolithiasis in the IBD population. Yet, recent epidemiologic data suggests that the prevalence of nephrolithiasis in the adult IBD patients is as high as 28%. Enteric oxalate levels of IBD patients are significantly elevated compared with non-IBD patients, and recent studies have shown that the gut microbiota largely mediates this process. In particular, intestinal disruption and malabsorption in IBD patients lead to the decolonization of Oxalobacter formigenes which normally metabolizes oxalate in the gut lumen. As such, future studies are needed to clarify the role of O. formigenes in IBD patients with the goal of devising new therapeutic approaches for nephrolithiasis treatment and risk reduction. Enteric hyperoxaluria plays a large role in nephrolithiasis, a serious extra-intestinal manifestation of IBD that may progress to chronic kidney disease. The gut microbiota offers a promising approach to treating and preventing hyperoxaluria in the IBD population.

Lessons from rodent gastric bypass model of enteric hyperoxaluria

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. 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. 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.

LBA01-08 KIDNEY STONE RISK AND ASSOCIATION WITH URINE OXALATE (UOX) LEVELS IN ENTERIC HYPEROXALURIA (EH)

You have accessJournal of UrologyLate-Breaking Abstracts (LBA1)1 Apr 2020LBA01-08 KIDNEY STONE RISK AND ASSOCIATION WITH URINE OXALATE (UOX) LEVELS IN ENTERIC HYPEROXALURIA (EH) Charles Scales*, Christina Wyatt, Alicia Weeks, Christine Tosone, and Annamaria Kausz Charles Scales*Charles Scales* More articles by this author , Christina WyattChristina Wyatt More articles by this author , Alicia WeeksAlicia Weeks More articles by this author , Christine TosoneChristine Tosone More articles by this author , and Annamaria KauszAnnamaria Kausz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000946.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Introduction: EH occurs when fat malabsorption causes excessive oxalate absorption from the gastrointestinal (GI) tract, increasing renal oxalate load and in turn, kidney stone (KS) and chronic kidney disease (CKD) risk. The URIROX-1 RCT evaluated reloxaliase, a first-in-class oral enzyme that specifically targets and degrades oxalate within the gut, in EH. This is the first in-depth analysis of KS risk in this recently completed study and represents a robust profiling of KS risk in the EH population. Methods: URIROX-1, a Phase 3 double-blind RCT, evaluated efficacy and safety of reloxaliase (7,500 units or placebo [PBO] 3-5x/day orally for 4 weeks) in EH patients with 24h UOx = 50 mg/24h despite standard of care. The primary efficacy endpoint was percent change from baseline in 24h UOx. Secondary efficacy endpoints included proportion of subjects with = 20% reduction in 24h UOx and analysis of efficacy parameters in the bariatric surgery (BS) subgroup. Results: Reloxaliase produced a 22.6% reduction in 24h UOx vs 9.7% with PBO [difference -14.3% (p=0.0040)], with more profound effect in the BS subgroup [-16.2% (p=0.013)]. More subjects on reloxaliase (48.3%) vs PBO (31.6%) achieved a = 20% reduction in 24h UOx, with greater effect in BS (50% on reloxaliase vs 28.9% on PBO). GI adverse events were more common with reloxaliase, but most were mild or moderate in severity and no reloxaliase subject discontinued treatment as a result. Of 115 randomized subjects, 15 reported KS passage during the 8 week study, revealing a higher KS event rate (0.78/year) than anticipated by limited EH epidemiologic data available. Baseline 24h UOx levels of these 15 subjects was markedly higher (mean [median] 107.2 [98.5] mg/d vs 86.5 [77.5] mg/d). Conclusions: URIROX-1 is the first RCT examining a specific therapy targeting UOx reduction in EH, a clinically challenging and understudied population. The URIROX-1 study demonstrated a clinically meaningful reduction of 24h UOx in EH subjects on reloxaliase. Although the short duration of this study precludes assessment of its effect on KS risk, the URIROX-1 data underscores the utility of 24h UOx as a surrogate marker of KS risk and the value of the ongoing URIROX-2 adaptive design trial to quantify clinical benefits of reloxaliase with respect to KS disease progression and renal function. Source of Funding: Allena pharmaceuticals © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1022-e1022 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charles Scales* More articles by this author Christina Wyatt More articles by this author Alicia Weeks More articles by this author Christine Tosone More articles by this author Annamaria Kausz More articles by this author Expand All Advertisement PDF downloadLoading ...

Enteric hyperoxaluria: role of microbiota and antibiotics.

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. 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. 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.

Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

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.

ALLN-177, oral enzyme therapy for hyperoxaluria

PurposeTo evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria.MethodsSixteen 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.ResultsThe 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.ConclusionALLN-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.

Editorial Comment

This manuscript by Canales et al describes the effects of calcium and vitamin B6 supplementation on oxalate excretion in a rat Roux-en-Y gastric bypass model. Medical advances in the treatment of calcium oxalate stones have only made modest gains over the past several decades and the common misconception that excessive calcium in one's diet exacerbates stone formation has been hard to overcome. While this study deals specifically with enteric hyperoxaluria and Roux-en-Y gastric bypass, it does hold similarities between other calcium oxalate stone forming patients. The primary principles proven in this rat model indicate the importance of oral dietary calcium supplementation in patients with excessive oxalate in the gut. In the case of enteric hyperoxaluria, calcium becomes saponified by excessive fat in the intestine and is therefore unavailable to bind to dietary oxalate. In this study, dietary calcium supplementation decreased urinary oxalate excretion by 28% without a rise in urinary calcium. This same principle is often true in many calcium oxalate stone formers. Dietary supplementation with either milk or calcium-fortified orange juice taken with meals is an important treatment to reduce urinary oxalate. Prescribing calcium citrate to your stone forming patient with hyperoxaluria is also beneficial and should be in the armamentarium of all practicing urologists.

Pathophysiology and Treatment of Hyperoxaluria

Humans cannot degrade oxalate. Thus, oxalate that is generated in the liver and/or absorbed from the intestine must be eliminated by the kidneys. Among genetic causes, primary hyperoxaluria (PH) type 1 is the most common and occurs due to deficiency of hepatic peroxisomal alanine glyoxalate aminotransferase. PH2 is caused by deficiency of lysosomal glyoxalate reductase or hydroxypyruvate reductase, whereas PH3 results from deficiency of mitochondrial 4-hydroxy-2-oxoglutarate aldolase. Enteric hyperoxaluria is caused by excessive colonic oxalate absorption due to any type of fat malabsorption. The diagnosis of hyperoxaluria is based on the history, 24-hour urine studies, and genetic testing. Early diagnosis and timely intervention are essential. To treat PH, adequate fluid intake, inhibitors of calcium oxalate crystallization (citrate or neutral phosphorus), and pyridoxine-in responsive patients are all important. Intensive dialysis and prompt kidney or combined kidney-liver transplantation are essential to minimize systemic oxalosis if renal failure occurs. Dietary modifications (low fat, low oxalate, and adequate calcium) are key for enteric hyperoxaluria. Calcium can be used as an oxalate binder. Newer modalities including oxalate degrading bacteria, oral oxalate decarboxylase preparations, and inhibitory ribonucleic acids are all under investigation. This review contains 9 figures, 6 tables, and 90 references. Key Words: bariatric surgery, calcium oxalate, dialysis, enteric hyperoxaluria, fat malabsorption, genetic testing, kidney stone, nephrolithiasis, oxalate, oxalate decarboxylase, Oxalobacter formigenes, primary hyperoxaluria, pyridoxine, transplantation, urolithiasis

The Effect of Calcium and Vitamin B6 Supplementation on Oxalate Excretion in a Rodent Gastric Bypass Model of Enteric Hyperoxaluria

To test the effect of calcium and vitamin B6 therapies on urinary oxalate excretion in a rodent model of enteric hyperoxaluria after Roux-en Y gastric bypass (RYGB) surgery. Obese male Sprague-Dawley rats underwent sham (n = 7) or RYGB (n = 10). Animals were maintained on low oxalate (1.5%) and fat (10%; LOF), normal calcium (0.6 %) diet for 8 weeks and then completed a 2-phase crossover metabolic study. In the first 2-week phase, animals were fed a Low oxalate and fat (LOF), high calcium (2.4%; HC) diet. After a 2-week washout, rats were fed a LOF/normal calcium diet highly enriched with vitamin B6. Urine was collected before and after each intervention. Plasma pyridoxal 5'-phosphate (PLP) and metabolites were measured baseline and 11 weeks after sham or RYGB. Compared to baseline, sham animals on LOF/HC diet doubled their urinary calcium excretion but not oxalate. RYGB animals on LOF/HC diet decreased urinary oxalate excretion 28% (P = .001) without a significant rise in urinary calcium. Vitamin B6 supplementation decreased RYGB urinary oxalate by approximately 15% (P = .06), and serum PLP explained 63% of urinary oxalate variability. Based on the findings in this model, calcium supplementation appears to be a reasonable therapy to decrease urinary oxalate in RYGB patients who maintain a low fat and oxalate diet. Serum PLP had a fair correlation to urinary oxalate excretion and may be a useful screening tool in hyperoxaluric RYGB patients. Further experimental human studies after RYGB are necessary to determine whether these commonly employed supplements truly provide a benefit in enteric hyperoxaluria.

Renal lithiasis and inflammatory bowel diseases, an update on pediatric population.

Background and aim of the work: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population. The aim of the review was to analyze literature data in order to identify the main risk conditions described in literature and the proposed treatment. Methods: A research on the databases PubMed, Medline, Embase and Google Scholar was performed by using the keywords “renal calculi/lithiasis/stones” and “inflammatory bowel diseases”. A research on textbooks of reference for Pediatric Nephrology was also performed, with focus on secondary forms of nephrolithiasis. Results: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population, typically in patients who underwent extensive small bowel resection or in those with persistent severe small bowel inflammation. In IBD, kidney stones may arise from chronic inflammation, changes in intestinal absorption due to inflammation, surgery or intestinal malabsorption. Kidney stones are more closely associated with Crohn’s Disease (CD) than Ulcerative Colitis (UC) in adult patients for multiple reasons: mainly for malabsorption, but in UC intestinal resection may be an additional risk. Nephrolithiasis is often under-diagnosed and might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Secondary enteric hyperoxaluria the main risk factor of UL in IBD, this has been mainly studied in CD, whether in UC has not been completely explained. In the long course of CD recurrent urolithiasis and calcium-oxalate deposition may cause severe chronic interstitial nephritis and, as a consequence, chronic kidney disease. ESRD and systemic oxalosis often develop early, especially in those patients with multiple bowel resections. Even if we consider that many additional factors are present in IBD as hypomagnesuria, acidosis, hypocitraturia, and others, the secondary hyperoxaluria seems to finally have a central role. Some medications as parenteral vitamin D, long-term and high dose steroid treatment, sulfasalazine are reported as additional risk factors. Hydration status may also play an important role in this process. Intestinal surgery is a widely described independent risk factor. Patients with ileostomy post bowel resection may have relative dehydration from liquid stool, which, added to the acidic pH from bicarbonate loss, is responsible for this process. In this acidic pH, the urinary citrate level excretion reduces. The stones most commonly seen in these patients contain uric acid or are mixed. In addition, the risk of calcium containing stones also increases with ileostomy. The treatment of UL in IBD involves correction of the basic gastrointestinal tract inflammation, restricted dietary oxalate intake, and, at times, increased calcium intake. Citrate therapy that increases both urine pH and urinary citrate could also provide an additional therapeutic benefit. Finally, patients with IBD in a pediatric study had less urologic intervention for their calculosis compared with pediatric patients without IBD. (www.actabiomedica.it)

A Successful Approach to Kidney Transplantation in Patients With Enteric (Secondary) Hyperoxaluria.

BackgroundEnteric hyperoxaluria due to malabsorption may cause chronic oxalate nephropathy and lead to end-stage renal disease. Kidney transplantation is challenging given the risk of recurrent calcium-oxalate deposition and nephrolithiasis.MethodsWe established a protocol to reduce plasma oxalic acid levels peritransplantation based on reduced intake and increased removal of oxalate. The outcomes of 10 kidney transplantation patients using this protocol are reported.ResultsFive patients received a living donor kidney and had immediate graft function. Five received a deceased donor kidney and had immediate (n = 1) or delayed graft function (n = 4). In patients with delayed graft function, the protocol was prolonged after transplantation. In 3 patients, our protocol was reinstituted because of late complications affecting graft function. One patient with high-output stoma and relatively low oxalate levels had lost her first kidney transplant because of recurrent oxalate depositions but now receives intravenous fluid at home on a routine basis 3 times per week to prevent dehydration. Patients are currently between 3 and 32 months after transplantation and all have a stable estimated glomerular filtration rate (mean, 51 ± 21 mL/min per 1.73 m2). In 4 of 8 patients who underwent for cause biopsies after transplantation oxalate depositions were found.ConclusionsThis is the first systematic description of kidney transplantation in a cohort of patients with enteric hyperoxaluria. Common complications after kidney transplantation impact long-term transplant function in these patients. With our protocol, kidney transplantation outcomes were favorable in this population with unfavorable transplantation prospects and even previous unsuccessful transplants.

Plasma oxalate in relation to eGFR in patients with primary hyperoxaluria, enteric hyperoxaluria and urinary stone disease

BackgroundSince 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). MethodsThe 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. ResultsIn 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 (p<0.0001). 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. ConclusionsNew 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.

Enteric hyperoxaluria in chronic pancreatitis

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.

Calcium oxalate crystal related kidney injury in a patient receiving Roux-en Y hepaticojejunostomy due to gall bladder cancer

BackgroundCalcium oxalate nephropathy is rare in current practice. It was a common complication during jejunoileal bypass, but much less seen in modern gastric bypass surgery for morbid obesity. The major cause of it is enteric hyperoxaluria.Case presentationWe report on a patient here with acute kidney disease due to calcium oxalate nephropathy, rather than the conditions mentioned above. The male patient received a Roux-en Y hepaticojejunostomy and common bile duct drainage. In addition to enteric hyperoxaluria, chronic kidney disease related metabolic acidosis, chronic diarrhea related volume depletion, a high oxalate and low potassium diet, long term ascorbic acid intake and long term exposure to antibiotics, all predisposed him to having oxalate nephropathy.ConclusionThis is the first case with such conditions and we recommend that similarly diagnosed patients avoid all these predisposing factors, in order to avoid this rare disease and its undesired outcome.

Gut microbiota and oxalate homeostasis.

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.

From chronic kidney disease to kidney transplantation: The impact of obesity and its treatment modalities

Obesity is associated with worse short-term outcomes after kidney transplantation but the effect on long-term outcomes is unknown. Although some studies have reported worse outcomes for obese recipients when compared to recipients with a BMI in the normal range, obese recipients who receive a transplant have better outcomes than those who remain wait-listed. Whether transplant candidates should be advised to lose weight before or after transplant has been debated and this is mainly due to the gap in the literature linking pre-transplant weight loss with better outcomes post-transplantation. The issue is further complicated by the use of BMI as a metric of body fat, the obesity paradox in dialysis patients and the different ethical viewpoints of utility versus equity. Measures used to reduce weight loss, including orlistat and bariatric surgery (in particular those with a malabsorptive component), have been associated with enteric hyperoxaluria with consequent risk of nephrolithiasis and oxalate nephropathy. In this review, we discuss the evidence regarding the use of weight loss measures in the kidney transplant candidate and recipient with a view to recommending whether weight loss should be pursued before or after kidney transplantation.

Oxalate, inflammasome, and progression of kidney disease.

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.

The management of patients with enteric hyperoxaluria.

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 100mg/d (1.14mmol/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.

Weight loss at a high cost: Orlistat-induced late-onset severe kidney disease

AimThis report describes a case of kidney failure secondary to orlistat, a lipase inhibitor commonly used in the treatment of obesity. Case reportAn 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. ConclusionOxalate nephropathy may result from hyperoxaluria secondary to orlistat treatment. This suggests that kidney function and oxaluria be closely monitored in patients taking orlistat.