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Background: Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined. Methods: Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network. Results: We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure. Conclusion: Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis.

Abstract Bile acids are natural detergents that aid in the absorption of dietary lipids. Fatty acid binding protein 6 (Fabp6) is a component of the bile acid recovery system that operates in the small intestine. The aim of this study was to determine if Fabp6 deficiency causes dietary fat malabsorption. Wild‐type and Fabp6‐deficient mice were fed a Western‐style diet (WSD) or a reference low‐fat diet (LFD) for 10 weeks. The body weight gain, bile acid excretion, fat excretion, energy metabolism, and major gut microbial phyla of the mice were assessed at the end of the controlled diet period. Fabp6−/− mice exhibited enhanced excretion of both bile acids and fat on the WSD but not on the LFD diet. Paradoxically, male Fabp6−/− mice, but not female Fabp6−/− mice, had greater adiposity despite increased fat excretion. Analysis of energy intake and of expenditure by indirect calorimetry revealed sex differences in physical activity level and respiratory quotient, but these did not account for the enhanced adiposity displayed by male Fabp6−/− mice. Analysis of stool DNA showed sex‐specific changes in the abundance of major phyla of bacteria in response to Fabp6 deficiency and WSD feeding. The results obtained indicate that the malabsorption of bile acids that occurs in Fabp6−/− mice is associated with dietary fat malabsorption on the high‐fat diet but not on the low‐fat diet. The WSD induced a sexually dimorphic increase in adiposity displayed by Fabp6−/− mice and sexually distinct pattern of change in gut microbiota composition.

El páncreas es un órgano retroperitoneal que segrega agua, bicarbonato y enzimas digestivos a través del conducto pancreático principal (CPP) al duodeno. La pancreatitis crónica (PC) está causada típicamente en el adulto por abuso crónico de alcohol, y, con menor frecuencia, hipertrigliceridemia, hiperparatiroidismo primario o fibrosis quística. La disfunción exocrina ocasiona malabsorción grasa y la consiguiente esteatorrea. El daño en la función endocrina es un hallazgo tardío que se presenta como hiperglucemia o diabetes mellitus franca. El cuidado de pacientes con PC conlleva, de forma primordial, el tratamiento del dolor. Un cambio significativo en su patrón o la aparición súbita y persistente de otros síntomas obligan a descartar otras entidades, incluyendo úlcera péptica, obstrucción biliar, pseudoquistes, cáncer de páncreas, estenosis de conductos pancreáticos o litiasis. Por tanto es importante asegurar el diagnóstico. El manejo del dolor debe realizarse de forma escalonada y prudente tratando de evitar la dependencia de opiáceos. Debe advertirse a los pacientes que interrumpan la ingesta de alcohol. El tratamiento de la malabsorción grasa comienza con pequeñas tomas de alimento y restricción grasa. El uso de suplementos de enzimas pancreáticos puede mejorar los síntomas y reducir la malabsorción en pacientes que no respondan al tratamiento dietético. Deben usarse dosis elevadas de enzimas con cada comida. Se recomienda tratamiento supresor de la acidez gástrica para evitar la inactivación de los enzimas. Puede ser necesaria la suplementación con triglicéridos de cadena media (MCT) y vitaminas liposolubles. El manejo de otras complicaciones (como pseudoquistes, obstrucción biliar o duodenal, ascitis pancreática, trombosis de la vena esplénica y pseusoaneurismas) con frecuencia requiere maniobras agresivas manteniendo al paciente bajo nutrición parenteral para minimizar la estimulación pancreática.The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or chystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation.

High levels of plasma apolipoprotein B-100 (apoB-100), the principal apolipoprotein of LDL, are associated with cardiovascular disease. We hypothesized that suppression of apoB-100 mRNA by an antisense oligonucleotide (ASO) would reduce LDL cholesterol (LDL-C). Because most of the plasma apoB is made in the liver, and antisense drugs distribute to that organ, we tested the effects of a mouse-specific apoB-100 ASO in several mouse models of hyperlipidemia, including C57BL/6 mice fed a high-fat diet, Apoe-deficient mice, and Ldlr-deficient mice. The lead apoB-100 antisense compound, ISIS 147764, reduced apoB-100 mRNA levels in the liver and serum apoB-100 levels in a dose- and time-dependent manner. Consistent with those findings, total cholesterol and LDL-C decreased by 25–55% and 40–88%, respectively.Unlike small-molecule inhibitors of microsomal triglyceride transfer protein, ISIS 147764 did not produce hepatic or intestinal steatosis and did not affect dietary fat absorption or elevate plasma transaminase levels. These findings, as well as those derived from interim phase I data with a human apoB-100 antisense drug, suggest that antisense inhibition of this target may be a safe and effective approach for the treatment of humans with hyperlipidemia.

Malabsorption of fat in the adrenalectomized rat has been confirmed. The criteria for adrenal hypofunction were more rigorous than in previous studies. The malabsorption is not due to impaired intestinal lipolysis or inadequate intestinal intracellular glyceride synthesis. Delayed gastric emptying is probably secondary to the malabsorption rather than a cause. It is postulated that impaired intestinal fatty acid activation may be the key defect and that in some way this inhibits fatty acid transport across the mucosal membrane.