Disorder Of Oxalate Metabolism Research Articles

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.

Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria

BackgroundSecondary hyperoxaluria either based on increased intestinal absorption of oxalate (enteric), or high oxalate intake (dietary), is a major risk factor of calcium oxalate urolithiasis. Oxalate-degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption.MethodsTwenty healthy subjects were studied initially while consuming a diet normal in oxalate. Study participants were then placed on a controlled oxalate-rich diet for a period of 6 weeks. Starting with week 2 of the oxalate-rich diet, participants received 2.6 g/day of a lactic acid bacteria preparation for 5 weeks. Finally, subjects were examined 4 weeks after treatment while consuming again a normal-oxalate diet. Participants provided weekly 24-hour urine specimens. Analyses of blood samples were performed before and at the end of treatment.ResultsUrinary oxalate excretion increased significantly from 0.354 ± 0.097 at baseline to 0.542 ± 0.163 mmol/24 h under the oxalate-rich diet and remained elevated until the end of treatment, as did relative supersaturation of calcium oxalate. Plasma oxalate concentration was significantly higher after 5 weeks of treatment compared to baseline. Four weeks after treatment, urinary oxalate excretion and relative supersaturation of calcium oxalate fell to reach initial values.ConclusionsPersistent dietary hyperoxaluria and increased plasma oxalate concentration can already be induced in healthy subjects without disorders of oxalate metabolism. The study preparation neither reduced urinary oxalate excretion nor plasma oxalate concentration. The preparation may be altered to select for lactic acid bacteria strains with the highest oxalate-degrading activity.

Intestinal transport of pyrodoxine in experimental renal failure

Renal failure (RF) has been shown to alter intestinal transport of a number of nutrients. We studied jejunal absorption of pyridoxine (B 6) in rats rendered azotemic by subtotal nephrectomy (RF group) and compared the results with those obtained in normal rats subjected to sham operation (controls) and animals pair-fed (PF) with their RF counterparts. In vivo recirculating perfusion and in vitro everted sac techniques were employed. The in vitro experiments were repeated using sera from uremic and normal individuals to assess the possible effect of uremic chemical environment. The results showed significant reduction in B 6 absorption in vivo in the RF group as compared to the control and PF groups. Paradoxically, the rate of in vitro B 6 absorption determined for a wide range of concentrations was increased in the RF and PF groups as compared to the control group. The observed increase in B 6 absorption in vitro suggests enhanced permeability in the RF and PF groups due probably to reduced nutrient intake which was common to both groups. The disparity between the in vivo and in vitro results is indicative of some inhibitory factor(s) present in the RF animals. Sacs containing uremic serum showed significantly suppressed B 6 absorption in vitro as compared to those containing normal serum. These observations suggest that the uremic chemical environment may be, in part, responsible for the observed impairment of B 6 transport in RF animals despite in vitro evidence of hyperpermeability. Pyridoxine (B 6) is the major plant form of vitamin B 6, while pyridoxamine phosphate and pyridoxal phosphate are the primary forms in animals. Consumption of a B 6-deficient diet leads to rapid occurrence of B 6 deficiency (1) which is associated with neuromuscular irritability, central nervous system depression, convulsion, stomatitis, cheilosis, cutaneous lesions, peripheral neuropathy, disorders of oxalate metabolism, impaired immune response and anemia. (2–7) Earlier studies in our laboratory have revealed an impaired intestinal absorption of riboflavin, (8) tetrahydrofolate, (9) and vitamin D-3 (10) in experimental renal failure (RF). In addition, B 6 deficiency has been reported in patients with renal insufficiency. (11) However, the effect of RF on the intestinal absorption of B 6 has not been previously investigated. The present study was designed to determine the effect of experimental RF on the intestinal absorption of B 6 using the in vivo perfusion and in vitro everted sac techniques. (12)

Disorders of oxalate metabolism

Oxalate is a useless metabolic endproduct, formed as an unfortunate byproduct of the metabolism of glyoxylate and ascorbate. When formed it is excreted in the urine where it constitutes a hazard because of the insolubility of its calcium salt. In the majority of patients with calcium oxalate stones the urinary excretion of oxalate is normal. Reviewed herein are the acquired and genetic disorders associated with excessive oxalate excretion, in particular primary hyperoxaluria types I (glycolic aciduria) and II (glyceric aciduria). The demonstration of specific enzyme defects associated with these diseases has clarified the pathogenesis of oxalate production. Although rare, these diseases are important since they most frequently lead to early death from renal failure. Newer approaches to treatment are therefore being pursued; if successful, they might also find application in the treatment of patients with idiopathic calcium oxalate nephrolithiasis.