Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Overview

The purpose of this study was to determine the effect of two probiotic preparations (Agri-King Synbiotic and Oxadrop) on urinary oxalate excretion in patients with mild hyperoxaluria. Probiotics are live microorganisms thought to be beneficial to the host organism. Hyperoxaluria is a hereditary disorder that causes a special kind of stone to form in the kidney and urine. Oxalates are naturally-occurring substances found in plants, animals, and in humans. Excretion of oxalates in the urine is a risk factor for kidney stone formation. Our hypothesis was that the mild hyperoxaluria is due to over absorption of oxalate from food and that probiotics will improve gastrointestinal barrier function to decrease oxalate absorption across the gut (and hence its elimination in the urine). In the study, participants were randomized to placebo, Agri-King Synbiotic, or Oxadrop, and were treated for 6 weeks. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake and availability from food.

Renal manifestations of chronic hyperoxaluria include nephrolithiasis and, when extreme, interstitial scarring and progressive loss of function. The clinical outcome can be dismal. Although primary hyperoxaluria is relatively rare, hyperoxaluria secondary to gastrointestinal malabsorption is not. Furthermore, the formation of calcium oxalate kidney stones is extremely common, and evidence suggests that minimal, perhaps transient elevations in urinary oxalate concentration may be an important factor in at least a subgroup of these patients with "idiopathic" calcium oxalate urolithiasis. In the case of enteric hyperoxaluria the pathogenic role of oxalate is clear, and renal scarring is commonly observed as a consequence of oxalate exposure and calcium oxalate crystal deposition, in addition to stones. Unfortunately, few satisfactory specific treatments for enteric hyperoxaluria are available. Typical strategies include dietary restriction of oxalate to limit its delivery to the colon; low fat diets to limit malabsorption and distal colonic effects of fatty acids and bile acids; oral calcium to bind oxalate; and bile acid sequestrants like cholestyramine. In its entirety, this regimen is quite rigorous for patients, and even if compliance is achieved the therapy is not always effective. Previous studies have shown that components of the endogenous digestive microflora can utilize oxalate, potentially limiting its absorption from the intestinal lumen. A recent preliminary study demonstrated that a preparation of lactic acid bacteria degraded oxalate in vitro and reduced urinary oxalate excretion when given by mouth. We have recently demonstrated that the same preparation of lactic acid bacilli (Oxadrop) can reduce urinary oxalate excretion in patients with enteric hyperoxaluria. In the current proposal, in a placebo-controlled trial we will determine the effectiveness of this and another probiotic preparation (Agri-King Synbiotic) \[AKSB\] for the treatment of hyperoxaluria in patients with mild hyperoxaluria, as well as enteric hyperoxaluria. Specific Aims are: 1) Determine the effect of two probiotic preparations (AKSB and Oxadrop on urinary oxalate excretion in a well-defined group of patients with enteric hyperoxaluria; and 2) Determine the effect of two probiotic preparations (AKSB and Oxadrop) on urinary oxalate excretion in a well-defined group of patients with idiopathic calcium oxalate urolithiasis and mild hyperoxaluria. If results are positive, treatment for calcium oxalate kidney stones could be revolutionized.