Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.

About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium oxalate stone formers, 26 tested negative for O. formigenes and were compared with the 11 patients who tested positive. Patients provided 24-h urine samples on both a self-selected and a standardized diet. Urinary oxalate excretion did not differ significantly on the self-selected diet, but was significantly lower in O. formigenes-positive than in O. formigenes-negative patients under controlled, standardized conditions. Intestinal oxalate absorption, measured using [(13)C₂]oxalate, was similar in the patients with or without O. formigenes. Plasma oxalate concentrations were significantly higher in noncolonized (5.79 μmol/l) than in colonized stone formers (1.70 μmol/l). Colonization with O. formigenes was significantly inversely associated with the number of stone episodes. Our findings suggest that O. formigenes lowers the intestinal concentration of oxalate available for absorption at constant rates, resulting in decreased urinary oxalate excretion. Thus, dietary factors have an important role in urinary oxalate excretion. The data indicate that O. formigenes colonization may reduce the risk of stone recurrence.

Current treatment options in patients with primary and secondary hyperoxaluria are limited and do not always lead to sufficient reduction in urinary oxalate excretion. Intestinal oxalate degrading bacteria are capable of degrading oxalate to CO(2) and formate, the latter being further metabolized and excreted via the feces. It is speculated, that both endogenously produced, as well as dietary oxalate can be significantly removed via the intestinal tract. Oxalobacter formigenes, an obligate anaerobic microbe normally found in the intestinal tract has one oxalate degrading enzyme, oxalyl-CoA decarboxylase, which is also found in Bifidobacterium lactis. Other bacteria with possible oxalate degrading potency are lactic acid bacteria, as well as Enterococcus faecalis and Eubacterium lentum. However, specific therapeutic studies on humans are scarce and, except for Oxalobacter, data are not congruent. We found the oral application of Oxalobacter successful in patients with primary hyperoxaluria. However, long-term post-treatment follow-up of 1-2 years showed that constant intestinal colonization is not achieved in most patients. In one patient with constant colonization, urinary oxalate excretion normalized over time. Short-term studies with other bacteria such as lactic acid bacteria did not show a specific reduction in urinary oxalate excretion. O. formigenes might be a promising new therapeutic tool in patients with primary and secondary hyperoxaluria.

Despite hyperoxalurogenic eating habits relative to white subjects, South African blacks have urinary oxalate excretions, Tiselius risk indices (AP(CaOx)) and calcium oxalate saturations, which do not differ significantly from those of their white counterparts. The present study was undertaken to establish whether the BONN-Risk-Index (BRI) might discriminate between the urines of the two population groups and whether differences might exist in their respective gastrointestinal absorption rates of oxalate. Participants (n = 15 in each group) provided 24 h urines on their free diets for BRI determination. Gastrointestinal oxalate absorption was measured using the [13C2]oxalate absorption test. Results showed that BRI values were significantly lower in black subjects (2.04 vs 4.90, P = 0.034), but that there was no difference in the oxalate absorption between the groups (10.30 vs 9.95%, P = 0.87). These results suggest that South African black subjects handle dietary oxalate more efficaciously than white subjects and that this occurs via some endogenous mechanism, which has not yet been identified or characterized.

A sensitive and specific method for the simultaneous determination of bromisoval, carbromal, and methaqualone is described. The drugs are adsorbed from serum onto charcoal at pH 11 and eluted from it with organic solvent. The eluate is separated by high-pressure liquid-chromatography on reverse phase (RP 18) column using acetonitrile: water (26 : 74 by volume) as mobile phase. The eluted drugs are detected by uv-absorption at 210 nm. The method is sensitive, specific, precise, and accurate.