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.
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This work focuses on the in vitro calcium-oxalate (CaOx) crystallization behaviour of native and synthetic urine samples in order to establish a CaOx crystallization risk index for unprepared native urine. Native 24-h urine samples from healthy persons and from stone-formers were examined. Within a [Ca2+] versus added oxalate (Ox2-) diagram, we observed fields which allow the discrimination of each urine sample in terms of more or less risk. The [Ca2+]/(Ox2-) ratio is calculated and termed the "Bonn-Risk Index" (BRI; per litre). We propose that BRIs > 1/l denote samples "at risk", whereas BRIs < or = 1/l denote those "without risk". Second. the effects of different concentrations of citrate and Mg2+ on BRI were investigated in artificial urine. The transferability of BRI between native and synthetic urine samples is proved. To evaluate the impact of the proposed BRI, it is compared with the more familiar relative urine saturation index calculated for CaOx and brushite. Urine sampled from stone-formers shows risk indexes between 0.278 and 23.0/l (mean 2.87/l), while urine from healthy persons varied between 0.060 and 4.890/l (mean 1.05/l). Comparing the results of healthy volunteers and patients, the significance of BRI and relative urine supersaturation (RS) with respect to CaOx is P < 0.0005 and P = 0.013, respectively. Fast and easy to perform, determination of the risk index is a suitable tool for estimating the actual CaOx formation "status"--"at risk" or "without risk"--from the native urine of any person.
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