Browsing by Subject "enteric hyperoxaluria"

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    Randomized Placebo-Controlled Trial of Reloxaliase in Enteric Hyperoxaluria
    (NEJM Group, 2022-05-06) Lieske, John C.; Lingeman, James E.; Ferraro, Pietro M.; Wyatt, Christina M.; Tosone, Christine; Kausz, Annamaria T.; Knauf, Felix; Urology, School of Medicine
    BACKGROUND Enteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption. METHODS We randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup. RESULTS A total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study. CONCLUSIONS Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.)
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    Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria
    (Karger, 2016-09) Ekser, Burcin; Mangus, Richard S.; Kubal, Chandrashekhar A.; Fridell, Jonathan A.; Powelson, John A.; Nagaraju, Santosh; Mihaylov, Plamen; Phillips, Carrie L.; Saxena, Romil; Goggins, William C.; Department of Surgery, IU School of Medicine
    Background: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. Methods: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. Results: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. Conclusions: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use.