Kidney Stone Events and ESKD Incidence in Patients with Enteric Hyperoxaluria from Diverse Enteric Etiologies

Key Points Significant heterogeneity in patient characteristics, urine metabolic studies, and kidney outcomes exist among enteric hyperoxaluria patients from diverse etiologies. Structurally induced malabsorption and exocrine pancreatic insufficiency have the highest kidney stone event rates. Patients with structurally induced malabsorption have up to 18% ESKD incidence at 5 years. Background Enteric hyperoxaluria (EH) is a risk factor for calcium oxalate nephrolithiasis and kidney disease. The study compares patient characteristics and urine metabolic profiles at the time of EH diagnosis and kidney stones and ESKD events during follow-up in a cohort with diverse causes of EH. Methods Adult patients with newly documented elevated urinary oxalate excretion >40 mg/24 h between January 1, 2010, and October 10, 2023, and a known enteric diagnosis including inflammatory bowel disease, exocrine pancreatic insufficiency (EPI), celiac disease, structural intestinal malabsorption (SIM), or malabsorptive bariatric surgery (Bariatric) were identified. Event rates and cumulative incidence of kidney stones and ESKD were assessed. Results Among 814 identified patients, the most common enteric etiology was Bariatric ( n =524, 64%). Patients with ulcerative colitis had the highest prevalence of kidney stones at EH diagnosis (93.6%) compared with other enteric etiologies ( P = 0.002). Patients with SIM had the highest urinary oxalate, lower urinary citrate, and volume, compared with other enteric etiologies ( P < 0.05). Calcium oxalate supersaturation was similar among the enteric groups ( P = 0.67). Median stone event rate for the overall cohort was 0.70 stone events/year during a mean (SD) follow-up of 5.0 (3.9) years. The SIM and EPI groups experienced the highest stone events (median [IQR] 1.24 [0.28–2.40] and 1.20 [0.41–1.99] events/year, respectively) while the Bariatric group had the lowest event rates (median [IQR] 0.45 [0.00–1.66 events/year]; P < 0.001). The SIM group had the highest ESKD incidence (17.8% 5 years postdiagnosis; log-rank test P < 0.001). Conclusions We describe a large EH cohort from diverse enteric etiologies. Significant heterogeneity exists in patient characteristics, urine metabolic risk factors, and adverse kidney outcomes. Patients with SIM and EPI experienced the highest kidney stone events and patients with SIM had the highest ESKD incidence. This study highlights the urgent need for more granular information regarding the natural history and risk factors for kidney complications for patients with EH to support interventional trials to improve outcomes.