Abstract
Importance: Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD). Objective: To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure. Design, Setting, and Participants: This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018. Exposures: Twenty-four-hour urinary oxalate excretion. Main Outcomes and Measures: A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD). Results: This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m 2 . Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P <.001) and positively with 24-hour proteinuria (r = 0.22, P <.001). During 22318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event. Conclusions and Relevance: Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 542-551 |
| Number of pages | 10 |
| Journal | JAMA internal medicine |
| Volume | 179 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2019 |
Funding
Funding/Support: This study was supported by grant R01DK103784 from National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Dr Waikar). Funding for the Chronic Renal Insufficiency Cohort study was obtained from grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902 under a cooperative agreement from NIDDK. In addition, this work was supported in part by Clinical and Translational Science Award NIH/National Center for Advancing Translational Science UL1TR000003 from the Perelman School of Medicine at the University of Pennsylvania, grant UL1 TR-000424 from Johns Hopkins University, grant M01 RR-16500 from the General Clinical Research Center, University of Maryland, the Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the National Center for Advancing Translational Sciences component of the NIH and the NIH roadmap for Medical Research, grant UL1TR00043 from the Michigan Institute for Clinical and Health Research Center, Clinical and Translational Science Award UL1RR029879 from University of Illinois at Chicago, grant P20 GM109036 from Tulane Center of Biomedical Research Excellence for Clinical and Translational Research in Cardiometabolic Diseases, and grant UL1 RR-024131 from Kaiser Permanente, NIH/ National Center for Research Resources, University of California, San Francisco, Clinical & Translational Science Institute. reported receiving grants from National Institutes of Health during the conduct of the study and grants and personal fees from Allena outside the submitted work. Dr Shafi reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Hsu reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Feldman reported receiving grants from the National Institutes of Health and personal fees from Kyowa Hakko Kirin Com and the National Kidney Foundation during the conduct of the study. Dr Curhan reported receiving grants, personal fees, and other from Allena Pharmaceuticals, personal fees from Shire, and other from UpToDate during the conduct of the study and personal fees from AstraZeneca and grants from Shoebox Audiometry outside the submitted work. No other disclosures were reported.
ASJC Scopus subject areas
- Internal Medicine
