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Original Investigation
March 4, 2019

Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

Author Affiliations
  • 1Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 3Division of Nephrology, Johns Hopkins University, Baltimore, Maryland
  • 4Division of Nephrology, University of California, San Francisco
  • 5Division of Nephrology, University of Texas, San Antonio
  • 6Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
  • 7Department of Medicine, Tulane University, New Orleans, Louisiana
  • 8Department of Medicine, Tulane University, New Orleans, Louisiana
  • 9Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
  • 10Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 11Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA Intern Med. 2019;179(4):542-551. doi:10.1001/jamainternmed.2018.7980
Key Points

Question  Does higher urinary oxalate excretion predispose patients to kidney failure?

Findings  In this cohort study of 3123 individuals with chronic kidney disease, higher urinary excretion of oxalate was associated with a 37% greater adjusted risk of future end-stage kidney disease.

Meaning  Urinary oxalate excretion appears to be an independent risk factor for chronic kidney disease progression.

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 m2. 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 22 318 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.

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