TY - JOUR
T1 - Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression
AU - for the Chronic Renal Insufficiency Cohort study investigators
AU - Waikar, Sushrut S.
AU - Srivastava, Anand
AU - Palsson, Ragnar
AU - Shafi, Tariq
AU - Hsu, Chi Yuan
AU - Sharma, Kumar
AU - Lash, James P.
AU - Chen, Jing
AU - He, Jiang
AU - Lieske, John
AU - Xie, Dawei
AU - Zhang, Xiaoming
AU - Feldman, Harold I.
AU - Curhan, Gary C.
AU - Appel, Jaa
AU - Go, Alan S.
AU - Kusek, John W.
AU - Rao, Panduranga
AU - Rahman, Mahboob
AU - Townsend, Raymond R.
N1 - Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
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U2 - 10.1001/jamainternmed.2018.7980
DO - 10.1001/jamainternmed.2018.7980
M3 - Article
C2 - 30830167
AN - SCOPUS:85062332221
SN - 2168-6106
VL - 179
SP - 542
EP - 551
JO - JAMA internal medicine
JF - JAMA internal medicine
IS - 4
ER -