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

Sushrut S. Waikar, Anand Srivastava, Ragnar Palsson, Tariq Shafi, Chi Yuan Hsu, Kumar Sharma, James P. Lash, Jing Chen, Jiang He, John C Lieske, Dawei Xie, Xiaoming Zhang, Harold I. Feldman, Gary C. Curhan

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
JournalJAMA internal medicine
DOIs
StatePublished - Jan 1 2019

Fingerprint

Oxalates
Chronic Renal Insufficiency
Disease Progression
Chronic Kidney Failure
Glomerular Filtration Rate
Cohort Studies
Hyperoxaluria
Urine Specimen Collection
Inborn Genetic Diseases
Poisons
Proteinuria
Renal Insufficiency
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Waikar, S. S., Srivastava, A., Palsson, R., Shafi, T., Hsu, C. Y., Sharma, K., ... Curhan, G. C. (2019). Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression. JAMA internal medicine. https://doi.org/10.1001/jamainternmed.2018.7980

Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression. / Waikar, Sushrut S.; Srivastava, Anand; Palsson, Ragnar; Shafi, Tariq; Hsu, Chi Yuan; Sharma, Kumar; Lash, James P.; Chen, Jing; He, Jiang; Lieske, John C; Xie, Dawei; Zhang, Xiaoming; Feldman, Harold I.; Curhan, Gary C.

In: JAMA internal medicine, 01.01.2019.

Research output: Contribution to journalArticle

Waikar, SS, Srivastava, A, Palsson, R, Shafi, T, Hsu, CY, Sharma, K, Lash, JP, Chen, J, He, J, Lieske, JC, Xie, D, Zhang, X, Feldman, HI & Curhan, GC 2019, 'Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression', JAMA internal medicine. https://doi.org/10.1001/jamainternmed.2018.7980
Waikar, Sushrut S. ; Srivastava, Anand ; Palsson, Ragnar ; Shafi, Tariq ; Hsu, Chi Yuan ; Sharma, Kumar ; Lash, James P. ; Chen, Jing ; He, Jiang ; Lieske, John C ; Xie, Dawei ; Zhang, Xiaoming ; Feldman, Harold I. ; Curhan, Gary C. / Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression. In: JAMA internal medicine. 2019.
@article{33199a036aaa4f4e9ba8fd7ad4d78b4c,
title = "Association of Urinary Oxalate Excretion with the Risk of 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 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.",
author = "Waikar, {Sushrut S.} and Anand Srivastava and Ragnar Palsson and Tariq Shafi and Hsu, {Chi Yuan} and Kumar Sharma and Lash, {James P.} and Jing Chen and Jiang He and Lieske, {John C} and Dawei Xie and Xiaoming Zhang and Feldman, {Harold I.} and Curhan, {Gary C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamainternmed.2018.7980",
language = "English (US)",
journal = "JAMA Internal Medicine",
issn = "2168-6106",
publisher = "American Medical Association",

}

TY - JOUR

T1 - Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression

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 C

AU - Xie, Dawei

AU - Zhang, Xiaoming

AU - Feldman, Harold I.

AU - Curhan, Gary C.

PY - 2019/1/1

Y1 - 2019/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85062332221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062332221&partnerID=8YFLogxK

U2 - 10.1001/jamainternmed.2018.7980

DO - 10.1001/jamainternmed.2018.7980

M3 - Article

C2 - 30830167

AN - SCOPUS:85062332221

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

SN - 2168-6106

ER -