Key points
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Which means that urinary oxalate excretion appears to be an independent risk factor for the progression of chronic kidney disease.
Summary
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 possible contributor to more common forms of chronic kidney disease (CKD).
Aim :
To evaluate whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward renal failure.
Design, environment and participants :
This prospective cohort study evaluated 3123 participants with CKD stages 2 to 4 who were enrolled in the Chronic Kidney Disease Cohort Study from June 1, 2003 to September 30, 2008. Data analysis was performed from October 24, 2017. As of June 17, 2018.
Exposures: Twenty-four hours of urinary oxalate excretion.
Main results and measures :
A 50% decrease 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).
The mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) ml/min/1.73 m2. Median urinary oxalate excretion was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was inversely correlated with eGFR (r = −0.13, P < .001) and positively correlated with 24-hour proteinuria (r = 0.22, p < 0.001).
During 22,318 person-years of follow-up, 752 individuals achieved ESRD, and 940 individuals achieved the composite endpoint of ESRD or a 50% decrease in eGFR (CKD progression).
Higher oxalate excretion was independently associated with higher risks of both CKD and ESRD progression: compared to quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, <11.5 mg/24 hours) oxalate, ≥27.8 mg/24 hours) had a 33% increased risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% increased risk of ESKD (HR, 1.45 ; 95% CI, 1.09-1.93).
The association between oxalate excretion and progression of CKD and ESRD was nonlinear and showed a threshold effect in quintiles 3 to 5 versus quintiles 1 and 2.
Higher versus 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 a 37% higher ESRD (HR, 1.37; 95% CI, 1.15-1.63).
The results were similar when death was treated as a competing event.
Conclusions and relevance Increased 24-hour urinary oxalate excretion may be a risk factor for the progression of CKD and ESRD in individuals with CKD stages 2 to 4. There is clinical plausibility of our findings of oxalate as a risk factor for CKD progression, considering the fact that rare genetic diseases of oxalate overproduction, enteric hyperoxaluria, and ethylene glycol ingestion are well-known causes of renal failure. It is also biologically plausible to our findings based on data from animal models and tissue culture data showing multiple mechanisms for oxalate to cause kidney damage. In conclusion , we found that increased urinary oxalate excretion may be a novel risk factor for CKD progression. If our results are confirmed, future research on pharmacological or dietary measures to limit oxalate absorption and/or generation will be required to evaluate whether reducing urinary oxalate excretion is beneficial in CKD. |
