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Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD
Anand Srivastava1, Arnaud D Kaze2, Ciaran J McMullan2
1Renal Division, Brigham & Women's Hospital, Boston, MA; Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Insights
High serum uric acid is linked to kidney failure in early chronic kidney disease (CKD). Uric acid levels also show a J-shaped association with all-cause mortality in CKD patients.
Area of Science:
- Nephrology
- Internal Medicine
- Cardiovascular Disease
Background:
- Elevated serum uric acid is common in chronic kidney disease (CKD).
- High uric acid may contribute to kidney injury, endothelial dysfunction, and inflammation.
- The association between uric acid levels and kidney failure or mortality in CKD remains unclear.
Purpose of the Study:
- To investigate the association between baseline serum uric acid concentrations and the risk of kidney failure and all-cause mortality in individuals with CKD stages 2-4.
Main Methods:
- Prospective observational cohort study of 3,885 CKD patients from the Chronic Renal Insufficiency Cohort (CRIC) study.
- Participants were followed for a median of 7.9 years.
- Baseline serum uric acid concentrations were analyzed as a predictor for kidney failure and all-cause mortality.
Main Results:
- Higher uric acid concentrations were independently associated with an increased risk of kidney failure in CKD patients with estimated glomerular filtration rates (eGFRs) ≥ 45mL/min/1.73m².
- No significant association was found between uric acid and kidney failure in those with eGFRs < 30mL/min/1.73m².
- A J-shaped relationship was observed between uric acid concentration and all-cause mortality in the CKD cohort.
Conclusions:
- Serum uric acid concentration is an independent risk factor for kidney failure in earlier stages of CKD.
- A J-shaped relationship exists between uric acid concentration and all-cause mortality in CKD.
- Further research, including randomized controlled trials, is needed to determine if lowering uric acid can prevent CKD complications.
Background:
Serum uric acid concentrations increase in chronic kidney disease (CKD) and may lead to tubular injury, endothelial dysfunction, oxidative stress, and intrarenal inflammation. Whether uric acid concentrations are associated with kidney failure and death in CKD is unknown.
Study Design:
Prospective observational cohort study.
Settings & Participants:
3,885 individuals with CKD stages 2 to 4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and September 2008 and followed up through March 2013.
Predictor:
Baseline uric acid concentrations.
Outcomes:
Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality.
Results:
During a median follow-up of 7.9 years, 885 participants progressed to kidney failure and 789 participants died. After adjustment for demographic, cardiovascular, and kidney-specific covariates, higher uric acid concentrations were independently associated with risk for kidney failure in participants with estimated glomerular filtration rates (eGFRs) ≥ 45mL/min/1.73m2 (adjusted HR per 1-standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs<30mL/min/1.73m2. There was a nominally higher HR in participants with eGFRs of 30 to 44mL/min/1.73m2 (adjusted HR, 1.13; 95% CI, 0.99-1.29), but this did not reach statistical significance. The relationship between uric acid concentration and all-cause mortality was J-shaped (P=0.007).
Limitations:
Potential residual confounding through unavailable confounders; lack of follow-up measurements to adjust for changes in uric acid concentrations over time.
Conclusions:
Uric acid concentration is an independent risk factor for kidney failure in earlier stages of CKD and has a J-shaped relationship with all-cause mortality in CKD. Adequately powered randomized placebo-controlled trials in CKD are needed to test whether urate lowering may prove to be an effective approach to prevent complications and progression of CKD.
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