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Impact of Uric Acid Levels on Kidney Disease Progression
Hernan Rincon-Choles1, Stacey E Jolly2, Susana Arrigain3
1Department of Nephrology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Insights
Hyperuricemia is linked to worse outcomes in chronic kidney disease (CKD) stages 3 and 4. However, uric acid lowering therapy (UALT) did not reduce this risk, suggesting the association may not be causal.
Area of Science:
- Nephrology
- Internal Medicine
- Cardiorenal Medicine
Background:
- Hyperuricemia is a known comorbidity in chronic kidney disease (CKD).
- The causal relationship between hyperuricemia and CKD progression remains unclear.
- This study investigates hyperuricemia and uric acid lowering therapy (UALT) in CKD stages 3 and 4.
Purpose of the Study:
- To examine the association between hyperuricemia and CKD progression.
- To determine if UALT impacts CKD progression or adverse outcomes.
- To assess the potential causal link between uric acid levels and kidney disease advancement.
Main Methods:
- Retrospective analysis of 1,676 patients with CKD stages 3-4 from the Cleveland Clinic CKD registry (2005-2009).
- Uric acid (UA) levels and estimated glomerular filtration rate (eGFR) were tracked.
- Primary outcome: 50% eGFR drop or End-Stage Renal Disease (ESRD); secondary outcomes included mortality and eGFR decline. Cox and competing risks models were used.
Main Results:
- Higher UA levels (4th quartile, ≥8.9 mg/dL) were associated with a composite endpoint of CKD progression.
- Receipt of UALT was paradoxically linked to an increased risk of the composite outcome.
- Neither elevated UA nor UALT showed a significant association with mortality, ESRD, or eGFR decline.
Conclusions:
- Hyperuricemia is associated with an increased risk of CKD progression to ESRD in patients with stages 3 and 4 CKD.
- UALT did not appear to mitigate this risk in the studied cohort.
- The findings suggest that the association between hyperuricemia and CKD progression may not be causal.
Background:
Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry.
Methods:
We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models.
Results:
In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline.
Conclusions:
Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.