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Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in
Sascha Pilemann-Lyberg1, Tine Willum Hansen2, Nete Tofte2
1Steno Diabetes Center Copenhagen, Gentofte, Denmark sply@novonordisk.com.
Insights
Higher uric acid (UA) levels in type 1 diabetes (T1D) patients predict increased risk of kidney function decline, cardiovascular events (CVEs), and mortality. UA shows promise for improving risk prediction in T1D.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
- Metabolic Research
Background:
- Previous studies yielded inconclusive results regarding uric acid's role in risk prediction.
- Type 1 diabetes (T1D) patients face risks of kidney function decline, cardiovascular events (CVEs), and mortality.
- There is a need to enhance the precision of predictive models for these adverse outcomes in T1D.
Purpose of the Study:
- To investigate the predictive value of uric acid (UA) for kidney function decline, CVEs, and mortality in patients with T1D.
- To determine if UA improves risk stratification beyond conventional factors in T1D.
- To analyze the association of UA with the progression of kidney disease markers like albuminuria.
Main Methods:
- Plasma UA levels were measured in 670 T1D patients with varying degrees of albuminuria.
- Longitudinal analysis assessed associations between UA and composite endpoints: eGFR decline (≥30%), CVEs, and mortality.
- Hazard ratios (HRs) were calculated per doubling of UA, with multivariable adjustments and assessment of model improvement using the relative integrated discrimination index.
Main Results:
- A doubling in UA level significantly increased the risk of eGFR decline (HR 3.18), CVEs (HR 2.25), and mortality (HR 2.58) in adjusted analyses.
- Incorporating UA into risk models improved prediction for eGFR decline (12.6%), CVEs (6.5%), and mortality (11.8%).
- Higher UA was independently associated with a steeper decline in eGFR and a faster increase in albumin-to-creatinine ratio.
Conclusions:
- Elevated uric acid levels are independently associated with an increased risk of kidney function decline, CVEs, and mortality in T1D patients.
- Uric acid demonstrates a significant role in risk stratification for individuals with T1D.
- These findings support the utility of measuring UA for enhanced risk assessment in T1D management.
Objective:
Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D).
Research Design And Methods:
Plasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria. Associations of UA with an estimated glomerular filtration rate (eGFR) decline of ≥30%, CVEs, and mortality were analyzed. The median follow-up time was 5.3 years [interquartile range (IQR) 2.7-6.2 years] for a decline in eGFR of ≥30%, 5.8 years (2.5-6.4 years) for progression in albuminuria status, 5.1 years (4.7-5.6 years) for CVE, and 6.2 years (5.8-6.7 years) for mortality. Both univariable and multivariable associations of UA with relevant outcomes and variables were reported. Hazard ratios (HRs) were calculated per doubling of the UA level.
Results:
A doubling in UA level was associated with a higher risk of decline in eGFR of ≥30% (n = 89) (HR 3.18 [IQR 1.71-5.93]; P < 0.001), CVE (n = 94) (HR 2.25 [IQR 1.20-4.21]; P = 0.011), and mortality (n = 58) (HR 2.58 [IQR 1.12-5.90]; P = 0.025) in adjusted analyses. Adding UA to the adjusted model including conventional risk factors improved the relative integrated discrimination index by 12.6% for a decline in eGFR of ≥30% (P < 0.001), 6.5% for CVE (P = 0.010), and 11.8% (P = 0.003) for mortality. A doubling in UA level was also associated with a steeper decline in eGFR (P < 0.0026) and a steeper increase in urine albumin-to-creatinine ratio (P < 0.0027) in adjusted analysis.
Conclusions:
In individuals with T1D, a higher UA level is associated with a higher risk of decline in kidney function, CVE, and mortality, independently of other risk factors. Our results suggest that UA has a promising role in risk stratification among individuals with T1D.
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