Background/Purpose:  The 1-year cumulative incidence of gout in patients with new onset end stage renal disease is 5% and rises to 15% by 5 years, far exceeding the risk in the general population. This higher prevalence of gout could be explained by hyperuricemia as a consequence of reduced renal function and subsequent development of gout or due to common risk factors. Although the risk of developing gout is high among those with end stage renal disease, the risk of gout for those with moderate kidney dysfunction is unclear. We estimated the risk of developing gout over a range of estimated glomerular filtration rate (eGFR) values in participants enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study.

Methods: ARIC is a prospective population-based cohort recruited in 1987-1989 from 4 US communities, consisting of 4 visits over 9 years. Participants were included in this analysis if they answered the gout query and were free of gout at baseline. Incident gout was defined as self-reported onset after baseline. Serum creatinine was estimated using a modified kinetic Jaffé reaction. Glomerular filtration rate (eGFR) was estimated using the CKD-Epi equation and categorized as ≥90, 60-90, or <60 ml/min/1.73 m². Using a Cox Proportional Hazards model (age as time scale), we estimated the hazard ratio (HR) and 95% confidence intervals (CI) of incident gout by baseline eGFR, adjusted for confounders (sex, race, and center) and clinical factors (diuretic use, diabetes, hypertension, obesity, and alcohol intake). Additionally, we adjusted for visit 2 serum urate level (measured with the uricase method) to test for mediation.

Results: A total of 10,871 ARIC participants met the study criteria. The study population was 43% male, 21% African American and the mean age at cohort entry was 54 years (SD=5.7). The mean eGFR was 92 (SD=14.9) ml/min/1.73 m². At baseline, 217 (2%) participants were classified as having eGFR<60 ml/min/1.73 m²; 4,502 (41%) with an eGFR between 60 and 90 ml/min/1.73 m²; and 6,152 with an eGFR >90 ml/min/1.73 m² (57%). There were 274 incident gout cases. The results are presented in the table. After accounting for confounders and clinical factors, a 10 ml/min/1.73 m² decrease in eGFR was associated with increased risk of gout (HR=1.15, 95% CI: 1.10-1.25). Compared to those with an eGFR ≥90, the adjusted HR of incident gout was 1.13 (95% CI: 0.88-1.46) for those with an eGFR between 60 and 90 ml/min/1.73 m² and 2.57 (95% CI: 1.58-4.17) for those with an eGFR< 60 ml/min/1.73 m². eGFR was not associated with incident gout after accounting for V2 serum urate level, suggesting full mediation. There was no evidence of effect measure modification by race (p=0.46) or sex (p=0.39).

 

Table. Risk of Gout by eGFR
	HR of Gout (95% CI)	P-value
Model 1: Unadjusted
eGFR for each 10 unit decrease	1.12 (1.03, 1.22)	0.004
eGFR≥90	Ref	0.01
60£eGFR<90	1.08 (0.84, 1.38)
eGFR <60	2.80 (1.74, 4.50)
Model 2: Adjusted  sex, race, and center
eGFR for each 10 unit decrease	1.18 (1.09, 1.27)	<0.0001
eGFR≥90	Ref	0.002
60£eGFR<90	1.17 (0.91, 1.51)
eGFR <60	2.93 (1.82, 4.73)
Model 3: Adjusted sex, race, center, diuretic use, hypertension, diabeties, obesity, continuous alcohol intake
eGFR for each 10 unit decrease	1.15 (1.10, 1.25)	0.0003
eGFR≥90	Ref	0.009
60£eGFR<90	1.13 (0.88, 1.46)
eGFR <60	2.57 (1.58, 4.17)
Model 4: Adjusted sex, race, center, diuretic use, hypertension, diabeties, obesity, continuous alcohol intake, serum urate level at visit 2.
eGFR for each 10 unit decrease	0.97 (0.90, 1.05)	0.47
eGFR≥90	Ref	0.20
60£eGFR<90	0.82 (0.63, 1.06)
eGFR <60	0.88 (0.52, 1.48)

Conclusion: Moderately reduced kidney function was associated with a 2.6-fold increased risk of gout independent of comorbid conditions. These findings suggest that kidney function may be a risk factor for gout that is partially mediated by increased serum urate levels.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/kidney-function-and-the-risk-of-incident-gout-in-a-population-based-cohort-of-adults-atherosclerosis-risk-in-communities-study/