The Bidirectional Relationship between Chronic Kidney Disease and Hyperuricemia: Evidence from a Population-Based Prospective Cohort Study

Abstract

Background: Although several studies have examined the association between chronic kidney disease (CKD) and hyperuricemia (HUA), the direction of the association remains unclear. We aimed to investigate whether there was a bidirectional association between them.

Methods: The present study was conducted in three analyses. Analysis I included 25,433 participants free of HUA at baseline to evaluate the associations between CKD and estimated glomerular filtration rate (eGFR) with incident HUA. Analysis II had 28,422 participants free of CKD at baseline to analyze the relationships between HUA and serum uric acid (sUA) with new-onset CKD. Cox proportional hazards regression models were applied to evaluate the association involved in Analysis I and II. Analysis III included 31,028 participants with complete data and further dissected the bidirectional association between sUA and eGFR using cross-lag models.

Results: New-onset HUA and CKD were observed in the first round of the follow-up study among 1597 and 1212 participants, respectively. A significantly higher risk of HUA was observed in individuals with CKD compared to individuals without CKD (HR = 1.58, 95% CI: 1.28-1.95). The adjusted HRs (95% CIs) of HUA were 3.56 (2.50-5.05) for the participants in the group of eGFR less than 60 mL·min^-1·1.73 m^-2, 1.61 (1.42-1.83) for those in the group of eGFR between 60 and 90 mL·min^-1·1.73 m^-2, and 1.74 (1.42-2.14) for those in the group of eGFR more than 120 mL·min^-1·1.73 m^-2, compared with the group of eGFR between 90 and 120 mL·min^-1·1.73 m^-2. A higher risk of CKD was also observed in individuals with HUA compared to individuals without HUA (HR = 1.28, 95% CI: 1.12-1.47). Compared with the first quintile of sUA, the adjusted HR (95% CI) of CKD was 1.24 (1.01-1.51) for the participants in the fourth quantile. There was a bidirectional relationship between sUA and eGFR, with the path coefficients (ρ₁ = -0.024, p < 0.001) from baseline eGFR to follow-up sUA and the path coefficients (ρ₂ = -0.015, p = 0.002) from baseline sUA to follow-up eGFR.

Conclusions: The present study indicated that CKD and HUA were closely associated, and there was a bidirectional relationship between sUA and eGFR.

Keywords: chronic kidney disease; cohort study; cross lag panel model; estimated glomerular filtration rate; hyperuricemia.

Figure 1

Inclusion and exclusion criteria and flow chart of study participants. sUA, serum uric acid; eGFR, estimated glomerular filtration rate; HUA, hyperuricemia; CKD, chronic kidney disease.

Figure 2

Cumulative incidence of HUA and CKD. ((A): cumulative incidence of HUA in participants with CKD compared with non-CKD, (B): cumulative incidence of CKD in participants with HUA compared with non-HUA). HUA, hyperuricemia; CKD, chronic kidney disease.

Figure 3

Stratified associations between CKD and new-onset HUA by age, gender, BMI, smoking status, drinking status, and occupation. CKD, chronic kidney disease; HUA, hyperuricemia; BMI, body mass index; HR, hazard ratio; CI, confidence interval.

Figure 4

Stratified associations between HUA and new-onset CKD by age, gender, BMI, smoking status, drinking status, and occupation. HUA, hyperuricemia; CKD, chronic kidney disease; BMI, body mass index; HR, hazard ratio; CI, confidence interval.

Figure 5

Sub-analyses of the cross-lagged model of the association between sUA with eGFR, stratified by gender, age, and occupation.