Serum uric acid and the incidence of CKD and hypertension

Abstract

BackgroundUric acid (UA) levels correlate positively with the prevalence of chronic kidney disease (CKD) and/or hypertension. We tested the hypothesis that UA may also have a link to a new incidence of CKD and hypertension.MethodsStudy design is a cohort study and the predictor is UA levels. Of the 15,470 screened cases, 8223 participants without CKD were eligible for the analysis of the incidence of CKD. Among these CKD candidates, 7569 participants were eligible for the analysis of the new development of hypertension. The observation period was 4 years.ResultsRelationship of UA with new cases of CKD. Higher UA levels had a closer association with the new development of CKD; 1.1 % (UA < 5 mg/dL), 1.5 % (5.0–5.9 mg/dL), 1.7 % (6.0–6.9 mg/dL), and 3.4 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the CKD development were eGFR [Hazard Ratio (HR) 0.816, 95 % confidence intervals (CI) 0.791–0.840] and male gender (HR 0.562, 95 % CI 0.322–0.982). UA levels and new development of hypertension. Higher UA levels had a closer association with the new development of hypertension; 5.0 % (UA < 5 mg/dL), 8.9 % (5.0–5.9 mg/dL), 10.6 % (6.0–6.9 mg/dL), and 11.8 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the hypertension development were BMI (HR 1.190, 95 % CI 1.155–1.226), age (HR 1.021, 95 % CI 1.010–1.032), HDL-cholesterol (HR 1.013, 95 % CI 1.007–1.019), male gender (HR 1.791, 95 % CI 1.338–2.395), UA level (HR 1.112, 95 % CI 1.024–1.207), and eGFR (HR 1008, 95 % CI 1.002–1.013). Furthermore, the logistic analysis showed that the odds ratio (OR) to estimate hypertension in the high UA group (UA ≧ 7 mg/dL; OR 1.33, 95 % CI 1.01–1.80) was greater than that in the low UA group (UA < 5 mg/dL). Kaplan–Meier analysis also confirmed the finding that the higher the UA levels the greater the hypertension development (p < 0.001 by the Log-rank test and Cox proportional hazard analysis).ConclusionHigh UA levels are associated with the new development of hypertension, but not with the incidence of CKD.

Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years: a Propensity Score Analysis

“…Hyperuricemia has been among such risk factors because preceding investigations showed the positive results whereas not in other observational studies as reviewed in the recent literature [2]. The independent significance of serum uric acid (SUA) was indeed abolished when adjusted for the existence of kidney dysfunction [3][4][5][6]. The inconsistency may also be attributed to the test cohorts which differed in the grades of CKD stages, the presence or absence of other CKD risk factors, and additional comorbidities such as diabetes.…”

Time to target uric acid to retard CKD progression

“…Likewise, post hoc analysis of the Modification of Diet in Renal Disease (MDRD) study enrolling 838 patients with stage 3-4 CKD showed that hyperuricemia was associated with increased risk of all-cause mortality and cardiovascular disease mortality, but not with kidney failure [64]. In addition, certain Japanese cohorts did not show the independent significance of the effect of SUA on the incidence of CKD over 4-year observation period [10,[65][66][67] (Table 1).…”

“…This finding is compatible with the hypothesis that the link between hyperuricemia and CKD progression is causal in nature. However, there are some observational studies which showed no significant relationship between hyperuricemia and progression of CKD [63][64][65][66]. A prospective analysis of the Mild to Moderate Kidney Disease study enrolling 177 patients with non-diabetic CKD revealed that hyperuricemia predicts CKD progression only when the analysis was not adjusted for baseline kidney function parameters.…”

Management of Gout and Hyperuricemia in CKD

“…103–126 In a Japanese study of 48,177 subjects, SUA ≥6 mg/dL was an independent predictor of end-stage kidney disease in women, 104 and an increase in SUA over 10 years was an independent risk factor for eGFR decline. 115 Similarly, higher baseline SUA was also associated with kidney function decline in 16,186 patients with hyperuricemia enrolled in the Kaiser Permanente Southern California Health Plan.…”

“…107,108 On the other hand, several observational studies have failed to identify a significant relation of SUA to CKD. 121–126 For example, in the Modification of Diet in Renal Disease Study, which followed 840 subjects with eGFR between 13 and 55 mL/min for up to 3.5 years, baseline SUA was not associated with CKD progression. 121 The Cardiovascular Health Study, a prospective community-based cohort of 4610 subjects followed for a mean of 6.6 years, found no association between hyperuricemia and incident CKD, although there was a modest association with CKD progression.…”