Abstract
BackgroundSome observational studies have shown the relationships between hyperuricemia and chronic kidney disease (CKD); however, the threshold of serum uric acid (SUA) for deterioration of kidney function and the association between SUA and kidney injury by baseline kidney function remains unclear. This study aimed to clarify the relationships between SUA and reduced kidney function.MethodsWe analyzed a historical cohort of male Japanese individuals who underwent medical checkup between 1998 and 2007. Participants with baseline data and who were followed up for at least one year were included and stratified according to baseline kidney function. Kidney function was classified as normal [estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m2] or mildly reduced (eGFR 60–89 ml/min/1.73 m2). The outcome measured was kidney impairment defined as a decrease in eGFR to < 60 ml/min/1.73 m2. Associations between SUA and risk for outcome and eGFR slopes were assessed.ResultsA total of 41632 subjects with mean age 45.4 years were included. During a mean follow-up of four years, 3186 (7.6%) subjects developed kidney dysfunction. Subjects with SUA ≥ 6.0 mg/dL had a significantly increased risk for kidney impairment compared with subjects with SUA of 4–4.9 mg/dL. SUA threshold levels were different according to baseline kidney function; SUA ≥ 7.0 and ≥ 6.0 mg/dL for normal and mildly reduced kidney function, respectively. Approximately the same trends were observed for eGFR slopes.ConclusionIn the general population, hyperuricemia appears to be a risk factor for kidney impairment in males. For participants with mild kidney dysfunction, even a slight elevation of SUA can be a risk factor.
Highlights
Chronic kidney disease (CKD) is a known risk factor, for end-stage kidney diseases, and for cardiovascular mortality and all-cause mortality.[1]
Many factors, including low estimated glomerular filtration rate, elevated proteinuria, diabetes, and hypertension have been identified as risk factors for the development and progression of chronic kidney disease (CKD).[1]
Serum uric acid (SUA) was proposed as a potential risk factor for new onset of kidney disease in the general population [3, 4] From the pathophysiological perspective, hyperuricemia results in the progression of renal dysfunction through preglomerular arteriolopathy characterized by hyalinosis and wall thickening [5]; a meta-analysis suggested that allopurinol therapy retarded the progression of CKD.[6]
Summary
Chronic kidney disease (CKD) is a known risk factor, for end-stage kidney diseases, and for cardiovascular mortality and all-cause mortality.[1]. A study on type 1 diabetic patients demonstrated that risks for CKD stage 3 linearly increased with SUA levels across the normal range including SUA < 3.0 mg/dL.[8] For all-cause mortality, J-shape relationships between uric acid levels and risks were observed in a previous study.[9]. Some observational studies have shown the relationships between hyperuricemia and chronic kidney disease (CKD); the threshold of serum uric acid (SUA) for deterioration of kidney function and the association between SUA and kidney injury by baseline kidney function remains unclear. This study aimed to clarify the relationships between SUA and reduced kidney function
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