Increased Uric Acid Promotes Decline of the Renal Function in Hypertensive Patients: A 10-year Observational Study

Abstract

Objective Uric acid (UA) has shown to be a causal risk factor for the development and progression of renal disease. The aim of this study was to investigate the relationship between changes in the level of UA and trends in the renal function among hypertensive patients during a 10-year observation period. Methods The subjects included 104 hypertensive outpatients (60 women and 44 men, mean age 60±9 (SD) years at the first visit) who had undergone at least five instances of successful 24-hour home urine collection, with the first examination completed between 1998 and 2000 and the last examination completed between 2008 and 2010. Results The estimated glomerular filtration rate (eGFR) significantly decreased over the 10.4-year observation period, with an average change in eGFR of -0.66/mL/min/year. The uric acid clearance at the last examination was significantly lower than that observed at the first visit, while there were no significant differences in the serum UA levels during this period. The change in serum UA exhibited a significant negative correlation with the change in eGFR (r=-0.34, p<0.01). The patients whose UA level decreased more than 0.5 mg/ dL during the observation period demonstrated significantly smaller declines in eGFR compared to those whose UA level increased more than 0.5 mg/dL. In the multivariate analysis, the change in serum UA and the average urinary salt excretion during the observation period were found to be significantly associated with the change in eGFR, independent of age, sex, BP changes or an increased number of antihypertensive drugs. Conclusion Based on the findings observed over a 10-year observation period, increased UA is suggested to promote decline of the renal function in hypertensive patients. Controlling the level of UA as well as intensively restricting salt intake is required in order to preserve the renal function.

Renal function in relation to sodium intake: a quantitative review of the literature

“…Of the 247 full-text papers we read, 36 studies, including 73,482 participants, fulfilled the inclusion criteria and provided enough data to be included in at least one meta-analysis. Of these, 11 were crosssectional studies, [10][11][12][13][14][15][16][17][18][19][20] 5 were longitudinal cohort studies, [21][22][23][24][25] and 20 were intervention trials. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The weighted means of sodium intake were similar among studies in which consumption was assessed by means of spot urine samples 13,16,17,19 (mean, 156 mmol/d; range, 96-209 mmol/ d) 16,17 and 24-hour urine collections 10,11,14,15,…”

“…Seven studies were population based, 10,12,13,[15][16][17][18] and 2 had been conducted in diabetic patients 14,19 or hypertensive subjects. 11,20 Sodium intake was estimated from spot urine samples in 4 studies, 13,16,17,19 from 24-hour urine collections in 5, 10,11,14,15,20 from a food frequency questionnaire in 1, 18 and from dietary recall in 1. 12 Of the 11 cross-sectional studies, 8 were focused on albumin excretion 12,14,15,19 or the urinary albumin-to-creatinine ratio 13,16-18 as a dichotomous [12][13][14][15][17][18][19] or continuous outcome.…”

“…16 Estimated GFR was reported in 6 cross-sectional studies. [10][11][12][13][14]20 The quality assessment of each study, according to the method proposed by the Agency for Healthcare Research and Quality, 46,47 is illustrated in Supplementary Table S1. All but 2 studies 14,15 had a high risk of bias for 1 or more items in the Agency for Healthcare Research and Quality checklist.…”

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

“…1,2 Recently, evidence has accumulated showing that HU has a role in the pathogenesis of hypertension, metabolic syndrome, cardiovascular disease and the progression of CKD, indicating the necessity for treatment even in the absence of symptoms of gouty arthritis. [1][2][3][4] However, a major challenge in treating patients with HU is the occurrence of drug-related adverse effects that are often augmented in the presence of kidney dysfunction. 5 Allopurinol is primarily excreted in the urine as the metabolite oxypurinol, which can accumulate and cause toxicity in patients with kidney dysfunction.…”

Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study

“…When kidney disease is present, decreased glomerular filtration may cause a rise in serum uric acid and provide additional risk for progressive decline in kidney function. Large, longitudinal studies confirm that hyperuricemia predicts the development of CKD in adults as well as the deterioration of kidney function in CKD patients [2–4]. …”