Abstract
Background
Hyperuricemia has been proposed to be a risk factor for cardiovascular disease and chronic kidney disease. Since diabetes is often complicated by hypertension and hyperuricemia, efficient therapeutic strategy against these two complications is very important in diabetic treatment. It has been reported that the antihypertensive drug, irbesartan, inhibits the renal uric acid reabsorptive transporters, URAT1 and GLUT9; this result suggests that irbesartan decreases serum uric acid level (SUA).
Subjects and methods
A retrospective study of 107 patients with hypertension and diabetes was performed to analyze the effects of irbesartan on blood pressure, estimated glomerular filtration rate (eGFR), and SUA. The follow-up period was 6–12 months. Seventy percent of the patients were diagnosed with diabetic nephropathy stage II–IV. We excluded patients treated with drugs that influenced SUA. The multiple logistic regression analysis was introduced to identify the relative factors for SUA decline. The time-dependent SUA changes were examined in a mixed-linear model.
Results
Irbesartan reduced blood pressure significantly after 1, 6, and 12 months’ treatment. No subject showed significant change in eGFR from baseline level throughout the period. The multiple logistic regression analysis revealed that SUA baseline significantly influenced SUA decline after 6–12 months. In patients whose SUA baseline was ≥5.9 mg/dL, the SUA was significantly decreased from 6.6±0.16 mg/dL to 6.2±0.16 mg/dL (P=0.010), after 12 months’ irbesartan treatment. In the SUA baseline <5.9 mg/dL group, the SUA did not show significant change over the monitoring period.
Conclusion
Our results demonstrate that irbesartan reduces the risk of hyperuricemia. No decline in renal function was observed after the initiation of irbesartan treatment. The present report determines the criteria of SUA baseline for introducing an antihyperuricemic effect using irbesartan. Its antihypertensive effect coupled with SUA decline would be effective for the treatment of hypertension complicated by hyperuricemia.
Supplementary material
Figure S1 ROC analysis of SUA baseline values.
Notes: Decrease of SUA over 12 months was set to a positive influence and specificity and sensitivity of SUA baseline value were plotted. The cutoff point of SUA when the sum of specificity and sensitivity is maximized was 5.9 mg/dL (specificity, 0.860; sensitivity, 0.414). Area under the curve: 0.6540 and 95% CI: 0.5510–0.7569.
Abbreviations: CI, confidence interval; ROC, receiver operating characteristic; SUA, serum uric acid.
Table S1 SUA changes of the ARBs–IRB switch group by the pre-treatment of ARBs
Table S2 The baseline values of the subjects classified with the stages of diabetic nephropathy
Table S3 SUA changes from baseline after 6–12 months of irbesartan treatment
Table S4 Logistic regression analysis of the factors associated with SUA decline
Disclosure
This work was funded by Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan. The authors report no other conflicts of interest in this work.