Involvement of Serum Uric Acid in Essential Hypertension, Progressive Proteinuria and Impairment in Renal Function among Type-2 Diabetic Patients

Abstract

Type-2 diabetes is a metabolic disorder with vast complications. Uric acid (UA) was recently discovered as a risk biomarker for the development of type-2 diabetes. Several studies have found a significant association of Hyperuricemia with Hypertension (HTN), renal complications and cardiovascular disease. However, no study has found an association of hyperuricemia with the development of essential hypertension, nephropathy and Diabetic Kidney Disease (DKD) among type-2 diabetics. Moreover, in the past no study has found cut off points for serum uric acids for the development of DKD/CKD among diabetics with sensitivity and specificity, which was achieved in the current study. We collected 10,300 type-2 diabetics data for more than 15 years in a cross sectional retrospective manner. 17% demonstrated hyperuricemia while 16% were found to be DKD. Significant correlations were found between serum UA and other variables (serum creatinine, systolic and diastolic BP, microalbumin and spot urine protein). Levels of UA were observed to be elevated among patients with HTN, nephropathy and DKD (p<0.0001). Similarly, serum creatinine, systolic and diastolic BP, microalbuminuria and spot urine protein were higher for the group with hyperuricemia (p<0.0001). Pearson’s (χ²) and logistic regression with odds ratio demonstrated that hyperuricemia was significantly associated with HTN (odds ratio 2.5; 95% CI 1.8 to 23.4; p<0.0001). Similarly, hyperuricemia was significantly associated with the development of nephropathy and DKD/CKD; odds ratio 2.1 (95% CI 1.46 to 2.8; p<0.0001) and 27.3 (95% CI 14 to 53; p<0.0001), respectively. Moreover, regression model between serum UA and serum creatinine was also significantly associated with each other and proves our hypothesis that UA linearly causes an increase in the blood creatinine with the following relationship : Serum creatinine=0.221 + [0.154 × serum UA]. ROC for DKD and serum UA demonstrated that with AUC of 0.98 (95% CI 0.961 to 0.986), UA level of 6.8 was 91% sensitive and 79% specific for the development and significant association with DKD/CKD (p<0.0001). This is the first study of its kind that has demonstrated significant associations of UA with HTN, nephropathy and DKD. It is the time to revise the normal levels of UA among type-2 diabetics and to initiate regular screening for hyperuricemia to prevent further diabetes complications.