URINARY UROMODULIN DIRECTLY AND INDIRECTLY CONTRIBUTE TO LEFT VENTRICULAR HYPERTROPHY IN MIDDLE-AGED PREHYPERTENSIVES

Abstract

Objective: Recent GWAS studies found uromodulin gene polymorphisms to be associated with hypertension and atrial remodeling. This study analysed urinary uromodulin (UM), sodium excretion, blood pressure (BP) and echocardiogram in a group of middle-aged non-treated subjects. Design and method: We included 326 apparently healthy subjects (mean age 37). According to JNC-7 optimal BP (OBP), prehypertension (PHT) and hypertension (HT) were diagnosed in 103 subjects (72% m), 143 subjects (43% m), and 80 subjects (38% m), respectively. Fasting blood and urine samples were obtained and office and ambulatory BP were measured in all subjects. Sodium excretion was determined from the 24h-urine specimens in a subgroup of 175 subjects. All echocardiograms were performed by the same co-author. UM an alpha1 microglobulin (A1 M) from the morning spot urine sample were determined by ELISA (Cobas Roche, BioVendor) and Siemens Dade Behring BN II Nephelometer (Siemens, Germany), and were corrected to urine creatinine, respectively. Results: Nonsignificant trend to higher nonindexed UM (nUM, mg/ml) were found in HT/PHT compared to OBP, and opposite trend was observed for indexed UM (iUM, mg/g creatinine). nUM and iUM correlated positively with ABPM parameters in OBP group, but negatively in HT. In OBP and PHT groups iUM correlated positively with fractional sodium excretion (FENa) (Rho 0.272; P = 0.01) and FENa (Rho 0.208; P = 0.02), respectively, as well as with A1mCR (Rho 0.317; P < 0.001) and (Rho 0.347; P < 0.001), respectively. There were significant differences in interventricular septum diameter (IVSd) between first and second/ third terciles of nUM in the OBP group (P = 0.02) and first and third terciles in the PHT group (P = 0.04). nUM correlated positively with left ventricule mass (LVM) (Rho 0.221; P = 0.01) and IVSd (Rho 0.191; P = 0.03) in the whole group. In the PHT group nUM correlated positively with IVSd (Rho 0.399; P < 0.001). Conclusions: Positive association of UM with LVM suggests effect of uromodulin on left ventricule remodeling in middle-aged non-treated subjects.