The Impact of Urinary Uromodulin (Tamm-Horsfall Protein) on Renal Function and Haemodynamic Factors in a Community Sample with a High Prevalence of Hypertension

Abstract

Populations of African ancestry have a high prevalence of primary hypertension and its comorbidities. As they primarily exhibit a volume-dependent form of hypertension, the role of nephron components needs to be explored. Uromodulin is a potential biomarker for renal function and tubular reserve; however, its relationship with renal function, haemodynamic parameters, and hypertension in a population of African ancestry is unknown. I therefore explored the relationship between urinary uromodulin (uUMOD) concentration and renal as well as hemodynamic parameters in an African community with a high prevalence of volume-dependent hypertension. Haemodynamics (central pressures [SphygmoCor], echocardiographic aortic velocity and diameter in the outflow tract), uUMOD concentrations (ELISA assay), renal function (creatinine clearance from 24-hour urine [n = 370]) were determined in a community of African ancestry (n = 397). No relationships between uUMOD concentrations and renal function, age, BMI, BP or hypertension were noted. However, uUMOD concentrations were higher in females than males, even after adjusting for confounders (P = 0.0007). An inverse relationship was observed between stroke volume (SV) and uUMOD (P = 0.0023). This inverse relationship was independent of confounders and present in hypertensives (P= 0.007) but not normotensives (P = 0.43). Hypertensives had a higher SV than normotensives (P = 0.047). In a community sample with a high prevalence of volume-dependent primary hypertension, uUMOD was inversely related to SV, particularly in hypertensives. Although uUMOD is not a biomarker for renal function in this population, these data suggest the need to investigate mechanisms linking uUMOD to SV to assist in identifying novel pathways to better treat volume-dependent hypertension.