Renal Functional Reserve Is Related to the Nondipping Phenotype and to the Exercise Heart Rate Response in Patients with Essential Hypertension and Preserved Renal Function

Abstract

Background: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). Objective: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. Methods: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m² were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR <30 mL/min/1.73 m² and 15 had a RFR above this cutoff. A nondipping pattern of 24-h BP was significantly more frequent in patients with low RFR (57.1 vs. 25.0%, p < 0.05 for systolic BP and 52.3 vs. 10.0%, p < 0.02 for diastolic BP). Moreover, patients with lower RFR values showed a blunted heart rate (HR) response to exercise during treadmill test (r = 0.439, p < 0.05). None of the echocardiographic parameters differed between the two groups of patients. Conclusions: In hypertensive patients with preserved GFR, reduced RFR is related to nondipping BP phenotype as well as to attenuated exercise HR response. Overactivity of the SNS may be a common pathway. Since loss of RFR may represent a risk factor for acute or chronic kidney injury, hypertensive patients with blunted RFR might need a more careful renal follow-up.