Altered circadian hemodynamic and renal function in cirrhosis

Abstract

Background: Given that alterations in systemic hemodynamics have a profound influence on renal function in patients with cirrhosis, it is surprising that circadian variations in blood pressure (BP) and renal electrolyte excretion have scarcely been studied. Our aims were to define the relationship of 24-h ambulatory BP changes with renal tubular function and to determine the influence of endotoxemia on BP and urinary parameters. Methods: Forty healthy controls served as a comparator to 20 cirrhotic patients. They underwent 24-h ambulatory BP monitoring and 24-h urine collection. Results: Subjects with cirrhosis demonstrated significant diurnal variations in urinary excretion of sodium (57.7 mmol/min day versus 87 mmol/min night) and creatinine (826 mg/min day versus 1202 mg/min night). Increasing severity of cirrhosis was associated with a progressive reduction in ambulatory awake systolic (P-trend = 0.015), diastolic (P-trend < 0.001) and mean BP (P-trend < 0.001). In patients with cirrhosis, the magnitude of change in BP from awake to sleep state was blunted for systolic BP (5% reduction, P = 0.039) and pulse rate (2% reduction, P < 0.001). The amplitude of variation in pulse rate was blunted with increasing severity of cirrhosis (controls 6.5, Child-Pugh Class A 5.3, Child B 3.4, Child C 1.2, P = 0.03) and the acrophase was right-shifted with increasing severity of cirrhosis. Compared with sleep state, during the awake state, endotoxin was associated with less sodium excretion and a lower systolic BP. Compared with the awake state, endotoxin was associated with a higher sleeping pulse rate (P < 0.001). Conclusions: Patients with cirrhosis have altered diurnal profiles in renal tubular function and blood pressure that appear to be related to endotoxemia. Determining whether endotoxemia is causally related to these perturbations will require interventional studies.