Chronic renal failure-induced changes in serum and urine bile acid profiles

Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be accompanied by alterations in the BA balance. The aim of the present work was to evaluate the changes in BA serum concentrations and renal excretion in patients with different stage of CRF or after kidney transplantation and to elucidate whether these might play a role in the development of pruritus, a common symptom in this disease. This study was carried out on 125 patients. None of them had a history or signs of hepatobiliary malfunction. They belonged either to a control group (N = 31) or to one of the three following CRF groups: patients maintained only on a low-protein diet (diet group, N = 23); the same, together with periodic sessions of hemodialysis (dialysis group, N = 42); and patients who had undergone a kidney transplant more than 1 and less than 2 years before (transplanted group, N = 29). Serum and urine BA concentrations were assayed by gas chromatography-mass spectrometry. Pruritus was quantified by means of a questionnaire answered at the time of sample collection. A marked hypercholanemia together with a reduction in BA output into urine and profound alterations in the profiles of these compounds in both serum and urine in patients with CRF were observed. The levels of total BAs in serum, but not the proportions of molecular species, were corrected by hemodialysis. By contrast, kidney transplant reversed BA serum patterns to normality but, due to immunosuppressive therapy with cyclosporin A, total serum BA concentrations were consistently elevated in this group. Pruritus was more frequent in patients with impaired kidney function and hypercholanemia, although no significant correlation between the degree of this symptom and the magnitude of the serum concentrations of total or individual BAs were found. By contrast, in spite of hypercholanemia, once renal function had been restored by kidney transplantation, none of the patients suffered from pruritus. These results suggest that the kidney plays an important role in determining the serum BA pool size and composition and that hypercholanemia may be a contributing factor, but not the only one, determining the development of pruritus in patients with CRF.