EFFECT OF TREATMENT OF HEMODIALYSIS-PATIENTS WITH NIFEDIPINE ON METABOLISM AND FUNCTION OF POLYMORPHONUCLEAR

Both animals and patients with chronic renal failure have impaired pha gocytosis, which is most likely due to elevated basal levels of cytoso lic calcium {[Ca2+]i} and reduced adenosine triphosphate (ATP) content of their polymorphonuclear leukocytes (PMNLs), In animals with chroni c renal failure, these derangements are prevented or reversed by their treatment with a calcium channel blocker, This observation may have i mportant clinical implications if these drugs exert a similar effect i n humans with chronic renal failure, We examined the basal levels [Ca2 +]i, ATP content, and phagocytosis in PMNLs from 11 normal subjects, 1 8 hemodialysis patients (seven of whom had diabetes mellitus), and 18 hemodialysis patients treated with nifedipine (eight of whom had diabe tes mellitus), The basal levels of the [Ca2+]i content of the PMNLs in hemodialysis patients without nifedipine therapy were significantly ( P < 0.01) elevated (nondiabetic patients, 77 +/- 3.2 nmol/L; diabetic patients, 75 +/- 1.9 nmol/L) compared with normal values (42 +/- 0.9 n mol/L), Treatment with nifedipine was associated with the return of [C a2+]i toward normal values in both the nondiabetic (51 +/- 4.5 nmol/L) and diabetic (54 +/- 2.5 nmol/L) hemodialysis patients, The ATP conte nt of PMNLs from hemodialysis patient was significantly (P < 0.01) red uced compared with normal, and nifedipine therapy restored the ATP con tent to normal values, Phagocytosis was significantly (P < 0.01) impai red in hemodialysis patients (nondiabetic patients, 78 +/- 4.0 mu g oi l/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 mu g oil/10(7) PMNLs/ min), Nifedipine therapy returned the impaired phagocytosis toward nor mal (nondiabetic patients, 133 +/- 2.5 mu g oil/10(7) PMNLs/min; diabe tic patients, 129 +/- 6.4 mu g oil/10(7) PMNLs/min), The effect of nif edipine on the metabolism and function of PMNLs in hemodialysis patien ts occurred despite the elevated blood levels of parathyroid hormone, These data indicate that the calcium channel blocker interferes with t he parathyroid hormone-induced increase in [Ca2+]i of PMNLs from hemod ialysis patients and consequently improves their metabolism and functi on, If confirmed in other human cells, these observations would provid e for a rational therapeutic approach to ameliorate the signs and symp toms of uremia. (C) 1995 by the National Kidney Foundation, Inc.