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

Both animals and patients with chronic renal failure have impaired phagocytosis, which is most likely due to elevated basal levels of cytosolic calcium {[Ca2+]i} and reduced adenosine triphosphate (ATP) content of their polymorphonuclear leukocytes (PMNLs), In animals with chronic renal failure, these derangements are prevented or reversed by their treatment with a calcium channel blocker, This observation may have important clinical implications if these drugs exert a similar effect in humans with chronic renal failure, We examined the basal levels [Ca2+]i, ATP content, and phagocytosis in PMNLs from 11 normal subjects, 18 hemodialysis patients (seven of whom had diabetes mellitus), and 18 hemodialysis patients treated with nifedipine (eight of whom had diabetes 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 nmol/L), Treatment with nifedipine was associated with the return of [Ca2+]i toward normal values in both the nondiabetic (51 +/- 4.5 nmol/L) and diabetic (54 +/- 2.5 nmol/L) hemodialysis patients, The ATP content of PMNLs from hemodialysis patient was significantly (P < 0.01) reduced compared with normal, and nifedipine therapy restored the ATP content to normal values, Phagocytosis was significantly (P < 0.01) impaired in hemodialysis patients (nondiabetic patients, 78 +/- 4.0 mu g oil/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 mu g oil/10(7) PMNLs/min), Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 +/- 2.5 mu g oil/10(7) PMNLs/min; diabetic patients, 129 +/- 6.4 mu g oil/10(7) PMNLs/min), The effect of nifedipine on the metabolism and function of PMNLs in hemodialysis patients occurred despite the elevated blood levels of parathyroid hormone, These data indicate that the calcium channel blocker interferes with the parathyroid hormone-induced increase in [Ca2+]i of PMNLs from hemodialysis patients and consequently improves their metabolism and function, If confirmed in other human cells, these observations would provide for a rational therapeutic approach to ameliorate the signs and symptoms of uremia. (C) 1995 by the National Kidney Foundation, Inc.