title: Effect of treatment of hemodialysis patients with nifedipine on metabolism and function of polymorphonuclear leukocytes.
abstract: 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 micrograms oil/10(7) PMNLs/min; diabetic patients, 77 +/- 4.8 micrograms oil/10(7) PMNLs/min). Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 +/- 2.5 micrograms oil/10(7) PMNLs/min; diabetic patients, 129 +/- 6.4 micrograms oil/10(7) PMNLs/min).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles.
authors.forename: J M
authors.initials: JM
authors.lastname: Alexiewicz
authors.forename: M
authors.initials: M
authors.lastname: Smogorzewski
authors.forename: M
authors.initials: M
authors.lastname: Klin
authors.forename: M
authors.initials: M
authors.lastname: Akmal
authors.forename: S G
authors.initials: SG
authors.lastname: Massry
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000818:Animals; D002118:Calcium / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood / Q000628:therapy; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D006435:Renal Dialysis
chemical_list: D010281:Parathyroid Hormone; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium