Nifedipine reverses the abnormalities in [Ca2+]i and proliferation of B cells from dialysis patients.
Both animals and patients with chronic renal failure have impaired B cell function due, in part, to elevated levels of cytosolic calcium ([Ca2+]i). Treatment of HD patients with nifedipine has normalized [Ca2+]i of their polymorphonuclear leukocytes (PMNL) and caused marked improvement in the phagocytic property of the PMNL. This observation may have important clinical implications if this drug exerts a similar effect on other cells such as B cells. We examined [Ca2+]i, proliferation of B cells in response to mitogen, the magnitude of the PTH-induced inhibition of B cell proliferation, and the ATP content of mononuclear cells in 11 hemodialysis patients treated with nifedipine, 12 patients without nifedipine therapy and 11 normal subjects. Serum levels of IgG was also measured in the two groups of patients. There were no significant differences in the age, duration of hemodialysis, blood levels of calcium, phosphorus or PTH (571 +/- 193 vs. 484 +/- 127 pg/ml) among the two groups of patients. The hemodialysis patients without nifedipine therapy compared to those without nifedipine treatment have significantly (P < 0.01) higher levels of [Ca2+]i (120 +/- 1.9 nM vs. 94 +/- 2.2 nM), lower ATP content of mononuclear cells (0.45 +/- 0.06 nmol/10(6) cells vs. 0.68 +/- 0.04 nmoles/10(6) cells), impaired proliferation (5.8 +/- 0.31 x 10(3) cpm vs. 9.8 +/- 0.38 x 10(3) cpm) and smaller inhibition of B cell proliferation by PTH compared to those treated with nifedipine. The values in the patients treated with nifedipine were still modestly but significantly different than in normal subjects. The serum IgG levels of the patients without nifedipine therapy (1210 +/- 71 mg/dl) were significantly lower than those of the patients treated with nifedipine (1594 +/- 81 mg/dl). Thus, the treatment of hemodialysis patients with nifedipine produced marked and significant improvement in the metabolic and functional parameters of B cells despite no changes in blood levels of PTH. These data indicate that the calcium channel blocker, nifedipine, interferes with PTH-induced rise in [Ca2+]i of B cells of hemodialysis patients and consequently improves their metabolism and function. These observations if confirmed in other human cells may provide for a rational therapeutic approach to ameliorate the signs and symptoms of uremia.
Alexiewicz
J M
JM
Division of Nephrology, University of Southern California, School of Medicine, Los Angeles, USA.
Smogorzewski
M
M
Akmal
M
M
Klin
M
M
Massry
S G
SG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003956:Dialysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology
D007074:Immunoglobulin G; D008934:Mitogens; D010281:Parathyroid Hormone; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium