NIFEDIPINE REVERSES THE ABNORMALITIES IN [CA2-CELLS FROM DIALYSIS PATIENTS(]I AND PROLIFERATION OF B)

Both animals and patients with chronic renal failure have impaired B c ell function due, in part, to elevated levels of cytosolic calcium ([C a2+]i). Treatment of HD patients with nifedipine has normalized [Ca2+] i of their polymorphonuclear leukocytes (PMNL) and caused marked impro vement in the phagocytic property of the PMNL. This observation may ha ve important clinical implications if this drug exerts a similar effec t on other cells such as B cells. We examined [Ca2+]i, proliferation o f B cells in response to mitogen, the magnitude of the PTH-induced inh ibition of B cell proliferation, and the ATP content of mononuclear ce lls in 11 hemodialysis patients treated with nifedipine, 12 patients w ithout nifedipine therapy and 11 normal subjects. Serum levels of Ige was also measured in the two groups of patients. There were no signifi cant 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 t herapy compared to those without nifedipine treatment have significant ly (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 v s. 0.68+/-0.04 nmoles/10(6) cells), impaired proliferation (5.8+/-0.31 x10(3) cpm vs. 9.8+/-0.38x10(3) cpm) and smaller inhibition of B cell proliferation by PTH compared to those treated with nifedipine. The va lues in the patients treated with nifedipine were still modestly but s ignificantly different than in normal subjects. The serum IgG levels o f the patients without nifedipine therapy (1210+/-71 mg/dl) were signi ficantly lower than those of the patients treated with nifedipine (159 4+/-81 mg/dl). Thus, the treatment of hemodialysis patients with nifed ipine produced marked and significant improvement in the metabolic and functional parameters of B cells despite no changes in blood levels o f PTH. These data indicate that the calcium channel blocker, nifedipin e, interferes with PTH-induced rise in [Ca2+]i of B cells of hemodialy sis 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.