Effect of Treatment of Hemodialysis Patients With Nifedipine on Metabolism and Function of Polymorphonuclear Leukocytes Jadwiga M. Alexiewicz, MD, Miroslaw Smogorzewski, MD, Mariusz Klin, MD, Mohammad Akmal, MD, and Shaul G. Massty, MD l Both animals and patients with chronic renal failure have impaired phagocytosis, which is most likely due to elevated basal levels of cytosolic calcium ([Ca”]i) and reduced adenosine triphosphate (Alp) 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 [Ca*+]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 [Ca*‘]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 [Ca”]i toward normal values in both the nondiabetic (51 2 4.5 nmoML) and diabetic (54k2.5 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 pg oil/lO’ PMNLs/min; diabetic patients, 77 + 4.8 pg oil/lo7 PMNLs/min). Nifedipine therapy returned the impaired phagocytosis toward normal (nondiabetic patients, 133 2 2.5 pg oil/IO7 PMNLs/min; diabetic patients, 129 2 6.4 pg oil/lO’ 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 [Ca*‘]i of PMNLs from hemodialysis patients and consequently improves their me- tabolism and function. If confirmed in other human cells, these observations would provide for a rational therapeu- tic approach to ameliorate the signs and symptoms of uremia. 0 1995 by the National Kidney Foundation, Inc. INDEX WORDS: Diabetes mellitus; parathyroid hormone; phagocytosis; cytosolic calcium; adenosine triphosphate. A MULTITUDE of studies, which were re- viewed by Vanholder and Ringoir,’ have demonstrated that phagocytosis by polymorpho- nuclear leukocytes (PMNLs) of patients with end-stage renal failure is impaired. The mecha- nisms responsible for this abnormality are multi- factorial and may include uremic toxins, state of secondary hyperparathyroidism biocompatibil- ity, anemia, and iron overload.’ We previously have shown that a parathyroid hormone (PTH)-induced elevation in cytosolic calcium ([Ca”‘]i) could contribute to the im- paired phagocytosis in hemodialysis patients.2 Studies in rats have confirmed this proposition, From the Division of Nephrology,Department ofMedicine, University of Southern California School of Medicine, L.os Angeles, CA. Received August 31, 1994; accepted in revised form No- vember 8, 1994. Supported by grant no. DK-29955 from the National Insti- tute of Diabetes and Digestive and Kidney Diseases. Address reprint requests to Shaul G. Massry, MD, Division of Nephrology, Department of Medicine, LAC-USC Medical Center, 2025 Zonal Ave, GNH-4250, IAS Angeles, CA 90033. 0 1995 by the National Kidney Foundation, Inc. 0272~6386/95/2503-0012$3.00/O and indeed, PMNLs of rats with chronic renal failure (CRF) have elevated [Ca2’]i and display impaired phagocytosis.3 These derangements were prevented by prior parathyroidectomy of these CRF animals. Administration of calcium channel blockers to CRF animals from day 1 of CRF prevented both the increase in the [Ca2’]i of PMNLs and the impairment in their phagocytosis.3 In addition, treatment of hemodialysis patients with vera- pamil normalized the [Ca*‘]i of their PMNLs and reversed the derangements in their glucose metabolism.4*5 It is therefore possible that admin- istration of a calcium channel blocker to hemodi- alysis patients could improve phagocytosis as well. Diabetes mellitus also is associated with im- paired phagocytosis,6 and it is not well docu- mented whether the degree of impairment in phagocytosis in hemodialysis patients with and without diabetes mellitus is different. The present study examined [Ca”]i, adeno- sine triphosphate (ATP) content, and phagocyto- sis by PMNLs from normal subjects and from hemodialysis patients with and without diabetes mellitus who had or had not received therapy with nifedipine. 440 American Journal of Kidney Diseases, Vol 25, No 3 (March), 1995: pp 440-444