Impaired phagocytosis in chronic renal failure is mediated by secondary hyperparathyroidism

Impaired phagocytosis in chronic renal failure is mediated by secondary hyperparathyroidism. Patients with chronic renal failure (CRF) display impaired phagocytosis by the polymorphonuclear leucocytes (PMNL), and these cells have elevated basal levels of cytosolic calcium ([Ca2+]i) and reduced ATP content. It has been suggested that these changes in PMNL metabolism and function are mediated by the state of secondary hyperparathyroidism of CRF. To examine the role of excess PTH in these derangements of PMNL, we studied [Ca2+]i, ATP and phagocytic ability of PMNL in five groups of rats including: CRF, CRF normocalcemic parathyroidectomized (CRF-PTX), CRF and normal animals treated with verapamil (CRF-V), and normal-V, respectively. The level of [Ca2+]i in the PMNL of CRF rats (149 ± 2.7 nM) was significantly (P < 0.01) higher and the ATP content (4.2 ± 0.17 nmol/5 × 106 PMNL) significantly lower (P < 0.01) than in normal (108 ± 2.4 nM; 9.5 ± 0.15 nmol/5 × 106 PMNL), CRF-PTX (103 ± 2.9 nM; 9.2 ± 0.19 nmol/5 × 106 PMNL), CRF-V (107 ± 2.2 nM; 9.0 ± 0.2 nmol/5 × 106 PMNL) and normal-V (106 ± 1.8 nM; 9.2 ± 0.2 nmol/5 × 106 PMNL), despite sustained elevation in blood PTH in the CRF-V group. Phagocytosis was significantly (P < 0.01) impaired in CRF animals (5.6 ± 0.25 µg oil/107 PMNL/min) but was normal in CRF-PTX (9.3 ± 0.21 µg oil/107 PMNL/min) and CRF-V (9.5 ± 0.22 µg oil/107 PMNL/min) rats. The values of phagocytosis in normal and normal-V rats were 9.6 ± 44 and 9.6 ± 0.18 µg oil/107 PMNL/min, respectively. The data indicate that excess PTH in CRF is a major factor underlying the metabolic and functional derangements in PMNL and that these abnormalities are prevented by either reducing the blood levels of PTH or by blocking its action on PMNL by verapamil