Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients.
Studies in the uremic rat indicate that insulin resistance and glucose intolerance leading to dyslipidemia are associated with a hyperparathyroid-induced increase in cytosolic calcium ([Ca++i]). These alterations are reversed with verapamil, but recur after discontinuation of the drug, suggesting that increased [Ca++i] is responsible for the metabolic derangement. To our knowledge, no similar studies have been conducted in humans. We retrospectively examined, over 12-year period, the effects of factors that lower [Ca++i] on total serum cholesterol and triglycerides in 176 peritoneal dialysis (PD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on the morbidity and mortality outcome related to atherosclerotic vascular disease. Diabetic patients were excluded from the study, because their dyslipidemia and vascular disease are mediated via a different mechanism. The patients were classified into four groups. Group I [high parathyroid hormone (PTH) in the absence of calcium channel blockers (CCBs), n = 56] represented the highest [Ca++i]. Group II (high PTH in the presence of CCBs, n = 43) and group III (lower PTH in the absence of CCBs, n = 37) represented intermediate [Ca++i]. Group IV (lower PTH in the presence of CCBs, n = 40) represented the lowest [Ca++i]. High PTH was defined as > or = 3.0 times normal; lower PTH, as < 3.0 times normal. Lower [Ca++i] was achieved through the use of CCBs, or through lower PTH, or both. Lower PTH was achieved by parathyroidectomy or calcitriol administration. The four groups showed no differences in age, sex, race, weight, dialysis duration, or primary disease. Group I showed a mean serum cholesterol of 358 +/- 27 mg/dL and serum triglycerides of 469 +/- 41 mg/dL. Group II showed mean serum cholesterol of 198 +/- 21 mg/dL and serum triglycerides of 147 +/- 17 mg/dL. Group III showed a mean serum cholesterol of 205 +/- 20 mg/dL and serum triglycerides of 174 +/- 16 mg/dL. Group IV showed mean serum cholesterol of 184 +/- 10 mg/dL (p = 0.008) and serum triglycerides of 103 +/- 8 mg/dL (p = 0.005). The cardiovascular morbidity and mortality incidences were: group I, 64%; group II, 27%; group III, 31%; and group IV, 20% (p = 0.002). We conclude that, in non diabetic PD patients, dyslipidemia is related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++i]. Lowering [Ca++i] by decreasing the parathormone level (via parathyroidectomy or calcitriol administration), or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term morbidity and mortality related to atherosclerotic vascular disease.
Gadallah
M F
MF
Division of Nephrology and Hypertension, Department of Medicine, University of Florida, Jacksonville, Florida, USA.
el-Shahawy
M
M
Andrews
G
G
Ibrahim
M
M
Ramdeen
G
G
Hanna
D
D
Gorospe
W
W
Morkos
A
A
Abbassian
M
M
Moles
K
K
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D002784:Cholesterol / Q000097:blood*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology; D006961:Hyperparathyroidism / Q000209:etiology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010758:Phosphorus / Q000097:blood; D012189:Retrospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D014280:Triglycerides; D010758:Phosphorus; D002784:Cholesterol; D002118:Calcium