Nephrol Dial Transplant (2001) 16: 85-90
© 2001 European Renal Association-European Dialysis and Transplant Association
Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uraemic patients
Division of Nephrology, Dialysis and Hypertension, San Raffaele Scientific Institute, University of Milan, Milan, Italy
Background. Myocardial disorders are a remarkable cause of morbidity and mortality in chronic haemodialysed patients (HD). They could be favoured by alteration of cell Ca2+ handling. In previous studies we characterized an erythrocyte Ca2+ influx, sensitive to membrane potential and inhibited by Ca2+ antagonists. Since its maximal influx rate was decreased in HD patients, this study investigates if Ca2+ influx alterations are related to myocardial disorders in HD patients.
Methods. Voltage-sensitive erythrocyte Ca2+ influx was measured in 30 healthy controls and in 53 patients (47 HD patients and six patients with left ventricular hypertrophy and normal kidney function), using fura 2. In 29 HD patients and in six healthy subjects Ca2+ influx was also determined in the presence of parathyroid hormone (PTH) in vitro. Patients were classified according to Lown's ventricular arrhythmias classification after 24-h Holter electrocardiograph (ECG) monitoring. Forty-six patients underwent echocardiography.
Results. Voltage-sensitive erythrocyte Ca2+ influx was significantly reduced in HD patients. Maximal influx rate was significantly higher in HD patients of Lown's classes 3 and 4 (0.789±0.156 nmol/s, n=8; P<0.01) than in patients of classes 1 and 2 (0.499±0.055 nmol/s, n=15), or without ventricular arrhythmias (0.400±0.041 nmol/s, n=24). Maximal influx rate was directly correlated to left ventricular mass index (LVM) (r=0.353, P<0.05). Subjects with left ventricular hypertrophy and normal kidney function displayed erythrocyte Ca2+ influx similar to that of normal subjects. Multiple regression indicates that LVM and Ca2+ influx were independently related to severity of arrhythmias. When added to the influx assay, PTH increased the maximal influx rate only in patients with ventricular arrhythmias.
Conclusion. Myocardial dysfunction and altered ventricular excitability could be related in uraemic HD patients to alterations of calcium transport, as found in the erythrocyte model. Reduced resistance to PTH could contribute to this phenomenon.
Keywords: arrhythmias; Ca2+ influx; erythrocytes; left ventricular hypertrophy; parathyroid hormone; uraemia
Correspondence and offprint requests to: Dr Laura Soldati, Divisione di Nefrologia, Ospedale San Raffaele, Via Olgettina 60, I-20132 Milano, Italy.
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