Low Ca2+ pump activity in diabetic nephropathy

Abstract Elevated cell Na + -H + exchange (NHE) activity characterizes diabetic nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent evidence suggests that NHE and the Ca 2+ pump share similar regulatory pathways, but whether abnormalities in Ca 2+ metabolism characterize DN is not known. We investigated Ca 2+ efflux rates, NHE activity, cytosolic Ca 2+ ([Ca 2+ ] i ) concentrations, and intracellular pH (pH i ) in human skin fibroblasts from 20 patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients with diabetes with normoalbuminuria matched for age, sex, and duration of diabetes; and 10 individuals without diabetes. Ca 2+ pump-mediated Ca 2+ efflux was significantly lower in patients with nephropathy than in patients with normoalbuminuria and individuals without diabetes (0.074 ± 0.01 versus 0.115 ± 0.01 versus 0.131 ± 0.02 nmol·mg protein −1 ·min −1 ; analysis of variance [ANOVA], P = 0.015). Elevated maximal velocity of the Na + -H + exchanger was confirmed in fibroblasts from patients with nephropathy (14.4 ± 1.2 versus 7.1 ± 0.7 versus 8.0 ± 1.2 mmol H + ·l cell −1 ·min −1 ; ANOVA, P 2+ pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca 2+ ] i concentrations and pH i were normal in all patients. Low Ca 2+ pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established. © 2001 by the National Kidney Foundation, Inc.