Low Ca2+ pump activity in diabetic nephropathy

Francesca Podeste, Giancarla Meregalli, Renata Ghelardi, Rosmina Del Giudice, Veronica Asnaghi, Anna Maestroni, Gianpaolo Zerbini

Research output: Contribution to journalArticle

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 Ca2+ pump share similar regulatory pathways, but whether abnormalities in Ca2+ metabolism characterize DN is not known. We investigated Ca2+ efflux rates, NHE activity, cytosolic Ca2+ ([Ca2+]i) concentrations, and intracellular pH (pHi) 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. Ca2+ pump-mediated Ca2+ 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·mgprotein -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+·I cell-1·min-1; ANOVA, P <0.0001). A reverse correlation between Ca2+ pump activity and NHE rates could be shown. Adjustment for glycated hemoglobin and plasma lipid levels did not affect these findings. Finally, [Ca2+]i concentrations and pHi were normal in all patients. Low Ca2+ pump activity is a concomitant event of elevated NHE rates in DN; the molecular dysfunction(s) underlying these abnormalities remains to be established.

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume38
Issue number3
Publication statusPublished - 2001

Keywords

  • Ca pump
  • Diabetic nephropathy (DN)
  • Human skin fibroblasts
  • Insulin-dependent diabetes mellitus (IDDM)
  • Na-H exchange (NHE)

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Podeste, F., Meregalli, G., Ghelardi, R., Del Giudice, R., Asnaghi, V., Maestroni, A., & Zerbini, G. (2001). Low Ca2+ pump activity in diabetic nephropathy. American Journal of Kidney Diseases, 38(3), 465-472.