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Related Experiment Videos

Low Ca(2+) pump activity in diabetic nephropathy.

F Podestá1, G Meregalli, R Ghelardi

  • 1Renal Pathophysiology Laboratory, Division of Medicine, Scientific Institute San Raffaele, University of Milan, Milan, Italy.

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
|September 5, 2001
PubMed
Summary

Diabetic nephropathy (DN) is linked to higher cell sodium-hydrogen exchanger (NHE) activity. This study found lower calcium (Ca2+) pump activity in patients with DN, suggesting a connection between impaired Ca2+ metabolism and NHE dysfunction in kidney disease.

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Area of Science:

  • Nephrology
  • Cell Physiology
  • Biochemistry

Background:

  • Diabetic nephropathy (DN) is characterized by elevated cell sodium-hydrogen exchanger (NHE) activity.
  • The underlying mechanisms of this NHE abnormality in DN remain unclear.
  • Potential links between calcium (Ca2+) metabolism and NHE regulation in DN require investigation.

Purpose of the Study:

  • To investigate Ca2+ efflux rates, NHE activity, cytosolic Ca2+ concentrations, and intracellular pH in human skin fibroblasts from patients with type 1 diabetes and nephropathy, diabetes with normoalbuminuria, and healthy individuals.
  • To determine if abnormalities in Ca2+ metabolism are associated with DN.
  • To explore the relationship between Ca2+ pump activity and NHE rates.

Main Methods:

  • Analysis of Ca2+ efflux rates, NHE activity, cytosolic Ca2+ ([Ca2+]i), and intracellular pH (pHi) in human skin fibroblasts.

Related Experiment Videos

  • Comparison between three groups: patients with type 1 diabetes and nephropathy (n=20), patients with diabetes and normoalbuminuria (n=20), and healthy controls (n=10).
  • Statistical analysis including analysis of variance (ANOVA).

    • Main Results:

    • Ca2+ pump-mediated Ca2+ efflux was significantly lower in patients with nephropathy compared to normoalbuminuric patients and controls (P = 0.015).
    • Elevated maximal velocity of the Na+-H+ exchanger (NHE) was confirmed in fibroblasts from patients with nephropathy (P < 0.0001).
    • A reverse correlation was observed between Ca2+ pump activity and NHE rates, independent of glycated hemoglobin and plasma lipid levels.

    Conclusions:

    • Low Ca2+ pump activity is a concomitant finding with elevated NHE rates in diabetic nephropathy.
    • The molecular basis for these associated abnormalities in Ca2+ metabolism and NHE activity in DN requires further elucidation.