Podocyte Number in Normotensive Type 1 Diabetic Patients With Albuminuria

  1. Kathryn E. White1,
  2. Rudolf W. Bilous1,
  3. Sally M. Marshall1,
  4. Meguid El Nahas2,
  5. Giuseppe Remuzzi3,
  6. Giampiero Piras4,
  7. Salvatore De Cosmo5,
  8. GianCarlo Viberti6 and
  9. on behalf of the European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT)
  1. 1Department of Medicine, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, U.K.
  2. 2Sheffield Kidney Institute, Northern General Hospital Trust, Sheffield, U.K.
  3. 3Mario Negri Institute for Pharmacological Research, Bergamo, Italy
  4. 4Diabetes Unit, Hospital Brotzu, Cagliari, Italy
  5. 5Division and Research Unit of Endocrinology, “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy
  6. 6Department of Diabetes, Endocrinology & Internal Medicine, Guy’s Hospital, King’s College London, London, U.K.

    Abstract

    We estimated glomerular cell number in 50 normotensive type 1 diabetic patients with raised albumin excretion rate (AER) and investigated any change after 3 years in a subgroup of 16 placebo-treated patients. Biopsies from 10 normal kidney donors were used as controls. Mesangial and endothelial cell number was increased in the 50 diabetic patients at the start of the study compared with control subjects. There was no difference in podocyte number. Glomerular volume was increased in diabetic patients, but surface area of glomerular basement membrane (GBM) underlying the podocytes did not differ between groups. AER correlated positively with mesangial cell number in microalbuminuric patients (r = 0.44, P = 0.012) and negatively with podocyte number in proteinuric patients (r = −0.48, P = 0.040). In the 16 placebo-treated patients, glomerular volume increased after 3 years owing to matrix accumulation and increased GBM surface area. Although overall cell number did not differ significantly from baseline, the decrease in podocyte number during follow-up correlated with AER at follow-up (r = −0.72, P = 0.002). In conclusion, cross-sectional analysis of podocyte number in type 1 diabetic patients with raised AER but normal blood pressure shows no significant reduction compared with nondiabetic control subjects. Longitudinal data provide evidence for an association between podocyte loss and AER, but whether cellular changes are a response to, a cause of, or concomitant with the progression of nephropathy remains uncertain.

    Footnotes

    • Address correspondence and reprint requests to Dr. K.E. White, Department of Medicine, Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH U.K. E-mail: k.e.white{at}ncl.ac.uk.

      Received for publication 20 February 2002 and accepted in revised form 12 July 2002.

      AER, albumin excretion rate; BP, blood pressure; ESPRIT, European Study for the Prevention of Renal Disease in Type 1 Diabetes; GBM, glomerular basement membrane; GFR, glomerular filtration rate.

    | Table of Contents