Molecular and Cellular Biochemistry

, Volume 259, Issue 1–2, pp 67–70 | Cite as

Evidence of apoptosis in human diabetic kidney

  • Dinender Kumar
  • Susan Robertson
  • Kevin D. Burns


Diabetic nephropathy is characterized by an early period of renal growth with glomerular and tubular cell hypertrophy, but this is followed by progressive glomerulosclerosis and tubulointerstitial fibrosis, associated with loss of renal tissue. We studied whether apoptotic cell death occurs in human diabetic nephropathy. Percutaneous renal biopsy samples were obtained from five patients with diabetic nephropathy who were receiving insulin and/or angiotensin-converting enzyme inhibitor therapy. Apoptosis was determined by the presence of DNA fragmentation, detected by in situ TUNEL staining, and by characteristic features on electron microscopy, such as chromatin condensation. Apoptosis was present in all five biopsy specimens, either in epithelial cells of the proximal or distal tubules, or in endothelial cells or interstitial cells. No apoptosis was detected in cells of the glomeruli. The present study provides evidence for apoptosis in human diabetic kidney, and suggests a role for apoptosis in the gradual loss of renal mass.

apoptosis diabetic kidney tubulointerstitium endothelial cell 


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  1. 1.
    Wolf G, Ziyadeh FN: The role of angiotensin II in diabetic nephropathy: Emphasis on nonhemodynamic mechanisms. Am J Kidney Dis 29: 153-163, 1997PubMedGoogle Scholar
  2. 2.
    Kumar D, Lou H, Singal PK: Oxidative stress and apoptosis in heart dysfunction. Herz 27: 662-668, 2002CrossRefPubMedGoogle Scholar
  3. 3.
    Woo D: Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 333: 18-25, 1995CrossRefPubMedGoogle Scholar
  4. 4.
    Daemen MA, van V, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, Vandenabeele P, Buurman WA: Inhibition of apoptosis induced by ischemia reperfusion prevents inflammation. J Clin Invest 104: 541-549, 1999PubMedGoogle Scholar
  5. 5.
    Morrissey JJ, Klahr S: Effect of AT2 receptor blockade on the pathogenesis of renal fibrosis. Am J Physiol 276: F39-F45, 1999PubMedGoogle Scholar
  6. 6.
    Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N: Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 47: 114-121, 1995PubMedGoogle Scholar
  7. 7.
    Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J: Mesangial cell apoptosis: The major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 94: 2105-2116, 1994PubMedGoogle Scholar
  8. 8.
    Schelling JR, Cleveland RP: Involvement of Fas-dependent apoptosis in renal tubular epithelial cell deletion in chronic renal failure. Kidney Int 56: 1313-1316, 1999CrossRefPubMedGoogle Scholar
  9. 9.
    Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota A: Apoptosis in glomerular sclerosis. Kidney Int 49: 103-111, 1996PubMedGoogle Scholar
  10. 10.
    Ortiz A, Ziyadeh FN, Neilson EG: Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Investig Med 45: 50-56, 1997PubMedGoogle Scholar
  11. 11.
    Kelly DJ, Cox AJ, Tolcos M, Cooper ME, Wilkinson-Berka JL, Gilbert RE: Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats. Kidney Int 61: 31-39, 2002CrossRefPubMedGoogle Scholar
  12. 12.
    Lorenzi M, Montisano DF, Toledo S, Barrieux A: High glucose induces DNA damage in cultured human endothelial cells. J Clin Invest 77: 322-325, 1986PubMedGoogle Scholar
  13. 13.
    Moudgil R, Menon V, Xu Y, Musat-Marcu S, Kumar D, Jugdutt BI: Postischemic apoptosis and functional recovery after angiotensin II type 1 receptor blockade in isolated working rat hearts. J Hypertens 19: 1121-1129, 2001CrossRefPubMedGoogle Scholar
  14. 14.
    Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J: Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II-dependent. Lab Invest 80: 513-527, 2000PubMedGoogle Scholar
  15. 15.
    Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW: Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102: 783-791, 1998PubMedGoogle Scholar
  16. 16.
    Jonassen AK, Brar BK, Mjos OD, Sack MN, Latchman DS, Yellon DM: Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism. J Mol Cell Cardiol 32: 757-764, 2000CrossRefPubMedGoogle Scholar
  17. 17.
    Chevalier RL, Thornhill BA, Wolstenholme JT: Renal cellular response to ureteral obstruction: Role of maturation and angiotensin II. Am J Physiol 277: F41-F47, 1999PubMedGoogle Scholar
  18. 18.
    Ortiz A, Lorz C, Catalan MP, Danoff TM, Yamasaki Y, Egido J, Neilson EG: Expression of apoptosis regulatory proteins in tubular epithelium stressed in culture or following acute renal failure. Kidney Int 57: 969-981, 2000CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Dinender Kumar
    • 1
  • Susan Robertson
    • 2
  • Kevin D. Burns
    • 3
  1. 1.Cardiovascular Research Centre, Department of MedicineUniversity of WisconsinMadisonUSA
  2. 2.Department of Laboratory MedicineOttawa HospitalOttawaCanada
  3. 3.Department of Cellular and Molecular Medicine and Department of Medicine, Division of Nephrology, Kidney Research Centre, Ottawa Health Research InstituteUniversity of OttawaCanada

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