ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO344

Autophagy Activation in Circulating Proangiogenic Cells (PAC) Aggravates Interstitial Fibrosis Post-AKI in Type I Diabetes Mellitus

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration


  • Patschan, Daniel, Brandenburg Medical School, Brandenburg an der Havel, Brandenburg, Germany
  • Mueller, Gerhard A., Georg-August University, Gottingen, Germany

Diabetes mellitus increases the risk for AKI under experimental and clinical conditions. Circulating proangiogenic cells (PAC) have been proven as effective tool in ischemic AKI in recent years. Autophagy (AP) serves as endogenous mechanism of self-defense in situations of increased metabolic stress. Aim of the study was to analyze consequences of AP activation in syngeneic murine PAC, administered to diabetic animals suffering from ischemic AKI.


Insulin-dependent diabetes was induced in male, 8-12 weeks old C57/Bl6N mice by repeated i.p. injection of streptozotocin. Six weeks later, AKI was induced by bilateral renal ischemia of 45 minutes. Animals were injected with either untreated or pharmacologically preconditioned murine PAC (106) at the time of reperfusion. Preconditioning was performed with zVAD or MD132, two established AP inducers. Animals were analyzed 48 hours and 6 weeks later.


Excretory function (serum cystatin C) – ischemia induced significant kidney dysfunction in the short-term (48 h), IDDM aggravated this situation even further. Cell therapy did neither attenuate nor aggravate AKI. At week 6, excretory dysfunction remained affected in non-diabetic and diabetic mice without cell therapy. Administration of both, zVAD and MD132 pretreated PAC resulted in aggravated dysfunction in non-diabetic animals, serum cystatin C was lower in diabetic mice receiving zVAD treated PAC. Fibrosis – at 48 h, significant interstitial matrix accumulation was exclusively detected in diabetic mice receiving MD132 treated cells. At week 6 however, fibrosis occurred in almost every group with two exceptions (non-diabetic and diabetic AKI +native PAC). The morphological findings were most pronounced in diabetic mice undergoing treatment with preconditioned cells. EndoMT – mesenchymal transition of endothelium cells was detected in a significant manner in the following groups: 48 h – IDDM + zVAD and + MD132; 6 weeks – IDDM + MD132.


zVAD-/MD132-induced AP activation in PAC does not result in any functional improvement in diabetic AKI. Postischemic structural abnormalities however are being aggravated. Thus, pharmacalogical stimulation of autophagy in PAC has not been identified as effective strategy for improving the cells′ renoprotective capacity in diabetic AKI.