Treatment of the post-ischaemic inflammatory syndrome of diabetic nephropathy.
BACKGROUND
Diabetes mellitus and its complications are a public health problem of epidemic proportions. Both diabetes and chronic kidney disease (CKD) increase the risk of acute kidney injury (AKI). Months after a single episode of acute ischaemia to the diabetic kidney, we have found an accelerated progression of nephropathy, with impaired function, severe renal inflammation, microvascular dysfunction, fibrosis and apoptotic cell death. We termed this entity the post-ischaemic inflammatory syndrome. We now test the hypothesis that blocking inflammation ameliorates the post-ischaemic inflammatory syndrome.


METHODS
Obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were treated with mycophenolate mofetil (MMF), subjected to renal ischaemia or sham surgery, and monitored via the powerful technique of intravital microscopy.


RESULTS
Amelioration of post-ischaemia inflammation with MMF therapy improved long-term renal function, microvascular dysfunction, fibrosis and apoptosis.


CONCLUSIONS
These data support the hypothesis that the post-ischaemic inflammatory syndrome accelerates diabetic CKD, is a critical determinant of injury, and can be successfully treated.
Kelly
K J
KJ
1Indiana University School of Medicine, Indianapolis, IN, USA. kajkelly@iupui.edu
Dominguez
Jesus H
JH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004903:Erythrocyte Aggregation / Q000187:drug effects; D005355:Fibrosis; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009393:Nephritis / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D051127:Scavenger Receptors, Class E / Q000235:genetics; D013577:Syndrome
D007166:Immunosuppressive Agents; C495136:OLR1 protein, rat; D051127:Scavenger Receptors, Class E; D018799:Intercellular Adhesion Molecule-1; D009173:Mycophenolic Acid