Treatment of the post-ischaemic inflammatory syndrome of diabetic nephropathy

Abstract

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