Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury

Abstract

Ischemic acute kidney injury in experimental diabetes mellitus (DM) is associated with a more severe deterioration in renal function than shown in nondiabetic animals. We evaluated whether the early recovery phase from acute kidney injury is associated with a more prolonged and sustained decrease in renal perfusion in diabetic mice, which could contribute to the impaired recovery of renal function. Perfusion to the renal cortex and medulla was evaluated by laser-Doppler flowmetry in 10- to 12-wk-old anesthetized mice with type 2 DM (db/db), heterozygous mice (db/m), and nondiabetic (control) mice (C57BL/6J). After baseline measurements were obtained, the right renal artery was clampedfor 20 min followed by reperfusion for 60 min. The data demonstrated that, in all three groups studied, the reperfusion phase was characterized by a significant increase in the medullary-to-cortical blood flow ratio. Moreover, during recovery from ischemia, there was a marked prolongation in the time (in min) required to reach peak reperfusion in the cortex (db/db: 20.7 +/- 4.0, db/m: 12.92 +/- 1.9, C57BL/6J: 9.3 +/- 1.3) and the medulla (db/db: 20.8 +/- 3.2, db/m: 12.88 +/- 1.89, C57BL/6J: 11.2 +/- 1.2). Additionally, the slope of the recovery phase was lower in db/db mice (cortex: 61.9 +/- 23.1%/min, medulla: 16.3 +/- 3.6%/min) than in C57BL/6J mice (cortex: 202.2 +/- 41.6%/min, medulla: 42.1 +/- 7.2%/min). Our findings indicate that renal ischemia is associated with a redistribution of blood flow from cortex to medulla, not related to DM. Furthermore, renal ischemia in db/db mice results in a marked impairment in reperfusion of the renal cortex and medulla during the early postischemic period.

TNF-α mediates increased susceptibility to ischemic AKI in diabetes

“…Increased susceptibility of the kidney to ischemic insults has been reported in experimental models of diabetes and in clinical studies involving patients with diabetes (17,25,31,32,47). The mechanisms underlying this susceptibility remain unclear.…”

“…Treatment with insulin prior to the ischemic event reduced ischemic injury whereas administration of insulin after the ischemic insult had no beneficial effect (32). A study in a murine model of type 2 diabetes mellitus (DM) (db/db) also demonstrated an increased risk for ischemic acute renal failure (47). In that study, a delayed recovery of renal blood flow after the ischemic event was noted in the diabetic mice.…”

“…AN INCREASED SUSCEPTIBILITY of the diabetic kidney to ischemic insults has been reported in experimental models of diabetes and in humans with diabetes (17,25,31,47). Studies in rats with streptozotocin (STZ)-induced type 1 diabetes indicated that diabetic rats had significantly greater histological damage, tubular apoptosis, and long-term fibrosis after ischemia than nondiabetic rats (31,32).…”

Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy

“…We focused on ischemia-reperfusion renal injury, because it drastically depresses capillary renal blood flow in the postischemic period in obese-diabetic mice and, subsequently, reduces renal blood flow (44). Renal hemodynamic and inflammatory changes may interact and worsen renal injury.…”

Renal Endothelial Dysfunction in Acute Kidney Ischemia Reperfusion Injury

“…After release of renal artery occlusion, total renal blood flow (RBF) is restored to baseline levels within minutes followed by a subsequent decline in RBF, which takes place over several hours [29, 30] [31-33]. Methods that discriminate regional blood flow in the kidney, suggest that outer medullary RBF undergoes an earlier and more significant impairment relative to whole kidney RBF [32-35].…”