Diabetes is a major epidemic, and diabetic nephropathy is the most common cause of end-stage renal disease. Two critical components of diabetic nephropathy are persistent inflammation and chronic renal ischemia from widespread vasculopathy. Moreover, acute ischemic renal injury is common in diabetes, potentially causing chronic kidney disease or end-stage renal disease. Accordingly, we tested the hypothesis that acute renal ischemia accelerates nephropathy in diabetes by activating proinflammatory pathways. Lean and obese-diabetic ZS rats (F1 hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were subjected to bilateral renal ischemia or sham surgery before the onset of proteinuria. The postischemic state in rats with obesity-diabetes was characterized by progressive chronic renal failure, increased proteinuria, and renal expression of proinflammatory mediators. Leukocyte number in obese-diabetic rat kidney was markedly increased for months after ischemia. Intrarenal blood flow velocity was decreased after ischemia in lean control and obesediabetic rats, although it recovered in lean rats. At 2 mo after ischemia, blood flow velocity decreased further in sham-surgery and postischemia obese-diabetic rats, so that RBC flow velocity was only 39% of control in the obese-diabetic rats after ischemia. In addition, microvascular density remained depressed at 2 mo in kidneys of obese-diabetic rats after ischemia. Abnormal microvascular permeability and increases in interstitial fibrosis and apoptotic renal cell death were also more pronounced after ischemia in obese-diabetic rats. These data support the hypothesis that acute renal ischemia in obesity-diabetes severely aggravates chronic inflammation and vasculopathy, creating a self-perpetuating postischemia inflammatory syndrome, which accelerates renal failure.
Systemic infusion of a TP antagonist demonstrated an important role of TXA2/TP signalling in our model of streptozotocin induced type-1 diabetic nephropathy by reducing kidney damage including proteinuria.
Thistle for Treatment of Diabetic Nephropathy.
These studies are compatible with the hypothesis that slow-track Type 1 diabetic patients, strongly protected from diabetic nephropathy, have distinct cellular behaviors that may be associated with reduced ECM production.",
Diabetic Nephropathy | SpringerLink
These studies are compatible with the hypothesis that slow-track Type 1 diabetic patients, strongly protected from diabetic nephropathy, have distinct cellular behaviors that may be associated with reduced ECM production.
Effect of Captopril on Heavy Proteinuria in Azotemic …
AB - Background. Calcium channel blockers (CCBs) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy. No clinical study, however, has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability. We, therefore, tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane, hence changing its permeability. Methods. Twenty-one patients with type 2 diabetcs and the presence of nephropathy with hypertension were randomized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure, urinary protein excretion, glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearances were obtained. Glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearance were measured every three months, arterial pressure and heart rate every month. Patients were followed for 21 months. Results. At 21 months, both patient groups had similar levels of blood pressure control, however, only the diltiazem group had a change in proteinuria (4 ± 10%Δ, nifedipine vs. -57 ± 18%Δ, diltiazem; P
of high GFR by the MDRD equation
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