Renoprotective and anti-hypertensive effects of combined valsartan and perindopril in progressive diabetic nephropathy in the transgenic (mRen-2)27 rat

Background. We have previously reported that severe glomerulosclerosis prog ressively develops in the streptozotocin (STZ) diabetic transgenic (mRen-2) 27 rat. In this diabetic model, monotherapy with either angiotensin convert ing enzyme inhibition (ACEI) or angiotensin type 1 (AT(1)) receptor blockad e is largely renoprotective. The objective of the present study was to dete rmine if a combination therapy at lower doses than monotherapy would confer greater reno-protection. Methods. At 6 weeks of age, non-diabetic control and STZ diabetic female he terozygous Ren-2 rats were randomized to receive vehicle, the AT(1) recepto r blocker valsartan (V, 20 mg/kg/day), the ACEI perindopril (P. 6 mg/kg/day ), or a combination of low-dose V+P(V, 3 mg/kg/day plus P, 0.5 mg/kg/day) f or 12 weeks. Results. Systolic blood pressure was lowered with all treatments, but the g reatest reductions were observed with V monotherapy and combination V+P the rapy. All treatments reduced albuminuria, the decline in glomerular filtrat ion rate, and cortical collagen staining, to the same extent. The glomerulo sclerotic index was increased with diabetes and reduced with V and P monoth erapy. However, the low-dose combination therapy was more effective than si ngle therapy and reduced severe glomerulosclerosis to levels observed in no n-diabetic controls. Conclusions. Monotherapy with either V or P reduced blood pressure and reta rded the decline in renal function and glomerulosclerosis in the diabetic R en-2 rat. Combination therapy has the additional benefit of requiring only low doses of AT(1) receptor blockade and ACEI to achieve superior renoprote ctive effects in this diabetic nephropathy model.