A War against Everolimus And The Way To Beat It

103 These studies mostly included nondiabetic kidney disease patients, and thus it is hard to extrapolate their findings and assume that DKD patients will respond similarly. To address this issue, post hoc analysis of RENAAL104 and Irbesartan Diabetic Nephropathy Trial (IDNT)105 found that higher BP targets (140�C149 mmHg for RENAAL, and >145 mmHg for IDNT) resulted in higher risk of composite outcome. These studies also found that a tighter BP control (systolic Cofactor any benefit in this population. At the same time, these data were later challenged and questioned by the findings of increased risk of adverse outcomes (cardiac events, stroke, and falls) in different populations (especially elderly) and current guidelines have raised the target to 140 mmHg systolic.106�C109 Several studies have evaluated the role of ACEi in halting DKD progression. The Captopril-Diabetes study evaluated type 1 diabetic patients with nephrotic Everolimus range proteinuria and showed a significant reduction in proteinuria along with lower GFR decline rate compared to placebo.110,111 The ADVANCE trial compared perindopril�Cindapamide combination to placebo in over 11,000 patients with DM, and found a significantly lower microalbuminuria, and lower worsening macroalbuminuria incidence rate in all groups studied, including normotensive patients.112,113 The importance and significance of the effects of proteinuria reduction on renal outcomes was questioned since the treatment groups had better blood pressure control, which might have played a big Palbociclib cell line role in preventing disease progression. Later studies showed that lowering proteinuria in patients with diabetic nephropathy (regardless of the agent used) is associated with improved outcomes and a decreased risk of ESRD.114�C117 The IDNT and the RENAAL trial studied ARBs therapy in patients with DKD and found similar beneficiary results. ARB therapy was superior to placebo and amlodipine in decreasing proteinuria, lower rates of doubling creatinine, or the development of ESRD and mortality.34,118 No significant difference was found between ACEi and ARB in patients with early DKD.