Treatment and Landmark Clinical Trials for Renoprotection

During the last two decades, many large-scale randomized clinical trials have confirmed the importance of lowering blood pressure and inhibiting the renin-angiotensin-aldosterone system (RAAS) to preserve renal function in patients with chronic kidney disease due to different causes. With growing epidemic of type 2 diabetes, the burden of diabetic nephropathy (DN) will continue to grow. Based on a large body of epidemiological, experimental and interventional studies, strict glycemic control, blood pressure lowering and RAAS blockade are now the recommended strategies in the prevention and control of DN. Both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) have been shown unequivocally to reduce proteinuria and preserve renal function in affected patients. Importantly, therapeutic responses are dose dependent, and these drugs should be given in maximal dosages as tolerated. Combined use of ACEI and ARB reduced proteinuria and rate of decline of renal function, although it did not appear to confer extra renoprotection over the use of either agent alone. Spironolactone and aliskiren are alternative drugs that block the RAAS and have been demonstrated to further reduce proteinuria when added to ACEI or ARB. In the absence of long-term data about their safety and efficacy on renal function, combined use of these agents must be administered with caution after careful consideration of risk-benefit ratio with close monitoring for adverse effects, notably hyperkalemia. Pending further evidence, the use of a team approach to attain multiple treatment goals will improve renal outcomes in these high risk subjects.