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4.1 Pre-Dialysis - Retarding Progression and Reducing the Comorbid Burden in Renal Disease 4.1.2 Retarding Disease Progression Hypertension There is strong evidence that hypertension accelerates the loss of renal function in patients with chronic renal failure and that treatment of hypertension slows the rate of progression (ref.42). The deleterious effect of blood pressure may be more important in patients with proteinuria (see below) in whom lower blood pressures are required to achieve the same protection of renal function. The rate of decline in renal function tends to be faster in hypertensive African Americans compared with hypertensive whites (ref.43). Reduction of Proteinuria. Proteinuria (leakage of protein in the urine) is an abnormal state usually associated with glomerulonephritis although it can occur across the whole range of kidney diseases. There is good evidence to suggest that the higher the level of proteinuria the more rapid the progression of the renal disease (ref.44,45). A reduction of dietary protein can reduce proteinuria and lead to a better outcome (ref.46) but there is diminishing enthusiasm for this approach given the risks of malnutrition and the more powerful and predictable effects achievable with drug therapy; particularly angiotension converting enzyme inhibitors (ACEI). In addition to lowering blood pressure, ACE inhibitors also lower the filtration pressure inside the kidney which in turn reduces the amount of proteinuria. Meta-analyses have suggested that ACE inhibitors reduce the relative risk of ESRF significantly (ref.47,48). In patients with proteinuria, lowering of blood pressure with an ACEI appears to delay progression to a greater degree than with other antihypertensive agents (ref.49). Dual reduction of blood pressure and proteinuria seems to be the prerequisite for an effective reduction in the rate of progression of CRF. Diabetic Nephropathy. The main efforts to ameliorate the clinical course of diabetic nephropathy have concentrated on tight control of blood sugar and blood pressure. There is good evidence that good glycaemic control can slow progression of renal failure particularly in the early phases of diabetic nephropathy (ref.50,52). Numerous studies have shown that control of systemic hypertension has a major effect on reducing proteinuria and slowing progression to renal failure in both type I and type II diabetes (ref.53). It is now well known that ACE inhibitors can reduce proteinuria over a range of kidney diseases by 40-50%, an effect which may be independent of the blood pressure lowering effect of these drugs (ref.54,55). Several studies have shown that ACE inhibitors will reduce proteinuria in both types of diabetes56. Furthermore, studies have shown that ACE inhibitors can reduce the risk of death or dialysis in diabetes (ref.57). Guidelines on the detection and management of microalbuminuria (small amounts of protein) in diabetics are anticipated in the National Service Framework (NSF) for diabetes.  |