MANAGING CHRONIC RENAL INSUFFICIENCY: INTERVENTIONS TO SLOW PROGRESSION OF CHRONIC RENAL INSUFFICIENCY
Aggressive Control of Hypertension
Hypertension accelerates the progression of chronic renal insufficiency irrespective of the primary cause of kidney failure. Aggressive blood pressure control slows progression of renal insufficiency and is by far the most important available tool to slow progression of renal failure. The optimal blood pressure in persons with chronic renal insufficiency is uncertain. The threshold blood pressure below which the risks of blood pressure reduction outweighs benefits in progressive chronic renal insufficiency is not established, and may never be known because of difficulties in designing such a study. A reasonable, though difficult to attain, target blood pressure is 120/75 mmHg. In general, in the absence of symptoms of hypotension, the lower, the better the outcomes.
Hypertension is often moderate to severe, worsening with progressive disease due to salt and water retention. Even in the absence of edema, a diuretic should be part of the antihypertensive drug regimen. Because of concomitant loss of lean body mass, many azotemic patients do not evince an absolute gain in body weight (over pre-illness weight) and may not express pulmonary or pedal edema.
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Loop diuretics such as furosemide in higher than usual (80 to 200 mg bid) should be used because of their potency. Maximum diuresis can be achieved by combining a loop diuretic with metolazone (10 to 20 mg bid).
Treatment with Angiotensin Converting Enzyme Inhibitor
The choice of drugs to be combined with diuretics should be determined by cost, side-effect profile, compliance, efficacy and the presence of comorbid illnesses. Angiotensin converting enzyme (ACE) inhibitors are renoprotective (benefits not explained solely by blood pressure reduction) in patients with renal insufficiency due to diabetes mellitus, hypertension and glomerulonephritis. Current evidence suggests that ACE inhibitors by reducing angiotensin A, reduce the activity of transforming growth factor-beta (TGF-3), and consequently, fibrogenesis within the mesangium.
Some investigators suggest substantial clinical benefits (reduced albuminuria, slowed progression of renal disease) in diabetic patients when blood pressure is reduced using drugs other than ACE inhibitors. However, therapy with ACE inhibitors or angiotensin receptor blockers also afford benefits that are not solely dependent upon systemic blood pressure reduction.
Reduction of Proteinuria
Protein trafficking through the glomerulus is believed to be harmful to the kidney, possibly via increased constitutive TGF-3 leading to mesangial fibrogenesis. An advantage of blood pressure reduction with ACE inhibitors is greater reduction of proteinuria when compared to other agents. Normotensive diabetic individuals with or without microalbuminuria, as well as normotensive individuals with nonnephrotic proteinuria, should be treated with an ACE inhibitor. For patients who are not able to tolerate ACE inhibitors, the angiotensin-2 receptor blockers and certain calcium channel blockers such as diltiazem have been shown to reduce proteinuria.
Adequate Blood Sugar Control
Hyperglycemia per se is injurious to tissues of those. Inadequate glycemic control shortens the interval between onset of diabetes and onset of clinical proteinuria; the risk of developing macroalbuminuria is four to five times greater in patients with poor control than in those with satisfactory regulation of glycemia.
The Diabetes Control and Complications Trial (DCCT) showed that near normoglycemia resulted in a 39% reduction in the occurrence of microalbuminuria and a 54% reduction in albuminuria. By one projection, comprehensive treatment of type 2 diabetes, maintaining an HbAlc value of 7.2% would reduce the cumulative incidence of blindness, ESRD, and lower-extremity amputation by 72%, 87%, and 67%, respectively. canadian antibiotics
In the UK Prospective Diabetes Study (UKPDS) of type A2 diabetics, intensive blood-glucose control with either sulfonylurea or insulin was compared with conventional treatment in terms of microvascular and macrovascular complications in 3867 individuals of median age 54 years over 10 years. The intensive group achieved a 12% reduction in every diabetes-related endpoint when compared to the usual care group.
Combination oral hypoglycemic drug therapy should be used to facilitate attainment of eug-lycemia. Troglitazone and rosiglitazone increase peripheral glucose disposal but are incompletely evaluated in azotemia. Metformin, which decreases endogenous glucose production is thought to increase the risk of lactic acidosis in azotemic patients, but few data have been reported in those with reduced glomerular filtration rates.
Treatment of Hyperlipidemia
Hyperlipidemia is recognized as a risk factor for progression of nephropathy in diabetes independent of hyperglycemia and hypertension. In the nephrotic syndrome, hyperlipidemia is present, but prospective trials have not documented any relationship between deranged lipid metabolism and coronary or cerebral artery disease in patients with nephrotic syndrome. Clear evidence of an isolated benefit of lipid reduction in progressive renal insufficiency is limited, though it is reasonable to infer the same potential benefits found in those with normal renal function.
Dietary manipulation (reduced intake of saturated fat and simple sugars), will improve nephrotic hyperlipidemia, but the need for such intervention is not established.
Restriction of Dietary Protein Intake
Whether dietary protein restriction appreciably delays progression of renal insufficiency, is controversial. Several prospective randomized and controlled trials were inconsistent when analyzed individually, but a meta-analysis found a low protein diet reduced progression of renal disease to renal failure or death in non-diabetic patients by 33%. tadalis sx 20
In type 1 diabetes, dietary protein restriction slowed decline in renal function by 44% and reduced proteinuria. Similarly, substantial protein restriction in primary care of type 2 diabetic patients also reduced proteinuria Additional analyses of the Modification of Diet in Renal Disease study showed a benefit of low protein diet to those patients who had more than one gram of urinary protein excretion in a 24-hour period The effectiveness of a protein restricted diet is compromised by poor compliance and malnutrition.