Longterm Risk Of Esrd In Diabetic Patients Treated With Different Antihypertensive Drugs

The incidence of ESRD in diabetic patients has continued to increase despite the extensive use of ACEi to prevent DN. Recently, Suissa, et al. (75) have assessed the long-term effect of ACEi on the risk of ESRD in a population-based cohort of all diabetic patients treated with antihypertensive drugs between 1982 and 1986. The cohort of 6102 patients, in which 102 cases developed ESRD until 1997, were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of ESRD associated with the use of ACEi was 2.5, whereas it was 0.8 for BB and 0.7 for CCB. The rate ratio of ESRD with the use of ACEi was 0.8 during the first 3 years of follow-up, but increased to 4.2 after 3 years. The authors concluded that ACEi use does not appear to decrease the long-term risk of ERSD in diabetes. The finding of an elevated risk may have at least two possible explanations. First, it could be that ACEi prolong life, thus increasing the opportunity for ESRD incidence. Alternatively, ACEi, while apparently providing an early benefit to the kidney, could damage the kidney in the longer term by mechanisms still unknown. In proteinuric rats (76) and in experimental renal transplantation (77), ACEi regimens induced renal fibrosis in spite of a reduction in proteinuria and blood pressure, that is, an improvement of the established clinical criteria for a good response to therapy.


Although a number of monotherapies and multidrug therapies are available for the treatment of hypertension, current guidelines provide evidence-based recommendations for the use of specific antihypertensive agents in patients with diabetes. The guidelines from the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommend the use of either ACEi or ARB as initial therapy to achieve the BP target in patients with T2DM (78). If one class is not tolerated, the other should be substituted if it is not contraindicated. According to the JNC-7, starting therapy with 2 drugs, separately or as fixed dose combinations, may be considered when SBP is > 20 mm Hg or diastolic BP is > 10 mm Hg above the desired goal for the individual patient (78). Neither ACEi nor ARB appear to produce any clinically significant changes in metabolic measurements, such as blood glucose and the lipid profile, which is an important consideration in the presence of diabetes. Based on the studies discussed above, ACEi or ARB are specified as the preferred firstline agents for the treatment of patients with hypertension, T2DM, and microalbuminuria as both drug classes delay progression to macroalbuminuria. A recent study (79) provides strong clinical evidence implying that a reduction of microalbuminuria in type 2 diabetic patients is an integrated indicator for renal and CV risk reduction.

Very recently, new joint guidelines (80,81) were published from both the American Heart Association (AHA) and the American Diabetes Association (ADA) as well as from the European Society of Cardiology (ESC) and the European Association for Study of Diabetes (EASD) for reducing the high vascular risk of diabetic patients. Strict blood pressure control and antihypertensive combination therapy is in the center of both recommendations. The joint ESC-EASD guidelines (80) recommend for patients with diabetes and hypertension a target BP level of 130/80 mm Hg. In addition, combination of several anti-hypertensive drugs is recommended for satisfactory BP control and a RAS-inhibitor should be part of the BP-lowering treatment. The joint AHA-ADA guidelines (81) recommend that all patients with diabetes and hypertension should be treated with a regimen that includes either an ACEi or an ARB. If one class is not tolerated, the other should be substituted. Other drug classes demonstrated to reduce CV events in patients with diabetes (BB, thiazide diuretics, and CCB)

should be added as needed to achieve BP targets. Multiple-drug therapy generally is required to achieve blood pressure targets.

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