|arznei-telegramm 2003; 34: 97|
DIABETIC NEPHROPATHY |
... How well founded are very low blood pressure targets?
The lowering of raised blood pressure has been shown in controlled intervention trials to delay the progression of diabetic nephropathy (a-t 1999; no. 11: 117). According to epidemiological studies, an increasing blood pressure level increases the risk of deterioration of the renal disease even when the level remains within the normal range. In international guidelines, therefore, much lower blood pressure targets than usual are recommended for diabetic patients with nephropathy, for example below 140/80 mmHg (1) or below 130/80 mmHg (2).
A systematic review now evaluates the evidence for a beneficial renal effect of these very low target levels from randomised controlled trials (3). The authors found five long-term studies with follow-up of at least two years in which a total of 1.203 diabetic patients with microalbuminuria or overt nephropathy took part (4-8). The studies compared the effects of different normotensive blood pressure targets, for example, diastolic pressure below 75 mmHg versus 80-89 mmHg (4), or an antihypertensive treatment of normotensive patients with non-treatment or placebo.
None of the studies provides data about the clinical endpoint of renal failure requiring dialysis. Measured by the course of the glomerular filtration rate, a surrogate parameter which is regarded as valid, a beneficial effect of lower blood pressure targets on progression of nephropathy was not demonstrated in any study. In the majority of the studies, stricter blood pressure control is associated with more or less clearly reduced albuminuria. However, in these as in other studies, this does not correlate with the course of the glomerular filtration rate. The reduced protein excretion in the urine due to therapeutic intervention thus once again proves to be an unsuitable surrogate parameter for delayed progression of diabetic nephropathy (a-t 2000; 31: 2) (3,9).
In one of the studies analysed, the two-arm ABCD* study, the greater reduction in blood pressure in hypertensive diabetic patients is associated with lower overall mortality (4). In the normotensive patients in the other arm of the study, antihypertensive treatment delays the progression of retinopathy and reduces the rate of stroke (5). This points into the same direction as the results of the HOT** trial, in which the risk of cardiovascular complications and cardiovascular mortality was reduced in patients with diabetes mellitus by reducing the diastolic blood pressure to 80 mmHg or lower (10). A fault of these studies, however, is that no (10) or no adequate (4,5) systolic blood pressure targets (below 140 mmHg) are required. The systolic blood pressure thus remains undertreated in a great part of the patients, and this particularly affects the groups with laxer control. Therefore, it cannot be excluded that the higher complication rates in these patients can be explained only by poorer reduction of the hypertensive systolic blood pressure.
Thus, clear evidence of a clinical benefit of very low blood pressure targets in patients with diabetes and nephropathy is lacking. Controlling blood pressure at normotensive levels (below 140/90 mmHg), which is difficult often enough but is well founded by studies, should therefore not be complicated by setting goals which are rather unrealistic and the benefit of which is not proven (9).
(R = randomised study)
Scottish Intercollegiate Guidelines Network: "Management of Diabetes. A national clinical guideline" Nov. 2001; to be found on: http://www.show.scot.nhs.uk/sign/guidelines/published/index.html
Nationales Programm für Versorgungs-Leitlinien bei der Bun-des-ärztekam-mer: Nationale Versorgungsleitlinien Diabetes mellitus Typ 2, short version, corrected version of 1st April 2003; http://www.leitlinien.de/versorgungsleitlinien/index/dokumente/diabetes/pdf/nvldiabetes
KAISER, T. et al.: Brit. J. Diab. Vasc. Dis. 2003: 3: 278-81
SAWICKI, P.T., KAISER, T.: Brit. J. Diab. Vasc. Dis. 2003; 3: 285
HOT = Hypertension Optimal Treatment
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