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Renal protection in diabetes: lessons from ONTARGET.

Ritz E, Schmieder RE, Pollock CA - Cardiovasc Diabetol (2010)

Bottom Line: Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase.There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan.These effects cannot be solely attributed to blood pressure control.

View Article: PubMed Central - HTML - PubMed

Affiliation: Universitat Erlangen, Medizinische Klinik IV, Erlangen, Germany.

ABSTRACT
Hypertension is an important independent risk factor for renal disease. If hypertension and chronic renal disease co-exist, as is common in patients with diabetes mellitus, the risk of cardiovascular disease is heightened. The importance of rigorous blood pressure control is recognized in current guidelines, with a recommended target of office blood pressure of < 130/80 mmHg; although ambulatory blood pressure may be more appropriate in order to identify the 24-hour hypertensive burden. Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase. Albuminuria not only indicates renal damage, but is also a powerful predictor of cardiovascular morbidity and mortality at least in patients with high cardiovascular risk and potentially pre-existing vascular damage. Management of the multiple factors for renal and cardiovascular disease is mandatory in the diabetic patient. The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal disease, as well as in hypertension and target-organ damage. The use of agents that target the RAS confer renoprotection in addition to antihypertensive activity. There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan. In addition to providing 24-hour blood pressure control, clinical studies in patients with diabetes show that telmisartan improves renal endothelial function, prevents progression from microalbuminuria to macroalbuminuria, slows the decline in glomerular filtration rate and reduces proteinuria in overt nephropathy. These effects cannot be solely attributed to blood pressure control. In contrast to other members of the ARB class, the renoprotective effect of telmisartan is not confined to the management of diabetic nephropathy; slowing the progression of albuminuria has been demonstrated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), which included diabetic and non-diabetic patients at high risk of cardiovascular events.

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Kaplan-Meier curve showing progression from microalbuminuria (30-300 mg/24 hours) to overt albuminuria (>300 mg/24 hours) in patients with type 2 diabetes during conventional and intensive blood pressure lowering [46].
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Figure 1: Kaplan-Meier curve showing progression from microalbuminuria (30-300 mg/24 hours) to overt albuminuria (>300 mg/24 hours) in patients with type 2 diabetes during conventional and intensive blood pressure lowering [46].

Mentions: The evidence is more conclusive for patients with type 2 diabetes. Over a 5-year follow-up, intensive control (mean SBP/DBP 128/75 mmHg) slowed the progression from normoalbuminuria to microalbuminuria, and from microalbuminuria to macroalbuminuria, compared with conventional control, which resulted in mean SBP/DBP of 137/81 mmHg (Figure 1) [46]. The benefit of vigorous blood pressure control in patients with diabetes is supported by recently reported findings from the ADVANCE trial: renal events were least frequent if SBP was < 110 mmHg and increased log-linearly with increasing SBP [47]. Although the Irbesartan in Diabetic Nephropathy Trial (IDNT) also observed that the incidence of a renal endpoint gradually fell with the progressive lowering of SBP to < 121 mmHg after 1 year, a similar reduction in mortality was apparent only to an SBP of 121-130 mmHg, and an SBP < 121 mmHg was associated with a three-fold increase in all-cause mortality [48]. The increase in mortality may be explained by the difference in the patient populations studied: patients in IDNT were at higher cardiovascular risk because of established diabetic nephropathy and 29% had a history of cardiovascular disease [49]. However, the lower the better may not be true, as shown in the Action to Control CardiOvascular Risk in Diabetes (ACCORD) trial, in which patients with type 2 diabetes at high cardiovascular risk did not benefit from SBP lowering below 120 mmHg [50].


Renal protection in diabetes: lessons from ONTARGET.

Ritz E, Schmieder RE, Pollock CA - Cardiovasc Diabetol (2010)

Kaplan-Meier curve showing progression from microalbuminuria (30-300 mg/24 hours) to overt albuminuria (>300 mg/24 hours) in patients with type 2 diabetes during conventional and intensive blood pressure lowering [46].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959007&req=5

Figure 1: Kaplan-Meier curve showing progression from microalbuminuria (30-300 mg/24 hours) to overt albuminuria (>300 mg/24 hours) in patients with type 2 diabetes during conventional and intensive blood pressure lowering [46].
Mentions: The evidence is more conclusive for patients with type 2 diabetes. Over a 5-year follow-up, intensive control (mean SBP/DBP 128/75 mmHg) slowed the progression from normoalbuminuria to microalbuminuria, and from microalbuminuria to macroalbuminuria, compared with conventional control, which resulted in mean SBP/DBP of 137/81 mmHg (Figure 1) [46]. The benefit of vigorous blood pressure control in patients with diabetes is supported by recently reported findings from the ADVANCE trial: renal events were least frequent if SBP was < 110 mmHg and increased log-linearly with increasing SBP [47]. Although the Irbesartan in Diabetic Nephropathy Trial (IDNT) also observed that the incidence of a renal endpoint gradually fell with the progressive lowering of SBP to < 121 mmHg after 1 year, a similar reduction in mortality was apparent only to an SBP of 121-130 mmHg, and an SBP < 121 mmHg was associated with a three-fold increase in all-cause mortality [48]. The increase in mortality may be explained by the difference in the patient populations studied: patients in IDNT were at higher cardiovascular risk because of established diabetic nephropathy and 29% had a history of cardiovascular disease [49]. However, the lower the better may not be true, as shown in the Action to Control CardiOvascular Risk in Diabetes (ACCORD) trial, in which patients with type 2 diabetes at high cardiovascular risk did not benefit from SBP lowering below 120 mmHg [50].

Bottom Line: Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase.There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan.These effects cannot be solely attributed to blood pressure control.

View Article: PubMed Central - HTML - PubMed

Affiliation: Universitat Erlangen, Medizinische Klinik IV, Erlangen, Germany.

ABSTRACT
Hypertension is an important independent risk factor for renal disease. If hypertension and chronic renal disease co-exist, as is common in patients with diabetes mellitus, the risk of cardiovascular disease is heightened. The importance of rigorous blood pressure control is recognized in current guidelines, with a recommended target of office blood pressure of < 130/80 mmHg; although ambulatory blood pressure may be more appropriate in order to identify the 24-hour hypertensive burden. Even lower blood pressure may further reduce the progression of chronic kidney disease, but the incidence of cardiovascular events may increase. Albuminuria not only indicates renal damage, but is also a powerful predictor of cardiovascular morbidity and mortality at least in patients with high cardiovascular risk and potentially pre-existing vascular damage. Management of the multiple factors for renal and cardiovascular disease is mandatory in the diabetic patient. The renin-angiotensin system (RAS) plays a pivotal role in the progression of renal disease, as well as in hypertension and target-organ damage. The use of agents that target the RAS confer renoprotection in addition to antihypertensive activity. There is extensive evidence of the renoprotective effect of angiotensin II receptor blockers (ARBs), and specifically telmisartan. In addition to providing 24-hour blood pressure control, clinical studies in patients with diabetes show that telmisartan improves renal endothelial function, prevents progression from microalbuminuria to macroalbuminuria, slows the decline in glomerular filtration rate and reduces proteinuria in overt nephropathy. These effects cannot be solely attributed to blood pressure control. In contrast to other members of the ARB class, the renoprotective effect of telmisartan is not confined to the management of diabetic nephropathy; slowing the progression of albuminuria has been demonstrated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), which included diabetic and non-diabetic patients at high risk of cardiovascular events.

Show MeSH
Related in: MedlinePlus