Renoprotective therapy: titration against urinary protein excretion

Jong, de Paul; Navis, Gerarda; Zeeuw, de Dick

doi:10.1016/s0140-6736(99)90122-8

Cited by 96 publications

(59 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Amelioration of the progression of renal disease has always been associated with a decrease of proteinuria (10,23). Furthermore, in diabetic renal disease, residual albuminuria during treatment is a predictor of the decline in GFR (9); therefore, UAE should be reduced as far as possible (11). Recent studies have demonstrated clearly the antiproteinuric effect and the renoprotective efficacy of ARB in patients with type 2 diabetes (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Interventions that have ameliorated the progression of DN have always been associated with a reduction in urinary protein excretion (10), with residual albuminuria during treatment being a predictor of the rate of decline in the GFR (9). Therefore, renoprotective therapy should aim to achieve the maximal antiproteinuric effect (11). Recent prospective randomized studies have shown that the interruption of the renin-angiotensin system (RAS) with angiotensin II receptor blockers (ARB) in patients with type 2 diabetes and overt nephropathy delays the progression of renal disease (12,13).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Navarro¹,

Mora²,

Muros³

et al. 2005

Journal of the American Society of Nephrology

115

View full text Add to dashboard Cite

Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n ‫؍‬ 30) or to a control group (n ‫؍‬ 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-␣ (R ‫؍‬ 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was ؊16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-␣ also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-␣ in patients who were treated with PTF (R ‫؍‬ 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-␣ excretion.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Navarro¹,

Mora²,

Muros³

et al. 2005

Journal of the American Society of Nephrology

115

View full text Add to dashboard Cite

show abstract

“…Studies of diabetic and nondiabetic kidney disease suggest the initial degree of reduction in albuminuria after blockade of the reninangiotensin system (RAS) predicts an attenuated rate of decline in GFR, as reviewed by Rossing (1). As a consequence, albuminuria may serve as a surrogate end point for monitoring treatment efficacy and prognosis in DN (4).…”

mentioning

confidence: 99%

Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Jacobsen¹,

Andersen²,

Jensen³

et al. 2003

Journal of the American Society of Nephrology

194

146

View full text Add to dashboard Cite

Abstract. Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m 2 . Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes (1,2). Antihypertensive treatment, especially ACE-I, has been shown to reduce albuminuria, to diminish loss of kidney function, and to improve survival in type I patients with DN (1-3). Studies of diabetic and nondiabetic kidney disease suggest the initial degree of reduction in albuminuria after blockade of the reninangiotensin system (RAS) predicts an attenuated rate of decline in GFR, as reviewed by Rossing (1). As a consequence, albuminuria may serve as a surrogate end point for monitoring treatment efficacy and prognosis in DN (4).A superior effect on BP and a tendency toward a more pronounced drop in urinary albumin excretion of dual blockade of the RAS compared with single blockade has been reported in type II patients with microalbuminuria (5). We have recently shown additional drop in albuminuria and diastolic BP when adding an angiotensin receptor blocker (ARB) to angiotensinconverting enzyme inhibitor (ACE-I) treatment in type l patients with albuminuria Ͼ1 g/24 h and BP Ͼ135/85 mmHg, despite conventional antihypertensive therapy including three different agents (6). However, this subgroup is highly selected; therefore, it may differ from the patients in general with DN, especially with regard to RAS activity and ...

show abstract

“…The antiproteinuric response upon blockade of the RAS has been demonstrated to predict the subsequent long-term rate of decrease in glomerular filtration rate (GFR), i.e., the greater the initial decrease in albuminuria, the less the long-term decrease in kidney function (8,9). Consequently, the short-term reduction in albuminuria may serve to monitor treatment efficacy and long-term prognosis in diabetic nephropathy, and it has previously been advocated that albuminuria should be reduced as far as possible to obtain maximal renoprotective effects (10).…”

mentioning

confidence: 99%

Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy

et al. 2003

View full text Add to dashboard Cite

OBJECTIVE -We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy. RESEARCH DESIGN AND METHODS -A total of 20 patients (17 men and 3 women)with type 2 diabetes along with hypertension and nephropathy were enrolled in this doubleblind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the 51 Cr-EDTA plasmaclearance technique.RESULTS -During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349Ϫ1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 Ϯ 3/72 Ϯ 2 mmHg (mean Ϯ SE); and GFR was 77 Ϯ 6 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 (mean Ϯ SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17Ϫ38) compared with ACEI alone (P Ͻ 0.001). There was a modest reduction in systolic/ diastolic 24-h ABP of 3/2 mmHg (Ϫ2 to 8 systolic, Ϫ2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (Ϫ1 to 9) ml ⅐ min -1 ⅐ 1.73 m -2 .CONCLUSIONS -Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy. Diabetes Care 26:2268 -2274, 2003D iabetic nephropathy occurs in 30 -40% of all diabetic patients and has become the leading cause of endstage renal disease in the western world (1). In diabetic patients, albuminuria independently predicts poor renal and cardiovascular outcome (1). Several clinical studies have clearly demonstrated that blockade of the renin-angiotensin system (RAS), either by an ACE inhibitor (ACEI) or an angiotensin II receptor blocker (ARB), reduces albuminuria, retards the progressive loss in renal function, and improves survival (2-7). The antiproteinuric response upon blockade of the RAS has been demonstrated to predict the subsequent long-term rate of decrease in glomerular filtration rate (GFR), i.e., the greater the initial decrease in albuminuria, the less the long-term decrease in kidney function (8,9). Consequently, the short-term reduction in albuminuria may serve to monitor treatment efficacy and long-term prognosis in diabetic nephropathy, and it has previously been advocated that albuminuria should be reduced as far as possible to obtain maximal renoprotective effects (10).Despite the proven benefit of ...

show abstract

Renoprotective therapy: titration against urinary protein excretion

Cited by 96 publications

References 10 publications

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy

Contact Info

Product

Resources

About