Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients

Parving, Hans‐Henrik; Hommel, E.; Jensen, Bente; Hansen, Henrik Post

doi:10.1046/j.1523-1755.2001.00790.x

Cited by 90 publications

(53 citation statements)

References 18 publications

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“…Further study showed that an ARB-losartan (10), irbesartan (9), or valsartan (8)-significantly decreased urinary albumin excretion in normotensive type 2 diabetes. Consistent with the data obtained by these studies performed in Western countries (8,9,20,21), the present study demonstrates that telmisartan treatment elicits renoprotective effects in Japanese normotensive type 2 diabetic patients with microalbuminuria. Since changes in UACR were not significantly correlated with changes in blood pressure in normotensive subjects (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…The ACE-Inhibitor Trial to Lower Albuminuria in Normotensive Insulin-Dependent Subjects (ATLANTIS) study demonstrated that treatment with ramipril had no effect on glomerular filtration rate, but significantly decreased microalbuminuria in normotensive type 1 diabetic patients (20). Similarly, captopril significantly decreased albuminuria in normotensive type 1 diabetic patients with albuminuria > 300 mg/d (21). Further study showed that an ARB-losartan (10), irbesartan (9), or valsartan (8)-significantly decreased urinary albumin excretion in normotensive type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

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Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study

et al. 2008

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study

et al. 2008

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“…Whether ROS production in this model is persistent seems unlikely, because treatment with DMTU (6 h before and for only 1 wk after Adriamycin administration) partially prevents proteinuria, loss of HS, and heparanase overexpression at later stages. Treatment with an angiotensin-converting enzyme (ACE) inhibitor or AT1A ameliorates proteinuria in both human and experimental renal diseases, including AN, and provides renoprotection (21,(25)(26)(27)(28)(29)(30). Antiproteinuric treatment with AT1A in this study led to a partially restored glomerular HS expression.…”

Section: Discussionmentioning

confidence: 64%

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Kramer¹,

Hoven²,

Rops³

et al. 2006

Journal of the American Society of Nephrology

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Heparan sulfate (HS) in the glomerular basement membrane (GBM) is important for regulation of the charge-dependent permeability. Heparanase has been implicated in HS degradation in several proteinuric diseases. This study analyzed the role of heparanase in HS degradation in Adriamycin nephropathy (AN), a model of chronic proteinuria-induced renal damage. Expression of heparanase, HS, and the core protein of agrin (to which HS is attached) was determined on kidney sections from rats with AN in different experiments. First, expression was examined in a model of unilateral AN in a time-course study at 6-wk intervals until week 30. Second, rats were treated with the hydroxyl radical scavenger dimethylthiourea (DMTU) during bilateral AN induction. Finally, 6 wk after AN induction, rats were treated with angiotensin II receptor type 1 antagonist (AT1A) or vehicle for 2 wk. Heparanase expression was increased in glomeruli of rats with AN, which correlated with HS reduction at all time points and in all experiments. Treatment with DMTU prevented the increased heparanase expression, the loss of GBM HS, and reduced albuminuria. Finally, treatment of established proteinuria with AT1A significantly reduced heparanase expression and restored glomerular HS. In conclusion, an association between heparanase expression and reduction of glomerular HS in AN was observed. The effects of DMTU suggest a role for reactive oxygen species in upregulation of heparanase. Antiproteinuric treatment by AT1A decreased heparanase expression and restored HS expression. These results suggest involvement of radicals and angiotensin II in the modulation of GBM permeability through HS and heparanase expression.

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“…Activation of the renin angiotensin system (RAS) is associated with progression of both diabetic and nondiabetic kidney disease (2). Numerous studies have demonstrated that RAS blockade lowers the rate of urinary albumin excretion (UAE) and retards decline of renal function in diabetes (3)(4)(5)(6)(7). This protective effect probably reflects both the hemodynamic and nonhemodynamic effects of ACE inhibitors and angiotensin II (Ang II) receptor blockers.…”

mentioning

confidence: 99%

Oral Contraceptives, Angiotensin-Dependent Renal Vasoconstriction, and Risk of Diabetic Nephropathy

et al. 2005

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OBJECTIVE -Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear.RESEARCH DESIGN AND METHODS -Renal plasma flow (RPF) response to captopril, as an index of RAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1-24).RESULTS -Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril (9 Ϯ 10 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , P ϭ 0.6). In comparison, nondiabetic OC users showed a significant increase (69 Ϯ 35 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , P ϭ 0.02) (P ϭ 0.04 vs. nondiabetic OC nonusers). Diabetic OC nonusers demonstrated the anticipated vasodilator response (58 Ϯ 12 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , P Ͻ 0.0001). Diabetic OC users showed the largest responses (84 Ϯ 12 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , P ϭ 0.002) (P ϭ 0.04 vs. diabetic OC nonusers). Plasma renin activity did not vary with OC use (P ϭ 0.3). The RPF responses to captopril and angiotensin receptor blocker were highly correlated (r ϭ 0.72, P Ͻ 0.001), suggesting clear involvement of the RAS. In the observational study, 18% (6/33 [95% CI 4.3-32.1]) of OC users developed macroalbuminuria compared with 2% (2/81 [0 -5.9]) of OC nonusers (P ϭ 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression model, OC use remained a predictor for the development of macroalbuminuria (relative risk 8.90 , P ϭ 0.008).CONCLUSIONS -The strong association of OC use with angiotensin-dependent control of the renal circulation and the development of macroalbuminuria suggest that OC use may be a risk factor for diabetic nephropathy. Large prospective studies are required to further investigate this relationship. 28:1988 -1994, 2005 D iabetes is the leading cause of endstage renal disease in the U.S. Moreover, the number of patients diagnosed each year with end-stage renal disease secondary to diabetes is expected to grow from 41,000 in the year 2000 to 300,000 in the year 2030 (1). Activation of the renin angiotensin system (RAS) is associated with progression of both diabetic and nondiabetic kidney disease (2). Numerous studies have demonstrated that RAS blockade lowers the rate of urinary albumin excretion (UAE) and retards decline of renal function in diabetes (3-7). This protective effect probably reflects both the hemodynamic and nonhemodynamic effects of ACE inhibitors and angiotensin II (Ang II) receptor blockers. Diabetes CareFemale sex is a protective factor in the development of renal disease (8), but the mechanism remains elusive. Estrogen plays a role ...

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Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients

Cited by 90 publications

References 18 publications

Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study

Microalbuminuria Reduction with Telmisartan in Normotensive and Hypertensive Japanese Patients with Type 2 Diabetes: A Post-Hoc Analysis of the Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Oral Contraceptives, Angiotensin-Dependent Renal Vasoconstriction, and Risk of Diabetic Nephropathy

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