ACE inhibition induces regression of proteinuria and halts progression of renal damage in a genetic model of progressive nephropathy

Remuzzi, Andrea; Fassi, Anna; Bertani, Tullio; Perico, Norberto; Remuzzi, Giuseppe

doi:10.1016/s0272-6386(99)70385-9

Cited by 61 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the experience in clinical trials may not be immediately translated to the clinical practice, these reassuring figures challenge the common belief that even a transient increase in serum potassium or creatinine levels should lead physicians to withdraw RAS inhibitor therapy (9). The rationale for such an attitude remains difficult to understand if one considers that in animal models RAS inhibition has been reported to be antiproteinuric and renoprotective even when treatment is initiated late in the course of renal disease (11). Similarly, post hoc analyses of the Ramipril Efficacy in Nephropathy trial found that RAS inhibitor therapy offers renoprotection and is well tolerated in patients with nondiabetic chronic nephropathies, even when the GFR is Ͻ30 ml/ min per 1.73 m 2 (12).…”

mentioning

confidence: 99%

Continuum of Renoprotection with Losartan at All Stages of Type 2 Diabetic Nephropathy

Remuzzi¹,

Ruggenenti²,

Perna³

et al. 2004

Journal of the American Society of Nephrology

113

View full text Add to dashboard Cite

Abstract. Renin angiotensin system inhibitor therapy is seldom offered to individuals who have diabetes and advanced chronic kidney disease because of safety concerns. In this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and overt nephropathy. Incidence of ESRD, hospitalizations for heart failure, withdrawals for adverse events, and proteinuria during losartan or conventional treatment were compared within three tertiles of baseline serum creatinine concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9 to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in highest, middle, and lowest tertiles, respectively. For every 100 patients with serum creatinine Ͼ2.0, 1.6 to 2.0, or Ͻ1.6 mg/dl, respectively, 4 yr of losartan therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855, US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest and middle tertile, respectively. Withdrawals for adverse events other than heart failure were comparable between tertiles and treatment groups. Proteinuria decreased more on losartan than on placebo in all tertiles (highest, 24 versus Ϫ8%; middle, 16 versus Ϫ8%; lowest, 15 versus Ϫ10%). In proteinuric individuals with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for heart failure and was well tolerated at all levels of renal function. Angiotensin II antagonism is a suitable and welltolerated treatment for individuals with type 2 diabetes even with GFR levels approaching renal replacement therapy.Pharmacologic interruption of the renin angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) is increasingly advocated as a standard therapeutic intervention for patients with chronic nephropathies, regardless of whether systemic hypertension is an associated feature (1). Prospective, randomized, placebocontrolled trials found that, at comparable BP control, ACEi are more effective than non-ACEi therapy in limiting progression to ESRD in patients with type 1 diabetic nephropathy (2) or with nondiabetic, proteinuric chronic nephropathies (3-5).

show abstract

mentioning

confidence: 99%

Continuum of Renoprotection with Losartan at All Stages of Type 2 Diabetic Nephropathy

Remuzzi¹,

Ruggenenti²,

Perna³

et al. 2004

Journal of the American Society of Nephrology

113

View full text Add to dashboard Cite

show abstract

“…In many animal models and some clinical studies (24)(25)(26)(27), such protection has already been established. An experimental study by the Remuzzi group (26) showed that ACEI therapy could indeed suspend proteinuria and glomerulosclerosis development, interrupting the progression of chronic allograft dysfunction in rodents.…”

Section: Discussionmentioning

confidence: 99%

Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

Moscoso-Solorzano¹,

Kirsztajn

Ozaki

et al. 2008

Braz J Med Biol Res

View full text Add to dashboard Cite

A major problem in renal transplantation is identifying a grading system that can predict long-term graft survival. The present study determined the extent to which the two existing grading systems (Banff 97 and chronic allograft damage index, CADI) correlate with each other and with graft loss. A total of 161 transplant patient biopsies with chronic allograft nephropathy (CAN) were studied. The samples were coded and evaluated blindly by two pathologists using the two grading systems. Logistic regression analyses were used to evaluate the best predictor index for renal allograft loss. Patients with higher Banff 97 and CADI scores had higher rates of graft loss. Moreover, these measures also correlated with worse renal function and higher proteinuria levels at the time of CAN diagnosis. Logistic regression analyses showed that the use of angiotensin-converting enzyme inhibitor (ACEI), hepatitis C virus (HCV), tubular atrophy, and the use of mycophenolate mofetil (MMF) were associated with graft loss in the CADI, while the use of ACEI, HCV, moderate interstitial fibrosis and tubular atrophy and the use of MMF were associated in the Banff 97 index. Although Banff 97 and CADI analyze different parameters in different renal compartments, only some isolated parameters correlated with graft loss. This suggests that we need to review the CAN grading systems in order to devise a system that includes all parameters able to predict long-term graft survival, including chronic glomerulopathy, glomerular sclerosis, vascular changes, and severity of chronic interstitial fibrosis and tubular atrophy.

show abstract

“…The pathogenesis of angiotensin II effects on the transglomerular passage of protein includes modulation of efferent arterioler tone, inter-glomerular pressure and glomerular plasma flow [3], [4]. The presence of functional receptors for angiotensin II on glomerular podocytes may directly contribute to the pathogenesis of proteinuria via increased expression of the podocyte slit protein nephrin [5].…”

Section: Introductionmentioning

confidence: 99%

ACE Gene Polymorphism Frequency in Steroid Resistance and Steroid Sensitive in Patients with Idiopathic Nephrotic Syndrome

2016

IJSR

View full text Add to dashboard Cite

Background: The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been suggested as a modifier factor in benign renal diseases. However, the direct evidence from genetic association studies in adult Egyptian patients with idiopathic nephrotic syndrome remains inconclusive. Therefore, the present study aimed to investigate the frequency of ACE gene polymorphism I/D alleles, DD and II genotypes in Egyptian adult nephrotic patients and its association to their steroid response. Methods: One hundred and ninety-eight adult patients older than 19 years of age with idiopathic nephrotic syndrome were enrolled in this study. Another 102 healthy adults with no history of kidney disease volunteered were participate. The distribution frequencies of the DD, ID, II genotypes were determined were determined using a PCR method. Results: The frequency of ACE gene polymorphism Dallele and DD genotypes were significantly higher in steroid responsive adult patients with idiopathic nephrotic syndrome compared with healthy control. In contrast, the frequency of polymorphism I allele and the heterozygous of ID genotype were significantly lower in steroid responsive adult patients idiopathic nephrotic syndrome compared with healthy control. Finally, the frequency of II genotype was not significantly different between the steroid resistance, steroid sensitive and control groups. Conclusions: These findings suggest that the D allele or DD homozygous genotype could be significant genetic markers for the development of steroid response in adult Egyptian patients with idiopathic nephrotic syndrome.

show abstract

ACE inhibition induces regression of proteinuria and halts progression of renal damage in a genetic model of progressive nephropathy

Cited by 61 publications

References 27 publications

Continuum of Renoprotection with Losartan at All Stages of Type 2 Diabetic Nephropathy

Continuum of Renoprotection with Losartan at All Stages of Type 2 Diabetic Nephropathy

Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

ACE Gene Polymorphism Frequency in Steroid Resistance and Steroid Sensitive in Patients with Idiopathic Nephrotic Syndrome

Contact Info

Product

Resources

About