ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1

Perna, Annalisa; Ruggenenti, Piero; Testa, Alessandra; Spoto, Belinda; Benini, Roberto; Misefari, Valerio; Remuzzi, Giuseppe; Zoccali, Carmine

doi:10.1046/j.1523-1755.2000.00818.x

Cited by 79 publications

(54 citation statements)

References 18 publications

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“…This differential response to ACE inhibitor treatment was also observed in the EURODIAB Controlled Trial of Lisinopril in IDDM [5]. Curiously, while the D allele has been linked with higher ACE activity [6], several studies have indicated that the DD genotype could be associated with better response to the anti-proteinuric effect of ACE inhibitors in patients with diabetic nephropathy [75] and other renal diseases [76]. With these counter-intuitive findings, the precise manner in which the ACE genotype modifies response to ACE inhibitors remains unresolved.…”

Section: Discussionmentioning

confidence: 67%

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

et al. 2005

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Section: Discussionmentioning

confidence: 67%

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

et al. 2005

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“…These different trends were not explained by differences in patient characteristics that were similar between different genotypes. Of note, finding that BP control was also similar between groups suggests that different outcomes reflected a specific effect of the ACE I/D polymorphism on intrinsic kidney responsiveness to ACE inhibitor therapy (19). Consistently, a smaller study in patients with IgA nephropathy found more treatment-induced proteinuria reduction in those with the DD than in those with the ID or II genotype (55).…”

Section: Ace Inhibitorsmentioning

confidence: 76%

“…One randomized, double-blind, placebo-controlled, clinical trial, the Ramipril Efficacy In Nephropathy (REIN) study (34), was formally designed to test whether glomerular protein traffic and its modification by ACE inhibitor therapy influenced chronic renal disease progression. This study prospectively evaluated the relationships between ACE I/D polymorphism and kidney function loss by serial GFR measurements by goldstandard techniques in patients with different nondiabetic renal diseases (19). Data in 212 genotyped patients showed a similar rate of GFR decline and incidence of ESKD in different ACE I/D subgroups, an effect, however, that was the result of different response to ACE inhibitor and conventional therapy in considered groups.…”

Section: Nondiabetic Renal Diseasementioning

confidence: 99%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.

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“…12,[15][16][17] However, this relationship is controversial in some studies. 18,19 It has been suggested that DD genotype can have some impact on the rate of renal function loss, but that the impact of the genotype can be obscured by other risk factors. 20 Unfortunately, the contrasting studies are hard to compare, because of the heterogeneity in ethnic background, possible interactions with other genetic or environmental renal risk factors, and mostly small sample size.…”

Section: Discussionmentioning

confidence: 99%

DD Genotype of ACE Gene in Boys: May it be a Risk Factor for Minimal Change Nephrotic Syndrome?

2011

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It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

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ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1

Cited by 79 publications

References 18 publications

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

DD Genotype of ACE Gene in Boys: May it be a Risk Factor for Minimal Change Nephrotic Syndrome?

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