Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme

Nonoguchi, Hiroshi; Nakayama, Yushi; Shiigai, Tatsuo; Inoue, T; Inoue, Hideki; Kohda, Yukimasa; Honda, Yu; Tomita, Kimio

doi:10.5414/cnp68209

Cited by 6 publications

(7 citation statements)

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“…There have been various studies (Yong et al 2006;Nonoguchi et al 2007) reporting on varying renal outcome in patients with IgAN in respect of their ACE gene profile. The D alelle is believed to affect the renoprotective effects of ACEI/ARB therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies showed that patients with the DD genotype do not respond to therapy and have a higher incidence of developing ESRF. Nonoguchi et al (2007), in a recent study (113 patients with CKD of which 75 had IgAN), reported that ARB therapy extended the time to ESRF for patients with the II and ID genotype but not the DD genotype, suggesting that DD patients have diminished response to ARB in terms of renoprotection. Ng et al (2005), in a meta analysis of 14,724 diabetic patients, reported a protective role of the II genotype for Asian patients with diabetic nephropathy, whereby there was a reduction in the number with ESRF when they were treated with ACEI/ATRA.…”

Section: Discussionmentioning

confidence: 99%

“…There have also been recent reports (Yong et al 2006;Nonoguchi et al 2007) that ACE ID polymorphism influences the responses of patients with IgAN to ACEI/ARB therapy. In a recent report, Dillon (2004) suggested that polymorphism of the ACE gene may have so far failed to predict either susceptibility to or progression of IgA nephropathy, but the D allele could predict a favourable response to renin-angiotensin blockade.…”

Section: Introductionmentioning

confidence: 98%

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High dose Losartan and ACE gene polymorphism in IgA nephritis

Woo

Chan

Choong

et al. 2008

HUGO J

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Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 ± 0.8 gm/day compared to 1.7 ± 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min -1 year -1 for high dose ARB compared to 3.2-3.5 ml min -1 year -1 for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P \ 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P \ 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

High dose Losartan and ACE gene polymorphism in IgA nephritis

Woo

Chan

Choong

et al. 2008

HUGO J

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“…This polymorphism has been postulated to affect the efficacy of ACEIs and ARBs on BP control, renal protection, and proteinuria; however, despite a large number of studies, there is no consensus, on the basis of an individual's ACE genotype, on whether ACEI or ARB treatment is preferential or should be modified. Literature can be found showing that the response to ACEIs or ARBs is not dependent on the polymorphism (28,29), is dependent on the II genotype (30,31), or is dependent on the DD genotype (32-34). It should be pointed out that differences in salt intake, underlying kidney disease, race/ethnicity, and initial level of renal function often make the interpretation and direct comparison between studies difficult.…”

Section: Therapy Based On Drug Target Variantsmentioning

confidence: 99%

Can We Personalize Treatment for Kidney Diseases?

Rovin

McKinley

Birmingham

2009

Clinical Journal of the American Society of Nephrology

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The idea of individualizing therapies to obtain optimal clinical results is not new but has only recently been applied to kidney diseases. Nonetheless, kidney disorders present a variety of opportunities to personalize medicine. Here, the heterogeneity of kidney disorders is reviewed to provide a rationale for pursuing personalized medicine. Data on adjusting therapy on the basis of pharmacogenetics/genomics and pharmacodynamics are summarized to demonstrate where the field is, and biomarker studies that reflect the future of personalized medicine are discussed. The goal of this review is to demonstrate that we can personalize therapy for kidney diseases but that considerable investment in new research will be required for personalized medicine to be routinely used in nephrology clinics. Clin J Am Soc Nephrol 4: 1670 -1676. doi: 10.2215 T he phrase personalized medicine has been used with increasing frequency in the lay press, and academia has embraced this concept by forming centers of personalized medicine within their health systems. The goal of determining the right drug, for the right patient, at the right time is not new, however, and has been actively pursued for some time in oncology using genomic tools to look for gene mutations or variations in gene expression that may affect therapy. Other disciplines, including nephrology, have joined this endeavor, although the data on personalized therapies for kidney diseases are still very preliminary. This mini-review presents these data to provide a framework for expanding research into individualized therapies for kidney diseases. Building a Case for Personalized Medicine in Kidney DiseasesThere is ample evidence that kidney disorders that are characterized by a specific constellation of clinical signs and symptoms display the molecular and biochemical heterogeneity that lends itself to individualized medicine. For example, despite similar clinical and histologic phenotypes, pediatric allograft rejection could be divided into three molecular groups by microarray analysis of total renal biopsy RNA expression (1). One of these acute rejection molecular groups was enriched for expression of B cell genes, and by immunohistochemistry, abundant B cells were found to be present in renal biopsy tissue from this subset of patients. Although the numbers were small, recovery from rejection and steroid responsiveness were significantly better in the patients who did not have B cells infiltrating their allografts. These data suggest that determining the molecular subtype of acute rejection before treatment may be used to identify patients who are likely to be steroid resistant and who may benefit from a different antirejection protocol (2).Molecular heterogeneity is also found in primary and secondary glomerular diseases. Pediatric patients who had FSGS and displayed nephrotic-range proteinuria or renal insufficiency could be differentiated from patients who did not have nephrosis or renal insufficiency, respectively, on the basis of unique renal cortical RNA expression (3...

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“…count when using ARBs as a means of renoprotective therapy (94). A meta-analysis of randomized clinical trials of RAS inhibitor therapy in diabetics and non-diabetics was performed on progression to ESRD as the primary outcome variable in DD, ID, or II genotypes considered separately.…”

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confidence: 99%

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

2012

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Abstract. About 80% of CKD (chronic kidney disease) patients are hypertensive, and kidney function and blood pressure are clearly related to both physiologic and pathologic conditions in a "vicious cycle". In this pathologic scenario, there is a renin-angiotensin system (RAS) hyperactivity associated to progression of renal damage. Current guidelines indicate as the first choice of antihypertensive intervention, the pharmacologic blockade of the RAS. Nonetheless, both response to treatment and renal protection have considerable inter-individual variability. The main aims of this review are to describe the genetic characteristics of RAS components and to identify the possible pharmacogenetic implications for RAS-blocker drugs in the hypertension-CKD scenario. To date, RAS polymorphisms have not been consistently associated to antihypertensive response and studies focusing on CKD are scarce. Nonetheless, pharmacogenetic studies for the RAS-blocker drugs could still be further explored, especially with new generation tools and focusing not only on the antihypertensive response, but also on renal protection as well.

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Low-responders to angiotensin II receptor blockers and genetic polymorphism in angiotensin-converting enzyme

Cited by 6 publications

References 0 publications

High dose Losartan and ACE gene polymorphism in IgA nephritis

High dose Losartan and ACE gene polymorphism in IgA nephritis

Can We Personalize Treatment for Kidney Diseases?

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

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