Trial reportJournal of the American Society of Nephrology : JASN2008
ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy.
Trial report in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00308347 (A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes Mellitus and Nephropathy), which is not on this map. Cited by 42 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients With Non-insulin Dependent Diabetes Mellitus and Nephropathy
Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.The Cochrane database of systematic reviews · 2024Pooled it
- Do genetic variants of the Renin-Angiotensin system predict blood pressure response to Renin-Angiotensin system-blocking drugs?: a systematic review of pharmacogenomics in the Renin-Angiotensin system.Current hypertension reports · 2011Pooled it
- Serum C-Terminal Agrin Fragment With Acute and Long-Term Exercise and Angiotensin II Type I Receptor Blockade.Journal of cachexia, sarcopenia and muscle · 2025Trial
- Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKD.Journal of the American Society of Nephrology : JASN · 2018Trial
- The angiotensin-I converting enzyme gene I/D variation contributes to end-stage renal disease risk in Chinese patients with type 2 diabetes receiving hemodialysis.Molecular and cellular biochemistry · 2016Trial
- Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.Diabetologia · 2024Article
- Kunxian capsule alleviates podocyte injury and proteinuria by inactivating β-catenin in db/db mice.Frontiers in medicine · 2023Article
- SGLT2 inhibitors improve kidney function and morphology by regulating renal metabolic reprogramming in mice with diabetic kidney disease.Journal of translational medicine · 2022Article
- Precision Nephrology in Patients with Diabetes and Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- OMICS in Chronic Kidney Disease: Focus on Prognosis and Prediction.International journal of molecular sciences · 2021Review
- Precision medicine approaches for diabetic kidney disease: opportunities and challenges.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Review
- RHAPSODY, Biomarkers and Novel Clinical Trial design in type 2 diabetes (T2D) and prediabetes.Endocrinology, diabetes & metabolism · 2021Article
- Perspectives on a Way Forward to Implementation of Precision Medicine in Patients With Diabetic Kidney Disease; Results of a Stakeholder Consensus-Building Meeting.Frontiers in pharmacology · 2021Article
- Contribution of Predictive and Prognostic Biomarkers to Clinical Research on Chronic Kidney Disease.International journal of molecular sciences · 2020Review
- The Role of Prognostic and Predictive Biomarkers for Assessing Cardiovascular Risk in Chronic Kidney Disease Patients.BioMed research international · 2020Review
- Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria.BMJ open sport & exercise medicine · 2020Article
- Multimarker Panels in Diabetic Kidney Disease: The Way to Improved Clinical Trial Design and Clinical Practice?Kidney international reports · 2019Review
- Impact of a Complement Factor H Gene Variant on Renal Dysfunction, Cardiovascular Events, and Response to ACE Inhibitor Therapy in Type 2 Diabetes.Frontiers in genetics · 2019Article
- New clinical trial designs for establishing drug efficacy and safety in a precision medicine era.Diabetes, obesity & metabolism · 2018Review
- Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene predicts renal outcomes and death and influences the effect of losartan in these patients. Pharmacogenetic analyses were performed comparing losartan with placebo administered with conventional blood pressure-lowering therapy in 1435 (95%) of the 1513 RENAAL study patients. The primary endpoint was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease (ESRD) or death. Cox regression models were stratified on baseline proteinuria and included treatment, geographic region, ACE/ID genotype, and treatment x genotype interaction. Within the placebo group, subjects with the ID or DD genotype were more likely than those with the II genotype to reach the composite endpoint (by 17.5% and 38.1%, respectively, P = 0.029) or its individual components. Within the losartan group, genotype did not correlate with reaching the composite endpoint. Compared with placebo, however, losartan reduced the risk of reaching the composite endpoint by 5.8% (95% confidence interval, -23.3, 28.0), 17.6% (3.8, 29.4), and 27.9% (7.0, 44.1) among those with the II, ID, and DD genotypes, respectively. Similar trends were demonstrated for the individual endpoints. In conclusion, proteinuric type 2 diabetic patients with the D allele of the ACE gene have an unfavorable renal prognosis, which can be mitigated and even improved by losartan.
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