Influence of the ACE gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease

1999 ◽  
Vol 34 (2) ◽  
pp. 273-278 ◽  
Author(s):  
Laureano Pérez-Oller ◽  
Roser Torra ◽  
Celia Badenas ◽  
Montserrat Milà ◽  
Alejandro Darnell
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Gene Polymorphism ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Ace Gene ◽  
Ace Gene Polymorphism ◽  
Progression Of Renal Failure ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Association between the ACE I/D gene polymorphism and progressive renal failure in autosomal dominant polycystic kidney disease: A meta-analysis

2019 ◽  
Author(s):  
Noel Pabalan ◽  
Phuntila Tharabenjasin ◽  
Yardnapar Parcharoen ◽  
Adis Tasanarong
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Gene Polymorphism ◽  
Polycystic Kidney Disease ◽  
Fixed Effects ◽  
Autosomal Dominant ◽  
Meta Analysis ◽  
Polycystic Kidney ◽  
Progressive Renal Failure ◽  
Autosomal Dominant Polycystic Kidney

AbstractObjectiveThe angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism is involved in a wide range of clinical outcomes. This makes ACE I/D an important genetic marker. Updating the genetic profile of ACE I/D and raising the evidence for its role in renal disease is therefore needed. Reported associations of ACE I/D with progressive renal failure (PRF) in autosomal dominant polycystic kidney disease (ADPKD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.MethodsMulti-database search yielded 18 articles for inclusion in the meta-analysis. Risks (odds ratios [ORs] and 95% confidence intervals) were estimated by comparing the ACE genotypes (heterozygote ID, homozygotes DD and II). Heterogeneous (random-effects) pooled associations were subjected to outlier treatment which yielded fixed-effects outcomes and split the findings into pre- (PRO) and post- (PSO) outlier status. Subgroup analysis was based on ethnicity (Asian/Caucasian) and minor allele frequency (maf). The ≥ 0.50 maf subgroup indicates higher frequency of the variant II genotype over that of the common DD genotype, otherwise, the subgroup is considered < 0.50 maf. Stability of the associative effects was assessed with sensitivity treatment. Temporal trend of association was examined with cumulative meta-analysis.ResultsIn the PSO analysis, overall effects were null (ORs 0.99-1.02) but not in the subgroups (Asian and ≥ 0.50 maf), where in presence of the D allele (DD/ID) and the I allele (II), increased (ORs 1.63-5.62) and reduced (OR 0.22) risks were observed, respectively. Of these pooled effects, the Asian and ≥ 0.50 maf homozygous DD genotypes had high ORs (5.01-5.63) indicating elevated magnitude of effects that were highly significant (Pa < 10−5) and homogeneous (I2 = 0%), in addition to their robustness. In contrast, the Caucasian and < 0.50 maf subgroup effects were: (i) non-heterogeneous (fixed-effects) at the outset, which did not require outlier treatment and (ii) non-significant (ORs 0.91-1.10, Pa = 0.15-0.79). Cumulative meta-analysis revealed increased precision of effects over time.ConclusionsPRF in ADPKD impacted the Asian and ≥ 0.50 maf subgroups where DD homozygote carriers were up to 6-fold susceptible. The high magnitude of these effects were highly significant, homogeneous and robust indicating strong evidence of association.

scholarly journals Evaluation of common polymorphisms of eNOS gene and ACE gene in autosomal dominant polycystic kidney disease patients and their association with hypertension and renal failure

2019 ◽  
Vol 10 (1) ◽  
pp. e04-e04
Author(s):  
Tahereh Malakoutian ◽  
Bahareh Madadi ◽  
Ahmad Ebrahimi
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Enos Gene ◽  
Polycystic Kidney ◽  
Ace Gene ◽  
Control Subjects ◽  
Significant Difference ◽  
Autosomal Dominant Polycystic Kidney

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most hereditary renal disease that leads to end-stage renal disease (ESRD). Objectives: Since there is no available parameter to assess the clinical course of ADPKD and its outcome, yet, the aim of our study was evaluation of the association of common polymorphisms of eNOS and ACE genes with clinical manifestations (kidney failure and hypertension) in ADPKD. Patients and Methods: Seventy-five ADPKD patients and 100 control subjects participated in our study. Around 7.5 cc of whole blood was taken from each participant and sent to the genetic laboratory. DNA was obtained from them by the phenol chloroform extraction and ethanol precipitation techniques. Then genotyping for I/D polymorphism of ACE gene and Glu298 ASP and T786C polymorphisms of eNOS gene was performed by PCR electrophoresis and molecular evaluation by special primers for two genes. Results: The frequency of DD polymorphism of ACE gene and TC polymorphism of T786C of eNOS were considerably elevated in ADPKD individuals than control subjects. No significant difference between groups regarding Glu298 ASP polymorphisms of eNOS gene was detected. In ADPKD patients, 29 patients (39%) had hypertension, 5 patients (6.7%) had diabetes and 43 patients (57%) had glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 . The polymorphisms of ACE and eNOS genes were not meaningfully different regarding diabetes, high blood pressure, GFR and plasma creatinine in ADPKD individuals (P>0.05). Conclusion: In our study, we could not find any association between polymorphisms of ACE and eNOS genes with renal insufficiency and hypertension in ADPKD patients.

scholarly journals Recent advances in the clinical management of autosomal dominant polycystic kidney disease

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 116 ◽  
Author(s):  
Roser Torra
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Hepatic Cysts ◽  
Live Births ◽  
Recent Advances ◽  
Systemic Disorder ◽  
Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic systemic disorder causing the development of renal and hepatic cysts and decline in renal function. It affects around 1 in 1,000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. This article reviews recent advances in ADPKD and focuses mainly on diagnosis, management, and prediction of the course of the disease.

scholarly journals Factors influencing progression of renal failure in autosomal dominant polycystic kidney disease.

1995 ◽  
Vol 6 (6) ◽  
pp. 1634-1642
Author(s):  
G Choukroun ◽  
Y Itakura ◽  
G Albouze ◽  
J L Christophe ◽  
N K Man ◽  
...  
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Protein Intake ◽  
Pressure Control ◽  
Polycystic Kidney ◽  
Rate Of Progression ◽  
Progression Of Renal Failure ◽  
Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.

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