Biomedical subjects

Annalisa Perna

Publications and source records attributed to Annalisa Perna.

22 records · Page 2Linked to original sources

PubMed2002

Single Strand Conformation Polymorphism (SSCP) as a quick and reliable method to genotype M235T polymorphism of angiotensinogen gene.

OBJECTIVES: Conflicting results on the relationship between M235T polymorphism of angiotensinogen (AGT) gene and diabetic nephropathy are reported in the literature, probably due to the small number of subjects, to different inclusion criteria and the different genotype analysis methods used. The aim of the present study was to set up a fast, cheap and reliable method to allow the genotyping of M235T polymorphism in a large number of subjects. DESIGN AND METHODS: We developed in our laboratory a new specifically designed PCR-SSCP method for M235T genotyping whose specificity was compared with that of Allele Specific PCR (ASPCR) and Mutagenically Separated PCR (MS-PCR). The exact M235T genotype was estabilished by direct sequencing. The new PCR-SSCP method was then used to genotype a population of 1171 hypertensive, normoalbuminuric type II diabetes mellitus patients. The patients were also genotyped for ACE I/D polymorphism. For comparison a group of hypertensive non diabetic patients (n = 88) were also screened. RESULTS: The PCR-SSCP method identified the M235T polymorphism with no misinterpretation at variance with ASPCR and MS-PCR methods that showed a preferential amplification of the T allele. The rare Y248C polymorphism of the AGT gene was also detected by PCR-SSCP. In diabetic hypertensive patients the prevalence of TT genotype was higher than in normotensive healthy controls and equivalent to that found in hypertensive non diabetic patients. CONCLUSIONS: The PCR-SSCP method for detection of M235T polymorphism is a powerful and sensitive tool for rapid, cheap and efficient screening of a large number of samples. The results obtained with this method demonstrate an association of the TT genotype of AGT gene with hypertension, both in diabetic and non diabetic patients.

Adult↗

PubMed2001

ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy.

In this post hoc, secondary analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, an angiotensin-converting enzyme (ACE) inhibition risk/benefit profile was assessed in 322 patients with nondiabetic, proteinuric chronic nephropathies and different degrees of renal insufficiency. The rate of GFR decline (Delta GFR) and the incidence of end-stage renal disease (ESRD) during ramipril or non-ACE inhibitor treatment were compared within three tertiles of basal GFR. Delta GFR was comparable in the three tertiles, whereas the incidence of ESRD was higher in the lowest tertile than in the middle and highest tertiles. Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively. Delta GFR reduction was predicted by basal systolic (P < 0.0001), diastolic (P = 0.02), and mean (P < 0.001) BP and proteinuria (P < 0.0001) but not by basal GFR (P = 0.12). ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001). Adverse events were comparable among the three tertiles and within each tertile in the two treatment groups. Thus, disease progression and response to ACE inhibition do not depend on severity of renal insufficiency. The risk of ESRD and the absolute number of events saved by ACE inhibition is highest in patients with the lowest GFR. However, renoprotection is maximized when ACE inhibition is started earlier and when long-lasting treatment may result in GFR stabilization and definitive prevention of ESRD.

Adult↗

PubMed2000

Chronic proteinuric nephropathies. II. Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism. Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen)

In the Ramipril Efficacy in Nephropathy study, ramipril decreased the rate of GFR decline (deltaGFR) and progression to end-stage renal disease (ESRD) in 352 patients with proteinuric chronic nephropathies. This study investigated whether in these patients disease outcome and response to treatment were affected by gender or insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. deltaGFR (0.43 +/- 0.05 versus 0.48 +/- 0.08 ml/min per 1.73 m2) and incidence of ESRD (23 and 22%, respectively) were comparable in male and female patients. However, compared to conventional treatment, ramipril decreased deltaGFR (-52% versus -19%) and progression to ESRD (-74% versus -40%) more effectively in women than in men. Thus, the relative risk (95% confidence interval [CI]) of events (ESRD) between conventional and ramipril treatment was 5.52 (1.59 to 19.17, P = 0.003) in women, but only 1.80 (1.08 to 2.97, P = 0.02) in men. This gender-related effect of ramipril was associated with more reduction in proteinuria (-7.8 +/- 4.2% versus -21.9 +/- 5.7%, P = 0.05) and was still evident even after correction for potentially confounding factors such as baseline GFR, daily sodium intake, ramipril dose, BP control, and concomitant treatment with diuretics or dihydropyridinic calcium channel blockers (adjusted RR [95% CI]: women, 5.07 [1.26 to 20.38], P = 0.02; men, 1.44 [0.85 to 2.44], P = 0.17). Ramipril uniformly decreased deltaGFR and incidence of ESRD in women with either DD (-39% and - 100%) or II + ID (-71% and -82%) genotype, and in men (-25% and -50%) with the DD genotype, but had no beneficial effect in men with the II + ID genotype (+18% and +34%). Thus, the relative risk of events (ESRD) between conventional and ramipril-treated men was higher in subjects with the DD genotype (1.85; 0.69 to 4.94) and lower in those with the II +/- ID genotype (0.71; 0.28 to 1.80). Again, in parallel with deltaGFR and events, proteinuria decreased in women with DD (-23.3 +/-8.0%) or II + ID (-16.0 +/- 9.5%) genotype and in men with the DD genotype (-14.8 +/- 7.0%), but did not change in men with II + ID genotype (+ 1.0 +/- 7.8%). Of note, the ACE genotype-related effect of ramipril was still evident even after correction for the above potentially confounding factors (adjusted RR [95% CI]: DD, 2.52 [0.83 to 7.63], P = 0.10; II + ID, 0.35 [0.12 to 1.01], P = 0.05). Thus, among patients with chronic proteinuric nephropathies, men are at increased risk of progression due to their lower response to ACE inhibitor treatment. ACE inhibition is uniformly renoprotective in women regardless of the ACE polymorphism, and in men with the DD genotype, but is virtually devoid of beneficial effects in men with the II or ID genotype. This information may help to guide therapeutic interventions in clinical practice and to interpret the results of prospective trials in chronic renal disease.

Adolescent↗

PubMedDate not supplied

Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.

BACKGROUND: In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease. METHODS: We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5-10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat. FINDINGS: Of 338 patients who were randomised, three (two assigned intensified and one allocated conventional blood-pressure control) never took study drugs and they were excluded. Over a median follow-up of 19 months (IQR 12-35), 38/167 (23%) patients assigned to intensified blood-pressure control and 34/168 (20%) allocated conventional control progressed to end-stage renal disease (hazard ratio 1.00 [95% CI 0.61-1.64]; p=0.99). INTERPRETATION: In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy, no additional benefit from further blood-pressure reduction by felodipine could be shown.

Adolescent↗