Ane Claudia Fernandes Nunes

Meta-Analysis of the Association of 4 Angiotensinogen Polymorphisms With Essential Hypertension A Role Beyond M235T?

Angiotensinogen (AGT) gene polymorphisms have been linked to increased risk of hypertension, but the data remain controversial. In this study we review the most commonly investigated polymorphisms at the AGT locus (other than M235T) and provide summary estimates regarding their association with essential hypertension, while addressing heterogeneity, as well as publication biases. Data on 26 818 subjects from 46 studies for the 4 most-studied AGT variants (T174M in exon 2 and 3 promoter variants: A-6G, A-20C, and G-217A) were meta-analyzed. Statistically significant associations with hypertension were identified for the T174M (odds ratio [OR]: 1.19; 95% CI: 1.07 to 1.33; P=0.002) and G-217A (OR: 1.37; 95% CI: 1.17 to 1.59; P=0.00006) polymorphisms. A dual but consistent effect was observed for the −20C allele, which was associated with a decreased risk of hypertension in populations of mixed and European ancestries (OR: 0.64; 95% CI: 0.44 to 0.92; P=0.02 and OR: 0.77; 95% CI: 0.65 to 0.91; P=0.003, respectively), but with a 24% increase in the odds of hypertension in Asian subjects (OR: 1.24; 95% CI: 1.04 to 1.48; P=0.02). No association of the A-6G variant with hypertension was detected. Current studies support the notion that single variants at the AGT might modulate the risk of hypertension but indicate caution in interpreting these results because of the putative presence of publication bias and gene-environment interactions.

Kidney Function and 24-Hour Proteinuria in Patients with Fabry Disease during 36 Months of Agalsidase Alfa Enzyme Replacement Therapy: A Brazilian Experience

Background. Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. Methods. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance (51Cr-EDTA mL/min/ 1.73 m2) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR ≥ 90mL/min/1.73 m2, stage II as 60–89 mL/min/1.73m2, stage III as 30–59 mL/min/1.73 m2, stage IV as 15–29 mL/min/1.73m2, and stage V as < 15 mL/min/1.73m2. Results. Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 ± 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered. Conclusion. Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests that agalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.

Prevalence of 4977bp Deletion in Mitochondrial DNA from Patients with Chronic Kidney Disease Receiving Conservative Treatment or Hemodialysis in Southern Brazil

Background. Damage to mitochondrial DNA (mtDNA) has been described in patients with chronic kidney disease (CKD). The presence of mtDNA 4977bp deletion in many different tissues can serve as a marker of this damage. However, no attempt has been made to detect the presence of mtDNA 4977bp in blood cells of patients with CKD. Methods. Polymerase chain reaction techniques (PCR) were used to detect mtDNA 4977bp deletion in blood samples of 94 CKD patients. Results. The prevalence of 4977bp deletion in mtDNA was 73.1% (38/52) in patients with CKD undergoing hemodialysis, 57.1% (27/42) in patients with CKD receiving conservative treatment, and 27.8% (15/54) in control samples (p < 0.001). Higher prevalence of this mutation was not associated with patient age (p = 0.54) or time on hemodialysis (p = 0.70). Conclusion. The higher prevalence of mtDNA 4977bp deletion in patients in this study indicates that the CKD can induce damage to mtDNA in blood cells and could be exacerbated by hemodialysis.

Renal Aspects and Enzyme Replacement Therapy of Fabry Disease

Ane Claudia Fernandes Nunes1, Elvino Jose Guardao Barros2, Virgilio Pimentel Delgado3 and Alvimar Goncalves Delgado4 1Laboratory of Cellular, Genetic and Molecular Nephrology (LIM-29) Division of Nephrology, Sao Paulo University Medical School University of Sao Paulo, Sao Paulo/ 2Service of Nephrology, Clinical Hospital of Porto Alegre Federal University of Rio Grande do Sul, Porto Alegre 3Service of Nephrology, Clementino Fraga Filho Hospital Federal University of Rio de Janeiro, Rio de Janeiro Federal Hospital of Bonsucesso, Rio de Janeiro 4Service of Nephrology, Clementino Fraga Filho Hospital Federal University of Rio de Janeiro, Rio de Janeiro Brazil