RESUMO
BACKGROUND: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. METHODS: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). RESULTS: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). CONCLUSION: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Adulto , Método Duplo-Cego , Feminino , Hong Kong , Humanos , Masculino , Valina/uso terapêutico , ValsartanaRESUMO
BACKGROUND: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated. METHODS: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF). RESULTS: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF. CONCLUSION: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.