ABSTRACT
BACKGROUND: Immunoglobulin (Ig) A nephropathy (IgAN) is characterized by mesangial deposits of IgA1 and C3, often with co-deposits of IgG. We attempted to clarify the clinical significance of mesangial IgG deposition in patients with IgAN. METHODS: We retrospectively reviewed 57 patients who were diagnosed with IgAN on the basis of pathological examination of renal biopsy specimens obtained between October 2006 and December 2010. Subjects were divided into two groups: IgA+IgG deposition (IgA-IgG) group (n = 29) and IgA deposition alone (IgA) group (n = 28). The study outcome was complete remission (CR), defined as negative proteinuria by dipstick urinalysis and urinary erythrocytes of less than 1-4/high-power field. RESULTS: Proteinuria was greater in the IgA-IgG group than the IgA group (1.1 ± 0.8 vs. 0.7 ± 0.6 g/day, Mann-Whitney U test, P = 0.042). Capillary wall IgA deposits were noted more frequently in the IgA-IgG group than the IgA group (59 vs. 11 %, Fisher's exact test, P = 0.014). During the median follow-up period of 33.3 months (range 6-55 months) in the 57 patients, we observed CR in 24 cases (42.1 %). After the start of treatment, urinary abnormalities disappeared earlier in the IgA group than in the IgA-IgG group (log rank test, P = 0.012). Cox's regression model showed that IgG deposition reduced the hazard ratio for CR (hazard ratio 0.35; 95 % confidence interval 0.14-0.82, P = 0.014). Therefore, IgG deposition is a risk factor for persistent urinary abnormalities. CONCLUSION: Mesangial IgG deposition is associated with more severe clinical features in patients with IgAN.
Subject(s)
Glomerular Mesangium/immunology , Glomerulonephritis, IGA/immunology , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Adolescent , Adult , Biopsy , Female , Fluorescent Antibody Technique , Glomerular Mesangium/pathology , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Proportional Hazards Models , Proteinuria/immunology , Proteinuria/pathology , Reagent Strips , Remission Induction , Retrospective Studies , Risk Factors , Severity of Illness Index , Treatment Outcome , Urinalysis/instrumentation , Urine/cytology , Young AdultABSTRACT
BACKGROUND: Cinacalcet has been shown to be effective in lowering serum intact parathyroid hormone (iPTH) levels in patients with advanced secondary hyperparathyroidism (SHPT). We investigated clinical factors influencing therapeutic response to cinacalcet for SHPT refractory to active vitamin D sterols. METHODS: A total of 57 hemodialysis patients with SHPT (iPTH >300 pg/mL) were enrolled in this 28-week, prospective, observational study. Cinacalcet was started at an initial dose of 25 mg/day; the dose of cinacalcet was titrated to achieve the following: 3.5 ≤ phosphate (P) ≤ 6.0 mg/dL; 8.4 ≤ adjusted calcium (Ca) ≤ 10.0 mg/dL; 60 ≤ iPTH ≤ 180 pg/mL). Parathyroid ultrasonographic examination was performed at the start of cinacalcet treatment. Patients were divided into two groups on the basis of iPTH levels after 28 weeks: Group A, iPTH ≤180 pg/mL; Group B, iPTH >180 pg/mL. RESULTS: Serum iPTH and P levels at baseline were significantly higher in Group B than Group A. The number of enlarged parathyroid glands (PTGs) (estimated volume ≥500 mm(3) or major axis ≥10 mm), which presumably had nodular hyperplastic lesions, and the largest and the total volume of detectable PTGs were significantly greater in Group B compared with Group A. In our multivariate logistic regression analysis, patients with two or more enlarged PTGs had a significant risk of poor response to cinacalcet treatment (odds ratio 5.68, 95% confidence interval 1.19-32.66, P = 0.0363). CONCLUSION: These results indicate that the number of enlarged PTGs could predict therapeutic response of cinacalcet in patients with advanced SHPT.
