No abstract

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.

Our study and meta-analysis suggest caution in the interpretation of results from association studies enrolling heterogeneous populations. Further studies using new tests, which are free of the bias due to population stratification and ethnicity, are warranted.

ABSTRACT. Primary IgA nephropathy (IgAN) is characterized by recurrent episodes of macroscopic hematuria accompanied by upper respiratory tract infections or persistent asymptomatic microscopic hematuria with or without proteinuria. IgAN may involve one or more members of a family. Three generations of a cohort of 110 patients with biopsy-proven IgAN, living in Southern Italy, were checked for urinalysis, and the relative risk (RR) of developing the disease was evaluated. A total of 19 unrelated familial, 37 suspected, and 54 sporadic cases of IgAN were identified. Renal survival was estimated by the Kaplan-Meier method for censored data and compared by use of the log-rank test. More than 50% of the patients with IgAN clustered in kindred with more than two probably affected relatives. In 19 unrelated IgAN families, 8 had single-generation (SG) and 11 multigenerational (MG) involvement showing a prevalent vertical transmission of the trait. The RR was 16 times higher in first-degree relatives (odds ratio [OR], 16.4; 95% confidence interval [CI], 5.7 to 47.8; P < 0.0001) and >2 times higher, even if NS, in second-degree relatives (OR, 2.4; 95 % CI, 0.7 to 7.9; P = 0.145). The clinical and histologic picture of familial and sporadic IgAN appeared to be similar. The 20-yr renal survival rate from the apparent onset of the disease was significantly poorer in patients with familial (41%) than in patients with sporadic (94%) IgAN (P = 0.003). Furthermore, 15-yr renal survival from the time of renal biopsy was significantly worse in familial IgAN (P = 0.02); end-stage renal disease was present in 64% of familial and only in 8% of patients with sporadic IgAN. Finally, renal survival was significantly worse in patients belonging to families with SG rather than with MG involvement (P = 0.03). These data show, for the first time, that familial IgAN may be considered a nonbenign disease that occurs frequently in first-degree relatives. Familial IgAN has a poorer outcome than sporadic IgAN. Therefore, an accurate family history and urinalysis in all family members is urgently recommended in clinical practice. This procedure might avoid late referral of subjects with persistent and underestimated urinary abnormalities and late diagnosis of the disease.

No abstract