32 INTRODUCTION IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the general popula- tion. In a significant percentage of cases, the disease progresses slowly evolving into renal failure, and even- tually leading to end-stage renal disease (ESRD). In re- lation to its high incidence and because it affects the young adult population, IgAN is a major cause of ESRD. Specific treatment is not available, but many therapeutic approaches have been investigated. Cur- rently, there has been no consensus reached concern- ing treatment. A systematic review (1) of immunosup- pressive therapy in IgAN based on 13 eligible random- ized controlled trials involving 623 patients estab- lished that steroids were associated with a lower risk of progression to ESRD and lower urinary protein excre- tion; the use of alkylating agents demonstrated re- duced urinary protein excretion. Pozzi et al (2, 3) ob- tained improved renal survival using a high-dose steroid protocol in patients with preserved renal func- tion and proteinuria >1 g/day. Another recent trial demonstrated an advantage conferred by the com- bined use of cortisone and cytotoxic therapy in a pop- ulation characterized by a progressive course (4). Tak- en as a whole, these studies confirm the efficacy of im- munosuppressants in disease control; however, given the wide spectrum of clinical outcomes in the natural history of IgAN, the benefits of their use must out- weigh the risk of their serious adverse effects. There- fore, immunosuppressive therapy cannot always be justified. Hence, identification of reliable prognostic indices that can be used to guide treatment decision- making in these patients is warranted. A number of studies have investigated the clinical and pathological predictors of long-term outcomes in IgAN. However, these results have never been extrap- olated to other clinical settings. Unfortunately, since results can be “biased” by local clinical strategies, it is evident that they might not be used with the same JNEPHROL 2006; 19: 32-40 O O RIGINAL RIGINAL INVESTIGA INVESTIGA TION TION www.sin-italy.org/jnonline/vol19n1/ A validated model of disease progression in IgA nephropathy Riccardo Magistroni 1 , Luciana Furci 1 , Marco Leonelli 1 , Mario Masellis 2 , Giulia Ligabue 1 , Leonardo Lucchi 1 , Antonio Lupo 3 , Brigida Brezzi 3 , Giovanni Gambaro 3 , Luca Manganelli 1 , Giada Pedrazzi 1 , Marco Ricardi 1 , Luisa Bormioli 1 , Alberto Albertazzi 1 1 Division of Nephrology, University of Modena and Reggio Emilia - Italy 2 Division of Neurology, Faculty of Medicine, University of Toronto, Toronto - Canada 3 Division of Nephrology, University of Verona, Verona - Italy ABSTRACT: Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the general population. There is accumulating evidence that immunosuppressive treatment is efficacious in IgAN. However, it is critical to define appropriate indicators for this therapy especially in the wake of potentially deleterious side effects to immunosuppressives. Methods: This study retrospectively reviewed IgAN cases collected since 1981 to identify clinical and/or histological parameters for disease progression; 310 patients with biopsy proven IgAN, diagnosed from January 1981 to March 2004, were included. Results: We defined a clinical prognostic index (CPI) using multivariate analysis, which incorporated these clinical/ histological parameters. Semiquantitative scores were assigned as follows: 2 points if creatinine (Cr) was >1.4 mg/dL, 1 point if proteinuria was >1 g/24 hr, 1 point if a patient was affected by hypertension, and 1 point if a patient was older than 30 yrs. Dividing our population into two groups (scores 0-2 = low CPI group; scores 3-5 = high CPI group), we demonstrated a significantly different 10-yr renal survival rate; in the low CPI group, renal survival since time of biopsy at 10 yrs was 91.7%; in the high CPI group the renal survival at 10 yrs was 35%. We validated the CPI in an independent sample from Verona (validation group) and demonstrated similar results for the CPI. Conclusions: The CPI is convenient to use for defining the risk of disease progression. Key words: IgAN, Proteinuria, Histology, Corticosteroids, Cyclophosphamide, Progression