Primary membranoproliferative glomerulonephritis (MPGN) represents a group of rare kidney disorders associated with complement activation. There is no specific therapy and the prognosis is unfavorable: about half of all patients, mostly children, develop end-stage renal disease and need dialysis within 10 years of onset. MPGN is heterogeneous and patients have abnormal activation at different levels of the complement system. Several drugs targeting complement have been already approved or are investigated in trials for other conditions. However, trials to test new therapeutics will be heavily influenced by the heterogeneity of MPGN. The current classification into C3 glomerulopathy (C3G) and immunecomplex- mediated MPGN (IC-MPGN) based on only histological data, does not reflect the etiology and is inefficient. Thus, there is an obligation in future trials to ensure that each patient is maximally characterised in order to receive the right drug.

Previous studies identified four patient clusters, instrumental to define early and late complement activation. DECODE will implement this strategy by combining omics approaches (i.e. WES, proteomics and metabolomics) and hierarchical clustering analysis to define a precise stratification of patients with C3G/IC-MPGN, and to identify specific biomarkers, which will be instrumental for diagnosis, predicting prognosis and tailoring the right therapeutic strategy for the right patients.