Personalized Treatment in IgA Nephrpopathy (PersTIgAN)

IgA Nephropathy (IgAN) is the most common primary glomerulonephritis, a major cause of end stage renal disease. Different therapeutic options are available, but only a fraction of patients responds to specific treatments. Guidance predicting response is currently lacking. To serve this urgent need, the project aims at developing a biomarker-based algorithm that predicts drug response in IgAN, personalizing intervention and significantly improving patient management. The project is based on extensive previous work on urinary peptide/protein biomarkers and on IgAN by consortium members. The applicants have demonstrated that classifiers based on urinary peptides enable early detection and intervention in chronic kidney disease, guided by specific, personal, molecular profiles. Further studies demonstrated the presence of specific biomarkers for IgAN. The ability of urinary peptides to display drug response could be demonstrated in recent studies. The technology, capillary electrophoresis coupled mass spectrometry (CE-MS), is a routine analytical technique applied for individual diagnosis, also in large randomized clinical trials. Further, partners in PersTIgAN have conducted large IgAN registry projects. Based on these extensive previous data, the application of CE-MS to guide personalized intervention in IgAN is proposed. Using samples from patients with known outcome from multiple clinical centres, urinary peptides significantly associated with response to specific treatment will be identified. An algorithm to predict response based on the urinary peptides and, if applicable, on other relevant variables, will be developed and tested in an independent sample. If the algorithm enabling personalized intervention in IgAN shows significant benefit, a well powered clinical trial will be designed to support implementation in routine care. The large number of leading clinical centres as partners in the consortium will substantially ease clinical implementation.

IgA Nephropathy (IgAN) is the most common primary glomerulonephritis and a major cause of end stage renal disease in adult patients. Different therapeutic options are available, but only a fraction of patients responds to specific treatments. Guidance predicting prognosis and response to treatment can either be only used at time of biopsy or has limited potential for the individual patient (i.e. limited personalisation). To serve this urgent need, the project aimed at developing a biomarker-based algorithm that predicts the prognosis and if possible also drug response in IgAN, personalising intervention and significantly improving patient management. The project was based on extensive previous work on urinary peptide/protein biomarkers and on IgAN by consortium members. The technology used for identification of urinary proteomic profiles was capillary electrophoresis coupled mass spectrometry (CE-MS). This is a routine analytical technique applied for individual diagnosis, also in large randomised clinical trials. Based on the analysis of IgAN patients urine samples and clinical data the consortium Perstigan has now identified a urinary proteomic profile, which was called IgAN237. The specific, personal, molecular profile IgAN237 demonstrated risk stratification comparable to a (invasive) biopsy-guided stratification, and a significant better prediction of kidney prognosis compared to conventional clinical parameters. An added pragmatic prospective study (addendum to the project proposal) will now demonstrate the usability of that concept in daily medical practice. Further, partners in Perstigan have conducted large IgAN registry projects. An algorithm to predict response based on the urinary peptides and on other relevant variables was developed and tested in an independent test population sample.