Multicentre Prospective Open Label Clinical Study to Evaluate the Effect of Personalized Therapy on Patients With Immunoglobulin A Nephropathy.

BACKGROUND AND RATIONALE. Idiopathic Immunoglobulin A nephropathy (IgAN) is the most common biopsy-proven glomerulonephritis in the world. It is more prevalent in Asia than in Europe and the US. Approximately 40% of IgAN patients reach end-stage kidney disease (ESKD) 20 years after their kidney biopsy. The high prevalence of ESKD shows that IgAN has a significant economic impact in the all countries because renal replacement therapy is costly. Moreover, the disease's onset in the second and third decades of life represents a social challenge because young adult patients are very active and highly productive in the workplace. This challenge is one more reason to move from a generalized therapy for all patients to a personalized therapy.

The first edition of the KDIGO guidelines, published in 2012, suggested different therapeutic approaches for IgAN patients based on the clinical setting. However, the KDIGO guidelines do not consider the presence of active (endocapillary and extracapillary lesions) and chronic (tubulointerstitial lesions) renal lesions at the time of the kidney biopsy for therapy decision. The investigators of the clinical study in IgAN patients (CLIgAN) will consider for the patient's stratification the type of renal lesions, preliminarily, and then the clinical parameters as estimated glomerular filtration rate (eGFR) and proteinuria because the categorization of proteinuria and eGFR is not enough for a complete diagnosis of the disease.

AIMS. Considering the critical role of kidney biopsy, in the CLIgAN study the investigators plan to evaluate (i) the effect of corticosteroids combined with RASBs in IgAN patients with active renal lesions (ACIgAN) versus RASBs for 3 months followed by oral corticosteroids to determine whether the renal lesions are reversed by immediate corticosteroid therapy; (ii) the effect of SGLT2i in patients with chronic or moderate renal lesions (CHRONIgAN) to determine whether a delay of the ESKD onset is achieved; (iii) after the prediction of ESKD through the IgAN CDSS tool (DialCheck), to determine whether personalized therapy delays the impairment of the renal function; (iv) finally, on a small cohort of active and chronic IgAN patients enrolled in the CLIgAN study, a cutting edge-molecular study will be conducted to evaluate the effect of precision therapy (PRECIgAN).

STUDY DESIGN. The investigators have designed a prospective, multicentre, open-label clinical study that includes two multicentre randomized controlled trials (RCTs) based on the kidney biopsy report.

In the first RCT, patients with active renal lesions (E1 and/or C1), daily proteinuria >0.5 g and GFR ≥ 30 ml/min/1.72 m2 will be enrolled. They will be randomized to receive corticosteroids combined with RASBs in the experimental arm or RASBs alone in the control arm. Aim of this trial is to demostrate the benefit of corticosteroids in patients with active renal lesions.