B Cells in Idiopathic Nephrotic Syndrome (BLADE)

Inclusion Criteria: Male or female children (≥6 and <18 years old) and adults. Patients with biopsy-proven MCD or FSGS or MesGN candidate to (prospective cohort) or treated with (retrospective cohort) anti-CD20 monoclonal antibodies (when possible) due to INS and fulfilling the following conditions: SDNS: defined as two consecutive relapses of the NS during corticosteroid therapy, or within 14 days of ceasing therapy; FRNS: defined as two or more relapses within 6 months of initial response, or four or more relapses in any 12-month period; Note: relapse in pediatric patients is defined as a urinary protein to creatinine ratio > 2000 mg/g or a positive urine dipstick (≥ 3+) for 3 consecutive days; in adult is defined as a urinary protein to creatinine ratio > 3500 mg/g or by proteinuria >3.5 g/day after remission has been obtained. Patients will be included irrespective of previous (retrospective cohort) or planned (prospective cohort) treatments with anti-CD20 monoclonal antibodies. SRNS not associated with known genetic abnormalities of the glomerular barrier consisting in persistent nephrotic-range proteinuria (no complete/partial remission) despite prednisone 1 mg/kg/day or 2 mg/kg every other day for >4 months (adults) or despite prednisone 60 mg/m2/day or 2 mg/kg/day to a maximum 60 mg/day (pediatrics), having no pathogenic mutations at the sequencing analysis for the known genes associated with NS (see appendix Table 1 for the full list of genes); Note: patients with biopsy-proven MCD/MesGN/FSGS recurrence in the kidney graft after renal transplantation with clinical features NS will be also considered. SRNS due to mutations in podocyte genes consisting in persistent nephrotic-range proteinuria (no complete/partial remission) despite prednisone 1 mg/kg/day or 2 mg/kg every other day for > 4 months (adults) or despite prednisone 60 mg/m2/day or 2 mg/kg/day to a maximum 60 mg/day (pediatrics), harbouring pathogenic mutations at the sequencing analysis for genes associated with NS (see appendix Table 1for the full list of genes). This last condition will not consider possible treatments for the enrolment, as the patients usually are not treated with anti-CD20 monoclonal antibodies. For adults: written informed consent according to the guidelines of the Declaration of Helsinki. For children: written informed consent (according to the guidelines of the Declaration of Helsinki) of parent(s) or guardian. Healthy volunteers Healthy subjects (>18 years) not known to suffer of any significant illness, not assuming any medication or drug on a regular basis, and whose mental state is such that they are able to understand and give valid consent to the study will be recruited among researchers and personnel of the IRCSS - Mario Negri Institute for Pharmacological Research. Only healthy subjects with negative urine analysis (urine dipstick, multistick will be considered for this study. Exclusion Criteria: Reasonable possibility of a secondary cause of NS: active hepatitis B or C infection, or other chronic systemic infections; malignancy; drug abuse. Legal incapacity, intellectual disability/mental retardation, dementia, uncooperative attitude or any other evidence that patient will not be able to understand the study procedures and aims and to give written informed consent.