Primary glomerulonephritides with nephrotic syndrome. Limitations of therapy in adult patients

Thirty years of clinical studies have shown that a correct therapeutic approach to human glomerulonephritides with nephrotic syndrome requests the evaluation of three important parameters such as renal biopsy, long monitoring of daily proteinuria and renal function. In addition, age and clinical manifestations should be considered. Corticosteroids, alkylating agents (cyclophosphamide, chlorambucil) and purine analogues are currently used in the treatment of primary glomerulonephritis (minimal-change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous (MGN) and membranoproliferative glomerulonephritis (MPGN)), however results are different. Patients with nephrotic syndrome in MCD when treated with corticosteroids and/or cytotoxic drugs have complete or partial remission in a more than 90% of cases. On the contrary, nephrotic FSGS remits completely or partially only in 50% of treated cases when a more aggressive and prolonged immunosuppressive therapy is carried out. Data from clinical trials in MGN patients are controversial, however it is evident that a greater percentage of patients with stage 1 and stage 2 renal lesions benefit from corticosteroids in association with immunosuppressive drugs. Finally, no encouraging data have been obtained by clinically controlled trials in patients with MPGN. Future perspectives suggest the use of other drugs such as receptor blockade of cytokines and growth factors, administration of cytokine antagonists, intracellular signalling blockade and gene therapy with antisense oligonucleotides. Unfortunately, until specific therapies become available, we have to use unspecific or only symptomatic therapy.