Rapidly progressive glomerulonephritis (RPGN) is clinical syndrome defined by the rapid loss of renal function, accompanied by features of a nephritic syndrome with proteinuria, glomerular haematuria and often oliguria. Although relatively uncommon, early recognition and prompt diagnosis and treatment are crucial to prevent irreversible loss of renal function.
RPGN is a nephrology emergency which needs special attention. If the disease left untreated typically progresses to end-stage renal disease over a period of weeks to a few months.
CGN is commonly categorized based on the pattern of immunoglobulin deposition by immunohistochemistry, and is most frequently caused by:
• Anti-glomerular basement membrane (GBM) disease with linear immunoglobulin deposition.
• Immune complex glomerulonephritis with granular immunoglobulin deposition.
• Pauci-immune glomerulonephritis most often associated with anti- neutrophil cytoplasm antibody (ANCA).
Important differential diagnoses include primary vasculitis syndrome, Goodpasture syndrome, SLE, IgA vasculitis, malignancies, cryoglobulinemia, infectious diseases such as post-streptococcal acute glomerulonephritis, infectious endocarditis, and type C hepatitis infection. It is important to first exclude infectious diseases and malignancies.
Early diagnosis and initiation of appropriate therapy is essential to minimize the degree of irreversible renal injuries. The therapy of most patients involves pulse methyl-prednisolone followed by daily oral prednisone, oral or intravenous (IV) cyclophosphamide, and in some cases plasmapheresis. Empiric therapy with IV methylprednisolone should be begun in patients with severe disease with adding of plasmapheresis especially if the patient has hemoptysis .If a renal biopsy performs soon after initiating empiric therapy the histological abnormalities will not alter.
Despite various immunosuppressive therapy protocols mortality of ANCA positive RPGN patients is still high, also prognosis of anti-GBM antibody disease is poor , actually treatment of RPGN and AAV are serious challenges in nephrology medicine which needs more clinical trial studies in larger groups of patients.
Advances in our understanding of the pathogenesis of various forms of CGN have led to the discovery of novel therapeutic targets as:,
Fostamatinib is a spleen tyrosine kinase inhibitor, which blocks intracellular signalling and Fc receptor activation
Imatinib is a tyrosine kinase inhibitor with specificity for c-Abl, c-Kit and platelet-derived growth factor receptors
Bortezomib (velcade) is a protease inhibitor, which targets plasmablasts and mature plasma cells.
Erlotinib is an epithelial growth factor receptor (EGFR)
Eculizumab is a monoclonal antibody that blocks cleavage of C5 to C5a.
Programmed Death-1 Receptor, C-jun Amino Terminal Kinase (JNK) Signalling , Seleciclib (Roscovitine), Stem Cell Therapy
These are the future potential therapies and the use of these agents already established for the treatment of other diseases shows some promise; however, we are some way from the widespread clinical implementation of these treatments. The results of early clinical trials of newer agents, as well as larger multi-Centre trials designed to clarify the role of established therapies such as TPE are eagerly awaited. |
