Crescents in membranous nephropathy
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Prevalence and Clinical Significance of Crescents in Membranous Nephropathy
Crescents are a rare finding in membranous nephropathy (MN), with reported prevalence ranging from 0.1% to 1.4% in large biopsy series Alawieh2020Rodriguez2014Qian2016. Their presence is much less common in primary MN compared to secondary forms, and when present, they often indicate a more severe or complex disease process Alawieh2020Li2024Rodriguez2014.
Pathogenesis and Associated Conditions: ANCA, Anti-GBM, and PLA2R
Crescents in MN can occur in both primary and secondary forms of the disease. They are frequently associated with superimposed conditions such as anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis or anti-glomerular basement membrane (GBM) disease Alawieh2020Basford2011Rodriguez2014+1 MORE. Some cases are linked to anti-PLA2R antibodies, indicating primary MN, but crescents are more often seen in secondary MN, which may be related to malignancies, infections, or autoimmune diseases Alawieh2020Rodriguez2014Qian2016. Rarely, crescents can develop in MN without any identifiable secondary cause or associated autoantibodies Sunder2023Hill1978.
Clinical Presentation: Proteinuria, Hematuria, and Renal Dysfunction
Patients with MN and crescents typically present with heavy proteinuria, significant hematuria, and often a rapid decline in kidney function Alawieh2020Li2024Wang2015+1 MORE. Compared to MN without crescents, these patients are more likely to have hypertension, higher serum creatinine, lower glomerular filtration rate (GFR), and more severe histological changes such as segmental sclerosis, arteriosclerosis, and interstitial fibrosis Li2024Wang2015Qian2016. Pulmonary symptoms may also be present, especially in cases associated with ANCA or anti-GBM antibodies Alawieh2020Balafa2015.
Prognosis and Outcomes: Risk of Progression to ESRD
The presence of crescents in MN is associated with a worse prognosis. Patients with crescents have lower rates of remission, poorer renal function at follow-up, and a higher risk of progression to end-stage renal disease (ESRD) compared to those without crescents Alawieh2020Li2024Wang2015+1 MORE. The percentage of glomeruli with crescents correlates with the risk of poor outcomes . However, some patients, especially those with only focal crescent involvement and mild chronic changes, may maintain better renal function Alawieh2020Rodriguez2014Qian2016.
Treatment Approaches: Immunosuppression and Rituximab
Most patients with MN and crescents receive immunosuppressive therapy, commonly corticosteroids and cyclophosphamide, with some also receiving mycophenolate mofetil, azathioprine, or rituximab Alawieh2020Sunder2023Wang2015+1 MORE. Plasmapheresis is used in cases with anti-GBM or severe ANCA-associated disease . Rituximab has shown promise in achieving remission and recovery of kidney function in some cases . Despite aggressive treatment, the overall prognosis remains guarded, and more aggressive or tailored therapies may be needed Li2024Wang2015.
Pathological Features: Histology and Immunofluorescence
Histologically, MN with crescents shows a membranous pattern with varying degrees of crescent formation, often accompanied by segmental sclerosis, capillary loop necrosis, and interstitial fibrosis Alawieh2020Li2024Rodriguez2014+1 MORE. Immunofluorescence typically reveals granular subepithelial IgG and complement deposition, with weaker IgG4 staining in cases with crescents . PLA2R positivity is seen in a subset, supporting a diagnosis of primary MN in some cases Alawieh2020Li2024Rodriguez2014+1 MORE.
Conclusion
Crescents in membranous nephropathy are rare but signal a more aggressive disease course, often associated with secondary causes or superimposed autoimmune processes. Their presence is linked to worse renal outcomes and a higher risk of progression to ESRD. Early recognition and aggressive management are crucial, but further research is needed to clarify the best treatment strategies and the underlying mechanisms driving crescent formation in MN Alawieh2020Li2024Wang2015+3 MORE.
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