From the Guidelines
A NELL-1 positive biopsy in membranous nephropathy is a significant finding that requires careful consideration of the patient's prognosis and treatment options, although the provided evidence does not directly address NELL-1, emphasizing the importance of relying on the most recent and highest quality studies available. When managing membranous nephropathy, it is crucial to consider the latest clinical practice guidelines, such as those discussed in the 2021 KDIGO clinical practice guideline for the management of glomerular diseases, as commented on in the 2023 American Journal of Kidney Diseases publication 1.
Key Considerations
- The initial presentation of membranous nephropathy can range from asymptomatic proteinuria to severe nephrotic syndrome, and the disease course is unpredictable, as noted in the commentary on the KDIGO guideline 1.
- Risk stratification has historically relied on the degree of proteinuria, eGFR at the time of kidney biopsy, and the extent of irreversible histologic damage, but recent prognostication may use anti-PLA2R antibody titers, highlighting the evolving understanding of the disease 1.
- The significance of a NELL-1 positive biopsy, while not directly addressed in the provided evidence, suggests a distinct disease subtype that may require targeted treatment approaches, potentially including immunosuppressive therapy and thorough cancer screening due to associations with malignancies.
Treatment Approach
Given the lack of direct evidence on NELL-1 in the provided studies, treatment should be guided by the most recent clinical guidelines and expert consensus, prioritizing a personalized approach based on the patient's specific clinical presentation, disease activity, and potential underlying conditions. This may involve:
- Immunosuppressive therapy, potentially including corticosteroids and calcineurin inhibitors, tailored to the patient's response and disease severity.
- Regular monitoring of renal function, proteinuria, and, when available, NELL-1 antibody levels to assess treatment response and disease activity.
- A thorough cancer screening, considering the potential association between NELL-1 associated membranous nephropathy and underlying malignancies.
From the Research
Significance of NELL-1 Positive Biopsy in Membranous Nephropathy
- A NELL-1 positive biopsy in membranous nephropathy indicates the presence of autoantibodies against the NELL-1 antigen, which is a rare but recognized target antigen in membranous nephropathy 2, 3, 4.
- NELL-1 associated membranous nephropathy is more likely to be associated with malignancy, and up to a third of patients with NELL-1-associated MN have associated cancer 4.
- The presence of NELL-1 autoantibodies can be used as a diagnostic biomarker, and immunosuppressive treatments directed against B-cells and antibody production may be effective in treating NELL-1 positive membranous nephropathy 2, 3.
- Thrombotic complications such as renal vein thrombosis are recognized but less reported in NELL-1-positive MN, and further research is needed to explore serum anti-NELL-1 antibodies as biomarkers and optimal anticoagulation strategies in MN patients at risk of thrombotic events 3.
- Mercury exposure has been associated with the development of NELL-1 positive membranous nephropathy, and cessation of mercury exposure and treatment with immunosuppressive agents may lead to improvement in patients with this condition 5.
Clinical Implications
- Patients with NELL-1 positive membranous nephropathy require evaluation for underlying malignancy and thrombotic complications 3, 4.
- Immunohistochemical staining for NELL-1 antigen can be used to confirm the diagnosis of NELL-1 associated membranous nephropathy 3, 4.
- Treatment of NELL-1 positive membranous nephropathy may involve immunosuppressive therapy, anticoagulation, and cessation of mercury exposure 2, 3, 5.