Nerve Epidermal Growth Factor-Like 1 Protein (NELL-1) Expression in Mercury-Related Membranous Nephropathy: Is It a True Association or a Chance Occurrence?

Background: Neural epidermal-like growth factor-like 1 (NELL-1) is a protein kinase C binding protein expressed in osteoblasts and renal tubules. It is expressed in 5%–25% glomerular cells at the mRNA level. Membranous Nephropathy (MN) is characterized by the presence of antibodies against certain types of antigens on the glomerular basement membrane. The most common one implicated in primary MN is an antibody against PLA2R. Many newer antigens have been discovered in the recent past, which are proven to cause secondary MN, one of which is NELL-1. NELL-1 has been associated with malignancy-associated MN and also recently associated with traditional indigenous medications containing mercury. In this study, we study the expression of NELL-1 in mercury-associated MN. Materials and Methods: Records of ten cases of Mercury -associated MN were retrieved from the Institute medical archives and NELL-1 Immunohistochemistry was performed in all ten cases. Results: NELL-1 was found to be positive in 50% of the cases of Mercury associated MN. In addition, mass spectrometric studies was performed, which revealed the common Mercuric compound associated to be ‘Swaskalpa’, Sudarshana Melugu’ and Rasagandhi Mezhugu’. Conclusion: This study highlights why it is important to diagnose mercury-associated MN by a pathologist by picking up the finer histopathological clues and by using NELL-1 immunohistochemistry, especially in PLA2R-negative patients. The former is true as most of the time a history of mercuric compound intake is missed out.