Rheumatoid Arthritis and Pla2r-associated Mebranous Nephropathy . Cause or Coincidence?

Abstract

Background: Rheumatoid arthritis affects 0.5% of adults in our country. It is an inflammatory disease that predominantly affects the joints causing destruction of the articular cartilage. Approximately 50% of patients present with extra-articular manifestations. Renal involvement is relatively frequent and clinically significant because it worsens the course and mortality of the primary disease. The histological renal damage observed in such patients includes a wide variety of entities and histological patterns with both glomerular and tubulointerstitial involvement, with secondary membranous nephropathy being one of the most common. Coexistence with primary membranous nephropathy is rare. Case Presentation: A 46-year-old man recently diagnosed with rheumatoid arthritis was referred to the nephrology department for deterioration of renal function and subnephrotic proteinuria. The autoimmune study showed positive anti-PLA2R. Due to the unusual association between both entities, it was decided to perform a renal biopsy which showed abundant spikes. The immunofluorescence study showed contiguous parietal IgG positivity (3+). Immunohistochemistry showed positive granular IgG4, confirming the diagnosis of PLA2R-associated membranous nephropathy. Conclusions: Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. The determination of anti-PLA2R has been a great advance in the rapid differential diagnosis of MN. In recent years, new target antigens associated with certain underlying pathologies have been discovered. However, PLA2R is not associated with any disease or exposure and therefore remains the antigen responsible for 80% of primary NMs. Anti-PLA2R antibodies can be produced by loss of central or peripheral tolerance. Whether these mechanisms are triggered by rheumatoid arthritis itself is difficult to prove. The cytokine TNF-like weak inducer of apoptosis (TWEAK) has been associated with rheumatoid arthritis. This proinflammatory molecule increases the expression of PLA2R in podocytes, sensitising them to the damaging action of anti-PLA2Rs, which could justify a causal relationship between the two pathologies. Treatment should be tailored to the individual risk profile for progression. Rituximab could be an optimal option for both entities.