Secondary Membranous Nephropathy Related to Amyotrophic Lateral Sclerosis

Introduction: Membranous nephropathy (MN) can be subdivided into primary and secondary forms. Primary form is an autoimmune disease and characterized by nephrotic syndrome, accounting for 70% of MN. In most, there are autoantibodies against phospholipase A2 receptor (PLA2R). The remaining cases of MN may be secondary to causes such as infections, drugs, cancer or autoimmune diseases, with treatment targeted to the underlying etiology. We present a case of membranous nephropathy felt to be secondary form, in a patient with newly diagnosed amyotrophic lateral sclerosis (ALS). Case Description: 63 year old male with longstanding sarcoidosis (prior lymph node biopsy with poorly formed granulomas suggestive) presented with 1-1.5 g/g proteinuria (preserved serum albumin). Serum creatinine 0.65 mg/dL. Kidney biopsy showed MN with negative PLA2R immunostain, favoring secondary form. No significant tubulointerstitial scarring seen, consistent with recent disease onset. Additional immunohistochemical stains of subepithelial deposits negative. At first, sarcoidosis deemed the cause, despite disease quiescence otherwise (CT chest with stable lung nodules, ACE level within range). Renal literature scant on sarcoid driven secondary MN, but trial of steroids undertaken without any proteinuria reduction whatsoever. Max dose ARB and SGLT2 inhibitor without any impact. Meanwhile, neurologic history, clinical exam and electrodiagnostic studies were consistent with diagnosis of motor neuron disease, likely spinal onset of ALS. Discussion: A link between ALS and any form of MN has not been well defined in literature. Only mentioned is a case of NELL-1 MN on allograft biopsy in a kidney transplant recipient who suffered from ALS and developed nephrotic syndrome post transplant. A causal link was felt to be unlikely. Our patient was diagnosed with secondary membranous nephropathy, having an autoimmune driver already established (sarcoidosis). However, he did not respond to treatment with steroids, raising possibility of other driving forces -- such as newly diagnosed ALS. While this has not been described, one need consider the association. It will be noteworthy if proteinuria reduction occurs after starting treatment with Riluzole, a glutamate release inhibitor use to slow ALS progression. Perhaps ALS (and possibly other neurologic conditions) should be added to the list of secondary MN causes.