Long-term Exposure to Complementary and Alternative Medicine Leads to Neural Epidermal Growth Factor-like 1...

Membranous nephropathy is a type of glomerular disease which results in nephrotic syndrome that can be seen in adults. In most cases of membranous nephropathy, the target antigen has been phospholipase A2 receptor (PLA2R). In recent times, another antigen named neural epidermal growth factor-like 1 (NELL-1) has been labeled. We present a case report of NELL-1-positive membranous nephropathy due to intake of complementary and alternative medication, mercury being the possible content.

A case report-50-year-old female, brought to emergency department with breathing difficulty, bilateral swelling of legs, and reduced urine output for 3 days. Patient had periorbital edema, facial puffiness, and bilateral limb edema on examination. Family members revealed a past history of rheumatoid arthritis for which she is on complementary and alternative medication. Vitals-blood pressure (BP)-70/50 mm Hg, in view of shock, patient was started on inotropes at emergency medical department (EMD). On evaluation, her complete blood count showed anemia, neutrophilic leukocytosis, erythrocyte sedimentation rate (ESR) was high. Serum electrolytes showed hyponatremia. Urine complete showed albuminuria with high urine spot protein-creatinine ratio (PCR). Renal function test showed increase in creatinine level which rapidly worsened on serial monitoring. Liver function test showed severe hypoalbuminemia with albumin-globulin (AG) reversal. Lipid profile showed high cholesterol, triglyceridemia, with increased low-density lipoprotein (LDL). Serum electrophoresis showed hypoalbuminemia with relative increase in alpha 2 fraction, suggestive of nephrotic syndrome. In view of shock and hypotension, adrenal insufficiency was considered and patient was started on steroids. With the clinical presentation and laboratory parameters, the differential diagnoses considered here were membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis. So, we proceeded with renal biopsy after optimizing her renal parameters, and it was reported as membranous nephropathy and acute interstitial nephritis. Antigen panel for membranous nephropathy was sent and came out to be NELL-1-positive. She was started on IV pulse steroid therapy.

In our case report, we conclude that NELL-1 has been shown to cause a rare form of membranous nephropathy when negative for PLA2R and thrombospondin type 1 domain containing 7A (THSD7A). Our possible explanation is mercury-induced membranous nephropathy.

Our patient was started on pulse steroids and slowly tapered. Her renal parameters gradually improved. Since everything resolved without any active intervention for rheumatoid arthritis, thereby eliminating the inciting agent.