ABSTRACT
Introduction: Minimal Change Disease (MCD) is described as diffuse podocyte foot process effacement on kidney biopsy, resulting in nephrotic proteinuria, >3 grams/day. Glucocorticoids (GC) are the mainstay of therapy and most patients achieve complete remission in a few months. 7-12% patients, however, have GC-resistance and thus limited treatment options. Often, they are suspected of having focal segmental glomerulosclerosis (FSGS) due to biopsy sampling error. We present a challenging case of GC-resistant MCD, managed with immunosuppression, and ultimately lipid (LDL) apheresis. Case Description: An otherwise healthy 20-year-old male presented for sudden onset lower extremity swelling and 10-pound weight gain. Work up including ANA, C3, C4, p-ANCA, c-ANCA, serum and urine immunofixation and renal ultrasound were unremarkable. Notably, LDL was 390 mg/dL, proteinuria of 9 grams/day and serum creatinine (Scr) of 0.96 mg/dL. Kidney biopsy revealed diffuse podocyte effacement, consistent with MCD. He was treated with oral prednisone 1 mg/kg/day and diuretics for several weeks with minimal symptomatic improvement and had worsening kidney function, Scr 1.5 mg/dL and proteinuria of 36 grams/day. Unfortunately, he also contracted COVID-19 disease prior to second kidney biopsy. Repeat kidney biopsy revealed acute tubular necrosis along with widespread podocyte effacement, without sclerotic lesions, ∼10% interstitial fibrosis and tubular atrophy. He was empirically treated with tacrolimus for FSGS. However, proteinuria continued to worsen and peaked at 83 grams/day. Ultimately diagnosed as GC-resistant MCD, he was weaned off steroids, he was referred for LDL-apheresis therapy. He is maintained on tacrolimus and LDL apheresis with symptomatic improvement, still has significant proteinuria of 67 grams/day and advanced chronic kidney disease (CKD). Discussion: The exact pathophysiology of nephrotic syndromes is unclear, mechanisms of T-cell dysfunction causing production of glomerular permeability factor and nephrotoxic hyperlipidemia have been described. In cases of GC-resistant diseases, immunosuppression has only been partially successful. LDL-apheresis has a role in the management of such nephrotic syndromes, thought to reduce circulating lipid induced disruption of podocyte integrity, and help prevent decline of kidney function and decrease proteinuria as seen in this patient.