A Minimal Change: Obesity-Related Glomerulopathy (ORG) and Intermittent Nonsteroidal Anti-inflammatory Drug (NSAID) Use as a Precursor to Minimal Change Disease in an Adult Patient

Introduction: Minimal change disease (MCD) is predominantly idiopathic and rare in adults, accounting for only 10-15% of proteinuric glomerulopathy cases. The proportion caused by NSAID use is even lower. Typically, obesity-related glomerulopathy (ORG) presents as Focal Segmental Glomerular Sclerosis (FSGS) or Membranous Nephropathy (MN). We present a unique case of adult-onset MCD in an obese female precipitated by intermittent NSAID use. Case Description: The patient is a 19-year-old Egyptian female studying in the US who abruptly develops edema. She has a BMI of 34.71 kg/m2. Her urinalysis revealed a 3+ proteinuria. The patient admits to taking Advil intermittently one week per month during her menstrual cycle. She has no family history of renal disease or dialysis. The patient exhibited hypercholesterolemia, random urine protein/creatinine ratio of 9.28 g, 24-hour urine collection of over 7.5 g of proteinuria, and hypoalbuminemia of <2.5 g/dL. CT-guided renal biopsy showed global foot process effacement on electron microscopy, with no deposits, sclerosis, crescent formation, or spikes. Serological workup was negative for C3, RPR, RF factor, ANA, MPO/PR3, HIV, and hepatitis. Post-stabilization, she was discharged on anticoagulation, an ACE inhibitor, steroids with GI and bone prophylaxis, lipid-controlling agents, and advised on lifestyle modifications. Discussion: FSGS is far more commonly seen in ORG, and MCD is less common in adults. However, recent studies identify obesity as an independent risk factor leading to glomerular enlargement and proteinuria. Obesity also triggers biochemical pathways, such as TGF-β and RAAS, exacerbating kidney damage and altering gene expression related to lipid metabolism and inflammation. Studies also reveal ORG increasing in incidence, especially in BMIs ranging from 30.9-62.7 kg/m2. The mechanism of NSAIDs in adult onset MCD is also poorly understood. This case suggests that obesity may lead to MCD in adults, with NSAID use potentially lowering the threshold confounded by underlying immunological effects from obesity. Obesity may also increase the metabolic clearance rate of steroids, necessitating higher doses for full remission. Understanding these dynamics is crucial for managing MCD-type nephrotic syndrome in a growing population of obese patients.