Rethinking Risk Stratification in IgAN: A Case Challenging the MEST-C Paradigm

Introduction: Immunoglobulin A nephropathy (IgAN) typically presents with asymptomatic hematuria and varying degrees of proteinuria. Around 30% of patients with proteinuria greater than 1 g/day develop kidney failure within 10 years. The MEST-C scoring system, which includes mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C), is a valuable prognostic tool for risk stratification. Higher proteinuria levels correlate with more severe histological damage. Here we report a patient with nephrotic range proteinuria and progression despite low MEST-C score challenging its prognostic utility. Case Description: A 50-year-old Hispanic female with hypertension and dysmenorrhea presented for evaluation of nephrotic range proteinuria found incidentally during a life insurance exam 5 months prior to referral. The urine protein creatinine ratio (UPCR) was 4.52 gm/gm. She was asymptomatic. Home medications included valsartan and as needed ibuprofen. Urinalysis showed microscopic hematuria and proteinuria. UPCR was 3.4 gm/gm and serum creatinine was 0.96 mg/dL at the first visit. Serologic work up was unremarkable except a positive ANA. SPEP showed no monoclonal protein band. Kidney biopsy showed 2/12 glomeruli with segmental sclerosis, IgA dominant glomerular deposits and scattered mesangial electron dense deposits consistent with IgAN with a MEST-C score of 1 for segmental sclerosis. Considering these results valsartan was maximized. Persistent proteinuria at 6-months post biopsy and elevation in serum creatinine from 0.7 mg/dL to 1.16 mg/dL, prompted addition of prednisone 50 mg PO daily. On the following visit, she reported discontinuing prednisone after taking it for 2 months due to significant edema. Proteinuria testing showed UPCR of 0.4 gm/gm without improvement in renal function. Discussion: This case challenges the prognostic value of the MEST-C scoring system. Initial histology led to the choice of non-immunosuppressive approach which may have led to deterioration in renal function. A short course of steroids significantly reduced proteinuria, albeit with noticeable side effects leading to treatment discontinuation. Nephrotic-range proteinuria in IgAN, even in the absence of severe histologic inflammation, should raise consideration for immunosuppressive