IgA nephropathy presenting with an atypical nephrotic phenotype in an adolescent: a diagnostic challenge

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide and classically presents with recurrent hematuria, variable proteinuria, and slowly progressive renal impairment. However, atypical presentations mimicking nephrotic syndrome with generalized edema and extrarenal fluid overload are uncommon, particularly in adolescents, posing significant diagnostic challenges. We report the case of a 17-year-old male admitted with progressive facial edema evolving to generalized edema, abdominal distension, dyspnea, and bilateral pleural effusion. Laboratory evaluation revealed subnephrotic-range proteinuria associated with severe nephrotic-like manifestations, including hypoalbuminemia, hypercholesterolemia, microscopic hematuria and hypertension., and transient deterioration of renal function. Initial differential diagnoses included primary nephrotic syndrome, minimal change disease, seronegative autoimmune nephropathy, and secondary glomerular disorders. Autoimmune studies, including antinuclear antibodies (ANA), anti-double stranded DNA, anti-neutrophil cytoplasmic antibodies (ANCA), and anti-glomerular basement membrane antibodies, were negative. Renal biopsy demonstrated mesangial abnormalities consistent with IgA nephropathy, supporting the final diagnosis. The patient received multidisciplinary management with favorable clinical and renal evolution. IgA nephropathy may rarely present with an atypical nephrotic phenotype characterized by severe edema, pleural effusion, and systemic volume overload, particularly in younger patients. Histopathological assessment remains essential for diagnosis in atypical clinical scenarios. This case highlights the importance of considering IgA nephropathy in the differential diagnosis of nephrotic syndrome and underscores the relevance of integrating clinical, laboratory, and histopathological findings. In addition, a focused review of the literature is provided to contextualize uncommon nephrotic presentations of IgAN and their diagnostic implications.