Case Presentation: A 54-year-old man with diabetes, coronary artery disease, peripheral artery disease, and prior stroke presented from a skilled-nursing facility with fever, confusion, and purulent drainage from a left transmetatarsal amputation stump. He was tachycardic, hyperglycemic (468 mg/dL), and had leukocytosis of 42 K/µL with creatinine 1.14 mg/dL. CT of the ankle demonstrated a gas-forming soft-tissue infection. Blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA). He underwent below-knee amputation and was started on broad antimicrobials, later narrowed to ceftaroline.Despite surgical source control, creatinine rose to 4.99 mg/dL over the next week. Urinalysis showed new hematuria and proteinuria. Serologic testing (ANA, ANCA, complements, hepatitis panel) was unrevealing, and renal ultrasound showed no obstruction. Nephrology attributed the AKI to acute tubular injury from sepsis, contrast, or medication effects, while Infectious Disease considered antibiotic-associated nephrotoxicity.Over subsequent days, the clinical trajectory no longer fit these explanations. His hemodynamics stabilized, inflammatory markers declined, and infection improved, yet renal function worsened alongside persistent hematuria and proteinuria. This mismatch raised concern for a glomerular rather than tubular process. After multidisciplinary discussion, the hospital medicine team advocated for renal biopsy.Biopsy demonstrated endocapillary and mesangial hypercellularity with C3-dominant staining and subepithelial immune-complex deposits, consistent with infection-related glomerulonephritis (IRGN) associated with MRSA. Supportive management and continuation of MRSA-directed therapy led to gradual renal recovery without dialysis. Creatinine improved to 3.82 mg/dL by discharge, his mental status normalized, and he completed a six-week course of ceftaroline with outpatient follow-up.
Discussion: C3-dominant IRGN is an underrecognized cause of AKI in adults with S. aureus infection. Unlike classic post-streptococcal patterns, staphylococcal IRGN often develops during active infection as circulating immune complexes deposit in the glomeruli and activate the alternative complement pathway. Because renal injury may worsen even as bacteremia improves, the presentation frequently resembles septic acute tubular necrosis or drug-induced nephrotoxicity.Key features suggesting IRGN include new hematuria, proteinuria, and progressive kidney injury despite hemodynamic stability and appropriate antibiotics. Identifying IRGN is critical because management requires continuation of effective antimicrobial therapy and supportive renal care—rather than prematurely altering antibiotics or attributing injury to nephrotoxicity.
Conclusions: When AKI does not follow the expected course after sepsis stabilizes, hospitalists are often the first to recognize discrepancies between systemic improvement and renal decline. In this case, timely escalation to renal biopsy established C3-dominant IRGN, prevented premature antibiotic changes, and clarified management. Continuous bedside reassessment allowed the inpatient team to identify when biopsy became necessary, guiding appropriate therapy and prognosis.