Megalocytic Interstitial Nephritis in an Allograft Kidney

Introduction: Megalocytic interstitial nephritis (MIN) is a rare macrophage-rich chronic inflammatory disorder that can cause acute kidney injury (AKI). It is often associated with underlying infections and pathogenesis is thought to involve defective intracellular destruction of invading organisms by macrophages. Case Description: 36-year-old woman with history of hypertension, end-stage kidney disease of unknown etiology status post deceased donor kidney transplant ~1.5 years ago, presented with abdominal pain and was found to have diabetic ketoacidosis, E. coli transplant pyelonephritis and AKI (creatinine 3 mg/dL, baseline 0.8). CT scan showed markedly enlarged and edematous kidney allograft. Given worsening creatinine despite antibiotics, transplant kidney biopsy was pursued. Biopsy revealed diffuse infiltration of the renal parenchyma by large, plump, CD68-postive macrophages with granular eosinophilic cytoplasm, without identifiable Michaelis-Gutmann bodies. Von Kossa and iron stains were negative, and immunohistochemistry excluded hematolymphoid malignancy and viral infections. The findings were consistent with MIN. The patient was started on IV methylprednisolone 60 mg. After the second dose, she developed acute pancreatitis. Steroids were discontinued but creatinine continued to improve with eventual return to baseline. Discussion: MIN is a rare macrophage-rich inflammatory process that may occur in immunosuppressed patients with chronic infection. It can be associated with chronic urinary tract infection (UTI) by gram-negative bacteria. Key differentials include malakoplakia and xanthogranulomatous pyelonephritis, which look histologically similar, making biopsy essential for diagnosis. While there are no established treatment guidelines, a few case reports have shown that early high dose steroids, along with antibiotics, may improve AKI.Figure 1. (A) CT imaging (B) Low-power view stained with periodic acid-Schiff (PAS) (C) High-power (400x) PAS stain (D) Immunohistochemical staining for CD68