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What is the Diagnosis? A man in his 50s with diabetes, hypertension, and benign prostatic hyperplasia presented with sepsis secondary to urinary tract infection/pyelonephritis and AKI. Serum creatinine increased from a baseline of 0.7–1.1 mg/dl over the past year to 3.8–4.3 mg/dl, and his urine culture grew Escherichia coli. His creatinine remained elevated despite in-hospital hydration and antibiotics for 5 days, and kidney biopsy was performed. Image Description Kidney biopsy showed diffuse interstitial inflammation with abundant macrophages containing prominent periodic acid- Schiff–positive cytoplasmic granules (arrowhead) without calcium or iron. There were multifocal neutrophilic casts (asterisk), neutrophilic tubulitis, and diabetic glomerulosclerosis (not shown). Teaching Points Megalocytic interstitial nephritis (MIN) is a rare form of infectious interstitial nephritischaracterizedbyinfiltratingmacrophageswith cytoplasmic granules. 1,2 The epidemiology of MIN is not well documented, but it is commonly reported with Escherichia coli infections. 2,3 MIN may represent a precursor to malakoplakia, as both conditions demonstrate periodic acid-Schiff–positive granules within macrophages. 1,2,4,5 In contrast to malakoplakia, Michaelis-Gutmann bodies, which are concentric calcium phosphate concretions on a nidus of bacterial breakdown products, are absent in MIN. 1,5,6 Special stains for Prussian blue and von Kossa help to identify the iron and phosphate, respectively, within Michaelis-Gutmann bodies inclusions. Definitive diagnosis requires histopathologic examination, as imaging of any acute interstitial process, are often nonspecific and only suggestive of a diffuse or focal lesion. 7–10 Both malakoplakia and MIN are a result of defective macrophage function, where impaired phagolysosomal activity and intracellular trafficking lead to incomplete bacterial digestion, resulting in persistent infection and inflammation. 11,12 Owing to limited reported cases, optimal treatment strategies remain unclear but conceptually, prolonged antimicrobial therapy that has intracellular activity is required for infection control. After biopsy results, the patient was prescribed an extended course of antibiotics, and his last available creatinine showed modest improvement (3.2 mg/dl). References 1. Esparza AR, McKay DB, Cronan JJ, Chazan JA. Renal parenchymal malakoplakia. Histologic spectrum and its relationship to megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis. Am J Surg Pathol. 1989;13(3):225–236. doi:10.1097/00000478-198903000-00008 2. Kwon HJ, Yoo KH, Kim IY, Lee S, Jang HR, Kwon GY. Megalocytic interstitial nephritis following acute pyelonephritis with Escherichia coli bacteremia: a case report. J Korean Med Sci. 2015;30(1):110–114. doi:10.3346/jkms.2015.30.1.110 3. Barakat M, Aziz A, Vilayet S, Vishwajeeth P, Soliman K. 462 A kidney transplant recipient’s dilemma of recurrent abscesses, megalocytic interstitial nephritis and rejections. Am J Kidney Dis. 2024; 83(4 suppl 2):S142. doi:10.1053/j.ajkd.2024.01.465 4. Yi_giter M, Ilgici D, Celik M, Arda IS, Hic¸so¨ nmez A. Renal parenchymal malacoplakia: a different stage of xanthogranulomatous pyelonephritis? J Pediatr Surg. 2007;42(7):E35–E38. doi:10.1016/j.jpedsurg.2007.05.005 5. Garrett IR, McClure J. Renal malakoplakia. Experimental production and evidence of a link with interstitial megalocytic nephritis. J Pathol. 1982;136(2):111–122. doi:10.1002/path.1711360205 6. Kelly DR, Murad TM. Megalocytic interstitial nephritis, xanthogranulomatous pyelonephritis, and malakoplakia: an ultrastructural comparison. Am J Clin Pathol. 1981;75(3):333–344. doi:10.1093/ajcp/75.3.333 7. Gonzalez AC, Karcioglu Z, Waters BB, Weens HS. Megalocytic interstitial nephritis: ultrasonic and radiographic changes. Radiology. 1979;133(2):449–450. doi:10.1148/133.2.449 8. Jiao B, Liu S, Ma X, Wong C, Zhao H. Multiple-organ involvement of malakoplakia mimicking malignant neoplasms on 18 F-FDG PET/CT. Clin Nucl Med. 2023;48(8):694–696. doi:10.1097/rlu.0000000000004728 9. Jeong E, Park BS, Kim IH, et al. Radiologic evolution of biopsyproven acute interstitial nephritis: a multimodal imaging case report. KMJ. 2025;40(1):72–79. doi:10.7180/kmj.25.104 10. Van Liedekerke L, Beckers R, Carels K, De Cocker L. Acute interstitial nephritis manifesting as a persistent nephogram. Radiol Case Rep. 2023;18(1):184–187. doi:10.1016/j.radcr.2022.10.010 11. Abdou NI, NaPombejara C, Sagawa A, et al. Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo. N Engl J Med. 1977;297(26):1413–1419. doi:10.1056/nejm197712292972601 12. Jung YS, Chung DY, Kim EJ, Cho NH. Ultrastructural evidence of the evolutional process in malakoplakia. Histol Histopathol. 2020;35(2):177–184. doi:10.14670/hh-18-150 (Text and image provided by Chen Yu Jamie Lee, Cynthia C. Nast, and Hae Yoon Grace Choung, all of Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California) CJASN 21:6, 2026. DOI:10.2215/CJN.0000000815