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Emphysematous pyelonephritis (EPN) is a severe, acute necrotizing infection of the kidney with gas accumulation in the renal parenchyma, collecting ducts, and/or perirenal tissue. We report a case of EPN in a 66 year-old male with uncontrolled diabetes mellitus (DM), urinary tract infection and septic shock necessitating emergent bilateral radical nephrectomy. Morphologically, the kidney parenchyma revealed severe acute bacterial pyelonephritis with extensive abscesses, gas cysts, necrosis and foci of infarctions. The uninvolved background cortex parenchyma exhibited diabetic nephropathy (DN), Class IIB. Post-operatively, the patient remained dialysis-dependent with multiple re-admissions for recurrent multi-drug resistant E. coli pyocystitis, anemia and urinary retention.