Abstract Renal dysfunction in patients with acute myeloid leukemia (AML) can be multifactorial. We present the case of a 72‐year‐old male with relapsed myelomonocytic AML who presented with transient acute kidney injury (AKI) and severe persistent electrolyte derangements. In the setting of nephrotic‐range proteinuria and electrolyte wasting without significant albuminuria or glucosuria, a diagnosis of lysozymuria was made. Lysozymuria is a rare paraneoplastic complication of AML and chronic myelomonocytic leukemia characterized by lysozyme. This represents the first case of lysozymuria presenting primarily with refractory electrolyte derangements rather than severe AKI. Lysozymuria portends a poor clinical prognosis even with aggressive management.