Sachiko Minamiguchi

Lysozyme-associated nephropathy (LyN) is an underrecognized cause of kidney dysfunction, commonly associated with chronic myelomonocytic leukemia (CMML). We present two cases of LyN with distinct clinical manifestations. In Case 1, an 80-year-old man with primary myelofibrosis developed progressive monocytosis, kidney dysfunction, proteinuria, and elevated serum and urinary lysozyme levels. Kidney biopsy revealed lysozyme-positive intracytoplasmic granules within proximal tubular cells, confirming the diagnosis of LyN. Notably, the progressive increase in the number of lysozyme- positive bone marrow cells may serve as an indicator of LyN activity. Treatment with hydroxycarbamide, a cytoreductive agent, and ruxolitinib, a Janus kinase inhibitor, successfully stabilized kidney function. In Case 2, a 63-year-old man with CMML developed acute kidney injury. Although the etiology of kidney dysfunction could not be determined during life, autopsy revealed diagnostic features of LyN. To further investigate LyN pathophysiology, we performed the first mass spectrometry-based proteomic analysis of proximal tubules in two cases. LyN samples showed marked lysozyme accumulation and upregulation of proteins involved in lysosomal system, lipid metabolism, cellular stress, and chronic inflammation. These findings suggest that chronic lysozyme overload disrupts intracellular homeostasis and contributes to kidney injury. LyN is underdiagnosed as unexplained tubular damage or chronic kidney disease, highlighting the need for awareness of the clinicopathological features.