Lysozyme nephropathy in chronic myelomonocytic leukemia.

Lysozyme nephropathy is a frequently unrecognized cause of renal disease in chronic myelomonocytic leukemia and may serve as a novel indication for treatment in this patient population. We demonstrate that in newly diagnosed CMML patients, plasma lysozyme levels are positively correlated with both absolute monocyte count and serum creatinine.

A 60‐year‐old woman with white blood cell count of 70 × 103/μL with monocytosis, hemoglobin 11.2 g/dL, platelets 89 × 103/µL, and creatinine 1.41 mg/dL had bone marrow biopsy demonstrating chronic myelomonocytic leukemia (CMML). Subsequent nephrectomy revealed renal cell carcinoma (RCC). Proximal tubules uninvolved by RCC contained abundant eosinophilic droplets confirmed as lysozyme (Figure 1A,B). Serum and urine lysozyme concentrations were >10 µg/mL. She received 5‐azacitidine with reduction in monocytosis and serum lysozyme and creatinine, with complete normalization of these parameters following allogeneic stem cell transplant.

Figure 1

Lysozyme nephropathy in CMML. A, H&E stain demonstrating bright eosinophilic cytoplasmic granules within renal proximal tubule cells. B, Lysozyme immunohistochemical stain highlighting cytoplasmic droplets within the proximal tubule. C, Correlation of absolute monocyte count of newly diagnosed CMML patients with plasma lysozyme levels. D, Correlation of plasma lysozyme levels with concurrent serum creatinine measurements

Lysozyme is a bacteriolytic enzyme detectable in monocytes. Lysozyme is reabsorbed by renal proximal tubule cells until concentrations exceed 45 μg/mL and urinary excretion is observed.1 Increased serum and urine lysozyme are seen in diseases characterized by monocytic proliferation, including myeloid leukemia.1

We measured plasma lysozyme in CMML patients at diagnosis (N = 18), on therapy with hypomethylating agents (N = 10), and in healthy controls (N = 6). Median concentrations were highest at diagnosis (7.5 µg/mL) and correlated with monocyte count and serum creatinine (Figure 1C,D). Treatment reduced concentrations (1.59 µg/mL), without reaching those of controls (0.68 µg/mL).

Renal impairment in CMML may reflect age‐related comorbidities. However, intravenous lysozyme causes tubular damage in rats, arguing that monocyte‐derived lysozyme could cause renal injury in CMML that is amenable to reversal with cytoreduction.2

CONFLICT OF INTEREST

None declared.

AUTHOR CONTRIBUTION

ABP: wrote the initial draft of this manuscript. MWD: edited the manuscript and participated in clinical care. RRM: provided histologic images. All authors reviewed the final draft of the manuscript and approved its submission. ABP: is supported by an American Society of Hematology RTAF award.