Clinicopathologic Spectrum of Lysozyme-Associated Nephropathy

Satoru Kudose; L Nicholas Cossey; Pietro A Canetta; Miroslav Sekulic; Christine A Vanbeek; Forest B Huls; Isha Gupta; Lihong Bu; Mariam P Alexander; Lynn D Cornell; Mary E Fidler; Glen S Markowitz; Christopher P Larsen; Vivette D D'Agati; Samih H Nasr; Dominick Santoriello

doi:10.1016/j.ekir.2023.05.007

Clinicopathologic Spectrum of Lysozyme-Associated Nephropathy

Kidney Int Rep. 2023 May 15;8(8):1585-1595. doi: 10.1016/j.ekir.2023.05.007. eCollection 2023 Aug.

Authors

Satoru Kudose¹, L Nicholas Cossey², Pietro A Canetta³, Miroslav Sekulic¹, Christine A Vanbeek⁴, Forest B Huls⁵, Isha Gupta⁶, Lihong Bu⁷, Mariam P Alexander⁷, Lynn D Cornell⁷, Mary E Fidler⁷, Glen S Markowitz¹, Christopher P Larsen², Vivette D D'Agati¹, Samih H Nasr⁷, Dominick Santoriello¹

Affiliations

¹ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
² Arkana Laboratories, Little Rock, Arkansas, USA.
³ Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA.
⁴ AmeriPath, Oklahoma City, Oklahoma, USA.
⁵ Department of Pathology, Division of Laboratory Medicine, University of Alabama, Birmingham, Alabama, USA.
⁶ Middletown Medical, Middletown, New York, USA.
⁷ Mayo Clinic, Rochester, Minnesota, USA.

Abstract

Introduction: Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We report the clinicopathologic spectrum of LyN from a multi-institutional series.

Method: We identified 37 native kidney biopsies with LyN and retrospectively obtained clinicopathologic data.

Results: Thirty-seven patients had a median age of 74 years and included 78% males. Their most common presentation was acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) (66%) with median estimated glomerular filtration rate (eGFR) of 21.7 ml/min per 1.73 m², and proteinuria of 1.7 g. A minority (15%) had partial Fanconi syndrome. Serum lysozyme levels were elevated in all tested. Hematologic disorder (n = 28, 76%) was the most common etiology, including CMML (n = 15), acute myeloid leukemia (n = 5), and myelodysplastic syndrome (MDS) (n = 5). Nonhematologic causes (n = 5, 14%), included metastatic neuroendocrine carcinoma (n = 3), sarcoidosis, and leprosy. Etiology was unknown in 4 (11%). Pathology showed proximal tubulopathy with abundant hypereosinophilic intracytoplasmic inclusions, with characteristic staining pattern by lysozyme immunostain. Mortality was high (8/30). However, among the 22 alive, including 85% treated, 7 had improved kidney function, including 1 who discontinued dialysis and 6 with increase in eGFR >15 ml/min per 1.73 m² compared with eGFR at the time of biopsy.

Conclusion: Increased awareness of the full clinicopathologic spectrum of LyN may lead to prompt diagnosis, earlier treatment, and potentially improved outcome of this rare entity.

Keywords: chronic myelomonocytic leukemia; granulomas; kidney biopsy; lysozyme; lysozyme induced nephropathy; proximal tubulopathy.