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Kidney Week

Abstract: SA-PO098

Lysozyme Induced Nephropathy: A Rare Mechanism of Renal Sarcoidosis

Session Information

  • AKI: Mechanisms - III
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Prabhu, Sushmita, Saint Vincent Hospital, Worcester, Massachusetts, United States
  • Balakrishnan, Suryanarayanan, Saint Vincent Hospital, Worcester, Massachusetts, United States
  • Martin, Suzanne Gwen, Saint Vincent Hospital, Worcester, Massachusetts, United States
Introduction

Classic mechanisms of renal injury in sarcoidosis include hypercalcemia with afferent vasoconstriction, nephrocalcinosis, and acute interstitial nephritis with or without granulomas. Lysozyme is a small cationic enzyme with bactericidal properties produced by monocytes and macrophages, which drive disease activity. Lysozyme is freely filtered by glomeruli and reabsorbed in proximal tubules (PTs), where it causes toxicity in excessive quantities, known as lysozyme-induced nephropathy.

Case Description

75M presented with a creatinine of 5.87 mg/dL (eGFR 9cc/min) after not seeing a physician for years. He reported difficulty sweating and a 22lb weight loss over 18 months, but was otherwise asymptomatic. Blood pressure was 150/73 and exam was unremarkable. Urinalysis: specific gravity 1.020, pH 6, moderate blood, 100 protein, 100 glucose. Sediment: granular casts without RBCs or RBC casts. Urine albumin:Cr ratio (UACR) was 47 mg/g, urine protein:Cr ratio (UPCR) 1321 mg/g Cr, calcium 14 mg/dL, phosphate 6.3 mg/dL, PTH 1.57 pg/mL, PTHrP 30 pg/mL, and 1,25 OH2 vitamin D 138 pg/mL. Serum and urine immunofixation were negative. Renal biopsy showed moderately severe nephrocalcinosis, with a moderately severe chronic active interstitial nephritis without granulomas. Densely packed eosinophilic protein reabsorption granules were seen in PTs, which stained strongly for lysozyme. Advanced sclerosis was seen. He had high serum lysozyme (28mcg/mL) and ACE (84U/L) levels. Evaluation for Fanconi syndrome showed glycosuria and euglycemia, and a basic urine pH, but normal uric acid handling. He was treated with prednisone 1 mg/kg/day for 6 weeks followed by an 8-week taper, without improvement in GFR. BAL showed multinucleated giant cells, consistent with sarcoidosis.

Discussion

Rare case reports describe lysozyme-induced nephropathy in sarcoidosis. It is more commonly seen in chronic monocytic or myelomonocytic leukemia, as these clonal populations produce excessive lysozyme. Measurement of serum lysozyme levels could be considered in patients with sarcoidosis and a rising creatinine, or with UPCR and UACR discordance. This may guide future therapies directed at excessive macrophage activity, thereby improving renal function.