Kidney and Urinary Tract Involvement in Chronic Myelomonocytic Leukemia

Abstract

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy affecting the bone marrow and resulting in peripheral blood monocytosis. Kidney and urinary tract involvement is common and can present dramatically with life-threatening consequences. Kidney involvement can be the result of direct or indirect mechanisms, including prerenal azotemia, glomerular disease, tubulointerstitial involvement, and renovascular disorders. Urinary tract involvement, electrolyte and acid-base disorders, as well as nephrotoxicity from treatment of the disorder can also occur. Given this multifactorial pathogenesis involving several mechanisms concomitantly, nephrologists must exercise heightened awareness and maintain a low threshold for kidney biopsy. There is a pressing need for future research endeavors to elucidate and target the manifestations of CMML that involve the kidneys with the ultimate goal of augmenting overall prognosis and therapeutic outcomes.

Keywords: Chronic myelomonocytic leukemia; glomerulopathy; kidney injury; lysozyme-induced nephropathy; onconephrology; tumor lysis syndrome; vasculitis.

Figure 1

Major overlap syndromes between myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS). Although MDS and MPN have distinct defining features, certain syndromes combine both myeloproliferative characteristics, such as an elevated white blood cell count and splenomegaly, with myelodysplastic traits, including anemia, thrombocytopenia, and an excess of blasts. The 3 major overlap syndromes are chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, and MDS or MPN with ringed sideroblasts and thrombocytosis.

Figure 2

Renal involvement in chronic myelomonocytic leukemia (CMML). CMML can affect all the different renal compartments, including the glomeruli, tubulointerstitial space, and even blood vessels. Each compartment can be affected through multiple mechanisms of injury.

Figure 3

Mechanisms of glomerular injury in chronic myelomonocytic leukemia. Monocytes can cause direct injury by infiltrating the glomerulus or indirect injury through accumulation of immune complexes along the glomerular basement membrane or upregulation of TNF-α, leading to increased glomerular capillary permeability. Autoimmunity from abnormal T- and B-cell interactions can also potentiate glomerular damage.

Figure 4

Lysozyme-induced nephropathy. (A) There is no significant glomerular abnormality, whereas the proximal tubules show enlargement because of accumulated protein droplets (periodic acid–Schiff stain, 200×). (B) Epithelial cells of the proximal tubules are engorged by protein reabsorption droplets (periodic acid–Schiff stain, 400×) (C) Round eosinophilic and refractile protein reabsorption droplets fill out the entire cell, with epithelial cell nuclei pushed to the basolateral aspect of the cell (hematoxylin and eosin stain, 400×). (D) Immunohistochemistry staining for lysozyme reveals strong reaction in the intratubular protein reabsorption granules (100×). Courtesy of Dr Vanesa Bijol and Dr Yihe Yang, Nephropathologists at Northwell Health.

Figure 5

Urinary tract involvement in chronic myelomonocytic leukemia (CMML). CMML can lead to obstruction in either the upper or lower urinary tract. Upper urinary tract involvement can result from the infiltration of the pelvic kidney and ureter, uric acid nephrolithiasis, or retroperitoneal fibrosis. Lower urinary tract involvement is typically due to bladder outlet obstruction or prostate infiltration.