title: Lymphangiogenesis is upregulated in kidneys of patients with multiple myeloma.
abstract: Neolymphangiogenesis has recently been demonstrated in transplanted kidneys as well as in chronic interstitial nephritis and IgA nephropathy. However, its significance in kidney disease remains to be defined and a systematic study of renal lymphangiogenesis is warranted. We investigated patients with multiple myeloma (MM) presenting in the great majority with acute renal insufficiency. Controls were allograft kidney donors and patients with renal insufficiency due to acute renal failure (ARF). Lymph vessel length density (LVD) was quantified immunohistochemically by means of antipodoplanin staining followed by computer-assisted stereology. The mean LVD in kidneys of patients with MM (23.19 mm(-2)) was higher when compared with allograft donors (7.42 mm(-2), P = 0.0003) and patients with ARF (6.78 mm(-2), P = 0.0002). The higher LVD was significantly associated with interstitial inflammation, and the newly formed lymph vessels were accompanied by diffuse and nodular interstitial infiltrates composed mainly of CD20(+) B cells and CD27(+) plasma cells. The infiltrates in patients with MM also displayed a higher expression of the B-cell chemoattractant CXCL13. These results demonstrate for the first time that lymphangiogenesis is a prominent feature in MM kidneys and that it is associated with a significant accumulation of macrophages, CD20(+) and CD27(+) B lymphocytes. Further studies should clarify whether these changes represent a beneficial or detrimental factor in the progression of the myeloma-related kidney damage.
authors.affiliation: Department of Nephrology and Hypertension, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Zimmer
authors.forename: Suzan
authors.initials: S
authors.lastname: Dahdal
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.forename: Ivo P
authors.initials: IP
authors.lastname: Bergmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Gugger
authors.forename: Uyen
authors.initials: U
authors.lastname: Huynh-Do
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology; D054382:Chemokine CXCL13 / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000033:anatomy & histology* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000033:anatomy & histology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000473:pathology; D051437:Renal Insufficiency / Q000150:complications* / Q000473:pathology; D012189:Retrospective Studies; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000089982:ADP-Ribosylation Factor 6; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; C000715348:ARF6 protein, human