Protective action against kidney injury in myeloma

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Akira Arimura, Min Li, and Vecihi Batuman

US-Japan Biomedical Research Laboratories, Tulane University F. Edward Hebert Research Center, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA, Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA

The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that PACAP38 dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFB via both PAC₁- and VPAC₁-receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays, and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma.

Akira Arimura^*, Min Li, and Vecihi Batuman