Cast Nephropathy in Myeloma—Does PACAP38, a New Member of the Vasoactive Intestinal Peptide Family, Open a Therapeutic Window? Potential Protective Action of Pituitary Adenylate Cyclase-Activiating Polypeptide (PACAP38) on In Vitro and In Vivo Models of Myeloma Kidney Injury. Blood 107: 661–668, 2006

[摘要] Multiple myeloma is the sixth most common malignancy and accounts for 2% of all deaths from cancer (1). Renal damage from myeloma is an important cause of renal failure (2) with a poor prognosis. The main renal lesions are cast nephropathy characterized by cast formation in the distal nephron, resulting from coprecipitation of pathologic light chains with Tamm-Horsfall protein and marked interstitial fibrosis (3–6). Casts in the distal nephron cause breaks of the epithelial barrier, thus permitting leakage of Tamm-Horsfall protein into the interstitium (7–9). Tamm-Horsfall protein has recently been recognized as an important trigger involved in the genesis of interstitial inflammation (10, 11). In addition, proximal tubular reabsorption of aberrant light chains by endocytosis causes cellular protein overload and activates the central switch for inflammatory processes, activating NFκB (nuclear factor κB) and setting in motion the synthesis of inflammatory cytokines and activating signaling pathways (such as mitogen activated protein kinases [MAPK], extracellular signal regulated kinase 1/2 [ERK 1/2], Jun kinase [JNK], p38MAPK), thus promoting interstitial inflammation and fibrosis. A causal role of cast formation is suggested by the observation that the severity of cast formation as found by renal biopsy is predictive of outcome (12).

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome