Abstract
Multiple myeloma (MM) is a common plasma cell malignancy, which is responsible for significant mortality, often related to severe renal impairment (RI). Kidney injury can limit therapeutic choices and may often translate into poor outcomes, but it remains potentially reversible in a proportion of patients. The most accessible, conventional markers of RI are subject to several shortfalls, among which are the delayed onset following kidney insult, multiple interfering factors, and lesser sensitivity to mild changes in glomerular filtration. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have accumulated large interest in MM-RI due to being very sensitive markers of renal injury, as well as indicators of tubular-glomerular axis impairment. Of interest, recent data suggest that prediction of acute kidney injury may be aided by urinary tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), which both act to induce G1 cell cycle arrest, reflective of a state of pre-injury, and thus may be superior to other measures of kidney insult (NGAL, kidney injury molecule ((KIM-1)). Moreover, TIMP-2 seems to be a biomarker dedicated to distal tubular cells, whereas insulin-like growth factor-binding protein 7 (IGFBP7) secretion has been found in proximal tubule cells. IGFBP7 can also identify a subsection of the normal proximal nephron, even, maybe the one that is responding to insult. They may be adopted into a conceptual screening panel for MM-RI. Unfortunately, no biomarker is ideal (influence of non-renal, biologic factors), and novel measures are limited by economic constraints, availability, lack of standardization. With the emergence of more advanced diagnostic and prognostic MM models, markers reflective of disease processes (including RI) are of high interest. Candidate molecules also include peptidome markers.
Highlights
The most common lesion in MM-related Renal impairment (RI) Light-chain only myeloma may be often associated with severe RI Other renal lesions may coexist
In the few paragraphs, we have described the most promising biomarkers in RI related to MM and their utility
Neutrophil gelatinase-associated lipocalin (NGAL) is a small glycoprotein, existing in several molecular forms and expressed in various tissues, for which the assay in urine is of particular interest in suspicion of acute injury, as it is filtered and proximally reabsorbed, while its production occurs local to injured tubular cells [48,49]
Summary
In the United States, it has been estimated that multiple myeloma (MM), a plasma cell malignancy, will account for nearly 13,000 deaths in 2019, while over 32,000 new cases will be diagnosed [1]. Several kidney features may predispose this particular organ to be affected by circulating paraproteins—an abundance of renal capillaries with large blood flow, the concentration of filtered solutes, and the presence of a variety of exogenous and endogenous substances [14] Retrospective studies have previously suggested that in addition to novel chemotherapeutic agents, high-cut-off hemodialysis (HCO) may lead to renal recovery and improved survival in dialysis-dependent acute renal failure [20]. The French national registry on RRT in end-stage renal disease (without RRT for AKI (acute kidney injury)) was analyzed between 2002 and 2011 to determine the trend and survival of patients with monoclonal gammopathies on chronic dialysis. It was noted that kidney transplantation still remains a rare therapeutic measure in myeloma cast nephropathy, as well as light-chain deposition disease, with the risks of recurrence, Ig-mediated graft dysfunction, and infection counterbalancing the potential benefits. It has been proposed that the selection of “low risk” patients (absence of adverse indices of disease) might change the outlook on a kidney transplant in MM and shift the dismal implications of end-stage renal disease [32]
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