Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Renal Impairment in Patients With Multiple Myeloma

Chae, Hyojin; Ryu, Hyejin; Cha, Kyoungho; Kim, Myungshin; Kim, Yonggoo; Min, Chang‐Ki

doi:10.1016/j.clml.2014.07.014

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…It is noteworthy to consider the “Forest Fire Theory” of Mori and Nakano, which proposes NGAL as a marker indicative of real-time kidney damage, derived from continuous production by inflamed tubular cells, rather than as a consequence of nephron loss (which would be more accurately reflected in cystatin C concentrations) [ 23 ]. Moreover, plasma and urinary sources of NGAL may differ; injury in distal nephron segments leads to secretion into the urine, while plasma concentrations could also be derived from nonrenal sources (e.g., increased in inflammatory states) [ 24 ]. A response to kidney insult, rather than inflammation, seems to be the major inducer of NGAL in MM, while a rise in both urinary NGAL and serum cystatin C may be indicative of a tubular-glomerular axis impairment, for which these molecules are respective markers [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma

Banaszkiewicz

Małyszko

Batko

et al. 2020

Mediators of Inflammation

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Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival ( p = 0.06 ). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.

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Section: Discussionmentioning

confidence: 99%

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma

Banaszkiewicz

Małyszko

Batko

et al. 2020

Mediators of Inflammation

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“…Interestingly, the activation of these pathways plays a significant role in both myeloma pathogenesis and related kidney lesions (induced by excess FLC processing) [ 8 , 51 ]. Indeed, in MM patients, serum/plasma NGAL levels share a relationship with M protein levels, international staging system (ISS) stage, and disease status, indicating utility as a bimodal marker of tumor burden and renal injury [ 50 , 52 , 53 ]. NGAL has been examined as a clinical marker in several clonal disorders (particularly in chronic myeloid leukemia (CML), with a purported link with tyrosine kinase breakpoint cluster region-Abelson (BCR-ABL)), though its predictive and prognostic value is still uncertain [ 54 ].…”

Section: Tubular-glomerular Axis Impairmentmentioning

confidence: 99%

“…examined 199 samples from an equal number of MM patients (majority during follow-up visits) representing a heterogeneous group ( ~ 40% complete response, 30% progressive disease). Several predictors (eGFR, M protein, and cystatin C) were identified for NGAL, which itself correlated with CKD according to kidney disease improving global outcomes (KDIGO) in MM patients and markers of myeloma burden [ 52 ]. Serum assay may be potentially more versatile if the urine assay requires 24-h urine collection for reliability.…”

Section: Tubular-glomerular Axis Impairmentmentioning

confidence: 99%

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

Woziwodzka

Małyszko

Batko

et al. 2020

JCM

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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.

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“…Multipl myelom hücreleri pro-MMP-9 ve pro-MMP-9 / NGAL kompleksi üretir. Plazmada NGAL varlığı yalnızca böbrek fonksiyonlarının hassas bir biyobelirteci değil, aynı zamanda MM'lu hastalarda tümör yükünü yansıtan yararlı bir belirteç de olabilir (7,8) . Multipl myelom hastalığında NGAL ve / veya pro-MMP-9 / NGAL kompleksinin ekspresyon paternleri hakkında az sayıda çalışma bulunmaktadır.…”

Section: Introductionunclassified

“…Literatürde böbrek hasarı açısından yüksek riskli hastalarda, erken belirleme ve daha sonra doğrulanması için iki taraflı belirleyici olarak kanda ve/veya idrarda NGAL ve KIM1'in kullanılması gerektiği ile ilgili çok sayıda çalışma bulunmaktadır (1,7,13) . Fakat, multipl myelomlu hastaların kemik iliği biyopsisinde, neoplastik plazma hücrelerinde NGAL ve KIM1 ekspresyon varlığı ve prognostik önemine dair bir çalışma bulunmamaktadır.…”

Section: Introductionunclassified

KIM1 and NGAL Expression in Patients with Multiple Myeloma and Clinicopathological Significance

Kahraman¹,

Diniz²,

Kaya³

et al. 2019

IKSST

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Neutrophil Gelatinase-Associated Lipocalin as a Biomarker of Renal Impairment in Patients With Multiple Myeloma

Cited by 11 publications

References 31 publications

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

KIM1 and NGAL Expression in Patients with Multiple Myeloma and Clinicopathological Significance

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