Urinary NGAL for the diagnosis of the renal injury from multiple myeloma

Du, Wenhan; Shen, Ting; Li, Hui; Liu, Yingying; He, Lagu; Li, Tan; Hu, Min

doi:10.3233/cbm-160672

Cited by 9 publications

(8 citation statements)

References 15 publications

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“…This variation in serum Cr level and the subsequent overestimation of GFR has often led to inappropriate therapeutic interventions. Several studies on alternative biomarkers of RI in MM have recently begun to be reported [26–29]. Papassotiriou et al [29] reported that serum neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C, which are both reliable diagnostic biomarkers of AKI and chronic kidney disease [30–35], were also useful as biomarkers of RI in patients with NDMM.…”

Section: Discussionmentioning

confidence: 99%

Activin A: a novel urinary biomarker of renal impairment in multiple myeloma

et al. 2019

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Renal impairment (RI) is a common complication of multiple myeloma (MM) that significantly affects treatment efficacy and mortality. However, no useful biomarkers for early detection of renal damage in MM exist. Reports indicate that activin A, a multifunctional cytokine of the TGF-β superfamily, is involved in the development and progression of various kidney diseases. In the present study, we measured urinary activin A levels in patients with newly diagnosed MM (NDMM) (n=41), smoldering MM (SMM) (n=10), and monoclonal gammopathy of undetermined significance (MGUS) (n=28), including monoclonal gammopathy of renal significance (MGRS), and assessed the correlation between urinary activin A and several clinical parameters. Urinary activin A, undetectable in healthy volunteers, was significantly increased in NDMM patients but not in patients with SMM and MGUS (97.3, 25.0, and 6.61 mg/gCr, respectively, P<0.05). In all patients with NDMM, urinary activin A levels were significantly reduced after initial treatment regardless of the therapy regimen. There was a significant correlation of urinary activin A with spot urinary protein level (P<0.001) and serum M-protein (P=0.029) but not with estimated glomerular filtration rate (eGFR), serum creatinine (Cr), N-acetyl-glucosaminidase (NAG), and serum activin A level. Histological analysis using renal biopsy samples revealed that activin A, which was absent from normal kidneys, was detected in the renal tubular cells of patients with MGRS. These data suggest that urinary activin A reflects tubular injury in MM and might aid the early detection of RI in plasma cell neoplasms.

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Section: Discussionmentioning

confidence: 99%

Activin A: a novel urinary biomarker of renal impairment in multiple myeloma

et al. 2019

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“…Some authors indicate the role of disturbances of vitamin D and RBP in the etiology not only of bladder but also other cancers [ 32 ]. NAG is especially well known as a marker of diabetic nephropathy and other renal diseases [ 33 , 34 ]. NAG is present in free form in the lysosomes of many cells.…”

Section: Discussionmentioning

confidence: 99%

Low molecular weight proteins and enzymes in the urine of patients with bladder cancer - a pilot study

Marchewka

Szymańska

Dembowski

et al. 2018

Cent european J Uro

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IntroductionA steady increase in cases of bladder cancer (BC) has been observed. Detection of unfavorable changes, especially in the early stages of disease, is crucial to medical procedure. There is still a need to search for new, non-invasive biomarkers of BC. The aim of this study was to estimate the levels of selected low molecular weight proteins (LMWP) and enzymes in the urine of patients at different BC stages and grades.Material and methodsUrine samples from 46 patients with BC and 16 healthy controls were examined. We measured levels of LMWP such as: retinol-binding protein (RBP), β2 -microglobulin (β2M), enzymes: N-acetyl-β-D-glucosaminidase (NAG), isoform (NAG-B) and also neutrophil gelatinase-associated lipocalin (NGAL).ResultsThe levels of all examined parameters differed between patients and healthy subjects. Levels of NAG (p = 0.031), NAG-B (p = 0.023) and NGAL (p = 0.008), and total protein (p = 0.007) concentrations, were significantly higher in the BC patients than in the control group. Among the examined parameters, positive significant correlations were observed only between urinary NGAL concentration and tumor stages and grades. The highest percentages of changes in NGAL concentration were observed in tumor in situ (TIS) and G3grade patients.ConclusionsOur study showed that urinary NGAL concentrations, as well as NAG and NAG-B activity, could be helpful noninvasive parameters for the diagnosis of BC. The most promising seems to be NGAL determination, but further study is needed on a larger group of participants in order to confirm this observation.

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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%

“…Du et al [ 53 ] examined a panel of renal biomarkers in MM patients with CKD, MM with normal kidney function, and healthy volunteers, observing elevated NGAL levels in both serum and urine in the “MM-renal group”, as compared to the remaining two. The positive predictive value of serum NGAL for MM with renal damage was marginally higher (86% vs. 72%) than the urine form, which might be preferable in discriminating this unique group of patients.…”

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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Urinary NGAL for the diagnosis of the renal injury from multiple myeloma

Cited by 9 publications

References 15 publications

Activin A: a novel urinary biomarker of renal impairment in multiple myeloma

Activin A: a novel urinary biomarker of renal impairment in multiple myeloma

Low molecular weight proteins and enzymes in the urine of patients with bladder cancer - a pilot study

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

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