Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients

Woziwodzka, Karolina; Małyszko, Jolanta; Koc-Żórawska, Ewa; Żórawski, Marcin; Dumnicka, Paulina; Jurczyszyn, Artur; Batko, Krzysztof; Mazur, Paulina; Banaszkiewicz, Małgorzata; Krzanowski, Marcin; Gołasa, Paulina; Małyszko, Jacek; Drożdż, Ryszard; Kościelska‐Kasprzak, Katarzyna

doi:10.3390/medicina57121348

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…Renal insufficiency is considered reversible in about 50% of cases in some reports [ 8 , 9 ]. With the advent of novel drugs (e.g., proteasome inhibitors), prognosis for MM patients with renal insufficiency has remarkably improved [ 7 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

et al. 2021

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Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate—eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin—NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = −0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = −0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = −0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = −0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

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Section: Introductionmentioning

confidence: 99%

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

et al. 2021

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“…However, although in our study serum iron concentrations were correlated with renal function (serum creatinine, eGFR, and urine NGAL), we observed no such correlations in the case of serum ferritin, sTfR, and hepcidin. It is well known that renal impairment in MM reflects poor prognosis and determines the response to chemotherapy [ 3 ]. The lack of hepcidin correlation with renal function supports the role of hepcidin as a marker of poor prognosis in MM that is independent of renal injury.…”

Section: Discussionmentioning

confidence: 99%

“…It is often described as a “real-time indicator of renal injury”. It also shows a relationship with inflammation and tumor burden [ 3 , 41 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…The focus on timely diagnosis and prevention of organ damage drives the interest in diagnostic and prognostic biomarkers. In theory, a validated biomarker can act as a surrogate of underlying disease pathways and inform the physician on the alterations in organ-specific processes; for example, our previous studies demonstrated that urinary insulin growth factor binding protein 7 (IGFBP-7), neutrophil gelatinase-associated lipocalin (NGAL) monomer, and transgelin-2 may be markers of renal impairment in patients with MM [ 3 , 4 ]. The use of appropriate biomarkers may be crucial for adequate tailoring of the treatment plan.…”

Section: Introductionmentioning

confidence: 99%

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The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment

et al. 2022

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Background and objectives: Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Materials and methods: Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. Results: MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients’ 2-year survival. Conclusion: Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.

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Urinary Insulin-Like Growth Factor-Binding Protein 7 (IGFBp7), Urinary Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP2), and Serum Transgelin as Novel Biomarkers of Kidney Injury in Multiple Myeloma

Shoeib,

Hassan,

Habeeb

et al. 2023

Indian J Hematol Blood Transfus

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Renal dysfunction is a common complication of MM and is associated with poor prognosis, particularly when progressive. Early identification of renal dysfunction is essential for prompt treatment for disease control and restoration of renal function. Urinary insulin-like growth factor-binding protein 7 (IGFBP-7), urinary tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and serum transgelin levels were measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the prediction of renal impairment in patients with multiple myeloma. U IGFBP-7/creatinine ratio, U TIMP2/creatinine ratio, and serum transgelin levels were higher in patients with MM than healthy controls, and predicted renal insufficiency in MM. Serum transgelin, urinary IGFBp7, and TIMP2 levels may have utility as biomarkers of renal tubular injury and predict future renal impairment in patients with MM.

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Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients

Cited by 5 publications

References 47 publications

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

The Key Role of Hepcidin-25 in Anemia in Multiple Myeloma Patients with Renal Impairment

Urinary Insulin-Like Growth Factor-Binding Protein 7 (IGFBp7), Urinary Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP2), and Serum Transgelin as Novel Biomarkers of Kidney Injury in Multiple Myeloma

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