New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

Woziwodzka, Karolina; Małyszko, Jolanta; Batko, Krzysztof; Jurczyszyn, Artur; Koc-Żórawska, Ewa; Krzanowski, Marcin; Małyszko, J.; Żórawski, Marcin; Waszczuk‐Gajda, Anna; Kuźniewski, Marek; Kościelska‐Kasprzak, Katarzyna

doi:10.3390/jcm9061652

Cited by 11 publications

(9 citation statements)

References 90 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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“…Of note, the overexpression of the cystatin C gene by myeloma cells suggests that cystatin C also reflects the myeloma burden. Several studies have shown that serum cystatin C has a strong positive correlation with β2-microglobulin, which is a well-recognized indicator of tumor burden and renal insufficiency in patients with MM [58][59][60]. The strong positive correlation further confirms that elevated cystatin C levels similar to those of β2-microglobulin also reflect increased tumor burden.…”

Section: Prognostic Value Of Cystatin C In Multiple Myelomamentioning

confidence: 68%

The role of cystatin C as a proteasome inhibitor in multiple myeloma

Jiang

Zhang

et al. 2020

Hematology

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Objectives: Bone destruction and renal impairment are two frequent complications of multiple myeloma (MM). Cystatin C, an extracellular cysteine proteinase inhibitor, is encoded by the housekeeping gene CST3 and associated with human tumors. The role of cystatin C in multiple myeloma has been revealed recently. The purpose of this study was to explore the role of cystatin C as a proteasome inhibitor in multiple myeloma. Methods: A comprehensive literature review was conducted through Pubmed to summarize the published evidence on cystatin C in multiple myeloma. English literature sources since 1999 were searched, using the terms cystatin C, multiple myeloma. Results: cystatin C is a sensitive indicator for the diagnosis of myeloma nephropathy and has a dual role in myeloma bone disease. Also, cystatin C reflects tumor burden and is strongly associated with prognosis in patients with multiple myeloma. Conclusion: Cystatin C have great diagnostic and prognostic value in multiple myeloma. It can provide a new treatment direction for MM by designing and searching for antagonists of cystatin C or cysteine protease agonists using cystatin C as a therapeutic target.

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“…Early diagnosis and treatment are crucial to control and reverse renal failure. The use of new markers of renal failure in MM is a promising direction and should be considered in the future 27 . In a large study of patients diagnosed with myeloma before age 40, 28 at 5 years, relative survival compared with same age‐ and sex‐matched individuals was 83.5%, and estimated standardized mortality ratio was 69.9 confirming that MM dramatically shortens the survival of young patients despite an extended survival after diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma in a Young Adult with Renal Involvement

Hajji

Barbouch

Goucha

et al. 2023

Clinical Case Reports

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Ms. S.W, 34, with no medical history, was admitted for investigation of advanced renal failure. On admission, she was asthenic and complained of headache and gastric pain. On examination, she weighed 62 kg, she had normal blood pressure, correct hydration, and no abnormalities on cardiopulmonary auscultations. she had a preserved diuresis (1 L). The urine dipstick showed proteinuria: + and no hematuria.At biological assessment, she had serum creatinine at 707 μmol/L, normochromic normocytic anemia at 5.2 g/ dL with direct positive IgG-type Coombs test, serum calcium at 2.8 mmol/L and LDH level at 488 mmol/L. At protein electrophoresis: monoclonal peak in gamma position. Twenty-four-hour proteinuria dosage was 7 g/24 H, in contrast with low proteinuria with labstix. the blood ionogram showed a natremia at 140 mmol/L, a kalemia at 5.6 mmol/L and a chloremia at 110 mmol/L. At serum immunoelectrophoretic profile, the presence of a monoclonal gammopathy type Ig G Lambda (Figure 1). The serum-free light chains (FLC) ratio kappa/lambda was equal to 0.03. Urine immunoelectrophoresis showed positive urinary monoclonal protein (free lambda chain); The ratio of kappa to lambda chains in urine was 0.017. On the myelogram: 32% plasmacytosis. On the kidney ultrasound, she had two well-differentiated normalized kidneys. She had a renal biopsy, which showed an aspect of myelomatous tubulopathy (Figure 2). The spinal MRI was without abnormalities. CRAB criteria 6 in our patient, involved hypercalcemia, renal failure, and anemia but no bone damage. The retained diagnosis in our patient was: MM with IgG Lambda class III of Salmon and Durie. 7 R-ISS prognostic factors 8 included respectively serum

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New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

Cited by 11 publications

References 90 publications

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

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

The role of cystatin C as a proteasome inhibitor in multiple myeloma

Multiple Myeloma in a Young Adult with Renal Involvement

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