Glomerular Hyperfiltration and β-2 Microglobulin As Biomarkers of Incipient Renal Dysfunction in Cancer Survivors

Tibúrcio, Fernanda Rodrigues; Rodrigues, Karla Emília de Sá; Belisário, André Rolim; Silva, Ana Cristina Simões e

doi:10.4155/fsoa-2018-0045

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…When compared to non-SS sicca subjects, the two most upregulated of these proteins in pSS patients, FKBP1A and CD44, play a role in adaptive immunity through T-cell activation and proliferation [54, 55], in addition to promoting tumour growth and progression. Concurrently, B2MG is central in innate immunity by mediating antigen processing and presentation on MHC class I [56]. Comparing patients with pSS to healthy controls, CD44 was again identified, in addition to SLUR1, affecting acetylcholine receptor activity, cell migration and proliferation, and CLUS, playing a key role in innate immunity by modulating NF-kappa-B activity and TNF production [57, 58].…”

Section: Discussionmentioning

confidence: 99%

Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers

et al. 2019

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Background Mononuclear cell infiltration of exocrine glands, production of Ro/SSA and La/SSB autoantibodies, along with oral and ocular dryness, are characteristic features of primary Sjögren’s syndrome (pSS). Non-SS sicca subjects, an underexplored group in relation to pSS, display similar sicca symptoms, with possible mild signs of inflammation in their salivary glands, yet with no serological detection of autoantibody production. In this study, we investigated inflammatory manifestations in the salivary gland tissue, tear fluid and saliva of non-SS subjects, as compared to pSS patients and healthy individuals. Methods Fifteen non-SS, 10 pSS and 10 healthy subjects were included in the analyses. Histological evaluation of salivary gland biopsies was performed. Liquid chromatography-mass spectrometry (LC-MS) was conducted on tear fluid and stimulated whole saliva, and proteomic biomarker profiles were generated. Extracellular vesicle (EVs) isolation and characterisation from both fluids were also combined with LC-MS. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Functional Enrichment Analysis Tool (FunRich) were applied for functional analyses. Results Histopathological evaluation of salivary gland biopsies showed implications of milder inflammation in non-SS subjects through mononuclear cell infiltration, fibrosis and fatty replacement, as compared to pSS patients. Although unaffected in the non-SS group, upregulation of proinflammatory pathways and proteins involved in ubiquitination (LMO7 and HUWE1) and B cell differentiation (TPD52) were detected in tear fluid of pSS patients. Moreover, overexpression of proteins STOM, ANXA4 and ANXA1, regulating cellular innate and adaptive immunological pathways, were further identified in EVs from tear fluid of pSS patients. Finally, whole saliva and EVs isolated from whole saliva of pSS patients expressed proteins vital for innate MHC class I cellular regulation (NGAL) and T cell activation (CD44). Conclusions Non-SS sicca subjects may show implications of mild inflammation in their glandular tissue, while their protein profile was strikingly more similar to healthy controls than to pSS patients. Hence, the tear and salivary biomarkers identified could be implemented as potential non-invasive diagnostic tools that may aid in increasing diagnostic accuracy when evaluating non-SS subjects and pSS patients and monitoring disease progression. Electronic supplementary material The online version of this article (10.1186/s13075-019-1961-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers

et al. 2019

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“…ratio among CCS were reported. The association between urinary β2M and nephrotoxicity for the first time was described by Tiburcio et al in a study of 41 CCS [25]. They reported in short-term survivors that urinary β2M level was significantly higher in the study group and was positively correlated with plasma creatinine concentration and negatively corre-lated with glomerular filtration rate.…”

Section: Discussionmentioning

confidence: 60%

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

Latoch

Konończuk

Taranta-Janusz

et al. 2021

JCM

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The objectives of this study were to evaluate urinary beta-2-microglobulin (β2M) levels in long-term childhood cancer survivors and to establish its association with anticancer drug-induced nephrotoxicity. The study consisted of 165 childhood cancer survivors (CCS) who were in continuous complete remission. We reported that CCS had a significantly higher level of β2M (p < 0.001) and β2M/Cr. ratio (p < 0.05) than healthy peers. Among all participants, 24 (14.5%) had decreased eGFR (<90 mL/min/1.73 m2). A significant positive correlation between β2M/Cr. ratio and body mass index (coef. 14.48, p = 0.046) was found. Furthermore, higher levels of urinary β2M were detected among CCS with a longer follow-up time (over 5 years) after treatment. Subjects with decreased eGFR showed statistically higher urinary β2M levels (20.06 ± 21.56 ng/mL vs. 8.55 ± 3.65 ng/mL, p = 0.007) compared with the healthy peers. Twelve survivors (7.2%) presented hyperfiltration and they had higher urinary β2M levels than CCS with normal glomerular filtration (46.33 ± 93.11 vs. 8.55 ± 3.65 ng/mL, p = 0.029). This study did not reveal an association between potential treatment-related risk factors such as chemotherapy, surgery, radiotherapy, and the urinary β2M level. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). We demonstrated that urinary beta-2-microglobulin may play a role in the subtle kidney injury in childhood cancer survivors; however, the treatment-related factors affecting the β2M level remain unknown. Further prospective studies with a longer follow-up time are needed to confirm the utility of urinary β2M and its role as a non-invasive biomarker of renal dysfunction.

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“…The positive correlation between increased eGFR values and intensity of immunosuppression suggested that hyperfiltration could be a surrogate marker of renal dysfunction. Another recent study has confirmed the role of hyperfiltration as a marker of incipient renal dysfunction in the pediatric population of cancer survivors [ 29 ]. In our population, the significantly elevated eGFR values in oncological patients compared to non-oncological ones seemed to confirm this assumption.…”

Section: Discussionmentioning

confidence: 92%

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children—A Single Center Experience

Musiał

Kałwak

Zwołińska

2021

JCM

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Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.

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Glomerular Hyperfiltration and β-2 Microglobulin As Biomarkers of Incipient Renal Dysfunction in Cancer Survivors

Cited by 9 publications

References 35 publications

Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers

Proteomic and histopathological characterisation of sicca subjects and primary Sjögren’s syndrome patients reveals promising tear, saliva and extracellular vesicle disease biomarkers

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children—A Single Center Experience

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