Identification of β2‐microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods

Johnston, Olwyn; Cassidy, Hilary; O’Connell, Séin; O'Riordan, Aisling; Gallagher, William M.; Maguire, Patricia B.; Wynne, Kieran; Cagney, Gerard; Ryan, Michael P.; Conlon, Peter J.; McMorrow, Tara

doi:10.1002/prca.201000160

Cited by 32 publications

(40 citation statements)

References 45 publications

(51 reference statements)

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“…A very promising approach (261) used surfaced-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to identify urinary proteins as biomarkers for chronic allograft damage. In this retrospective study, there were 34 renal transplant patients (disease group) with histologically proven chronic allograft damage, with an eGFR less than 45 ml/min who were more than 1-year posttransplantation.…”

Section: β2m In Kidney Transplantationmentioning

confidence: 99%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

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Section: β2m In Kidney Transplantationmentioning

confidence: 99%

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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“…It was also found that the combination of urinary CXCL-10 levels normalized to urine creatinine with donor-specific antibody monitoring significantly improved the non-invasive diagnosis of antibody-mediated rejection and may allow for the stratification of patients at high risk for graft loss 42 . Other protein markers that have shown promise in clinical validation trials are urinary CCL-2 (predictor of interstitial fibrosis and atrophy and kidney graft loss) 43 , urinary β2-microglobulin (chronic allograft nephropathy) 44 and serum aminoacylase-1 (long term outcome in patients with delayed kidney graft function) 45 . In addition, urinary kidney dysfunction markers that have originally been discovered in patients with acute kidney injury such as urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18 and kidney injury molecule-1 (KIM-1) have been studied in kidney transplant patients, but none of these seem as advanced in their development as CXCL-9 and CXCL-10 in this specific patient population 35 .…”

Section: Predictive Biomarkers In Transplantation Based On Targeted Pmentioning

confidence: 99%

Biomarkers in Transplantation—Proteomics and Metabolomics

Christians

Klawitter

2016

Therapeutic Drug Monitoring

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Modern multi-analyte “omics” technologies allow for the identification of molecular signatures that confer significantly more information than measurement of a single parameter as typically used in current medical diagnostics. Proteomics and metabolomics bioanalytical assays capture a large set of proteins and metabolites in body fluids, cells or tissues and, complementing genomics, assess the phenome. Proteomics and metabolomics contribute to the development of novel predictive clinical biomarkers in transplantation in two ways: They can be used to generate a diagnostic fingerprint or they can be used to discover individual proteins and metabolites of diagnostic potential. Much fewer metabolomics than proteomics biomarker studies in transplant patients have been reported and, in contrast to proteomics discovery studies, new lead metabolite markers have yet to emerge. Most clinical proteomics studies have been discovery studies. Several of these studies have assessed diagnostic sensitivity and specificity. Nevertheless, none of these newly discovered protein biomarkers has yet been implemented in clinical decision making in transplantation. The currently most advanced markers discovered in proteomics studies in transplant patients are the chemokines CXCL-9 and CXCL-10, which have successfully been validated in larger multi-center trials in kidney transplant patients. These chemokines can be measured using standard immunoassay platforms, which should facilitate clinical implementation. Based on the published evidence, it is reasonable to expect that these chemokine markers can help guiding and individualizing immunosuppressive regimens, may be able to predict acute and chronic T cell and anti-body mediated rejection and may be useful tools for risk stratification of kidney transplant patients.

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“…Therefore the development of novel, predictive indicators of CAI would be highly desirable. One strategy utilised to identify novel biomarkers has been urinary proteomic analysis in both the CsA mouse model (O'Connell et al 2011) and in a clinical patient cohort (Johnston et al, 2011) (Depicted in Figures 6 and 7 respectively). In the animal studies significant alterations in urinary podocin and uromodulin were observed which may be indicative of damage to the glomeruli and tubules after CsA treatment.…”

Section: In Vivo Data -Animal Models and Clinical Studiesmentioning

confidence: 99%