Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation

Stubendorff, Beatrice; Finke, Stephanie; Walter, M.; Kniemeyer, Olaf; Eggeling, Ferdinand von; Gruschwitz, Torsten; Steiner, Thomas; Ott, U.; Wolf, Günter; Wunderlich, Heiko; Junker, Kerstin

doi:10.1007/s00345-014-1263-z

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…The AMBP gene encodes α 1 -microglobulin/bikunin precursor protein; α 1 -MG (A1M) is the lipocalin—derived from proteolytic cleavage of AMBP [24]. A1M is secreted into plasma, where it can exist free, or bound, to immunoglobulin-A or albumin.…”

Section: Lipocalin Family In Humansmentioning

confidence: 99%

“…Although the molecular weight of A1M is 27.0 kDa, it is freely filtered through the glomerulus and reabsorbed by proximal tubular cells [25]; for this reason, A1M is a biomarker of proteinuria, i.e., increased levels in urine indicate a defect in proximal tubules. A1M is considered to be a major factor for progressive impairment of renal function, as well as for early diagnosis of acute allograft rejection [13, 24, 26]. Recent studies have shown A1M to be expressed in rat retinal explants and to have oxygen radical-scavenging and reductase properties; these findings suggest that A1M might protect against oxidative stress and possibly be involved in the response to retinal detachment [27, 28].…”

Section: Lipocalin Family In Humansmentioning

confidence: 99%

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Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”

et al. 2019

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Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN -like genes in the human genome, and 45 Lcn -like genes in the mouse genome, which include 22 major urinary protein ( Mup ) genes. The Mup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an “evolutionary bloom” that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. LCNs play important roles in physiological processes by binding and transporting small hydrophobic molecules —such as steroid hormones, odorants, retinoids, and lipids—in plasma and other body fluids. LCNs are extensively used in clinical practice as biochemical markers. LCN-like proteins (18–40 kDa) have the characteristic eight β-strands creating a barrel structure that houses the binding-site; LCNs are synthesized in the liver as well as various secretory tissues. In rodents, MUPs are involved in communication of information in urine-derived scent marks, serving as signatures of individual identity, or as kairomones (to elicit fear behavior). MUPs also participate in regulation of glucose and lipid metabolism via a mechanism not well understood. Although much has been learned about LCNs and MUPs in recent years, more research is necessary to allow better understanding of their physiological functions, as well as their involvement in clinical disorders.

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Section: Lipocalin Family In Humansmentioning

confidence: 99%

Section: Lipocalin Family In Humansmentioning

confidence: 99%

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”

et al. 2019

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“…HPT has been identified as a biomarker for several clinical outcomes, including acute allograft rejection [11], DN [21,22], chronic renal insufficiency [23], and glomerulonephritis. HPT is a heavily glycosylated alpha-2 sialoglycoprotein with a net negative charge [24].…”

Section: Discussionmentioning

confidence: 99%

“…AMBP is a stable urinary protein that has been used as a clinical parameter for the detection and differentiation of proteinuria. High-urine AMBP levels indicate proximal tubular dysfunction, and they are associated with interstitial fibrosis, tubular atrophy, and inflammation [11,21]. A previous study using ProteinChip (H50 chip) analysis has shown that urinary AMBP is increased in DN [22].…”

Section: Discussionmentioning

confidence: 99%

“…Proteins are functional executors of biological mechanisms, and they have been utilized as prognostic biomarkers for a number of diseases such as DN, cardiovascular disease, and cancer [9,10,11,12]. With the development of protein separation techniques and mass spectrometry, liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics has been widely applied to the analysis of clinical samples for the elucidation of protein changes in complex mixtures.…”

Section: Introductionmentioning

confidence: 99%

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Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients

Liao

Chang

Chen

et al. 2018

JCM

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Diabetic nephropathy (DN) is a major complication in diabetic patients. Microalbuminuria testing is used to identify renal disease; however, its predictive value is questionable. We aimed to identify urinary biomarkers to early diagnosis nephropathy before identifiable alternations in kidney function or urine albumin excretion occurs. Proteomic approaches were used to identify potential urinary biomarkers and enzyme-linked immunosorbent assay was performed to verify the results. The data identified haptoglobin (HPT) and α-1-microglobulin/bikunin precursor (AMBP) as two biomarkers with the highest ability to distinguish between healthy individuals and patients with nephropathy, and between diabetic patients with and without DN. Further, the HPT-to-creatinine ratio (HCR) was evaluated as an independent predictor of early renal functional decline (ERFD) in a cohort with an average follow-up of 4.2 years. The area under the curve (AUC) value for ERFD prediction was significantly improved when the HCR biomarker was included in the model with albumin to creatinine ratio (ACR) and baseline characteristics (AUC values were 0.803 and 0.759 for HCR and ACR, respectively; p value was 0.0423 for difference between models). In conclusion, our results suggest that HCR represents an early indicator of nephropathy, and a marker related to ERFD among diabetic patients in Taiwan.

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Biomarkers in Kidney Transplantation

Jain

Jani

2017

Biomarkers of Kidney Disease

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Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation

Cited by 12 publications

References 17 publications

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an “evolutionary bloom”

Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients

Biomarkers in Kidney Transplantation

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