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Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic Level.

ABSTRACT: The ribonuclease angiogenin is a component of the mammalian stress response that is secreted by renal epithelial cells on activation of the inositol-requiring enzyme 1? (IRE1?)-active spliced X-box binding protein 1 (sXBP1) axis and instrumental to the adaptation to AKI associated with endoplasmic reticulum stress. To determine whether the amount of angiogenin in urine of individuals with a kidney injury reflects the magnitude of the lesions and provides information on the risk of organ failure, we examined individuals referred for a kidney injury and determined the biochemical characteristics of urinary angiogenin and its diagnostic and prognostic values. Urinary angiogenin did not correlate with the urinary concentrations of high molecular weight proteins and correlated only weakly with low molecular weight proteins, suggestive of tubular production. In a cohort of 242 kidney transplant recipients with acute allograft dysfunction, higher urinary angiogenin concentrations at the time of the biopsy associated with worse renal function and higher proteinuria but did not correlate with histologic lesions as defined in the Banff classification. Kidney transplant recipients with urinary angiogenin amounts in the highest 50% had a risk of graft failure 3.59 times as high (95% confidence interval, 1.12 to 15.94) as that of patients with amounts in the lowest 50%. Finally, the amount of urinary angiogenin reflected the activity of the IRE1?-XBP1 axis in allografts. Our approach identified urinary angiogenin as a noninvasive indicator of the extent of tissue damage, independent of the histologic lesions, and a risk predictor of kidney allograft failure.

SUBMITTER: Tavernier Q

PROVIDER: S-EPMC5280019 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic Level.

Tavernier Quentin Q Mami Iadh I Rabant Marion M Karras Alexandre A Laurent-Puig Pierre P Chevet Eric E Thervet Eric E Anglicheau Dany D Pallet Nicolas N

Journal of the American Society of Nephrology : JASN 20160719 2

The ribonuclease angiogenin is a component of the mammalian stress response that is secreted by renal epithelial cells on activation of the inositol-requiring enzyme 1α (IRE1α)-active spliced X-box binding protein 1 (sXBP1) axis and instrumental to the adaptation to AKI associated with endoplasmic reticulum stress. To determine whether the amount of angiogenin in urine of individuals with a kidney injury reflects the magnitude of the lesions and provides information on the risk of organ failure, ...[more]

PMID: 27436854

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Project description:BACKGROUND:Acute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia. Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. RESULTS:In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. CONCLUSIONS:It was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-? (transforming growth factor ?) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, ?2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury.

Project description:Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury.Urine was collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels and microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined using Cox proportional hazards or linear regression models. Available kidney biopsy specimens were processed for immunohistochemistry.Mean urinary elafin levels to day 100 were higher in patients with micro- or macroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a normal ACR (adjusted mean difference, 1295 pg/ml; P<0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P<0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro- or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P<0.01). Each increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to 1.13; P<0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P<0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules.Higher urinary elafin levels are associated with an increased risk of micro- and macroalbuminuria, AKI and CKD, and death after HCT.

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Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic Level.

Publications

Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic Level.

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