Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Fibrosis is the unifying pathway leading to chronic kidney disease. Identifying biomarkers of fibrosis may help predict disease progression.

Methods

We performed a systematic review to evaluate the reliability of blood and urine biomarkers in identifying fibrosis on biopsy as well as predicting renal outcomes. Using MEDLINE and EMBASE, a two-stage search strategy was implemented. Stage I identified a library of biomarkers correlating with fibrosis on biopsy. Stage II evaluated the association between biomarkers identified in stage I, and renal outcomes. Only biomarkers with moderate positive correlation with fibrosis ( r > 0.40) or acceptable area under the curve (AUC >0.65) advanced to stage II.

Results

Stage I identified 17 studies and 14 biomarkers. Five biomarkers met criteria to advance to stage II, but only three were independently associated with renal outcomes. Transforming growth factor β (TGF-β) correlated with fibrosis ( r = 0.60), and was associated with 1.7–3.9 times the risk of worsening renal function in 426 patients. Monocyte chemoattractant protein-1 (MCP-1) diagnosed fibrosis with AUC of 0.66 and was associated with 2.3–11.0 times the risk of worsening renal function in 596 patients. Matrix metalloproteinase-2 (MMP-2) correlated with fibrosis ( r = 0.41), and was associated with 2.5 times the risk of worsening renal function.

Conclusions

Given the heterogeneity of the data due to diverse patient populations along with differing renal outcomes, a meta-analysis could not be conducted. Nonetheless we can conclude from the published data that TGF-β, MCP-1 and MMP-2 may identify patients at risk for renal fibrosis and hence worse renal outcomes.

Electronic supplementary material

The online version of this article (doi:10.1186/s12882-017-0490-0) contains supplementary material, which is available to authorized users.

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

Blockade of CCR2 ameliorates progressive fibrosis in kidney.

Kiyoki Kitagawa, Takashi Wada, Kengo Furuichi … (2004)

Fibrosis is a hallmark of progressive organ diseases. Monocyte chemoattractant protein (MCP)-1, also termed as macrophage chemotactic and activating factor (MCAF/CCL2) and its receptor, CCR2 are presumed to contribute to progressive fibrosis. However, the therapeutic efficacy of MCP-1/CCR2 blockade in progressive fibrosis remains to be investigated. We hypothesized that blockade of CCR2 may lead to the improvement of fibrosis. To achieve this goal, we investigated renal interstitial fibrosis induced by a unilateral ureteral obstruction in CCR2 gene-targeted mice and mice treated with propagermanium or RS-504393, CCR2 inhibitors. Cell infiltrations, most of which were F4/80-positive, were reduced in CCR2 knockout mice. In addition, dual staining revealed that CCR2-positive cells were mainly F4/80-positive macrophages. Importantly, CCR2 blockade reduced renal interstitial fibrosis relative to wild-type mice. Concomitantly, renal transcripts and protein of MCP-1, transforming growth factor-beta, and type I collagen were decreased in CCR2-null mice. Further, this CCR2-dependent loop for renal fibrosis was confirmed by treatment with CCR2 antagonists in a unilateral ureteral obstruction model. These findings suggest that the therapeutic strategy of blocking CCR2 may prove beneficial for progressive fibrosis via the decrease in infiltration and activation of macrophages in the diseased kidneys.

0 comments Cited 81 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.

Cary S Passik, Jay Koyner, … (2013)

AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.

0 comments Cited 78 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Tubular overexpression of transforming growth factor-beta1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells.

Robert Koesters, Brigitte Kaissling, Michel LeHir … (2010)

We recently showed in a tetracycline-controlled transgenic mouse model that overexpression of transforming growth factor (TGF)-beta1 in renal tubules induces widespread peritubular fibrosis and focal degeneration of nephrons. In the present study we have analyzed the mechanisms underlying these phenomena. The initial response to tubular cell-derived TGF-beta1 consisted of a robust proliferation of peritubular cells and deposition of collagen. On sustained expression, nephrons degenerated in a focal pattern. This process started with tubular dedifferentiation and proceeded to total decomposition of tubular cells by autophagy. The final outcome was empty collapsed remnants of tubular basement membrane embedded into a dense collagenous fibrous tissue. The corresponding glomeruli survived as atubular remnants. Thus, TGF-beta1 driven autophagy may represent a novel mechanism of tubular decomposition. The fibrosis seen in between intact tubules and in areas of tubular decomposition resulted from myofibroblasts that were derived from local fibroblasts. No evidence was found for a transition of tubular cells into myofibroblasts. Neither tracing of injured tubules in electron micrographs nor genetic tagging of tubular epithelial cells revealed cells transgressing the tubular basement membrane. In conclusion, overexpression of TGF-beta1 in renal tubules in vivo induces interstitial proliferation, tubular autophagy, and fibrosis, but not epithelial-to-mesenchymal transition.

0 comments Cited 78 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Sherry G. Mansour: sherry.mansour@yale.edu

Jeremy Puthumana: jeremy.puthumana@yale.edu

Steven G. Coca: steven.coca@mssm.edu

Mark Gentry: mark.gentry@yale.edu

Chirag R. Parikh: (203) 737-2676 , chirag.parikh@yale.edu

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2369

Publication date (Electronic): 20 February 2017

Publication date PMC-release: 20 February 2017

Publication date Collection: 2017

Volume: 18

Electronic Location Identifier: 72

Affiliations

[1 ]ISNI 0000000419368710, GRID grid.47100.32, Program of Applied Translational Research, Department of Medicine, , Yale University, School of Medicine, ; New Haven, CT USA

[2 ]ISNI 0000000419368710, GRID grid.47100.32, Section of Nephrology, , Yale University School of Medicine, ; 60 Temple Street, Suite 6C, New Haven, CT 06510 USA

[3 ]ISNI 0000 0001 0670 2351, GRID grid.59734.3c, Department of Medicine, Division of Nephrology, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA

[4 ]ISNI 0000000419368710, GRID grid.47100.32, Harvey Cushing/John Hay Whitney Medical Library, , Yale University, ; New Haven, CT USA

[5 ]Veterans Affairs Connecticut Healthcare System, New Haven, CT USA

Article

Publisher ID: 490

DOI: 10.1186/s12882-017-0490-0

PMC ID: 5319065

PubMed ID: 28219345

SO-VID: 08a4beae-6390-4dcb-9c95-9bf064209887

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 11 September 2016

Date accepted : 14 February 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: T32DK007276

Award Recipient : Sherry G. Mansour

Funded by: NIDDK

Award ID: K24DK090203

Award Recipient : Chirag R. Parikh

Custom metadata

ScienceOpen disciplines: Nephrology

Keywords: fibrosis,biomarkers,renal biopsy,chronic kidney disease,renal disease progression,outcomes

Data availability:

ScienceOpen disciplines: Nephrology

Keywords: fibrosis, biomarkers, renal biopsy, chronic kidney disease, renal disease progression, outcomes

Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review

Read this article at

Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Related collections

Journal of Circulating Biomarkers

Most cited references 39

Blockade of CCR2 ameliorates progressive fibrosis in kidney.

Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.

Tubular overexpression of transforming growth factor-beta1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 229

Cited by 43

Most referenced authors 648