Biomarkers for Predicting Outcomes in Chronic Kidney Disease

Overview

Journal Curr Opin Nephrol Hypertens

Specialties Cardiology & Vascular Diseases
Nephrology

Date 2016 Sep 17

PMID 27636773

Citations 15

Authors

Lekha Tummalapalli

Girish N Nadkarni

Steven G Coca

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Current biomarkers for chronic kidney disease (CKD) are limited by lack of sensitivity and inability to prognosticate CKD progression. Significant recent research has better characterized novel biomarker candidates that are associated with CKD progression and cardiovascular mortality in CKD. This review discusses the most significant advances within the past year.

Recent Findings: We discuss biomarkers for outcomes in CKD under two categories: emerging (defined as having been validated in an independent cohort), which include serum cystatin C, serum β-trace protein, β2-microglobulin, soluble urokinase-type plasminogen activator receptor, soluble tumor necrosis factor receptors 1/2, urinary monocyte chemotactic protein-1, neutrophil gelatin-associated lipocalin, kidney injury molecule-1, and fibroblast growth factor-23; and novel (which have shown associations in smaller observational studies but have not been validated yet), which include indoxyl sulfate, p-cresyl sulfate, trimethylamine-N-oxide, IL-18, Klotho, markers of endothelial dysfunction, vimentin, and procollagen type III N-terminal propeptide. Further, we also discuss future directions for biomarker research including unbiased -omics approaches.

Summary: There are a number of promising biomarkers that can better prognosticate outcomes in and progression of CKD. Further research is warranted to examine whether these biomarkers validate independently as well, and if their incorporation improves clinical practice or trial enrollment.

Citing Articles

Very low urinary marinobufagenin excretion reflects a high risk of disease progression in non-advanced CKD.

Bolignano D, Greco M, Tripodi L, DAgostino M, Cianfrone P, Misiti R Front Physiol. 2025; 16:1527805.

PMID: 39963657 PMC: 11830711. DOI: 10.3389/fphys.2025.1527805.

CKD patients comorbid with hypertension are associated with imbalanced gut microbiome.

Wang P, Shen Y, Yan K, Wang S, Jiao J, Chi H iScience. 2025; 28(2):111766.

PMID: 39911351 PMC: 11795142. DOI: 10.1016/j.isci.2025.111766.

Association of Small HDL Subclasses with Mortality Risk in Chronic Kidney Disease.

Stadler J, Borenich A, Pammer A, Emrich I, Habisch H, Madl T Antioxidants (Basel). 2025; 13(12.

PMID: 39765838 PMC: 11673888. DOI: 10.3390/antiox13121511.

A Comprehensive Review of Advanced Biomarkers for Chronic Kidney Disease in Older Adults: Current Insights and Future Directions.

Pradeep U, Chiwhane A, Acharya S, Daiya V, Kasat P, Sachani P Cureus. 2024; 16(9):e70413.

PMID: 39473640 PMC: 11519577. DOI: 10.7759/cureus.70413.

A Comprehensive Review of Biomarkers for Chronic Kidney Disease in Older Individuals: Current Perspectives and Future Directions.

Gupta A, Sontakke T, Acharya S, Kumar S Cureus. 2024; 16(9):e70262.

PMID: 39463626 PMC: 11512660. DOI: 10.7759/cureus.70262.

References

Scialla J, Xie H, Rahman M, Anderson A, Isakova T, Ojo A . Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2013; 25(2):349-60. PMC: 3904568. DOI: 10.1681/ASN.2013050465. View

Gohda T, Niewczas M, Ficociello L, Walker W, Skupien J, Rosetti F . Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. J Am Soc Nephrol. 2012; 23(3):516-24. PMC: 3294299. DOI: 10.1681/ASN.2011060628. View

Isakova T, Xie H, Yang W, Xie D, Anderson A, Scialla J . Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011; 305(23):2432-9. PMC: 3124770. DOI: 10.1001/jama.2011.826. View

Al-Lamki R, Mayadas T . TNF receptors: signaling pathways and contribution to renal dysfunction. Kidney Int. 2014; 87(2):281-96. DOI: 10.1038/ki.2014.285. View

Xie J, Yoon J, An S, Kuro-O M, Huang C . Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate. J Am Soc Nephrol. 2014; 26(5):1150-60. PMC: 4413766. DOI: 10.1681/ASN.2014040325. View

Pavkov M, Nelson R, Knowler W, Cheng Y, Krolewski A, Niewczas M . Elevation of circulating TNF receptors 1 and 2 increases the risk of end-stage renal disease in American Indians with type 2 diabetes. Kidney Int. 2014; 87(4):812-9. PMC: 4382420. DOI: 10.1038/ki.2014.330. View

Dong X, Swaminathan S, Bachman L, Croatt A, Nath K, Griffin M . Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. Kidney Int. 2007; 71(7):619-28. DOI: 10.1038/sj.ki.5002132. View

Nosadini R, Velussi M, Brocco E, Bruseghin M, Abaterusso C, Saller A . Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate. Diabetes. 2000; 49(3):476-84. DOI: 10.2337/diabetes.49.3.476. View

Kendrick J, Cheung A, Kaufman J, Greene T, Roberts W, Smits G . FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol. 2011; 22(10):1913-22. PMC: 3187186. DOI: 10.1681/ASN.2010121224. View

10.

Yassine H, Trenchevska O, Dong Z, Bashawri Y, Koska J, Reaven P . The association of plasma cystatin C proteoforms with diabetic chronic kidney disease. Proteome Sci. 2016; 14:7. PMC: 4807542. DOI: 10.1186/s12953-016-0096-7. View

11.

Verhave J, Bouchard J, Goupil R, Pichette V, Brachemi S, Madore F . Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy: a prospective study. Diabetes Res Clin Pract. 2013; 101(3):333-40. DOI: 10.1016/j.diabres.2013.07.006. View

12.

Rovin B, Rumancik M, Tan L, Dickerson J . Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis. Lab Invest. 1994; 71(4):536-42. View

13.

Wei L, Ye X, Pei X, Wu J, Zhao W . Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta-analysis. Clin Nephrol. 2015; 84(2):86-94. DOI: 10.5414/cn108525. View

14.

Black R, Rauch C, Kozlosky C, Peschon J, Slack J, Wolfson M . A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997; 385(6618):729-33. DOI: 10.1038/385729a0. View

15.

Inker L, Tighiouart H, Coresh J, Foster M, Anderson A, Beck G . GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD. Am J Kidney Dis. 2015; 67(1):40-8. PMC: 4695294. DOI: 10.1053/j.ajkd.2015.07.025. View

16.

Missailidis C, Hallqvist J, Qureshi A, Barany P, Heimburger O, Lindholm B . Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease. PLoS One. 2016; 11(1):e0141738. PMC: 4709190. DOI: 10.1371/journal.pone.0141738. View

17.

Parikh C, Thiessen-Philbrook H, Garg A, Kadiyala D, Shlipak M, Koyner J . Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol. 2013; 8(7):1079-88. PMC: 3700701. DOI: 10.2215/CJN.10971012. View

18.

Swan A, Stekel D, Hodgman C, Allaway D, Alqahtani M, Mobasheri A . A machine learning heuristic to identify biologically relevant and minimal biomarker panels from omics data. BMC Genomics. 2015; 16 Suppl 1:S2. PMC: 4315157. DOI: 10.1186/1471-2164-16-S1-S2. View

19.

Foster M, Coresh J, Hsu C, Xie D, Levey A, Nelson R . Serum β-Trace Protein and β2-Microglobulin as Predictors of ESRD, Mortality, and Cardiovascular Disease in Adults With CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2016; 68(1):68-76. PMC: 4921300. DOI: 10.1053/j.ajkd.2016.01.015. View

20.

Al-Lamki R, Wang J, Vandenabeele P, Bradley J, Thiru S, Luo D . TNFR1- and TNFR2-mediated signaling pathways in human kidney are cell type-specific and differentially contribute to renal injury. FASEB J. 2005; 19(12):1637-45. DOI: 10.1096/fj.05-3841com. View