Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females
Publication: Journal of Interferon & Cytokine Research
Volume 41, Issue Number 8
Abstract
Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.
Get full access to this article
View all available purchase options and get full access to this article.
References
Adiyanti SS, Loho T. 2012. Acute kidney injury (AKI) biomarker. Acta Med Indones 44(3):246–255.
Agarwal SK, Saikia UK, Sarma D, Devi R. 2018. Assessment of glomerular and tubular function in the evaluation of diabetic nephropathy: a cross-sectional study. Indian J Endocrinol Metab 22(4):451–456.
Barnett LMA, Cummings BS. 2018. Nephrotoxicity and renal pathophysiology: a contemporary perspective. Toxicol Sci 164(2):379–390.
Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B (Methodol) 57(1):289–300.
Castillo-Rodriguez E, Fernandez-Prado R, Martin-Cleary C, Pizarro-Sanchez MS, Sanchez-Nino MD, Sanz AB, Fernandez-Fernandez B, Ortiz A. 2017. Kidney injury marker 1 and neutrophil gelatinase-associated lipocalin in chronic kidney disease. Nephron 136(4):263–267.
Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. 2017. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol 32(4):577–587.
Lind L. 2019. Population-based cardiovascular cohort studies in Uppsala. Ups J Med Sci 124(1):16–20.
Moledina DG, Perazella MA. 2017. Drug-induced acute interstitial nephritis. Clin J Am Soc Nephrol 12(12):2046–2049.
Noraddin FH, Flodin M, Fredricsson A, Sohrabian A, Larsson A. 2012. Measurement of urinary cystatin C with a particle-enhanced turbidimetric immunoassay on Architect ci8200. J Clin Lab Analysis 26(5):358–364.
Oliva-Damaso N, Oliva-Damaso E, Payan J. 2018. Acute and chronic tubulointerstitial nephritis of rheumatic causes. Rheum Dis Clin North Am 44(4):619–633.
Pennemans V, Rigo J-M, Faes C, Reynders C, Penders J, Swennen Q. 2013. Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: are age and gender an issue? Clin Chem Lab Med 51(9):1795–1802.
Perazella MA. 2017. Clinical approach to diagnosing acute and chronic tubulointerstitial disease. Adv Chronic Kidney Dis 24(2):57–63.
Shirali AC, Perazella MA. 2014. Tubulointerstitial injury associated with chemotherapeutic agents. Adv Chronic Kidney Dis 21(1):56–63.
Wang D, Yu Y, Wang R, Cai Y, Li Y, Choe CM, Guan H, Wang X. 2019. A family with autosomal dominant distal renal tubular acidosis presents with atypical phenotype caused by a missence mutation (R388C) of the human kidney anion exchanger. Nephron 141(3):207–212.
Webster AC, Nagler EV, Morton RL, Masson P. 2017. Chronic kidney disease. Lancet 389(10075):1238–1252.
Willinger CC, Schramek H, Pfaller K, Pfaller W. 1992. Tissue distribution of neutrophils in postischemic acute renal failure. Virchows Arch B Cell Pathol Incl Mol Pathol 62(4):237–243.
Ysebaert DK, De Greef KE, Vercauteren SR, Ghielli M, Verpooten GA, Eyskens EJ, De Broe ME. 2000. Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant 15(10):1562–1574.
Information & Authors
Information
Published In
Journal of Interferon & Cytokine Research
Volume 41 • Issue Number 8 • August 2021
Pages: 283 - 290
PubMed: 34410878
Copyright
Copyright 2021, Mary Ann Liebert, Inc., publishers.
History
Published online: 17 August 2021
Published in print: August 2021
Accepted: 30 June 2021
Received: 9 May 2021
Topics
- Biomedical science, research and development
- Chemokine
- Chronic kidney disease
- Cytokines
- DNA and cell biology
- Genetic Engineering, Biotechnology, and Regenerative medicine
- Growth factors
- Intercellular signaling peptide
- Medicine, Surgery & Diagnosis
- Regenerative medicine
- Renal disorders
- Tissue engineering
- Tissue repair and regeneration
- Urogenital disease
Authors
Authors' Contributions
L.L. conceived the PIVUS study and performed the statistical analysis. All authors have been involved in the analysis of data from the PIVUS study. B.F. and A.L. conceptualized and organized the PEA assays in the study. B.F., A.L., and L.L. prepared the article. All authors have read and agreed to the submitted version of the article.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This study was supported financially by Njurfonden. Open access funding was provided by Uppsala University.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.