Urinary complement factor D is increased in primary malignant hypertension: a single-center, cross-sectional study.
Complement factor D
Malignant hypertension
Urinary biomarker
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
17
02
2024
accepted:
04
07
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
Kidney injury is one of the detrimental consequences of primary malignant hypertension (pMHTN). There is a paucity of non-invasive biomarkers to enhance diagnosis and elucidate the underlying mechanisms. This study aims to explore urine protein biomarkers for pMHTN associated renal damage. In the discovery phase, urine samples were collected from 8 pMHTN, 19 disease controls (DCs), and 5 healthy controls (HCs). In-gel digestion combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used for identification of proteins associated with pMHTN. In the validation phase, the differentially expressed proteins were validated by ELISA assay in cohort with 10 pMHTN patients, 37 DCs, and 30 HCs. Compared to DCs and HCs, a specific band between 15 and 25 kDa was found in 7 out of 8 patients with pMHTN. Further LC-MS/MS analysis revealed 5 differentially expressed proteins. ELISA validation demonstrated that urinary complement factor D (CFD) was significantly up regulated in pMHTN. By receiver operating characteristic curve analysis, urinary CFD/Cr showed moderate potential in discriminating pMHTN from DCs (the area under curve: 0.822, 95% CI 0.618-0.962). Urinary CFD may be a potential biomarker for pMHTN with its elevation indicative of the activation of the alternative complement pathway in pMHTN.
Identifiants
pubmed: 39009768
doi: 10.1038/s41598-024-66875-4
pii: 10.1038/s41598-024-66875-4
doi:
Substances chimiques
Biomarkers
0
Complement Factor D
EC 3.4.21.46
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16253Subventions
Organisme : National High Level Hospital Clinical Research Funding
ID : 2022-PUMCH-B-021
Organisme : National Key Research and Development Program of China
ID : No. 2016YFC0901500
Informations de copyright
© 2024. The Author(s).
Références
van den Born, B.-J.H. et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur. Heart J. Cardiovasc. Pharmacother. 5, 37–46 (2019).
doi: 10.1093/ehjcvp/pvy032
pubmed: 30165588
Kim, Y.-J. A new pathological perspective on thrombotic microangiopathy. Kidney Res. Clin. Pract. 41, 524–532 (2022).
doi: 10.23876/j.krcp.22.010
pubmed: 35791743
pmcid: 9576460
Cavero, T. et al. Thrombotic microangiopathy in patients with malignant hypertension. Nephrol. Dial. Transplant. 38, 1217–1226 (2023).
doi: 10.1093/ndt/gfac248
pubmed: 36002030
Amraoui, F., Bos, S., Vogt, L. & van den Born, B.-J. Long-term renal outcome in patients with malignant hypertension: A retrospective cohort study. BMC Nephrol. 13, 71 (2012).
doi: 10.1186/1471-2369-13-71
pubmed: 22846257
pmcid: 3470982
Rubin, S. et al. Malignant hypertension: Diagnosis, treatment and prognosis with experience from the Bordeaux cohort. J. Hypertens. 37, 316 (2019).
doi: 10.1097/HJH.0000000000001913
pubmed: 30160657
Guerin, C., Gonthier, R. & Berthoux, F. C. Long-term prognosis in malignant or accelerated hypertension. Nephrol. Dial. Transplant. 3, 33–37 (1988).
pubmed: 3132637
van den Born, B.-J.H., Koopmans, R. P., Groeneveld, J. O. & van Montfrans, G. A. Ethnic disparities in the incidence, presentation and complications of malignant hypertension. J. Hypertens. 24, 2299 (2006).
doi: 10.1097/01.hjh.0000249710.21146.38
pubmed: 17053554
Charles, L., Triscott, J. & Dobbs, B. Secondary hypertension: Discovering the underlying cause. AFP 96, 453–461 (2017).
Zhao, M. et al. A comprehensive analysis and annotation of human normal urinary proteome. Sci. Rep. 7, 3024 (2017).
doi: 10.1038/s41598-017-03226-6
pubmed: 28596590
pmcid: 5465101
Guo, Z. et al. Differential urinary glycoproteome analysis of type 2 diabetic nephropathy using 2D-LC-MS/MS and iTRAQ quantification. J. Transl. Med. 13, 371 (2015).
doi: 10.1186/s12967-015-0712-9
pubmed: 26608305
pmcid: 4660682
Tang, X. et al. 96DRA-Urine: A high throughput sample preparation method for urinary proteome analysis. J. Proteom. 257, 104529 (2022).
doi: 10.1016/j.jprot.2022.104529
Sun, Y. et al. Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis. Nat. Commun. 13, 2757 (2022).
doi: 10.1038/s41467-022-30391-8
pubmed: 35589723
pmcid: 9119985
Zhao, M. et al. A comparative proteomics analysis of five body fluids: Plasma, urine, cerebrospinal fluid, amniotic fluid, and saliva. Proteom. Clin. Appl. 12, 1800008 (2018).
doi: 10.1002/prca.201800008
Gao, Y. Urine-an untapped goldmine for biomarker discovery? Sci. China Life Sci. 56, 1145–1146 (2013).
doi: 10.1007/s11427-013-4574-1
pubmed: 24271956
Mathew, R. O., Nayer, A. & Asif, A. The endothelium as the common denominator in malignant hypertension and thrombotic microangiopathy. J. Am. Soc. Hypertens. 10, 352–359 (2016).
doi: 10.1016/j.jash.2015.12.007
pubmed: 26778772
Timmermans, S. A. M. E. G. et al. C5b9 formation on endothelial cells reflects complement defects among patients with renal thrombotic microangiopathy and severe hypertension. J. Am. Soc. Nephrol. 29, 2234–2243 (2018).
doi: 10.1681/ASN.2018020184
pubmed: 29858281
pmcid: 6065094
Timmermans, S. A. M. E. G. et al. Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities. Kidney Int. 91, 1420–1425 (2017).
doi: 10.1016/j.kint.2016.12.009
pubmed: 28187980
Zhang, Y. et al. Association between thrombotic microangiopathy and activated alternative complement pathway in malignant nephrosclerosis. Nephrol. Dial. Transplant. 36, 1222–1233 (2021).
doi: 10.1093/ndt/gfaa280
Barratt, J. & Weitz, I. Complement factor D as a strategic target for regulating the alternative complement pathway. Front. Immunol. 12, 712572 (2021).
doi: 10.3389/fimmu.2021.712572
pubmed: 34566967
pmcid: 8458797
Sanders, P. W., Volanakis, J. E., Rostand, S. G. & Galla, J. H. Human complement protein D catabolism by the rat kidney. J. Clin. Investig. 77, 1299–1304 (1986).
doi: 10.1172/JCI112434
pubmed: 3633925
pmcid: 424481
Pascual, M. et al. Metabolism of complement factor D in renal failure. Kidney Int. 34, 529–536 (1988).
doi: 10.1038/ki.1988.214
pubmed: 3199673
Volanakis, J. E., Barnum, S. R., Giddens, M. & Galla, J. H. Renal filtration and catabolism of complement protein D. N. Engl. J. Med. 312, 395–399 (1985).
doi: 10.1056/NEJM198502143120702
pubmed: 3844050
Hanna, R. M. et al. Thrombotic microangiopathy syndromes—Common ground and distinct frontiers. Adv. Chronic Kidney Dis. 29, 149-160.e1 (2022).
doi: 10.1053/j.ackd.2021.11.006
pubmed: 35817522
Cavero, T. et al. Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome. Kidney Int. 96, 995–1004 (2019).
doi: 10.1016/j.kint.2019.05.014
pubmed: 31420192
Fidalgo, P., Nora, D., Coelho, L. & Povoa, P. Pancreatic stone protein: Review of a new biomarker in sepsis. J. Clin. Med. 11, 1085 (2022).
doi: 10.3390/jcm11041085
pubmed: 35207355
pmcid: 8880320
Chen, Z., Downing, S. & Tzanakakis, E. S. Four decades after the discovery of regenerating islet-derived (Reg) proteins: Current understanding and challenges. Front. Cell Dev. Biol. 7, 235 (2019).
doi: 10.3389/fcell.2019.00235
pubmed: 31696115
pmcid: 6817481
Williams, J. A. Pancreatic ribonuclease. Pancreapedia: The Exocrine Pancreas Knowledge Base. https://doi.org/10.3998/panc.2018.20 (2018).
Post, F. A., Wyatt, C. M. & Mocroft, A. Biomarkers of impaired renal function. Curr. Opin. HIV AIDS 5, 524 (2010).
doi: 10.1097/COH.0b013e32833f203e
pubmed: 20978396
Garsen, M., Rops, A. L. W. M. M., Rabelink, T. J., Berden, J. H. M. & van der Vlag, J. The role of heparanase and the endothelial glycocalyx in the development of proteinuria. Nephrol. Dial. Transplant. 29, 49–55 (2014).
doi: 10.1093/ndt/gft410
pubmed: 24166469
Daryadel, A. et al. The C-terminal fragment of agrin (CAF), a novel marker of renal function, is filtered by the kidney and reabsorbed by the proximal tubule. PLoS ONE 11, e0157905 (2016).
doi: 10.1371/journal.pone.0157905
pubmed: 27380275
pmcid: 4933355
Winkler, P. W., Horvath, A. & Senorski, E. H. Calculation of statistical power and sample size. In Orthopaedic Sports Medicine: An Encyclopedic Review of Diagnosis, Prevention, and Management (eds Espregueira-Mendes, J. et al.) 1–15 (Springer, 2023).