Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis

Hypertension Research volume 44, pages 179–187 (2021)Cite this article

Abstract

Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD). Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video capillaroscopy provides a thorough assessment of capillary density and functional reserve. This study aimed to examine possible differences in structural and functional capillary density in CKD stages 2–4 with nailfold video capillaroscopy. Ninety-six CKD patients, divided into four equally sized groups according to CKD stage (2, 3a, 3b, 4), underwent nailfold video capillaroscopy, during which capillary density was measured at baseline, after 4-min arterial occlusion and after 2-min venous occlusion. Arterial stiffness and wave parameters were measured with applanation tonometry and common carotid intima-media thickness (ccIMT) with ultrasound. Baseline capillary density showed a progressive reduction with advancing CKD stages (stage 2: 32.6 ± 2.8, stage 3a: 31.2 ± 3.8, stage 3b: 32.5 ± 3.3, stage 4: 28.5 ± 3.1, p = 0.011). Similar reductions were observed during postocclusive hyperemia (39.4 ± 3.0, 37.6 ± 4.2, 38.4 ± 3.8, and 33.8 ± 3.3, respectively; p = 0.021) and after venous congestion (41.1 ± 3.1, 39.0 ± 4.4, 39.9 ± 3.5, and 35.2 ± 3.4; p = 0.032). Office PWV and ccIMT showed nonsignificant increasing trends with advancing CKD. In multivariate analysis, eGFR showed a positive association (per ml/min increase; β: 0.053, 95% CI: 0.004–0.101), whereas diabetes (β: −1.706, 95% CI: −3.176 to −0.236) and parathyroid hormone (PTH) (per pg/ml increase; β: −0.022, 95% CI: −0.036 to −0.008) had negative associations with postocclusive capillary density. Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may largely contribute to the increased cardiovascular risk of CKD patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Saran R, Li Y, Robinson B, Abbott KC, Agodoa LY, Ayanian J, et al. US Renal Data System 2015 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2016;67:S1–305.

    Article  Google Scholar 

  2. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  CAS  Google Scholar 

  3. Georgianos PI, Sarafidis PA, Lasaridis AN. Arterial stiffness: a novel cardiovascular risk factor in kidney disease patients. Curr Vasc Pharmacol. 2015;13:229–38.

    Article  CAS  Google Scholar 

  4. Townsend RR. Arterial stiffness in CKD: a review. Am J Kidney Dis. 2019;73:240–7.

    Article  Google Scholar 

  5. Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 2012;82:388–400.

    Article  Google Scholar 

  6. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97.

    Article  Google Scholar 

  7. Zoccali C. Endothelial dysfunction and the kidney: emerging risk factors for renal insufficiency and cardiovascular outcomes in essential hypertension. J Am Soc Nephrol. 2006;17:S61–3.

    Article  Google Scholar 

  8. Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease—what have we learned in 10 years? Semin Dial. 2010;23:498–509.

    Article  Google Scholar 

  9. Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, et al. Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging. 2014;15:736–46.

    Article  Google Scholar 

  10. Serne EH, de Jongh RT, Eringa EC, IJ RG, Stehouwer CD. Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension. 2007;50:204–11.

    Article  CAS  Google Scholar 

  11. Levy BI, Schiffrin EL, Mourad JJ, Agostini D, Vicaut E, Safar ME, et al. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 2008;118:968–76.

    Article  Google Scholar 

  12. Eringa EC, Serne EH, Meijer RI, Schalkwijk CG, Houben AJ, Stehouwer CD, et al. Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes. Rev Endocr Metab Disord. 2013;14:39–48.

    Article  Google Scholar 

  13. Feletou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol. 2006;291:H985–1002.

    Article  CAS  Google Scholar 

  14. Sarafidis PA, Loutradis C, Karpetas A, Tzanis G, Piperidou A, Koutroumpas G, et al. Ambulatory pulse wave velocity is a stronger predictor of cardiovascular events and all-cause mortality than office and ambulatory blood pressure in hemodialysis patients. Hypertension. 2017;70:148–57.

    Article  CAS  Google Scholar 

  15. Hinderliter A, Padilla RL, Gillespie BW, Levin NW, Kotanko P, Kiser M, et al. Association of carotid intima-media thickness with cardiovascular risk factors and patient outcomes in advanced chronic kidney disease: the RRI-CKD study. Clin Nephrol. 2015;84:10–20.

    Article  Google Scholar 

  16. Triantafyllou A, Anyfanti P, Pyrpasopoulou A, Triantafyllou G, Aslanidis S, Douma S. Capillary rarefaction as an index for the microvascular assessment of hypertensive patients. Curr Hypertens Rep. 2015;17:33.

    Article  Google Scholar 

  17. Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA. Structural skin capillary rarefaction in essential hypertension. Hypertension. 1999;33:998–1001.

    Article  CAS  Google Scholar 

  18. Serne EH, Gans RO, ter Maaten JC, Tangelder GJ, Donker AJ, Stehouwer CD. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension. 2001;38:238–42.

    Article  CAS  Google Scholar 

  19. Afsar B, Afsar RE, Dagel T, Kaya E, Erus S, Ortiz A, et al. Capillary rarefaction from the kidney point of view. Clin Kidney J. 2018;11:295–301.

    Article  CAS  Google Scholar 

  20. Chade AR. Renal vascular structure and rarefaction. Compr Physiol. 2013;3:817–31.

    PubMed  PubMed Central  Google Scholar 

  21. Thang OH, Serne EH, Grooteman MP, Smulders YM, ter Wee PM, Tangelder GJ, et al. Capillary rarefaction in advanced chronic kidney disease is associated with high phosphorus and bicarbonate levels. Nephrol Dial Transplant. 2011;26:3529–36.

    Article  CAS  Google Scholar 

  22. Edwards-Richards A, DeFreitas M, Katsoufis CP, Seeherunvong W, Sasaki N, Freundlich M, et al. Capillary rarefaction: an early marker of microvascular disease in young hemodialysis patients. Clin Kidney J. 2014;7:569–74.

    Article  CAS  Google Scholar 

  23. KDIGO CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1–150.

    Article  Google Scholar 

  24. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36:1953–2041.

    Article  CAS  Google Scholar 

  25. van Sloten TT, Czernichow S, Houben AJ, Protogerou AD, Henry RM, Muris DM, et al. Association between arterial stiffness and skin microvascular function: the SUVIMAX2 study and the maastricht study. Am J Hypertens. 2015;28:868–76.

    Article  Google Scholar 

  26. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.

    Article  Google Scholar 

  27. Sarafidis PA, Georgianos PI, Karpetas A, Bikos A, Korelidou L, Tersi M, et al. Evaluation of a novel brachial cuff-based oscillometric method for estimating central systolic pressure in hemodialysis patients. Am J Nephrol. 2014;40:242–50.

    Article  Google Scholar 

  28. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, et al. American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr. 2008;21:93–111.

    Article  Google Scholar 

  29. Sarafidis PA, Bakris GL. Review: insulin and endothelin: an interplay contributing to hypertension development? J Clin Endocrinol Metab. 2007;92:379–85.

    Article  CAS  Google Scholar 

  30. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126:753–67.

    Article  Google Scholar 

  31. Choi HR, Lee SW, Jeon DH, Hur NW, Youm Y, Kim HC. Association between estimated glomerular filtration rate (eGFR) and asymmetric dimethylarginine (ADMA) concentrations among the elderly in a rural community: a cross-sectional study. BMC Geriatr. 2019;19:370.

    Article  CAS  Google Scholar 

  32. Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA. Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. Hypertension.1999;34:655–8.

    Article  CAS  Google Scholar 

  33. Lundwall K, Jorneskog G, Jacobson SH, Spaak J. Paricalcitol, microvascular and endothelial function in non-diabetic chronic kidney disease: a randomized trial. Am J Nephrol. 2015;42:265–73.

    Article  CAS  Google Scholar 

  34. Kobayashi S, Oka M, Maesato K, Ikee R, Mano T, Hidekazu M, et al. Coronary artery calcification, ADMA, and insulin resistance in CKD patients. Clin J Am Soc Nephrol. 2008;3:1289–95.

    Article  Google Scholar 

  35. Fujimi-Hayashida A, Ueda S, Yamagishi S, Kaida Y, Ando R, Nakayama Y, et al. Association of asymmetric dimethylarginine with severity of kidney injury and decline in kidney function in IgA nephropathy. Am J Nephrol. 2011;33:1–6.

    Article  CAS  Google Scholar 

  36. Raptis V, Georgianos PI, Sarafidis PA, Sioulis A, Makedou K, Makedou A, et al. Elevated asymmetric dimethylarginine is associated with oxidant stress aggravation in patients with early stage autosomal dominant polycystic kidney disease. Kidney Blood Press Res. 2013;38:72–82.

    Article  CAS  Google Scholar 

  37. Ginsberg C, Houben A, Malhotra R, Berendschot T, Dagnelie PC, Kooman JP, et al. Serum phosphate and microvascular function in a population-based cohort. Clin J Am Soc Nephrol. 2019; 14:1626–33.

  38. London GM, Pannier B. Arterial functions: how to interpret the complex physiology. Nephrol Dial Transplant. 2010;25:3815–23.

    Article  Google Scholar 

  39. Samdani AF, Dawson TM, Dawson VL. Nitric oxide synthase in models of focal ischemia. Stroke. 1997;28:1283–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    Maria Schoina, Charalampos Loutradis, Evangelos Memmos, Aikaterini Papagianni & Pantelis Sarafidis

  2. Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    Theodoros Dimitroulas, Eleni Pagkopoulou & Alexandros Garyfallos

  3. Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    Michael Doumas & Asterios Karagiannis

Authors
  1. Maria Schoina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charalampos Loutradis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evangelos Memmos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Theodoros Dimitroulas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eleni Pagkopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Doumas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Asterios Karagiannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexandros Garyfallos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aikaterini Papagianni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pantelis Sarafidis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pantelis Sarafidis.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schoina, M., Loutradis, C., Memmos, E. et al. Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis. Hypertens Res 44, 179–187 (2021). https://doi.org/10.1038/s41440-020-0525-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-020-0525-y

Keywords

This article is cited by

Search

Advanced search

Quick links