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:

Structural changes in renal arterioles are closely associated with central hemodynamic parameters in patients with renal disease

Hypertension Research volume 44, pages 1113–1121 (2021)Cite this article

Abstract

Although central hemodynamics are known to be closely associated with microvascular damage, their association with lesions in the small renal arteries has not yet been fully clarified. We focused on arterioles in renal biopsy specimens and analyzed whether their structural changes were associated with noninvasive vascular function parameters, including central blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV). Forty-four nondiabetic patients (18–50 years of age) with preserved renal function underwent renal biopsy. Wall thickening of arterioles was analyzed based on the media/diameter ratio, and hyalinosis was analyzed by semiquantitative grading. Associations of these indexes (arteriolar wall remodeling grade index (RG index) and arteriolar hyalinosis index (Hyl index)) with clinical variables were analyzed. Multiple regression analyses demonstrated that the RG index was significantly associated with central systolic BP (β = 0.97, p = 0.009), serum cystatin C-based estimated glomerular filtration rate (β = −0.36, p = 0.04), and high-density lipoprotein cholesterol levels (β = −0.37, p = 0.02). The Hyl index was significantly associated with baPWV (β = 0.75, p = 0.01). Our results indicate that aortic stiffness and abnormal central hemodynamics are closely associated with renal microvascular damage in young to middle-aged, nondiabetic kidney disease patients with preserved renal function.

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: Comparison of histopathological findings among the subgroups according to cSBP and baPWV (n = 44).

Similar content being viewed by others

References

  1. Mitchell GF. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol. 2008;105:1652–60.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48:1012–7.

    Article  CAS  PubMed  Google Scholar 

  3. Renna NF, de Las Heras N, Miatello RM. Pathophysiology of vascular remodeling in hypertension. Int J Hypertens. 2013;2013:808353.

    PubMed  PubMed Central  Google Scholar 

  4. Hill GS, Heudes D, Jacquot C, Gauthier E, Bariéty J. Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension. Kidney Int. 2006;69:823–31.

    Article  CAS  PubMed  Google Scholar 

  5. Kubo M, Kiyohara Y, Kato I, Tanizaki Y, Katafuchi R, Hirakata H, et al. Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama study. Kidney Int. 2003;63:1508–15.

    Article  PubMed  Google Scholar 

  6. Tracy RE, MacLean CJ, Reed DM, Hayashi T, Gandia M, Strong JP. Blood pressure, nephrosclerosis, and age autopsy findings from the Honolulu Heart Program. Mod Pathol. 1988;1:420–7.

    CAS  PubMed  Google Scholar 

  7. Ikee R, Kobayashi S, Saigusa T, Namikoshi T, Yamada M, Hemmi N, et al. Impact of hypertension and hypertension-related vascular lesions in IgA nephropathy. Hypertens Res. 2006;29:15–22.

    Article  PubMed  Google Scholar 

  8. Zhang Y, Sun L, Zhou S, Xu Q, Xu Q, Liu D, et al. Intrarenal arterial lesions are associated with higher blood pressure, reduced renal function and poorer renal outcomes in patients with IgA nephropathy. Kidney Blood Press Res. 2018;43:639–50.

    Article  CAS  PubMed  Google Scholar 

  9. Shimizu M, Furuichi K, Toyama T, Kitajima S, Hara A, Kitagawa K, et al. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy. Diabetes Care. 2013;36:3655–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Moriya T, Omura K, Matsubara M, Yoshida Y, Hayama K, Ouchi M. Arteriolar hyalinosis predicts increase in albuminuria and GFR decline in normo- and microalbuminuric Japanese patients with type 2 diabetes. Diabetes Care. 2017;40:1373–8.

    Article  CAS  PubMed  Google Scholar 

  11. McGill HC Jr., Strong JP, Tracy RE, McMahan CA, Oalmann MC. Relation of a postmortem renal index of hypertension to atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol. 1995;15:2222–8.

    Article  PubMed  Google Scholar 

  12. Burchfiel CM, Tracy RE, Chyou PH, Strong JP. Cardiovascular risk factors and hyalinization of renal arterioles at autopsy. The Honolulu Heart Program. Arterioscler Thromb Vasc Biol. 1997;17:760–8.

    Article  CAS  PubMed  Google Scholar 

  13. Ochi N, Kohara K, Tabara Y, Nagai T, Kido T, Uetani E, et al. Association of central systolic blood pressure with intracerebral small vessel disease in Japanese. Am J Hypertens. 2010;23:889–94.

    Article  PubMed  Google Scholar 

  14. Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31:1865–71.

    Article  PubMed  Google Scholar 

  15. Roman MJ, Okin PM, Kizer JR, Lee ET, Howard BV, Devereux RB. Relations of central and brachial blood pressure to left ventricular hypertrophy and geometry: the Strong Heart Study. J Hypertens. 2010;28:384–8.

    Article  CAS  PubMed  Google Scholar 

  16. Briet M, Collin C, Karras A, Laurent S, Bozec E, Jacquot C, et al. Arterial remodeling associates with CKD progression. J Am Soc Nephrol. 2011;22:967–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236–41.

    Article  CAS  PubMed  Google Scholar 

  18. Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B, et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003;34:1203–6.

    Article  PubMed  Google Scholar 

  19. Briet M, Bozec E, Laurent S, Fassot C, London GM, Jacquot C, et al. Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease. Kidney Int. 2006;69:350–7.

    Article  CAS  PubMed  Google Scholar 

  20. Woodard T, Sigurdsson S, Gotal JD, Torjesen AA, Inker LA, Aspelund T, et al. Mediation analysis of aortic stiffness and renal microvascular function. J Am Soc Nephrol. 2015;26:1181–7.

    Article  CAS  PubMed  Google Scholar 

  21. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  PubMed  Google Scholar 

  22. Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S. GFR estimation using standardized serum cystatin C in Japan. Am J Kidney Dis. 2013;61:197–203.

    Article  CAS  PubMed  Google Scholar 

  23. Namikoshi T, Fujimoto S, Yorimitsu D, Ihoriya C, Fujimoto Y, Komai N, et al. Relationship between vascular function indexes, renal arteriolosclerosis, and renal clinical outcomes in chronic kidney disease. Nephrology. 2015;20:585–90.

    Article  CAS  PubMed  Google Scholar 

  24. Kohagura K, Kochi M, Miyagi T, Kinjyo T, Maehara Y, Nagahama K, et al. An association between uric acid levels and renal arteriolopathy in chronic kidney disease: a biopsy-based study. Hypertens Res. 2013;36:43–9.

    Article  CAS  PubMed  Google Scholar 

  25. Bader H, Meyer DS. The size of the juxtaglomerular apparatus in diabetic glomerulosclerosis and its correlation with arteriolosclerosis and arterial hypertension: a morphometric light microscopic study on human renal biopsies. Clin Nephrol. 1977;8:308–11.

    CAS  PubMed  Google Scholar 

  26. Prewitt RL, Chen II, Dowell RF. Microvascular alterations in the one-kidney, one-clip renal hypertensive rat. Am J Physiol. 1984;246:H728–32.

    CAS  PubMed  Google Scholar 

  27. Grassi G, Seravalle G, Scopelliti F, Dell’Oro R, Fattori L, Quarti-Trevano F, et al. Structural and functional alterations of subcutaneous small resistance arteries in severe human obesity. Obesity. 2010;18:92–8.

    Article  CAS  PubMed  Google Scholar 

  28. Ikee R, Honda K, Ishioka K, Oka M, Maesato K, Moriya H, et al. Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease. Hypertens Res. 2010;33:499–504.

    Article  CAS  PubMed  Google Scholar 

  29. Miyagi T, Kohagura K, Ishiki T, Kochi M, Kinjyo T, Kinjyo K, et al. Interrelationship between brachial artery function and renal small artery sclerosis in chronic kidney disease. Hypertens Res. 2014;37:863–9.

    Article  CAS  PubMed  Google Scholar 

  30. Biava CG, Dyrda I, Genest J, Bencosme SA. Renal hyaline arteriolosclerosis. an electron microscope study. Am J Pathol. 1964;44:349–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Snanoudj R, Royal V, Elie C, Rabant M, Girardin C, Morelon E, et al. Specificity of histological markers of long-term CNI nephrotoxicity in kidney-transplant recipients under low-dose cyclosporine therapy. Am J Transplant. 2011;11:2635–46.

    Article  CAS  PubMed  Google Scholar 

  32. Hill GS, Heudes D, Bariéty J. Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation. Kidney Int. 2003;63:1027–36.

    Article  PubMed  Google Scholar 

  33. Bidani AK, Griffin KA. Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2004;44:595–601.

    Article  CAS  PubMed  Google Scholar 

  34. Zamami R, Kohagura K, Miyagi T, Kinjyo T, Shiota K, Ohya Y. Modification of the impact of hypertension on proteinuria by renal arteriolar hyalinosis in nonnephrotic chronic kidney disease. J Hypertens. 2016;34:2274–9.

    Article  CAS  PubMed  Google Scholar 

  35. Hashimoto J, Ito S. Central pulse pressure and aortic stiffness determine renal hemodynamics: pathophysiological implication for microalbuminuria in hypertension. Hypertension. 2011;58:839–46.

    Article  CAS  PubMed  Google Scholar 

  36. Tsioufis C, Tzioumis C, Marinakis N, Toutouzas K, Tousoulis D, Kallikazaros I, et al. Microalbuminuria is closely related to impaired arterial elasticity in untreated patients with essential hypertension. Nephron Clin Pract. 2003;93:c106–11.

    Article  CAS  PubMed  Google Scholar 

  37. Hashimoto J, Ito S. Aortic blood flow reversal determines renal function: potential explanation for renal dysfunction caused by aortic stiffening in hypertension. Hypertension. 2015;66:61–7.

    Article  CAS  PubMed  Google Scholar 

  38. Takase H, Dohi Y, Kimura G. Distribution of central blood pressure values estimated by Omron HEM-9000AI in the Japanese general population. Hypertens Res. 2013;36:50–7.

    Article  PubMed  Google Scholar 

  39. Reference Values for Arterial Stiffness’ Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’. Eur Heart J. 2010;31:2338–50.

  40. Zamami R, Ishida A, Miyagi T, Yamazato M, Kohagura K, Ohya Y. A high normal ankle-brachial index is associated with biopsy-proven severe renal small artery intimal thickening and impaired renal function in chronic kidney disease. Hypertens Res. 2020;43:929–37.

    Article  PubMed  Google Scholar 

  41. Hashimoto J. Central hemodynamics for management of arteriosclerotic diseases. J Atheroscler Thromb. 2017;24:765–78.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nordstrand N, Gjevestad E, Hertel JK, Johnson LK, Saltvedt E, Røislien J, et al. Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients-a nonrandomized clinical trial. Obesity. 2013;21:690–7.

    Article  CAS  PubMed  Google Scholar 

  43. Rule AD, Amer H, Cornell LD, Taler SJ, Cosio FG, Kremers WK, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010;152:561–7.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hashimoto J, Imai Y, O’Rourke MF. Indices of pulse wave analysis are better predictors of left ventricular mass reduction than cuff pressure. Am J Hypertens. 2007;20:378–84.

    Article  PubMed  Google Scholar 

  45. Hashimoto J, Westerhof BE, Westerhof N, Imai Y, O’Rourke MF. Different role of wave reflection magnitude and timing on left ventricular mass reduction during antihypertensive treatment. J Hypertens. 2008;26:1017–24.

    Article  CAS  PubMed  Google Scholar 

  46. Ong KT, Delerme S, Pannier B, Safar ME, Benetos A, Laurent S, et al. Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients. J Hypertens. 2011;29:1034–42.

    Article  CAS  PubMed  Google Scholar 

  47. Tanaka H, Munakata M, Kawano Y, Ohishi M, Shoji T, Sugawara J, et al. Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness. J Hypertens. 2009;27:2022–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are indebted to Dr. Helena Akiko Popiel of the Department of International Medical Communications at Tokyo Medical University for her editorial review of the English manuscript. We also wish to thank Dr. Tatsuya Isomura of the Department of Clinical Consultation, Medical Research Institute, Tokyo Medical University, for providing statistical advice and the nephrologists of Tokyo Medical University for ensuring compliance with clinical study protocols.

Author information

Authors and Affiliations

  1. Department of Nephrology, Tokyo Medical University, Tokyo, Japan

    Yoshitaka Miyaoka, Tomonari Okada, Atsuko Morikawa, Sho Rinno, Miho Kato, Ryuji Tsujimoto, Rie Suzuki, Rieko China, Miho Nagai, Yume Nagaoka & Yoshihiko Kanno

  2. Department of Cardiology, Tokyo Medical University, Tokyo, Japan

    Hirofumi Tomiyama

  3. Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan

    Toshitaka Nagao

Authors
  1. Yoshitaka Miyaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomonari Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirofumi Tomiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsuko Morikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sho Rinno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miho Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ryuji Tsujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rie Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rieko China
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Miho Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yume Nagaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshitaka Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yoshihiko Kanno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshitaka Miyaoka.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miyaoka, Y., Okada, T., Tomiyama, H. et al. Structural changes in renal arterioles are closely associated with central hemodynamic parameters in patients with renal disease. Hypertens Res 44, 1113–1121 (2021). https://doi.org/10.1038/s41440-021-00656-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-021-00656-8

Keywords

This article is cited by

Search

Advanced search

Quick links