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Vasa recta hyalinosis reflects severe arteriolopathy in renal allografts

  • Hideyo OguchiEmail author
  • Ken Sakai
  • Yutaka Yamaguchi
  • Tetuo Mikami
  • Tetsuo Nemoto
  • Yasushi Ohashi
  • Takeshi Kawamura
  • Masaki Muramatsu
  • Yoshihiro Itabashi
  • Kazunobu Shinoda
  • Yoji Hyodo
  • Yusuke Takahashi
  • Yuki Kawaguchi
  • Hiroka Onishi
  • Yuko Hamasaki
  • Kazutoshi Shibuya
  • Seiichiro Shishido
Original article
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Abstract

Aim

We examined the clinicopathologic significance of hyalinosis in the vasa recta in the medulla of allograft kidney biopsies.

Method

We analyzed biopsy specimens from January 2010 to December 2015, obtained from both the cortex and medulla (including the vasa recta) ≥ 1 year after living-donor kidney transplantation. We excluded biopsy specimens from recipients who had undergone transplantation due to diabetic nephropathy or who had diabetes mellitus after transplantation. We evaluated hyaline arteriolopathy in the cortex using the aah score determined by the Banff 2007 classification.

Result

Among 381 biopsy specimens obtained from 248 transplant recipients ≥ 1 year after transplantation, 36 specimens obtained from 34 recipients showed vasa recta hyalinosis (VRH) in the medulla. Among these 36 specimens, 17 had a score of aah3, 16 had a score of aah2, and 3 had a score of aah1. The incidence of VRH was 1.9% at ≥ 1 to < 4 years, 7.1% at ≥ 4 to < 8 years, and 50.0% at ≥ 8 years. The aah scores and the proportion of hyalinosis in the arteriolar media among all muscular arterioles in the cortex were significantly higher in the VRH group at ≥ 8 years in the late-phase biopsy (P < 0.01). The graft survival was worse in the VRH group (P = 0.024), although there was no significant difference in the graft survival between the ≥ aah2 and < aah2 groups at ≥ 8 years in the late-phase biopsy (P = 0.159).

Conclusion

VRH in renal allografts reflects severe arteriolopathy of the cortex. VRH in the late-phase biopsy may be a prognostic factor for graft survival.

Keywords

Kidney transplantation Vasa recta hyalinosis Aah score Arteriolopathy 

Notes

Acknowledgements

We are grateful to Dr Takayuki Abe, Department of Preventive Medicine and Public Health, Biostatistics Unit at Clinical Translational Research Center, Keio University School of Medicine, for helpful comments about statistics analysis.

Compliance with ethical standards

Conflict of interest

Kazutoshi Shibuya received research grants from Pfizer Inc. Dainippon-Sumitomo Pharma and Astellas Pharma Inc, and also received payments for lecture from Dainippon-Sumitomo Pharma.

Human and animal rights

Our study was approved by Toho University Omori Medical Center Ethics Committee (approval number 27-260).

Informed consent

After approval of the Ethics Committee, the contents of this retrospective research and message to contact us if the patient cannot accept this research were posted on homepage of Toho University Omori Medical Center.

References

  1. 1.
    Bennett WM, DeMattos A, Meyer MM, Andoh T, Barry JM. Chronic cyclosporine nephropathy: the Achilles’ heel of immunosuppressive therapy. Kidney Int. 1996;50:1089–100.CrossRefGoogle Scholar
  2. 2.
    Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003;349:2326–33.CrossRefGoogle Scholar
  3. 3.
    Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant. 2008;8:753–60.CrossRefGoogle Scholar
  4. 4.
    Snanoudj R, Royal V, Elie C, Rabant M, Girardin C, Morelon E, Kreis H, Fournet JC, Noel LH, Legendre C. 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.CrossRefGoogle Scholar
  5. 5.
    Morozumi K, Thiel G, Albert FW, Banfi G, Gudat F, Mihatsch MJ. Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in renal allografts. Clin Nephrol. 1992;38:1–8.Google Scholar
  6. 6.
    Pallone TL, Turner MR, Edwards A, Jamison RL. Countercurrent exchange in the renal medulla. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1153–75.CrossRefGoogle Scholar
  7. 7.
    Evans RG, Eppel GA, Anderson WP, Denton KM. Mechanisms underlying the differential control of blood flow in the renal medulla and cortex. J Hypertens. 2004;22:1439–51.CrossRefGoogle Scholar
  8. 8.
    Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, et al. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus (Revision for International Harmonization of HbA1c in Japan. J Jpn Diabetes Soc. 2012;55:485–504.Google Scholar
  9. 9.
    Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55:713–23.CrossRefGoogle Scholar
  10. 10.
    Manual for pathological diagnosis of diabetic nephropathy and hypertensive nephrosclerosis. Nihon Jinzo Gakkai Shi. 2015;57:649–725.Google Scholar
  11. 11.
    Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MC, David DS, David-Neto E, Bagnasco SM, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant. 2014;14:272–83.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 13.
    Yagisawa T, Omoto K, Shimizu T, Ishida H, Tanabe K. Arteriosclerosis in zero-time biopsy is a risk factor for tacrolimus-induced chronic nephrotoxicity. Nephrology (Carlton). 2015;20(Suppl 2):51–7.CrossRefGoogle Scholar
  14. 14.
    Morozumi K, Takeda A, Uchida K, Mihatsch MJ. Cyclosporine nephrotoxicity: how does it affect renal allograft function and transplant morphology? Transplant Proc. 2004;36:251S–256S.CrossRefGoogle Scholar
  15. 15.
    Pillebout E, Nochy D, Hill G, Conti F, Antoine C, Calmus Y, Glotz D. Renal histopathological lesions after orthotopic liver transplantation (OLT). Am J Transplant. 2005;5:1120–9.CrossRefGoogle Scholar
  16. 16.
    Pichler RH, Franceschini N, Young BA, Hugo C, Andoh TF, Burdmann EA, Shankland SJ, Alpers CE, Bennett WM, Couser WG, et al. Pathogenesis of cyclosporine nephropathy: roles of angiotensin II and osteopontin. J Am Soc Nephrol. 1995;6:1186–96.Google Scholar
  17. 17.
    Arima S. Role of angiotensin II and endogenous vasodilators in the control of glomerular hemodynamics. Clin Exp Nephrol. 2003;7:172–8.CrossRefGoogle Scholar
  18. 18.
    Mihatsch MJ, Bach JF, Coovadia HM, Forre O, Moutsopoulos HM, Drosos AA, Siamopoulos KC, Noel LH, Ramsaroop R, Hallgren R, et al. Cyclosporin-associated nephropathy in patients with autoimmune diseases. Klin Wochenschr. 1988;66:43–7.CrossRefGoogle Scholar
  19. 19.
    Cowley AW Jr. Role of the renal medulla in volume and arterial pressure regulation. Am J Physiol. 1997;273:R1–15.Google Scholar
  20. 20.
    Nankivell BJ, Chapman JR. Chronic allograft nephropathy: current concepts and future directions. Transplantation. 2006;81:643–54.CrossRefGoogle Scholar
  21. 21.
    Karpe KM, Talaulikar GS, Walters GD. Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients. Cochrane Database Syst Rev. 2017;7:Cd006750.Google Scholar

Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  • Hideyo Oguchi
    • 1
    Email author
  • Ken Sakai
    • 1
  • Yutaka Yamaguchi
    • 2
  • Tetuo Mikami
    • 3
  • Tetsuo Nemoto
    • 4
  • Yasushi Ohashi
    • 5
  • Takeshi Kawamura
    • 5
  • Masaki Muramatsu
    • 1
  • Yoshihiro Itabashi
    • 1
  • Kazunobu Shinoda
    • 1
  • Yoji Hyodo
    • 1
  • Yusuke Takahashi
    • 1
  • Yuki Kawaguchi
    • 1
  • Hiroka Onishi
    • 1
  • Yuko Hamasaki
    • 1
  • Kazutoshi Shibuya
    • 4
  • Seiichiro Shishido
    • 1
  1. 1.Department of NephrologyToho University Faculty of MedicineTokyoJapan
  2. 2.Yamaguchi’s Pathology LaboratoryChibaJapan
  3. 3.Department of PathologyToho University Faculty of MedicineTokyoJapan
  4. 4.Department of Surgical PathologyToho University Faculty of MedicineTokyoJapan
  5. 5.Department of Nephrology, Sakura Medical CenterToho UniversityChibaJapan

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