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Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria

Hypertension Research volume 44, pages 88–97 (2021)Cite this article

Abstract

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27–79) and 1.9 g/g creatinine (IQR 0.2–4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

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References

  1. Cremer A, Amraoui F, Lip GY, Morales E, Rubin S, Segura J, et al. From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency. J Hum Hypertens. 2016;30:463–6.

    CAS  PubMed  Google Scholar 

  2. Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol. 1998;9:133–42.

    CAS  PubMed  Google Scholar 

  3. Peixoto AJ. Acute severe hypertension. N. Engl J Med. 2019;381:1843–52.

    PubMed  Google Scholar 

  4. Rubin S, Cremer A, Boulestreau R, Rigothier C, Kuntz S, Gosse P. Malignant hypertension: diagnosis, treatment and prognosis with experience from the Bordeaux cohort. J Hypertens. 2019;37:316–24.

    CAS  PubMed  Google Scholar 

  5. Gonzalez R, Morales E, Segura J, Ruilope LM, Praga M. Long-term renal survival in malignant hypertension. Nephrol Dial Transpl. 2010;25:3266–72.

    Google Scholar 

  6. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2019). Hypertens Res. 2019;42:1235–481.

    PubMed  Google Scholar 

  7. Healton EB, Brust JC, Feinfeld DA, Thomson GE. Hypertensive encephalopathy and the neurologic manifestations of malignant hypertension. Neurology. 1982;32:127–32.

    CAS  PubMed  Google Scholar 

  8. Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol. 2008;29:1036–42.

    CAS  PubMed  Google Scholar 

  9. Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015;14:914–25.

    PubMed  Google Scholar 

  10. Nagayama Y, Inoue Y, Inui K, Yoshimura A. Comparison of renal outcome among japanese patients with or without microangiopathic hemolysis in malignant phase hypertension: a single-center retrospective study. Nephron. 2017;137:197–204.

    CAS  PubMed  Google Scholar 

  11. Hayreh SS, Servais GE, Virdi PS. Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. Ophthalmology. 1986;93:1383–400.

    CAS  PubMed  Google Scholar 

  12. Lee CS, Choi EY, Lee M, Kim H, Chung H. Serous retinal detachment in preeclampsia and malignant hypertension. Eye (Lond). 2019;33:1707–14.

    CAS  Google Scholar 

  13. van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension. 2005;45:246–51.

    PubMed  Google Scholar 

  14. Ito S. Cardiorenal syndrome: an evolutionary point of view. Hypertension. 2012;60:589–95.

    CAS  PubMed  Google Scholar 

  15. Ito S, Nagasawa T, Abe M, Mori T. Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk. Hypertens Res. 2009;32:115–21.

    PubMed  Google Scholar 

  16. Nagasawa T, Mori T, Ohsaki Y, Yoneki Y, Guo Q, Sato E, et al. Albuminuria indicates the pressure-associated injury of juxtamedullary nephrons and cerebral strain vessels in spontaneously hypertensive stroke-prone rats. Hypertens Res. 2012;35:1024–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Rizzoni D, Rizzoni M, Nardin M, Chiarini G, Agabiti-Rosei C, Aggiusti C, et al. Vascular aging and disease of the small vessels. High Blood Press Cardiovasc Prev. 2019;26:183–9.

    PubMed  Google Scholar 

  18. Wong TY, Mitchell P. The eye in hypertension. Lancet. 2007;369:425–35.

    PubMed  Google Scholar 

  19. Aguilar MI, O’Meara ES, Seliger S, Longstreth WT Jr., Hart RG, Pergola PE, et al. Albuminuria and the risk of incident stroke and stroke types in older adults. Neurology. 2010;75:1343–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wong CW, Wong TY, Cheng CY, Sabanayagam C. Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways. Kidney Int. 2014;85:1290–302.

    PubMed  Google Scholar 

  21. Chua J, Chin CWL, Hong J, Chee ML, Le TT, Ting DSW, et al. Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography. J Hypertens. 2019;37:572–80.

    CAS  PubMed  Google Scholar 

  22. Tamura K, Maeda A, Uneda K, Wakui H, Dejima T, Mitsuhashi H, et al. An increase in perfusion pressure and activation of the renin-angiotensin system in the pathogenesis of hypertension and injury: strain vessels and the cerebrovascular-renal connection. Hypertens Res. 2012;35:972–4.

    PubMed  Google Scholar 

  23. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, et al. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol. 2007;11:41–50.

    PubMed  Google Scholar 

  24. Morimoto R, Ono Y, Tezuka Y, Kudo M, Yamamoto S, Arai T, et al. Rapid screening of primary aldosteronism by a novel chemiluminescent immunoassay. Hypertension. 2017;70:334–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Tamaki Y, Araie M, Kawamoto E, Eguchi S, Fujii H. Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon. Exp Eye Res. 1995;60:373–83.

    CAS  PubMed  Google Scholar 

  26. Isono H, Kishi S, Kimura Y, Hagiwara N, Konishi N, Fujii H. Observation of choroidal circulation using index of erythrocytic velocity. Arch Ophthalmol. 2003;121:225–31.

    PubMed  Google Scholar 

  27. Kunikata H, Nakazawa T. Recent clinical applications of laser speckle flowgraphy in eyes with retinal disease. Asia Pac J Ophthalmol (Philos). 2016;5:151–8.

    Google Scholar 

  28. Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab. 2008;7:476–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Feske SK. Posterior reversible encephalopathy syndrome: a review. Semin Neurol. 2011;31:202–15.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  31. Sanerkin NG. Vascular lesions of malignant essential hypertension. J Pathol. 1971;103:177–84.

    CAS  PubMed  Google Scholar 

  32. Delaey C, Van De, Voorde J. Regulatory mechanisms in the retinal and choroidal circulation. Ophthalmic Res. 2000;32:249–56.

    CAS  PubMed  Google Scholar 

  33. Kiel JW, Shepherd AP. Autoregulation of choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci. 1992;33:2399–410.

    CAS  PubMed  Google Scholar 

  34. Mishima E, Hashimoto J, Akiyama Y, Seiji K, Takase K, Abe T, et al. Posterior reversible encephalopathy syndrome treated with renin-angiotensin system blockade. J Neurol Sci. 2015;355:219–21.

    PubMed  Google Scholar 

  35. Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc. 2010;85:427–32.

    PubMed  PubMed Central  Google Scholar 

  36. Gao B, Lv C. Central-variant posterior reversible encephalopathy syndrome: more than meets the eye. AJR Am J Roentgenol. 2014;203:W454.

    PubMed  Google Scholar 

  37. Ho CM, Chan KH. Posterior reversible encephalopathy syndrome with vasospasm in a postpartum woman after postdural puncture headache following spinal anesthesia. Anesth Analg. 2007;105:770–2.

    PubMed  Google Scholar 

  38. Pilato F, Distefano M, Calandrelli R. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome: clinical and radiological considerations. Front Neurol. 2020;11:34.

    PubMed  PubMed Central  Google Scholar 

  39. Dewilde E, Huygens M, Cools G, Van Calster J. Hypertensive choroidopathy in pre-eclampsia: two consecutive cases. Ophthalmic Surg Lasers Imaging Retin. 2014;45:343–6.

    Google Scholar 

  40. Bourke K, Patel MR, Prisant LM, Marcus DM. Hypertensive choroidopathy. J Clin Hypertens (Greenwich). 2004;6:471–2.

    Google Scholar 

  41. Saito M, Noda K, Saito W, Hirooka K, Hashimoto Y, Ishida S. Increased choroidal blood flow and choroidal thickness in patients with hypertensive chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2020;258:233–40.

    PubMed  Google Scholar 

  42. Paronetto F. Immunocytochemical observations on the vascular necrosis and renal glomerular lesions of malignant nephrosclerosis. Am J Pathol. 1965;46:901–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Iwasaki T, Mishima E, Suzuki T, Kikuchi K, Toyohara T, Seiji K, et al. Kidney enlargement effect of angioplasty for nonatherosclerotic renovascular disease: reversibility of ischemic kidney. Hypertens Res. 2020. https://doi.org/10.1038/s41440-020-0473-6.

  44. Hayreh SS, Servais GE, Virdi PS. Cotton-wool spots (inner retinal ischemic spots) in malignant arterial hypertension. Ophthalmologica. 1989;198:197–215.

    CAS  PubMed  Google Scholar 

  45. Henderson AD, Bruce BB, Newman NJ, Biousse V. Hypertension-related eye abnormalities and the risk of stroke. Rev Neurol Dis. 2011;8:1–9.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Y. Sasaki for technical assistance. This work is partially supported by the Tohoku University Center for Gender Equality Promotion (TUMUG) Support Project and a grant from the Japan Foundation for Applied Enzymology.

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Author notes

  1. These authors contributed equally: Eikan Mishima, Yukino Funayama

Authors and Affiliations

  1. Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Eikan Mishima, Takehiro Suzuki, Takafumi Toyohara, Koichi Kikuchi, Mariko Miyazaki, Hideo Harigae, Sadayoshi Ito & Takaaki Abe

  2. Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yukino Funayama

  3. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Fumiko Mishima, Fumihiko Nitta, Hiroshi Kunikata & Toru Nakazawa

  4. Medical Center, Miyagi University of Education, Sendai, Japan

    Junichiro Hashimoto

  5. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Hideo Harigae

  6. Department of Medicine, Katta General Hospital, Shiroishi, Japan

    Sadayoshi Ito

  7. Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan

    Takaaki Abe

  8. Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takaaki Abe

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Mishima, E., Funayama, Y., Suzuki, T. et al. Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria. Hypertens Res 44, 88–97 (2021). https://doi.org/10.1038/s41440-020-0521-2

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