Arterial hypertension in kidney transplant recipients: pathophysiology, diagnostics, treatment

Relevance: Arterial hypertension (HTN) in kidney transplant recipients is a major risk factor for cardiovascular diseases, graft rejection and premature death. In the post-transplant period in 80% of cases persistent or refractory arterial hypertension develops which is difficult to correct with conventional drug therapy. Treatment difficulties include the ineffectiveness of many first-line drugs and the fact that the most common immunosuppressive drugs (cyclosporine, tacrolimus and methylprednisolone) contribute to the development of hypertension. This type of hypertension represents a significant problem in clinical practice due to the complexity of treatment and high mortality. The need to study the treatment of post-transplant hypertension is due not only to its clinical significance, but also to the potential opportunity to improve treatment results and life expectancy of kidney transplant recipients.

Objective: to study the genesis, risk factors, pathophysiology, diagnosis and treatment of posttransplant hypertension.

Materials and methods: 37 literary sources were analyzed.

Conclusions: High blood pressure exposes the recipient of a kidney transplant to the risk of CVD and mortality as well as increased systemic hypertension which can be a cause and a consequence of renal pathology. Hypertension is a modifiable risk factor contributing to the progression of renal failure. There is no any single treatment algorithm. It is often necessary to use several antihypertensive drugs to achieve the target blood pressure. 

1. Alexandrou ME, Ferro CJ, Boletis I, Papagianni A, Sarafidis P. Hypertension in kidney transplant recipients. World J Transplant. 2022;12(8):211-222. PMID: 36159073 https://doi.org/HYPERLINK "https://doi.org/10.5500/wjt.v12.i8.211"10.5500/wjt.v12.i8.211

2. Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis. 2011;57(2):331-341. PMID: 21251543 https://doi.org/HYPERLINK "https://doi.org/10.1053/j.ajkd.2010.10.048"10.1053/j.ajkd.2010.10.048

3. Weir MR, Burgess ED, Cooper JE, Fenves AZ, Goldsmith D, McKay D, et al. Assessment and management of hypertension in transplant patients. J Am Soc Nephrol. 2015;26(6):1248-1260. PMID: 25653099 https://doi.org/HYPERLINK "https://doi.org/10.1681/ASN.2014080834" 10.1681/ASN.2014080834

4. Mallamaci F, Tripepi R, D'Arrigo G, Porto G, Versace MC, Marino C, et al. Long-term blood pressure monitoring by office and 24-h ambulatory blood pressure in renal transplant patients: a longitudinal study. Nephrol Dial Transplant. 2019;34(9):1558-1564. PMID: 30476170 https://doi.org/10.1093/ndt/gfy355

5. Demiray A, Kanbay M. The assessment of hypertension in kidney transplant patients: time to change our approach? Clin Kidney J. 2021;15(1):1-4. PMID: 35035931https://doi.org/10.1093/ckj/sfab151

6. Pisano A, Mallamaci F, D'Arrigo G, Bolignano D, Wuerzner G, Ortiz A, et al. Assessment of hypertension in kidney transplantation by ambulatory blood pressure monitoring: a systematic review and meta-analysis. Clin Kidney J. 2021;15(1):31-42. PMID: 35035934 https://doi.org/10.1093/ckj/sfab135

7. Kim CS, Oh TR, Suh SH, Choi HS, Bae EH, Ma SK, et al. Uncontrolled hypertension is associated with increased risk of graft failure in kidney transplant recipients: a nationwide population-based study. Front Cardiovasc Med. 2023;10:1185001. eCollection 2023. PMID: 37522087 https://doi.org/HYPERLINK "https://doi.org/10.3389/fcvm.2023.1185001"10.3389/fcvm.2023.1185001

8. Campistol JM, Romero R, Paul J, Gutiérrez-Dalmau A. Epidemiology of arterial hypertension in renal transplant patients: changes over the last decade. Nephrol Dial Transplant. 2004;19 Suppl 3:iii62-6. PMID: 15192139 https://doi.org/HYPERLINK "https://doi.org/10.1093/ndt/gfh1018"10.1093/ndt/gfh1018

9. Kasiske BL, Vazquez MA, Harmon WE, Brown RS, Danovitch GM, Gaston RS, et al. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol. 2000;11:Suppl 15:S1-86. PMID: 11044969

10. Becker GJ, Wheeler DC, Zeeuw DD, Fujita T, Furth SL, Holdaas H, et al. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;2(5):337–414. https://doi.org/10.1038/kisup.2012.46

11. Opelz G, Döhler B; Collaborative Transplant Study. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant. 2005;5(11):2725-1731. PMID: 16212633 https://doi.org/10.1111/j.1600-6143.2005.01093.x

12. Wangueu LT, de Fréminville JB, Gatault P, Buchler M, Longuet H, Bejan-Angoulvant T, et al. Blood pressure management and long-term outcomes in kidney transplantation: a holistic view over a 35-year period. J Nephrol. 2023;36(7):1931-1943. PMID: 37548826 https://doi.org/10.1007/s40620-023-01706-9

13. Korogiannou M, Sarafidis P, Theodorakopoulou MP, Alexandrou ME, Xagas E, Boletis IN, Marinaki S. Diagnostic Performance of Office versus Ambulatory Blood Pressure in Kidney Transplant Recipients. Am J Nephrol. 2021;52(7):548-558. PMID: 34311458 https://doi.org/HYPERLINK "https://doi.org/10.1159/000517358"10.1159/000517358

14. Nassar M, Nso N, Lakhdar S, Kondaveeti R, Buttar C, Bhangoo H, et al. New onset hypertension after transplantation. World J Transplant. 2022;12(3):42-54. PMID: 35433331 https://doi.org/HYPERLINK "https://doi.org/10.5500/wjt.v12.i3.42"10.5500/wjt.v12.i3.42

15. Fatma LB, Haddad S. Mami I, Ben Kaab B, Jebali H, Smaoui W, et al. SAT-326 Arterial hypertension in kidney transplant recipients. Kidney International Reports. 2020;5(3, Suppl):S136-S137. https://doi.org/HYPERLINK "https://doi.org/10.1016/j.ekir.2020.02.346" 10.1016/j.ekir.2020.02.346

16. Zuziela MA, Vidal J, Knorr JP. Evaluating Factors Associated With Blood Pressure Control in the Early Post-Kidney Transplant Period. Hosp Pharm. 2021;56(4):359-367. PMID: 34381275 https://doi.org/HYPERLINK "https://doi.org/10.1177/0018578720906614 "10.1177/0018578720906614

17. Luke RG. Pathophysiology and treatment of posttransplant hypertension. J Am Soc Nephrol. 1991;2 (2 Suppl 1):S37-44. PMID: 1932642 https://doi.org/HYPERLINK "https://doi.org/10.1681/ASN.V22s37"10.1681/ASN.V22s37

18. Rebelo RNS, Rodrigues CIS. Arterial hypertension in kidney transplantation: huge importance, but few answers. J Bras Nefrol. 2023;45(1):8494. PMID: 36269977 https://doi.org/10.1590/2175-8239-JBN-2022-0109en

19. Palanisamy A, Reeves-Daniel AM, Freedman BI. The impact of APOL1, CAV1, and ABCB1 gene variants on outcomes in kidney transplantation: donor and recipient effects. Pediatr Nephrol. 2014;29(9):1485-1492. PMID: 23748364 https://doi.org/ HYPERLINK "https://doi.org/10.1007/s00467-013-2531-7"10.1007/s00467-013-2531-7

20. Lidberg KA, Annalora AJ, Jozic M, Elson DJ, Wang L, Bammler TK, et al. Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease. Sci Rep. 2021;11(1):4722. PMID: 33633318 https://doi.org/HYPERLINK "https://doi.org/10.1038/s41598-02184194-w"10.1038/s41598-021-84194-w

21. Melilli E, Manonelles A, Montero N, Grinyo J, Martinez-Castelao A, Bestard O, Cruzado J. Impact of immunosuppressive therapy on arterial stiffness in kidney transplantation: are all treatments the same? Clin Kidney J. 2018;11(3):413-421. PMID: 29988241 https://doi.org/ HYPERLINK "https://doi.org/10.1093/ckj/sfx120"10.1093/ckj/sfx120

22. Madken M, Gotra A, Qazi S, Fairhead T, Burns KD. Successful Endovascular Management of Resistant Hypertension Post Kidney Transplant: A Case Report. Can J Kidney Health Dis. 2022;9:20543581221119896. eCollection 2022. PMID: 36160314 https://doi.org/HYPERLINK "https://doi.org/10.1177/20543581221119896"10.1177/20543581221119896

23. Chan W, Bosch JA, Jones D, McTernan PG, Inston N, Moore S, et al. Hypervolemia and blood pressure in prevalent kidney transplant recipients. Transplantation. 2014;98(3):320-327. PMID: 24770615 https://doi.org/HYPERLINK "https://doi.org/10.1097/TP.0000000000000066 "10.1097/TP.0000000000000066

24. el-Agroudy AE, Wafa EW, Gheith OE, Shehab el-Dein AB, Ghoneim MA. Weight gain after renal transplantation is a risk factor for patient and graft outcome. Transplantation. 2004;77(9):1381-1385. PMID: 15167594 https://doi.org/HYPERLINK "https://doi.org/10.1097/01.tp.0000120949.86038.62"10.1097/01.tp.0000120949.86038.62

25. Molnar MZ, Lazar AS, Lindner A, Fornadi K, Czira ME, Dunai A, et al. Sleep apnea is associated with cardiovascular risk factors among kidney transplant patients. Clin J Am Soc Nephrol. 2010;5(1):125-132. PMID: 19965541 https://doi.org/HYPERLINK "https://doi.org/10.2215/CJN.04030609"10.2215/CJN.04030609

26. Molnar MZ, Szentkiralyi A, Lindner A, Czira ME, Szabo A, Mucsi I, Novak M. High prevalence of patients with a high risk for obstructive sleep apnoea syndrome after kidney transplantation--association with declining renal function. Nephrol Dial Transplant. 2007;22(9):2686-2692. PMID: 17478489 https://doi.org/HYPERLINK "https://doi.org/10.1093/ndt/gfm246"10.1093/ndt/gfm246

27. Masson G, Viva T, Huart J, Weekers L, Bonvoisin C, Bouquegneau A, et al. The Effect of Elective Ligation of the Arteriovenous Fistula on Cardiac and Renal Functions in Kidney Transplant Recipients. Kidney360. 2023;4(8):1130-1138. PMID: 37357344 https://doi.org/HYPERLINK "https://doi.org/10.34067/KID.0000000000000198"10.34067/KID.0000000000000198

28. Monzo L, Ferreira JP, Lamiral Z, Bozec E, Boivin JM, Huttin O. Isolated diastolic hypertension and target organ damage: Findings from the STANISLAS cohort. Clin Cardiol. 2021;44(11):1516-1525. PMID: 34523741 https://doi.org/HYPERLINK "https://doi.org/10.1002/clc.23713 "10.1002/clc.23713

29. Seeman, T. Hypertension after renal transplantation. Pediatr Nephrol. 2009; 24 (5): 959-972. PMID: 17955265 https://doi.org/10.1007/s00467-007-0627-7

30. Aziz F, Clark D, Garg N, Mandelbrot D, Djamali A. Hypertension guidelines: How do they apply to kidney transplant recipients. Transplant Rev (Orlando). 2018;32(4):225-233. PMID: 30293557 https://doi.org/10.1016/j.trre.2018.06.002

31. Onsøien MO, Midtvedt K, Reisæter AV, Aasarød K, Waldum-Grevbo B, Egil Vikse B, et al. Blood Pressure Treatment in Kidney Transplant Recipients - Can We Improve? Transplantation Direct. 2021.7(4): e688. PMID: 33786373 https://doi.org/10.1097/TXD.0000000000001142

32. Sandal S, Bansal P, Cantarovich M. The evidence and rationale for the perioperative use of loop diuretics during kidney transplantation: A comprehensive review. Transplant Rev (Orlando). 2018;32(2):92-101. PMID: 29242033 https://doi.org/HYPERLINK "https://doi.org/10.1016/j.trre.2017.11.002"10.1016/j.trre.2017.11.002

33. Moes AD, Hesselink DA, van den Meiracker AH, Zietse R, Hoorn EJ. Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial. Am J Kidney Dis. 2017;69(6):796-804. PMID: 28259499 https://doi.org/HYPERLINK "https://doi.org/10.1053/j.ajkd.2016.12.017"10.1053/j.ajkd.2016.12.017

34. González Monte E, Andrés A, Polanco N, Toribio MJ, Santana R, Gutiérrez Martínez E, et al. Addition of spironolactone to dual blockade of renin angiotensin system dramatically reduces severe proteinuria in renal transplant patients: an uncontrolled pilot study at 6 months. Transplant Proc. 2010;42(8):2899-2901. PMID: 20970564 https://doi.org/HYPERLINK "https://doi.org/10.1016/j.transproceed.2010.08.024 "10.1016/j.transproceed.2010.08.024

35. Kuźmiuk-Glembin I, Adrych D, Tylicki L, Heleniak Z, Garnier H, Wiśniewski J, et al. Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional Analyses. Kidney Blood Press Res. 2018;43(1):45-54. PMID: 29402869 https://doi.org/HYPERLINK "https://doi.org/10.1159/000486905"10.1159/000486905

36. Loutradis C, Sarafidis P, Marinaki S, Berry M, Borrows R, Sharif A, Ferro CJ. Role of hypertension in kidney transplant recipients. J Hum Hypertens. 2021;35(11):958-969. PMID: 33947943 https://doi.org/HYPERLINK "https://doi.org/10.1038/s41371-021-00540-5"10.1038/s41371021-00540-5

37. Shilliday IR, Sherif M. Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients. Cochrane Database Syst Rev. 2004;(1):CD003421. https://doi.org/10.1002/14651858.CD003421.pub2. Update in: Cochrane Database Syst Rev. 2005;(2):CD003421.