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Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction

Abstract

Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.

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Fig. 1: Mechanisms of action of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
Fig. 2: Nephroprotection offered by RAS blockade in patients with preserved and advanced CKD.

References

  1. 1.

    Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G, et al. Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2010;55:441–51.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Sarafidis PA, Li S, Chen SC, Collins AJ, Brown WW, Klag MJ, et al. Hypertension awareness, treatment, and control in chronic kidney disease. Am J Med. 2008;121:332–40.

    PubMed  Article  Google Scholar 

  3. 3.

    Sarafidis PA, Sharpe CC, Wood E, Blacklock R, Rumjon A, Al-Yassin A, et al. Prevalence, patterns of treatment, and control of hypertension in predialysis patients with chronic kidney disease. Nephron Clin Pr. 2012;120:c147–155.

    CAS  Article  Google Scholar 

  4. 4.

    Loutradis C, Sarafidis P. Pharmacotherapy of hypertension in patients with pre-dialysis chronic kidney disease. Expert Opin Pharmacother. 2020;21:1201–17.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Sarafidis PA, Bakris GL. Kidney disease and hypertension. In: Lip G, Hall J, editors. Comprehensive hypertension. London: Elsevier; 2007.

  6. 6.

    KDIGO. Clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;2:337.

  7. 7.

    Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13–e115.

    CAS  PubMed  Google Scholar 

  8. 8.

    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. Eur Heart J. 2018;39:3021–104.

    PubMed  Article  Google Scholar 

  9. 9.

    Palmer BF. Impaired renal autoregulation: implications for the genesis of hypertension and hypertension-induced renal injury. Am J Med Sci. 2001;321:388–400.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685–93.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Schmidt M, Mansfield KE, Bhaskaran K, Nitsch D, Sorensen HT, Smeeth L, et al. Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ. 2017;356:j791.

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Jackevicius CA, Wong J, Aroustamian I, Gee M, Mody FV. Rates and predictors of ACE inhibitor discontinuation subsequent to elevated serum creatinine: a retrospective cohort study. BMJ Open. 2014;4:e005181.

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Weir MR, Rolfe M. Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. Clin J Am Soc Nephrol. 2010;5:531–48.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Linde C, Bakhai A, Furuland H, Evans M, McEwan P, Ayoubkhani D, et al. Real-world associations of renin-angiotensin-aldosterone system inhibitor dose, hyperkalemia, and adverse clinical outcomes in a cohort of patients with new-onset chronic kidney disease or heart failure in the United Kingdom. J Am Heart Assoc. 2019;8:e012655.

    PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Sarafidis PA, Blacklock R, Wood E, Rumjon A, Simmonds S, Fletcher-Rogers J, et al. Prevalence and factors associated with hyperkalemia in predialysis patients followed in a low-clearance clinic. Clin J Am Soc Nephrol. 2012;7:1234–41.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Ku E, McCulloch CE, Vittinghoff E, Lin F, Johansen KL. Use of antihypertensive agents and association with risk of adverse outcomes in chronic kidney disease: focus on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. J Am Heart Assoc. 2018;7:e009992.

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF, et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pr. 2004;10:499–509.

    Article  Google Scholar 

  18. 18.

    Verbeke F, Lindley E, Van Bortel L, Vanholder R, London G, Cochat P, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure in non-dialysis-dependent chronic kidney disease: an endorsement with some caveats for real-life application. Nephrol Dial Transpl. 2014;29:490–6.

    Article  Google Scholar 

  19. 19.

    Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ, et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis. 2005;45:281–7.

    PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309–20.

    PubMed  Article  Google Scholar 

  21. 21.

    Lea J, Greene T, Hebert L, Lipkowitz M, Massry S, Middleton J, et al. The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension. Arch Intern Med. 2005;165:947–53.

    PubMed  Article  Google Scholar 

  22. 22.

    Sarafidis PA, Khosla N, Bakris GL. Antihypertensive therapy in the presence of proteinuria. Am J Kidney Dis. 2007;49:12–26.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Sarafidis PA, Ruilope LM. Aggressive blood pressure reduction and renin-angiotensin system blockade in chronic kidney disease: time for re-evaluation? Kidney Int. 2014;85:536–46.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349:1857–63.

    Article  Google Scholar 

  25. 25.

    Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421–31.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N. Engl J Med. 1993;329:1456–62.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N. Engl J Med. 2001;345:861–9.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl J Med. 2001;345:851–60.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Sarafidis PA, Stafylas PC, Kanaki AI, Lasaridis AN. Effects of renin-angiotensin system blockers on renal outcomes and all-cause mortality in patients with diabetic nephropathy: an updated meta-analysis. Am J Hypertens. 2008;21:922–9.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N. Engl J Med. 2004;351:1952–61.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Sarafidis PA, Bakris GL. Antihypertensive therapy and the risk of new-onset diabetes. Diabetes Care. 2006;29:1167–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Schjoedt KJ, Astrup AS, Persson F, Frandsen E, Boomsma F, Rossing K, et al. Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial. Diabetologia. 2009;52:46–49.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 2002;288:2981–97.

  35. 35.

    Chavers BM, Bilous RW, Ellis EN, Steffes MW, Mauer SM. Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria. N. Engl J Med. 1989;320:966–70.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N. Engl J Med. 2009;361:40–51.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Weil EJ, Fufaa G, Jones LI, Lovato T, Lemley KV, Hanson RL, et al. Effect of losartan on prevention and progression of early diabetic nephropathy in American Indians with type 2 diabetes. Diabetes. 2013;62:3224–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366:2026–33.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Mishima E, Haruna Y, Arima H. Renin-angiotensin system inhibitors in hypertensive adults with non-diabetic CKD with or without proteinuria: a systematic review and meta-analysis of randomized trials. Hypertens Res. 2019;42:469–82.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Ruggenenti P, Perna A, Remuzzi G. ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy. J Am Soc Nephrol. 2001;12:2832–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Remuzzi G, Ruggenenti P, Perna A, Dimitrov BD, de Zeeuw D, Hille DA, et al. Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. J Am Soc Nephrol. 2004;15:3117–25.

    PubMed  Article  Google Scholar 

  42. 42.

    Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N. Engl J Med. 2006;354:131–40.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Hsu TW, Liu JS, Hung SC, Kuo KL, Chang YK, Chen YC, et al. Renoprotective effect of renin-angiotensin-aldosterone system blockade in patients with predialysis advanced chronic kidney disease, hypertension, and anemia. JAMA Intern Med. 2014;174:347–54.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Arora N, Katz R, Bansal N. ACE inhibitor/angiotensin receptor blocker use patterns in advanced CKD and risk of kidney failure and death. Kidney Med. 2020;2:248–57.

    PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Suissa S, Hutchinson T, Brophy JM, Kezouh A. ACE-inhibitor use and the long-term risk of renal failure in diabetes. Kidney Int. 2006;69:913–9.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Oh YJ, Kim SM, Shin BC, Kim HL, Chung JH, Kim AJ, et al. The impact of renin-angiotensin system blockade on renal outcomes and mortality in pre-dialysis patients with advanced chronic kidney disease. PLoS ONE. 2017;12:e0170874.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  47. 47.

    Ahmed A, Jorna T, Bhandari S. Should we stop angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016;133:147–58.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Apperloo AJ, de Zeeuw D, de Jong PE. A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stability of renal function. Kidney Int. 1997;51:793–7.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Holtkamp FA, de Zeeuw D, Thomas MC, Cooper ME, de Graeff PA, Hillege HJ, et al. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function. Kidney Int. 2011;80:282–7.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Clase CM, Barzilay J, Gao P, Smyth A, Schmieder RE, Tobe S, et al. Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes. Kidney Int. 2017;91:683–90.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Ohkuma T, Jun M, Rodgers A, Cooper ME, Glasziou P, Hamet P, et al. Acute increases in serum creatinine after starting angiotensin-converting enzyme inhibitor-based therapy and effects of its continuation on major clinical outcomes in type 2 diabetes mellitus. Hypertension. 2019;73:84–91.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Chaumont M, Pourcelet A, van Nuffelen M, Racapé J, Leeman M, Hougardy JM. Acute kidney injury in elderly patients with chronic kidney disease: do angiotensin-converting enzyme inhibitors carry a risk? J Clin Hypertens. 2016;18:514–21.

    CAS  Article  Google Scholar 

  53. 53.

    Pecoits-Filho R, Fliser D, Tu C, Zee J, Bieber B, Wong MMY, et al. Prescription of renin-angiotensin-aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care. J Clin Hypertens. 2019;21:991–1001.

    Article  Google Scholar 

  54. 54.

    Jun M, Jardine MJ, Perkovic V, Pilard Q, Billot L, Rodgers A, et al. Hyperkalemia and renin-angiotensin aldosterone system inhibitor therapy in chronic kidney disease: A general practice-based, observational study. PLoS ONE. 2019;14:e0213192.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Maddirala S, Khan A, Vincent A, Lau K. Effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on serum potassium levels and renal function in ambulatory outpatients: risk factors analysis. Am J Med Sci. 2008;336:330–5.

    PubMed  Article  Google Scholar 

  56. 56.

    An JN, Lee JP, Jeon HJ, Kim DH, Oh YK, Kim YS, et al. Severe hyperkalemia requiring hospitalization: predictors of mortality. Crit Care. 2012;16:R225.

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Sarafidis PA, Georgianos PI, Bakris GL. Advances in treatment of hyperkalemia in chronic kidney disease. Expert Opin Pharmacother. 2015;16:2205–15.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Collins AJ, Pitt B, Reaven N, Funk S, McGaughey K, Wilson D, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46:213–21.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Loutradis C, Tolika P, Skodra A, Avdelidou A, Sarafidis PA. Prevalence of hyperkalemia in diabetic and non-diabetic patients with chronic kidney disease: A Nested Case-Control Study. Am J Nephrol. 2015;42:351–60.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Ueda Y, Ookawara S, Miyazawa H, Ito K, Hirai K, Hoshino T, et al. Changes in serum and urinary potassium handling associated with renin-angiotensin-aldosterone system inhibitors in advanced chronic kidney disease patients. Cureus. 2019;11:e5561.

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Kovesdy CP, Matsushita K, Sang Y, Brunskill NJ, Carrero JJ, Chodick G, et al. Serum potassium and adverse outcomes across the range of kidney function: a CKD prognosis consortium meta-analysis. Eur Heart J. 2018;39:1535–42.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Luo J, Brunelli SM, Jensen DE, Yang A. Association between serum potassium and outcomes in patients with reduced kidney function. Clin J Am Soc Nephrol. 2016;11:90–100.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169:1156–62.

    PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Evans M, Palaka E, Furuland H, Bennett H, Linde C, Qin L, et al. The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease. BMC Nephrol. 2019;20:31.

    PubMed  PubMed Central  Article  Google Scholar 

  65. 65.

    Chapman A, Gunning S. Real-world associations between renin-angiotensin-aldosterone system inhibition therapy, hyperkalemia, and outcomes: a clinical and scientific call to action. J Am Heart Assoc. 2019;8:e014845.

    PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32:820–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N. Engl J Med. 2015;372:211–21.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Spinowitz BS, Fishbane S, Pergola PE, Roger SD, Lerma EV, Butler J, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 Study. Clin J Am Soc Nephrol. 2019;14:798–809.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Burnier M. Renin-angiotensin system blockade in advanced kidney disease: stop or continue? Kidney Med. 2020;2:231–4.

    PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Murphy DP, Drawz PE, Foley RN. Trends in angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use among those with impaired kidney function in the United States. J Am Soc Nephrol. 2019;30:1314–21.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. 71.

    Mahmoudpour SH, Asselbergs FW, Souverein PC, de Boer A, Maitland-van der Zee AH. Prescription patterns of angiotensin-converting enzyme inhibitors for various indications: a UK population-based study. Br J Clin Pharm. 2018;84:2365–72.

    CAS  Article  Google Scholar 

  72. 72.

    Qiao Y, Shin JI, Sang Y, Inker LA, Secora A, Luo S, et al. Discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease. Mayo Clin Proc. 2019;94:2220–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. 73.

    Onuigbo MA, Onuigbo NT. Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients. Int Urol Nephrol. 2008;40:233–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Ahmed AK, Kamath NS, El Kossi M, El, Nahas AM. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transpl. 2010;25:3977–82.

    CAS  Article  Google Scholar 

  75. 75.

    Gonçalves AR, Khwaja A, Ahmed AK, El Kossi M, El Nahas M. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pr. 2011;119:c348–354.

    Article  Google Scholar 

  76. 76.

    van den Belt SM, Heerspink HJL, Kirchner M, Gracchi V, Thurn-Valsassina D, Bayazit AK, et al. Discontinuation of RAAS inhibition in children with advanced CKD. Clin J Am Soc Nephrol. 2020;15:625–32.

    PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Qiao Y, Shin JI, Chen TK, Inker LA, Coresh J, Alexander GC, et al. Association between renin-angiotensin system blockade discontinuation and all-cause mortality among persons with low estimated glomerular filtration rate. JAMA Intern Med. 2020;180:718–26.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78.

    Bhandari S, Ives N, Brettell EA, Valente M, Cockwell P, Topham PS, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transpl. 2016;31:255–61.

    CAS  Article  Google Scholar 

  79. 79.

    Eckardt KU, Bansal N, Coresh J, Evans M, Grams ME, Herzog CA, et al. Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a kidney disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018;93:1281–92.

    PubMed  PubMed Central  Article  Google Scholar 

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Loutradis, C., Price, A., Ferro, C.J. et al. Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction. J Hum Hypertens 35, 499–509 (2021). https://doi.org/10.1038/s41371-021-00504-9

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