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World J Transplant. Mar 18, 2022; 12(3): 42-54
Published online Mar 18, 2022. doi: 10.5500/wjt.v12.i3.42
Table 1 Management for hypertension following renal transplantation
Blood pressure management
Interventions
Comments
Non-pharmacological managementDietary sodium restriction; Weight reduction; Exercise; Smoking cessation; Stress reduction
Pharmacological therapyAntihypertensive medications: -Diuretics; -Calcium channel blockers; -Beta-blockers; -Renin-angiotensin aldosterone system blockade; -Alpha1 antagonists; -Alpha 2 agonistsMedication choice depends on patient characteristics, adverse effects, tolerability
Invasive interventions -Transplant renal artery angioplasty +/- stenting; -Continuous positive airway pressure; -Bilateral native nephrectomy; -Native renal denervation-Transplant renal artery stenosis; -Obstructive sleep apnea; -Failed native kidney; -Sympathetic overactivity
Adjustment of Immunosuppressive Medication-Steroid withdrawal protocol; -Minimize dose of calcineurin inhibitors; -Replace CsA by using less hypertensive and less nephrotoxic drugsOther drugs that can be used: -MMF: Mycophenolate mofetil; -Tacrolimus; -Sirolimus
Table 2 Target Blood pressure guideline for kidney transplant recipients
Medical Society/Guideline
Recommended BP target
ACC/AHA[65]< 130/80 mm Hg
JNC 8 (2014)[66]Not defined
Kidney disease outcomes quality initiative (KDOQI)[67]-Goal of 125/75 mm Hg for transplant recipients with proteinuria. -Goal of 130/85 in the absence of proteinuria
Kidney disease: Improving Global outcomes (KDIGO)[68]< 130/80
European Best Practice Guidelines for Renal Transplantation 2002[19]Target BP ≤ 125/75 mm Hg in proteinuria patients
Canadian Society of Nephrology[69]Patients with significant proteinuria; Target Blood pressure is < 130/80 mm Hg
British Renal Association[70]< 130/80 mm Hg
Table 3 Studies regarding the management of posttransplant hypertension

Study type
Title
Ref.
Intervention
Outcome
Conclusion
1Four cross-sectional Retrospective analysis Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional AnalysisKuxmiuk-Glembin et al[64], 2018-Beta-blockers 80%); -Calcium channel blockers (53%); -Diuretics (37%); -Alpha-blockers (35%); -Angiotensin-converting enzyme inhibitors (ACEi) (32%); -ARB (7%)Blood pressure controlled using BB (43.9 controlled, 56.1 not controlled P = 0.007); -Number of antihypertensive agents: 2.43 +/- 1.3 (controlled BP); 1.88 +/- 1.5 (Uncontrolled BP) P < 0.001. -ACEI &/ARB: Yes: 57.1 (controlled, 42.9 (Uncontrolled); No ACEI/ARB: 48 (Controlled), 52 (uncontrolled) P = 0.08The commonly used monotherapy agents:-BB followed by CCB. -Use of ACEI, diuretics, and alpha-blockers was about the same. -ARB therapy was least utilized. -Significant increase was observed in the mean number of antihypertensive drugs per patient in subsequent years
2Randomized controlled trials systemic reviewAntihypertensive treatment for kidney transplant recipientsCross et al[71], 200960 studies involving 3802 recipients. -29 studies (2262 participants) compared calcium channel blocker to placebo/no treatment. -10 studies (445 participants) compared ACEi to placebo/no treatment. -7 studies (405 participants) compared CCB to ACEi-CCB compared to placebo/no treatment reduced graft loss (RR 0.75, 95%CI: 0.57-0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95%CI: 2.22-6.68). -ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95%CI: -18.57-2.43) and variable for graft loss, precluding meta-analysis. -Direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95%CI: -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95%CI: -0.47 to -0.10), hyperkalaemia (RR 3.74, 95%CI: 1.89-7.43)CCB may be used as first-line agents for hypertensive kidney transplant recipients. ACEi have few detrimental effects in kidney transplant recipients
3Double-blind, randomized, placebo-controlled trial.Angiotensin II blockade in kidney transplant recipients.Ibrahim et al[72], 2013-The effect of losartan compared to placebo and initiated within three months of transplantationDoubling of renal cortical volume – Measure of interstitial fibrosis/tubular atrophy-Use of losartan tended to be protective, with an odds ratio (OR) of 0.39 (95%CI: 0.13–1.15, P = 0.08). -Losartan had no significant effect on time to a composite of ESRD, death, or doubling of creatinine level. The mean time to doubling of serum creatinine was longer in the losartan group, compared with placebo (1065 versus 450 d [hazard ratio (HR) 7.28, 95%CI: 2.22–32.78])
4Prospective Controlled TrialConverting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplantsMourad et al[73], 1993-6 mo after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor lisinopril (ACEI, alone or associated with frusemide; n = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; n = 11)-Before initiation of antihypertensive therapy, the two groups had similar mean arterial pressures and GFRs. -Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg), and identical trough blood levels cyclosporineIn cyclosporine-treated transplant recipients, satisfactory control of hypertension was obtained by ACEIs based on their potential to minimize arterial pressures
5Prospective Randomized TrialRandomized trial of steroid withdrawal in kidney recipients treated with mycophenolate mofetil and cyclosporinePellitier et al[74], 2006-121 patients were randomized either to discontinue or remain on steroids (60 patients per group)There were no significant differences in patient and graft survival rates at 1 year or at last follow-up (approximate 3.7y). -Incidence of acute and chronic rejection as well as graft function were the same within 1 yrSteroid withdrawal in low-risk kidney transplant recipients is safe and ameliorates many of the unwanted side effects of steroid use
6Retrospective studyLack of long-term benefits of steroid withdrawal in renal transplant recipientsSivaram et al[75], 2001-Retrospective review identified 58 patients administered cyclosporine, azathioprine, and prednisone who underwent complete steroid withdrawal-Post-steroid withdrawal follow up: 7.6 +/- 1.9 years; -9 patients restarted therapy; 3 patients lost their graft (2 of which are those who restarted prednisone therapy). -2 died with functioning graftsWhen prednisone dosage was tapered from 10 mg/d to 10 mg every other day, clinically significant improvements were seen in weight, systolic and diastolic blood pressures, glycosylated hemoglobin levels, and diabetes-related outcomes