S.Marinaki

Nephrology Department andRenal Transplant Unit

Medical school, Laiko Hospital, Athens

DO NOT UNDERESTIMATE THE PROBLEM

Foley RN, et al. Am J Kidney Dis 1998; 32 (5 suppl 3): S112–19

Kidney Tx recipients

Higher risk of CV mortalitycomparedto the general population

3-5 fold ↑CV mortalityespecially in the younger agegroups

Kidney Tx and CV mortality Leading cause of death after Tx

Liefeldt et al. Transpl Int. 2010 Dec;23(12):1191-204

Kidney Tx and cardiovascular riskfactors

Hypertension after kidney Tx

Prevalence: 70-90% of renal Tx recipients

Allograft failure

Death with functioning allograft

Atherosclerotic CVD

Disorders of cardiac function

❖ Risk factor for

Wadei HM, Textor SC. Transplant Rev (Orlando ) 2010; 24:105–20

Hypertension after kidney Tx

Lack of control despitetreatment

Study of 1300 patients

Only 12.4% had normal BP 1 year after Tx> 95% on antihypertensive therapy

At least 50% of renal Tx recipients do notreach BP targets

Kasiske BL, et al.Am J Kidney Dis 2004; 43:1071–1081

DEFINE THE TARGET

Hypertension after kidney Tx

AHA guidelines2017

ESH Guidelines

Target BP < 130/80 mmHg<125/75mmHg in proteinuric pts

DO NOT MISS DIAGNOSIS

White-coat HTN: common →12-65% of KTRMasked HTN: common → 15% of adult and up to 45% of pediatric KTR

Abnormal day-night BP patternsNon-dippingReverse dipping: common in KTR

↑LVMI↑major adverse cardiac

eventsPoor allograft function

How to measure BP in KTR?Office BP measurementHome BP readingsABPM

Diagnosis

Fresnedo G et al. RETENAL study. Trans Proc. 2012;44:2601–02

Wadei HM et al. J Am Soc Nephrol. 2007;18:1607–15

ABPM→ “gold standard” for BPmeasurement in KTR

Home BP readings→ reasonable alternativegood correlation with ABPM

(!) helpful for better adherence

Measurement of BP in kidney Tx recipients

Krakoff LR. Hypertension. 2006;47:29–34

UNDERSTAND THE

MULTIFACTORIAL ETIOLOGY

Recipient factorsAgeAfrican AmericanBMIDiabetes mellitusNative kidney diseasePreexisting HTNObstructive sleep apneaVascular calcificationSecondary Hyperparathyroidism

Donor factorsOlder ageHTN

Baseline GFRGenetic variants

Post-Tx factorsVolume overloadDGFAcute rejectionLow GFRImmunosuppressionRecurrent disease

Nonadherence

Hypertension and Tx

Glicklich D et al.Cardiology in Review 2017;25: 102–9

DEAL WITH THE COMPLEX ISSUE OF

IMMUNOSUPPRESSION

CNI + MPA’s + CS > 80 % of patientsafter kidney Tx

Immunosuppression after kidney Tx

Glicklich D et al.Cardiology in Review 2017;25: 102–9

Few studies in KTR

General goal of anti-HTN therapy in KTR↓

To prolong allograft survival and to minimize cardiovascular risk

Recommendations of the Joint National Committeeof the Canadian Hypertension Education Program

❖Lifestyle modifications

❖Pharmacological treatment

Treatment of AH after kidney Tx

Chobanian AV et al.Hypertension 42: 1206–52, 2004

INSIST ON LIFESTYLE MODIFICATIONS

USE ANTIHYPERTENSIVES CORRECTLY

All categories of antihypertensives may be used

Calcium-Chanel-blockers, CCB’s

Counteract the vasoconstrictive effects of CNI’s:↓ vascular resistance, ↑GFRMetaanalysis, 29RCT’s, n=2262 pts

CCB’s vs placebo↓ allograft loss, ↑GFR

DH-CCB’s: “Initial drug of choice in KTR?”Non-DH-CCB’s (verapamil, diltiazem): increase blood levels of CNI’s and mTORi’s

Cross NB et al.Cochrane Database Syst Rev.2009;3:CD003598

Renin-Angiotensin-Aldosterone-System Blockers (RAAS)

RAAS blockers→ Effective in lowering BP / more effective in decreasing proteinuria

Contrary to expectations, studies of RAAS blockers in KTRNO benefit of ACEI or ARB in allograft or patient survival

4 long-term RCT’s (ACE or ARB vs placebo)No benefit on patient or graft survivalOne study in 70 KTR with LVH, 10 years follow up→ ↓ major CV events in the ACE-group

Significant reductions in GFR and hemoglobin Elevated risk of hyperkalemia

Philipp T et al. results from SECRET. NDT. 2010;25:967–76Ibrahim HN et alJ Am Soc Nephrol. 2013;24:320–27Paoletti E et al. Transplantation. 2013;95:889–95Knoll GA et al.. Lancet Diabetes Endocrinol. 2016;4:318–26

Opelz, G et al.J Am Soc Nephrol 2006; 17(11):3257-62

In the presence of fluid retention Early posttransplantation period Late: Allograft dysfunction

Diuretics

Loop diuretics, new agents torasemideThiazide diureticsMineralocorticoid receptor antagonists: few data in KTR, (!) ↑K

3rd -generation beta blockers : combine a- and b-blocking effects (labetolol ,carvedilol) more potent antihypertensivesbeneficial effects on the lipid profileimprove survival in patients with CHF

Beta-Adrenergic Blockers

Wadei HM, Textor SC. In: Weir MR, Lerma EV, eds. Kidney Transplantation: Practical Guide to Management. New York, NY: Springer Science+Business Media; 2014:205–24.

Commonly used drugs after KTx

Counteract the reflex tachycardia induced by other drugs (CCB’s, vasodilators)

INDIVIDUALIZE TREATMENT

AND ENSURE COMPLIANCE

There are no specific antihypertensive agents to treat posttransplanthypertension and all agents can be used.

Prescription → taking into account the characteristics of each patient

Most patients need to be treated with several antihypertensive agents

CONCLUSIONS

DON’T FORGET!

HYPERTENSION AFTER KIDNEY TX

IMPORTANT MODIFIABLE RISK FACTOR