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