Tacrolimus Predose Concentration Is Associated With Hypertension in Pediatric Liver Transplant Recipients

Prytuła, Agnieszka; Vandekerckhove, Kristof; Raes, Ann; Wolf, Daniël De; Dehoorne, Jo; Walle, Johan Vande; Bruyne, Ruth De

doi:10.1097/mpg.0000000000001141

Cited by 8 publications

(44 citation statements)

References 42 publications

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“…Both might indicate a potential influence of immunosuppressive therapy. Trough levels, particularly of tacrolimus, with similar ranges to those in our cohort have been shown to be associated with both systolic and diastolic hypertension in pediatric LT recipients …”

Section: Discussionsupporting

confidence: 78%

“…Trough levels, particularly of tacrolimus, with similar ranges to those in our cohort have been shown to be associated with both systolic and diastolic hypertension in pediatric LT recipients. (39) Elevated IMT, compatible with nascent atherosclerosis, was present in 57% of children in our cohort. This frequency is in line with the recently published study by Perito et al (17) No exact prevalence of pathological IMT is reported in this study.…”

Section: Discussionmentioning

confidence: 59%

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High Burden of Subclinical Cardiovascular Target Organ Damage After Pediatric Liver Transplantation

et al. 2019

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Cardiovascular (CV) events account for 8%‐13% of deaths after liver transplantation (LT) in adulthood. Although CV risk factors (RFs) are present, little is known about the prevalence of subclinical CV target organ damage (TOD) in children after LT. The aim of this prospective observational study was to assess the prevalence of subclinical CV TOD in children after LT and to identify RFs contributing to CV damage as potential targets for clinical intervention. In this study, 104 children after LT (54% female, 46% male; aged 11.5 ± 3.8 years) underwent cross‐sectional assessment of subclinical TOD by carotid‐femoral pulse wave velocity (PWV), carotid intima‐media thickness (IMT), and left ventricular mass index (LVMI). Results were correlated with the presence of CV RFs (obesity, hypertension, dyslipidemia, renal impairment, anemia, and microinflammation). Of the patients, 22% were exposed to 2 CV RFs, and 36% displayed 3 or more CV RFs. Pathological results for PWV, IMT, and LVMI were found in 21.9%, 57.0%, and 11.1% of patients, respectively. In the multivariate analysis, diastolic blood pressure (P = 0.01) and estimated glomerular filtration rate (eGFR; P = 0.03) were independently associated with PWV, eGFR (P = 0.005), and age at LT (P = 0.048) with IMT and body mass index with LVMI (P = 0.004). In conclusion, patients after pediatric LT carry a substantial burden of subclinical CV TOD. Identification of modifiable CV RFs opens opportunities for targeted intervention in order to reduce CV morbidity and mortality in the future.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 59%

High Burden of Subclinical Cardiovascular Target Organ Damage After Pediatric Liver Transplantation

et al. 2019

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“…In those patients requiring treatment for hypertension, a potential screening strategy for secondary end organ damage includes 6-monthly testing for proteinuria, annual fundoscopy and annual cardiac sonography. 6,10,22,23,31,33,42,45,48 These investigations enable the detection of hypertensive end organ damage in an early subclinical phase and they can be considered as an intermediate endpoint for monitoring treatment. 48 Whether it is cost-effective to perform them in all patients with hypertension-even if well-controlled-remains to be determined by future research.…”

Section: Monitoringmentioning

confidence: 99%

Etiology, risk factors and management of hypertension post liver transplantation

Braekman,

De Bruyne,

Vandekerckhove

et al. 2023

Pediatric Transplantation

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BackgroundCardiovascular events are one of the most important causes of morbidity and mortality in the long‐term follow‐up of liver transplant recipients. Hypertension is a significant cardiovascular risk factor that occurs frequently after pediatric liver transplantation. Chronic use of immunosuppressants – mainly calcineurin inhibitors – plays a major role in the development of post‐transplant hypertension and circadian disturbances such as flattening of the nocturnal blood pressure dip. This requires special attention in children given the long timeframe during which immunosuppressive therapy is necessary. Careful and structured blood pressure monitoring and adequate treatment of hypertension are essential to optimize the quality of life and life expectancy of pediatric liver transplant patients. However, evidence‐based guidelines for monitoring and management of post‐transplant hypertension and its complications are lacking.MethodsWe conducted a comprehensive review of the current knowledge and practices concerning post‐transplant hypertension. The databases Pubmed, Embase, Web of Science and Google Scholar were scanned with the following keywords: pediatric liver transplantation, immunosuppression, tacrolimus, cardiovascular effects, hypertension, heart function, kidney function, circadian rhythm, mechanism, monitoring, and management.ResultsIn this review, we describe the incidence and etiology of hypertension in pediatric liver transplant recipients, the underlying mechanisms and characteristics of calcineurin inhibitor‐induced hypertension, and the consequences of and risk factors for post‐transplant hypertension. We hereby present an overview of the current practices in blood pressure monitoring and antihypertensive treatment as well as an algorithm for the evaluation and management of hypertension post liver transplantation. Finally, we discuss knowledge gaps and suggestions for future research.

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“…Whereas renal issues observed within 1-2 years from LTx were often related to acute injuries, the physiopathology of renal damage observed in the late "crucial pe- Moreover, HTN has been associated with tacrolimus predose concentration, with the need of amore intensive blood pressure surveillance in patients with high tacrolimus target to achieve. 106 Given the high prevalence of masked hypertension, it is recommended to perform the ambulatory blood pressure measurement on all liver transplanted children, not to under-diagnose HTN. 107 However, referrals to a pediatric nephrologist should be early made for patients with repeated blood pressures > 95th percentile, especially if associated with microalbumin/creatinine ratio > 32.5 mg/g.…”

Section: Chroni C K Idne Y D Is E a S E Af Ter Ped Iatri C Liver Trmentioning

confidence: 99%

“…Moreover, HTN has been associated with tacrolimus pre‐dose concentration, with the need of amore intensive blood pressure surveillance in patients with high tacrolimus target to achieve 106 …”

Section: Chronic Kidney Disease After Pediatric Liver Transplantmentioning

confidence: 99%

Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem

Lacquaniti

Campo

Tocco

et al. 2020

Clinical Transplantation

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Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.

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Tacrolimus Predose Concentration Is Associated With Hypertension in Pediatric Liver Transplant Recipients

Abstract: Given the high prevalence of masked hypertension, ABPM should be performed in all pediatric LT recipients. Systolic and diastolic hypertension is associated with TAC C0; therefore, children with a higher target TAC C0 require a more intensive blood pressure surveillance.

Cited by 8 publications

References 42 publications

High Burden of Subclinical Cardiovascular Target Organ Damage After Pediatric Liver Transplantation

High Burden of Subclinical Cardiovascular Target Organ Damage After Pediatric Liver Transplantation

Etiology, risk factors and management of hypertension post liver transplantation

Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem

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