Hypertension In Kidney Transplant Recipients Research Articles

#2169 Transplant renal artery stenosis in recipients with resistant arterial hypertension

Abstract Background and Aims Transplant Renal Artery Stenosis (TRAS) is a vascular complication after kidney transplantation. It worsens the prognosis of the graft and the patient's life. The aim was to study the incidence of TRAS as a cause of resistant arterial hypertension in kidney transplant recipients in the Republic of Belarus and the efficiency of its endovascular treatment. Method The study included 187 kidney transplant recipients. Blood pressure of 72 (38.5%) patients was less than 130/80 mmHg without taking antihypertensive drugs. Arterial hypertension was diagnosed in 115 (61.5%) recipients. The study included clinical, laboratory and instrumental methods (24-hour blood pressure monitoring, Doppler ultrasound, graft scintigraphy with captopril). Results 31 (16.6%) recipients needed to take one antihypertensive drug, 43 (23.0%)—2 drugs, 41 (21.9%)—3 or more. 17 (9.1%) recipients did not have target blood pressure correction while taking more than 4 antihypertensive drugs. There was decreased blood flow in the graft artery with a peak systolic velocity > 200 cm/s in 14 (7.5%) cases. These patients were submitted to the graft nephroscintigraphy with caplopril where 8 grafts (4.3%) were diagnosed signs of TRAS. These recipients were submitted to the renal angiography with the injection of 150 (100; 200) ml of contrast agent. 5 (2.7%) recipients were diagnosed with hemodynamically significant TRAS of more than 70 (65; 75) % and received percutaneous transluminal angioplasty and stenting. All these patients had a decrease of glomerular filtration rate and resistant arterial hypertension before operation. The average age of the patients with TRAS was 57.4 ± 11.0 years, the period after transplantation was 11 ± 3 months. Their blood tests did not show dyslipidemia, but 4 out of 5 cases had diabetes mellitus. Their postoperative period had no complications. The patient was placed on dual antiplatelet therapy with aspirin and clopidogrel. There was an increase in glomerular filtration rate by 27 ± 7 ml/min/1.73 m2 and a decrease in systolic blood pressure by 40 (40; 45) mm Hg in the early postoperative period. Graft artery stenting allowed reducing the number of antihypertensive drugs to one tablet in 4 out of 5 patients. Conclusion Transplant Renal Artery Stenosis is a rare but significant complication of the late postoperative period that may cause resistant hypertension in kidney transplant recipients. Timely identification and stenting of the graft artery improves the graft functioning and reduces blood pressure.

Predictive factors of post-transplant hypertension in kidney transplant recipients

Bevezetés: A vesetranszplantációt követő magas vérnyomás a krónikus allograftkárosodás fontos kockázati tényezője. Célkitűzés: A jelen vizsgálat célja a transzplantáció utáni hypertonia gyakoriságának és lehetséges kockázati tényezői szerepének meghatározása volt. Módszerek: Retrospektív kohorszvizsgálatot végeztünk a Szegedi Tudományegyetem Sebészeti Klinikáján 2007. január 1. és 2022. augusztus 19. között vesetranszplantáción átesett betegek körében, akik rendszeresen részt vettek otthoni vérnyomásmérésen. A recipiens demográfiai és laboratóriumi adatait, továbbá a donor jellemzőit a transzplantációt követő 6. és 12. hónapban elemeztük. A magas vérnyomás diagnózisát az Európai Hypertonia Társaság (ESH) iránymutatásai szerint határoztuk meg. Logisztikus regressziót alkalmaztunk a nem korrigált és a korrigált esélyhányados becslésére a transzplantáció utáni magas vérnyomás lehetséges kockázati tényezőinek felmérésére. Eredmények: A vizsgálatba 280 beteget vontunk be. A transzplantáció utáni magas vérnyomás prevalenciája a veseátültetést követően 6, illetve 12 hónappal 49,3%, illetve 53,5% volt. A többváltozós analízist elvégezve a vesetranszplantáció után 6 hónappal a hypertonia prediktív tényezői a férfinem (OR: 1,717, 95% CI: 1,007–2,927; p = 0,047) és a donor-hypertonia (OR: 2,038, 95% CI: 1,038–4,004; p = 0,039) voltak. A szérumhúgysavszint (OR: 1,004, 95% CI: 1,000–1,007; p = 0,033) és a férfinem (OR: 2,048, 95% CI: 1,161–3,614; p = 0,013) független kockázati tényező volt a vesetranszplantáció után 12 hónappal. Megbeszélés: A vesetranszplantáció után a hypertonia előfordulási gyakorisága 49,3% volt. Vizsgálatunk arra utal, hogy a férfinem, a hypertoniás donor és a szérumhúgysavszint a vesetranszplantáció utáni hypertonia lehetséges prediktorai. Következtetés: Az időben fel nem ismert és nem kezelt poszttranszplantációs hypertonia az allograft funkcionális romlásához vezet, s ezzel csökkenti a graft túlélését. Orv Hetil. 2024; 165(19): 734–741.

Office or home versus 24-hour blood pressure measurement in stable kidney transplant recipients.

The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure modalities in kidney transplant recipients (KTR). For this prospective cross-sectional study 89 stable KTR were recruited at the Charité Transplant Outpatient Clinic. For each study participant office (manual office blood pressure 'MOBP' and automated office blood pressure 'AOBP'), 7-day home (HBPM) and 24-hour ambulatory blood pressure measurement (24h-ABPM) were performed. 80 of the 89 patients recruited had sufficient blood pressure recordings. Mean blood pressure for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean≥130/80mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients respectively as 'uncontrolled hypertensive'. The Bland-Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and Daytime-ABPM (mean bias±SD: -1±13mmHg, -4±13mmHg, 1±10mmHg, respectively). Uncontrolled nighttime hypertension was present in 74 (93%) KTR, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between Daytime-ABPM/HBPM and Nighttime-ABPM (Pearson Correlation Coefficients: 0.62-0.73), followed by MOBP/AOBP (Pearson Correlation Coefficients: 0.49-0.59) was noted. eGFR and proteinuria displayed weak correlation with 24h-, Daytime- and Nighttime-ABPM (absolute values of Pearson Correlation Coefficients: 0.04-0.41). No robust association with either 24h-, Daytime- or Nighttime-ABPM was observed for volume status exams. Masked hypertension is highly prevalent in KTR, especially due to high rates of uncontrolled nighttime hypertension. HBPM shows the narrowest limits of agreement with Daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with Nighttime-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the '2023 ESH Guidelines for the Management of arterial hypertension', should not be withheld for the KTR population. Clinical trials evaluating treatment of hypertension in KTR are urgently needed.

Hypertension in kidney transplant recipients.

Kidney transplantation is considered the treatment of choice for end-stage kidney disease patients. However, the residual cardiovascular risk remains significantly higher in kidney transplant recipients (KTRs) than in the general population. Hypertension is highly prevalent in KTRs and represents a major modifiable risk factor associated with adverse cardiovascular outcomes and reduced patient and graft survival. Proper definition of hypertension and recognition of special phenotypes and abnormal diurnal blood pressure (BP) patterns is crucial for adequate BP control. Misclassification by office BP is commonly encountered in these patients, and a high proportion of masked and uncontrolled hypertension, as well as of white-coat hypertension, has been revealed in these patients with the use of ambulatory BP monitoring. The pathophysiology of hypertension in KTRs is multifactorial, involving traditional risk factors, factors related to chronic kidney disease and factors related to the transplantation procedure. In the absence of evidence from large-scale randomized controlled trials in this population, BP targets for hypertension management in KTR have been extrapolated from chronic kidney disease populations. The most recent Kidney Disease Improving Global Outcomes 2021 guidelines recommend lowering BP to less than 130/80 mmHg using standardized BP office measurements. Dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers have been established as the preferred first-line agents, on the basis of emphasis placed on their favorable outcomes on graft survival. The aim of this review is to provide previous and recent evidence on prevalence, accurate diagnosis, pathophysiology and treatment of hypertension in KTRs.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients.

Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Abstract P099: Pulse Pressure And Long-term Post-kidney Transplant Systolic Hypertension Among Different Age

Introduction: Wide pulse pressure (PP) is common in elderly and associated with poor cardiovascular outcomes. Association between PP and long-term hypertension (HTN) in kidney transplant recipients (KTR) among different age groups is unclear. Hypothesis: We hypothesize that PP at early post-kidney transplant (KT) predicts different long-term post-KT HTN among different age groups. Methods: This is a retrospective cohort study of consecutive KT recipient in a single center. With age categorized into < and ≥ 50 years old, association between PP at 4 and 12 weeks post-KT (when a baseline kidney allograft function is generally established) and post-KT systolic and diastolic HTN (SHTN and DHTN) at a 48-week post-KT defined by SBP and DBP ≥ 130 and 80 mmHg, respectively were examined by using multiple logistic regression. Results: Of all 105 KTR, 40 and 65 patients were <50 and 65 years old, respectively. Mean age±SD was 54±12 years with a median follow-up of 47.71 weeks. At a 4-week post-KT, mean PP was 54±13 mmHg with a mean difference young - old ±SE of -7±3 (p 0.011; 95%CI -11.55, -1.53). Mean PP at a 12-week post-KT was 56±16 mmHg and a mean difference±SE of -8±3 mmHg (p 0.018; 95%CI -13.95, -1.35). At 48-week post-KT, 50% of the young had SHTN 66% of the old had SHTN; whereas, 58% and 38% of the corresponding groups had DHTN. Mean SBP of the young and old groups were 129±16 and 135±16 mmHg, respectively (mean difference -6±3; p 0.076; 95%CI -12.66, 0.63). Mean DBP of the corresponding groups were 80±12 and 75± 10 with a mean difference 5±2; p 0.036; 95%CI 0.332, 9.394). After adjusted for pre-KT BMI, type of KT, and induction immunosuppression, every 1 mmHg increase in PP at the 4-week post-KT was associated with 6% greater the odds of developing SHTN at 48-week post-KT among the older age group (OR 1.06; p 0.041, 95%CI 1.002, 1.117); whereas, the risk was 2% increase in younger group (OR 1.02; p 0.400; 95%CI 0.969, 1.082). The association between PP at the 12-week post-KT and SHTN at 48-week post-KT were in the same direction, but it was attenuated (5%) in the older and strengthen the younger (7%) (OR old 1.048; p 0.033; 95%CI 1.004, 1.095 and OR young 1.087; p 0.050; 95%CI 1.000, 1.1801). There were no association between PP at 4- and 12-week post-KT and DHTN at 48-week post-KT. Conclusion: Higher early post-KT PP was associated with increased risk of long-term post-KT SHTN, but not DHTN. However, the magnitude of the association was greater among the older KTR at early post-KT, but higher in the younger at later post-KT period. Mechanism of increased PP and outcomes such as post-KT HTN in KTR needs to be further elucidated.

Role of hypertension in kidney transplant recipients.

Cardiovascular events are one of the leading causes of mortality in kidney transplant recipients. Hypertension is the most common comorbidity accompanying chronic kidney disease, with prevalence remaining as high as 90% even after kidney transplantation. It is often poorly controlled. Abnormal blood pressure profiles, such as masked or white-coat hypertension, are also extremely common in these patients. The pathophysiology of blood pressure elevation in kidney transplant recipients is complex and includes transplantation-specific risk factors, which are added to the traditional or chronic kidney disease-related factors. Despite these observations, hypertension management has been an under-researched area in kidney transplantation. Thus, relevant evidence derives either from studies in the general population or from small trials in kidney transplant recipients. Based on the relevant guidelines in the general population, lifestyle modifications should probably be applied as the first step of hypertension management in kidney transplant recipients. The optimal pharmacological management of hypertension in kidney transplant recipients is also not clear. Dihydropyridine calcium channel blockers are commonly used as first line agents because of their lack of adverse effects on the kidney, while other antihypertensive drug classes are under-utilised due to fear of the possible haemodynamic consequences on renal function. This review summarizes the existing data on the pathophysiology, diagnosis, prognostic significance and management of hypertension in kidney transplantation.

PREVALENCE, AWARENESS AND CONTROL OF HYPERTENSION WITH OFFICE BLOOD PRESSURE MEASUREMENTS AND AMBULATORY BLOOD PRESSURE MONITORING IN KIDNEY TRANSPLANT RECIPIENTS

Objective: The prevalence of hypertension in patients with chronic kidney disease (CKD) is estimated to 80–90% as determined by ambulatory blood pressure monitoring (ABPM), while adequate control is achieved in only 20–30% of these patients. Until now, few reliable data exist on the prevalence and blood pressure (BP) control in kidney transplant recipients, as determined by ABPM. The objective of this study is to examine these epidemiologic characteristics of hypertension in kidney transplant recipients using ABPM. Design and method: 150 kidney transplant recipients were included in this study. They underwent 24-hour ABPM with the Mobil-O-Graph NG device. Hypertension was defined as follows: (1) office BP (oBP) > or = 140/90 mmHg or use of antihypertensive agents, (2) ambulatory BP > or = 130/80 mmHg or use of antihypertensive agents. Awareness of arterial hypertension was determined according to their past medical history. Adequate control was defined as oBP <140/90 or 24-hr BP <130/80 mmHg. Results: Prevalence of hypertension was 88.0% according to office BP measurements and 93.3% according to ABPM data (p = 0,112 and kappa-statistics = 0,531, p < 0,001). Totally, 26,7% had office BP > or = 140/90 and 58,7% 24-hr BP > or = 130/80 mmHg (p < 0,001). Awareness of arterial hypertension was 88,6% irrespectively of the method (p = 0,987).83.3% of the patients were receiving antihypertensive agents. Adequate control according to office BP measurements had 69,7% of the hypertensive patients, whereas only the 37.1% of them achieved adequate control according to ABPM (p < 0,001 and kappa-statistics = 0,205, p = 0,005). In hypertensive patients, office BP > or = 140/90 mmHg was of poor predictive value in the diagnosis of 24-hour BP > or = 130/80 mmHg (AUC: 0,590, 95%CI: 0,499–0,681, sensitivity: 34,1%, specificity: 83,9%, positive predictive value: 75,0%, negative predictive value: 47,3%). Conclusions: The prevalence of arterial hypertension in kidney transplant recipients is extremely high. Office BP readings is a poor marker for assessment of BP control, as there appears to be a huge difference between office and ABPM in the rates of hypertension control.

Hypertension in Kidney Transplant Recipients: Where Are We Today?

Cardiovascular disease is the leading cause of death and allograft loss among kidney transplant recipients, and hypertension is an independent risk factor for cardiovascular morbidity of this patient population. The etiology of hypertension is multifactorial, including pre-transplant volume overload, post-transplant recipient and donor-associated variables, and transplant-specific causes (immunosuppressive medications, allograft dysfunction and surgical complications such as transplant artery stenosis). No randomized controlled trials have assessed the optimal blood pressure targets and explored the best antihypertensive regimen for kidney transplant recipients. According to the large observational studies, it is reasonable to achieve a blood pressure goal of equal to or less than 130/80 mmHg in the long-term follow-up for minimizing the cardiovascular morbidity. The selection of antihypertensive agents should be based on the patient's co-morbidities; however, the initial choice could be calcium channel blockers especially in the first few months of transplantation. In patients with cardiovascular indications of renin-angiotensin-aldosterone system inhibition, given the well-described benefits in diabetic and proteinuric patients, it is reasonable to consider the use of renin-angiotensin-aldosterone system inhibitors. There is a need for future prospective trials in the transplant population to define optimal blood pressure goals and therapies.

WHITE-COAT HYPERTENSION AND MASKED HYPERTENSION IN HYPERTENSIVE KIDNEY TRANSPLANT RECIPIENTS

Objective: Patients suffering from chronic kidney disease (CKD) have inadequate control of blood pressure (BP) ranging between 30 to 40%. In addition 35% of them have white-coat hypertension or masked hypertension. Recent epidemiologic data in the general population associate both of the aforementioned BP patterns with poor outcomes. The objective of this study is to examine the prevalence of these hypertension phenotypes in hypertensive kidney transplant recipients. Design and method: 150 kidney transplant recipients were included in this study. They underwent 24-hour ABPM with the Mobil-O-Graph NG device. Hypertension was defined as: (1) office BP (oBP) > or = 140/90 mmHg or use of antihypertensive agents, (2) ambulatory BP > or = 130/80 mmHg or use of antihypertensive agents. Patterns of BP control were defined as follows: (1) truly controlled BP (oBP < 140/90 and 24-hr BP < 130/80mmHg), (2) uncontrolled hypertension (oBP > or = 140/90 and 24-hr BP > or = 130/80mmHg), (3) white-coat hypertension (oBP > or = 140/90 and 24-hr BP < 130/80mmHg), (4) masked hypertension (oBP < 140/90 and 24-hr BP > or = 130/80mmHg). Results: The prevalence of hypertension was 88.0% according to office BP readings and 93.3% according to ABPM (p = 0,112). 125 individuals (89,3% of the total) were hypertensives receiving antihypertensive agents. Among them, according to office BP readings and 24-hr ABPM, 44 (31,0%) hypertensive patients had BP control and 30 (21,1%) had uncontrolled hypertension. Moreover, among the hypertensive patients, 10 (7,0 %) had the white-coat hypertension phenotype and 58 (40,8%) had masked hypertension (Fig 1). Conclusions: The use of ABPM in kidney transplant recipients reveals low control of BP, low prevalence of white-coat hypertension and markedly high prevalence of masked hypertension. The last finding is particularly important, considering the established association between masked hypertension and increased cardiovascular risk.

Prevalence of primary aldosteronism in hypertensive kidney transplant recipients: A cross-sectional study.

Due to high prevalence of primary aldosteronism (PA) in the general hypertensive population, and its association with worse cardiovascular and renal outcomes, the 2016 Endocrine Society Guidelines explicitly recognize PA as a major public health issue requiring urgent attention. Its prevalence in hypertensive kidney transplant recipients (KTRs) is unknown. In this cross-sectional study, we screened KTRs with hypertension who were on ≥4 antihypertensive medications, on 3 antihypertensive medications with BP≥140/90, and on potassium supplements, or were hypokalemic. 172 of 280 eligible patients successfully completed the testing. A positive screen for PA defined by an aldosterone-to-renin ratio of ≥20 and a plasma aldosterone concentration of >15ng/dL yielded a prevalence of 15.7%. Potassium supplement requirement (52% vs 27%, P=.01) and hypokalemia (25.9% vs 4.8%, P<.01) were more common in patients who screened positive compared with those who screened negative. 67% of patients who screened positive were on potassium supplements and/or were hypokalemic. Our study is the first to systematically explore the prevalence of PA among the hypertensive KTR population, which has inherently high cardiovascular risk. Further studies are needed to determine the cardiovascular and renal risk attributable to PA, and define optimal therapy for KTRs with PA.

P0947DIETARY HABITS, BODY COMPOSITION AND MUSCULAR STRENGTH ARE CORRELATED TO COGNITIVE IMPAIRMENT IN DALMATIAN HYPERTENSIVE KIDNEY TRANSPLANT RECIPIENTS (KTRS)

Abstract Background and Aims Cognitive impairment is correlated with increased mortality of chronic kidney disease patients and hypertension is a well known comorbidity. While transplantation offers various general health and cognitive function improvement over dialysis, kidney transplant recipients (KTRs) still show greater cognitive impairment than healthy control. Researched pathophysiological mechanisms in KTR population include infection and immunosuppressive induced neurotoxicity. The aim of this study was to determine what impact do body composition, dietary habits and muscular strength have on cognitive impairment of hypertensive KTRs. Method 48 (52.17 %) men and 44 (47.83%) women, aged 59.7 (range25-83) years were included. For each patient data about duration after Ktx, duration of dialysis before Ktx, age, gender, body weight and height were collected and BMI and waist-to-height ratio (WHtR) were calculated. Tanita MC780 Multi Frequency segmental body composition analyser was used to measure content of body fat, muscle mass, and visceral fat each study subject measured in kilograms (kg) and percentage (%.) Peripheral muscle strength of KtR was measured by using a standardized handgrip dynamometry protocol. The Mini Mental State Exam (MMSE) was used as an indicator of cognitive impairment. Mediterranean Diet Serving Score (MDSS) questionnaire was used to determine adherence to Mediterranean Diet (MeDi) considering the consumption of foods and food groups per meal, day or week. Results Out of 92 KTR patients with hypertension, 5 of them scored ≤ 24 points on MMSE scale implying serious cognitive dysfunction. Mean score of MMSE was 28.2, (range 22-30) Regarding MDSS score, 11 patients scored ≥ 16 meaning highest adherence, while 67 KTRs scored &amp;lt; 16 meaning low adherence to MeDi, (results range 2-18) . Positive correlations were found between MMSE score (higher score meaning better cognitive functioning) and MDSS score ( higher score implying better adherence to MeDi)( R=0,282, p=0,012), consuming 1-2 portions of fruits( R=0,266,p=0,016) or ≥ 2 portions of vegetables ( R=0,241,p=0,03) per main meal, skeletal muscle mass (%) (R=0,278, p=0,008), peripheral muscular strength( R=0,325,p=0,003) and fat free mass (kg)(R=0,212,p=0,045). On the other hand we found statistically significant negative correlation between MMSE score and WHtR ( R=-0,255, p= 0,023) . as well as PWV(R=-0,244, p=0,022). Conclusion Cognitive impairment correlations in this study are similar to ones in general population specially regarding Mediterrranean diet and muscle mass . Possible explanation of positive MeDi impact on cognitive function in KTRs could be its low phosphate intake which prevents vascular calcification and negative effects of hyperparatiroidism. Although benefits of MeDi in CKD patients can be argued due to high pottasium levels, after kidney Tx it should not be an obstacle anymore. These results suggest that lifestyle interventions such as following MeDi, building more muscle and reducing fat could provide hypertensive KTR patients with longer preservation of cognitive function.

"Smartphone Medication Adherence Saves Kidneys" for Kidney Transplantation Recipients: Protocol for a Randomized Controlled Trial.

BackgroundKidney transplant recipients’ poor medication adherence and poor control of comorbidities, particularly hypertension, are risk factors for graft rejection, graft loss, and death. Few randomized controlled trials (RCTs) have been successful in improving sustained medication adherence and blood pressure control among kidney transplantation recipients. We provide rationale for an RCT evaluating a mobile health medical self-management system for kidney transplantation recipients called Smartphone Medication Adherence Saves Kidneys (SMASK).ObjectiveOur objective is to determine whether SMASK is efficacious in improving medication adherence and sustaining blood pressure control among kidney transplantation recipients with uncontrolled hypertension and poor medication adherence compared to an enhanced standard care.MethodsThis two-arm, 6-month, phase II single-site efficacy RCT will involve 80 kidney transplantation recipients. Participants will be randomly assigned to the SMASK intervention arm or control arm. SMASK includes multilevel components: automated reminders from an electronic medication tray; tailored text messages and motivational feedback, guided by the self-determination theory; and automated summary reports for providers. Evaluations will be conducted preintervention, at 3 and 6 months, and posttrial at 12 months. Specific aims are to test the hypotheses that compared to standard care, the SMASK cohort will demonstrate significantly improved changes at 3, 6, and 12 months in the primary outcome variables medication adherence (proportion with electronic monitor-derived score >0.90) and blood pressure control (proportion meeting and sustaining adherence to the Kidney Disease Improving Global Outcomes [KDIGO] guidelines for blood pressure control); the secondary outcome variables provider adherence to KDIGO guidelines, measured by timing of medication changes and changes in self-determination theory constructs; and the exploratory outcome variables estimated glomerular filtration rate, variability in calcineurin inhibitor trough levels, and proportion of patients meeting and sustaining the 24-hour ambulatory blood pressure below 130/80 mm Hg. After the 6-month evaluation, interviews with a random sample of SMASK subjects (n=20) and health care providers (n=3-5) will assess user reactions including acceptability, usability, and aids/barriers to sustainability. Data from the RCT and interviews will be triangulated to further refine and optimize SMASK and prepare for a multisite effectiveness RCT.ResultsThe SMASK project received funding from National Institute of Diabetes and Digestive and Kidney Diseases in June 2016, obtained institutional review board approval in April 2016, and began data collection in July 2016. As of July 2018, we completed enrollment with a total of 80 participants.ConclusionsThis study will provide data regarding the efficacy of SMASK to improve medication adherence and blood pressure control in a cohort of hypertensive kidney transplant recipients. An efficacious SMASK intervention will pave the way for a larger, multicenter, effectiveness RCT powered sufficiently to evaluate clinical events in a real-world setting and with the potential to demonstrate improved outcomes at lower cost than standard care.International Registered Report Identifier (IRRID)DERR1-10.2196/13351

Hypertension in kidney transplantation is associated with an early renal nerve sprouting.

Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation.

NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity.

Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics. Our results show that in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus (n = 23), the abundance of both tNCC and pNCC in uEVs is 4–5 fold higher than in CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC prior to treatment with thiazides predicted the blood pressure response to thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and these increases correlate with the blood pressure response to thiazides. This implies that assessment of NCC in uEVs could represent an alternate method to guide anti-hypertensive therapy in kidney transplant recipients.

Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial

Chlorthalidone is a very effective antihypertensive drug, but it has not been studied prospectively in kidney transplant recipients with hypertension. Recent data indicate that calcineurin inhibitors activate the thiazide-sensitive sodium chloride cotransporter, providing further rationale to test thiazides in this population. Randomized noninferiority crossover trial (noninferiority margin,-2.8mmHg). Hypertensive kidney transplant recipients using tacrolimus (median duration, 2.4 years after transplantation; mean estimated glomerular filtration rate, 63±27 [SD] mL/min/1.73m2; mean systolic blood pressure [SBP], 151±12mmHg). Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) for 8 weeks (separated by 2-week washout). Average daytime (9 am to 9 pm) ambulatory SBP. Blood pressure and laboratory parameters. 88 patients underwent ambulatory blood pressure monitoring, of whom 49 (56%) with average daytime SBP>140mmHg were enrolled. 41 patients completed the study. Amlodipine and chlorthalidone both reduced ambulatory SBP after 8 weeks (mean changes of 150±12 to 137±12 [SD] vs 151±12 to 141±13mmHg; effect size,-4.2 [95% CI,-7.3 to 1.1] mmHg). Despite these similar blood pressure responses, chlorthalidone reduced proteinuria by 30% (effect size,-65 [95% CI,-108 to-35] mg/g) and also reduced physician-assessed peripheral edema (22% to 10%; P<0.05 for both). In contrast, chlorthalidone temporarily reduced kidney function and increased both serum uric acid and glycated hemoglobin levels. Open-label design, short follow-up, per-protocol analysis. Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. Cross-sectional and longitudinal national data from living KTRs a parts per thousand currency sign30 years of age (a parts per thousand yen1-year post-transplant, eGFR > 20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (a parts per thousand yen18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.

Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney Transplant Recipients.

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age-matched patients with chronic kidney disease without history of cardiovascular events. Twenty-four-hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.

24hr Ambulatory Blood Pressure Monitoring (ABPM) Risk Stratifies Hypertensive Kidney Transplant Recipients (KTRs).

Background and Methods: Systolic hypertension has been shown to be associated with adverse clinical outcomes after renal transplantation. In non-transplant patients, 24hr ambulatory blood pressure monitoring (ABPM) has been shown to be a superior predictor of clinical outcomes when compared to clinical blood pressure readings alone. In this study we have prospectively analysed129 kidney transplant recipients (KTR) diagnosed with hypertension based on the clinic blood pressure (CBP) of >130/80mm Hg. All these patients underwent ABPM and groups were stratified based on ABPM systolic (>/<130mm Hg) and diastolic blood pressure (</>80mm Hg) values (SBP & DBP). The primary outcome measure was a composite of graft loss, cardiovascular event or death over a 5year follow-up. Results: Of the 129 KTRs, only 64 had average 24hr SBP>130 mm Hg on ABPM. Overall, CBP significantly overestimated SBP even in the true hypertensive KTRs based on ABPM (CBP, 164± 16 mm Hg, ABPM, 143± 9 mm Hg, P<0.0001). Based on the ABPM readings, 33% of hypertensive KTRs required an increase in their anti-hypertensive therapy (P=0.01). Day time (P=0.002) and 24hr average SBP (P<0.001) were strongly associated with the composite end point in a univariate Kaplan Meier analysis. Whilst the 24hr average DBP (P=0.03) was significantly associated with poor event free survival, nocturnal dipper status was not significant. The influence of 24hr average SBP on event free survival was more significant in KTRs with diabetes (P=0.02), lower eGFR (P=0.001), proteinuria (P=0.007), who are younger (P=0.02) and female (P=0.01). Similar non-significant trends were seen with DBP as well. Despite a significant improvement in CBP in both the groups over 5 years, eGFR and proteinuria remained significantly worse in the true hypertensive group based on the assessment of ABPM during this period.Figure: No Caption available.Conclusions: To conclude, 24hr ABPM helps to risk stratify apparent hypertensive KTRs based on CBP. True hypertensives based on ABPM represent a significantly high risk population with adverse medium term outcomes despite appropriate therapy.