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Lee K, Kim BS, Jeon J, Shin DW, Lee JE, Huh W, Han KD, Jang HR. Resolution of hypertension after kidney transplantation is associated with improved kidney transplant outcomes: a nationwide cohort study. J Hypertens 2025; 43:529-537. [PMID: 39791265 DOI: 10.1097/hjh.0000000000003938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 11/13/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVES Patients with advanced chronic kidney disease suffer from hypertension, and kidney transplantation (KT) has potential to induce hypertension resolution. We hypothesized that hypertension resolution after KT is associated with better KT outcomes. METHODS We identified KT recipients (2006-2015) who had pretransplant hypertension. They were categorized into two groups based on their hypertension status after KT: persistent vs. resolved hypertension, using data from the Korea National Health Insurance System. Cox proportional hazard analyses were performed to assess the risk of graft failure and mortality, adjusting for various clinical factors. RESULTS Among 11 317 KT recipients with pretransplant hypertension, 7269 (64%) remained hypertensive, while 4048 (36%) experienced hypertension resolution. Recipients with resolved hypertension exhibited a lower prevalence of delayed graft function and major comorbidities, including diabetes, ischemic heart disease, and stroke. Graft failure and mortality rates were significantly lower in resolved hypertension group. After adjusting for multiple covariates, hazard ratios of resolved hypertension were 0.61 (95% confidence interval 0.52-0.72) for graft failure and 0.68 (0.56-0.81) for all-cause mortality. CONCLUSIONS A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft and overall survival. The post-KT hypertension resolution can be used as a prognostic indicator for predicting better KT outcomes.
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Affiliation(s)
- Kyungho Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Bong-Sung Kim
- Department of Statistics and Actuarial Science, Soongsil University
| | - Junseok Jeon
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Dong Wook Shin
- Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jung Eun Lee
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Wooseong Huh
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Kyung-Do Han
- Department of Statistics and Actuarial Science, Soongsil University
| | - Hye Ryoun Jang
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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Ould Rabah M, Morin L, Dali-Youcef N, Géri G, Mazloum M, Garcelon N, Husson J, Touam M, Moulin B, Caillard S, Legendre C, Anglicheau D, Prié D, Bienaimé F. Extracellular Fluid Volume and Mortality after Kidney Transplantation. KIDNEY360 2024; 5:1902-1912. [PMID: 39382974 DOI: 10.34067/kid.0000000587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 09/17/2024] [Indexed: 10/11/2024]
Abstract
Key Points
Post-transplantation extracellular fluid volume (ECV) is not only influenced by recipient characteristics and allograft function, but also by transplantation-specific factors.In multivariable cause-specific Cox analyses, increased ECV 3 months after kidney transplantation is independently associated with all-cause mortality but not graft loss.Multivariable linear regression further identified increased 3-month ECV as an independent predictor of reduced GFR measurement at 12 months.
Background
High extracellular fluid volume (ECV) is associated with an increased risk of death in nontransplanted patients with CKD. By contrast, both the determinants and the prognosis value of ECV in kidney transplant recipients remain unclear.
Methods
We studied a bicentric prospective cohort of 2057 kidney transplant recipients who underwent GFR measurement (mGFR) 3 months after transplantation. We calculated ECV from iohexol plasma disappearance curve and analyzed its association with patient's characteristics and outcomes.
Results
The mean ECV and mGFR were 14.6±2.6 L/1.73 m2 and 52±16 ml/min per 1.73 m2, respectively. Multiple linear regression identified male sex, older donor and recipient ages, deceased donor, nonpreemptive transplantation, diabetes, cardiac arrhythmia, heart failure, proteinuria, and higher mGFR as independent factors associated with increased ECV. In multivariable cause-specific Cox analyzes, higher tertiles of ECV were associated with increased mortality (tertile 1 as reference; hazard ratio [95% confidence interval] for tertile 2: 1.65 [1.11 to 2.47]; tertile 3: 1.80 [1.18 to 2.74]) but not graft loss. Increased ECV, 3 months after transplantation, was a predictor of reduced mGFR at 12 months after adjusting for 3-month mGFR and other confounding factors (β coefficient: −0.06; 95% confidence interval [−0.09 to −0.02]).
Conclusions
An elevated ECV 3 months after kidney transplantation is independently associated with increased mortality and decreased mGFR at 12 months, but not with graft loss.
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Affiliation(s)
- Melissa Ould Rabah
- Department of Physiology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
- Faculté de Médecine Necker, Université de Paris-Cité, Paris, France
| | - Lise Morin
- Department of Nephrology and Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Nassim Dali-Youcef
- Department of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg, France
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104/INSERM U1258, Université de Strasbourg, Strasbourg, France
| | - Guillaume Géri
- INSERM UMR1018, Université de Paris-Saclay, Boulogne-Billancourt, France
| | - Manal Mazloum
- Faculté de Médecine Necker, INSERM U1151, Université de Paris, Paris, France
| | - Nicolas Garcelon
- Imagine Institute, Data Science Platform, INSERM UMR 1163, Université de Paris, Paris, France
| | - Julien Husson
- Imagine Institute, Data Science Platform, INSERM UMR 1163, Université de Paris, Paris, France
| | - Malik Touam
- Department of Nephrology and Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Bruno Moulin
- Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
- INSERM UMR1109, Université de Strasbourg, Strasbourg, France
| | - Sophie Caillard
- Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
- INSERM UMR1109, Université de Strasbourg, Strasbourg, France
| | - Christophe Legendre
- Department of Nephrology and Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
- Faculté de Médecine Necker, INSERM U1151, Université de Paris, Paris, France
| | - Dany Anglicheau
- Department of Nephrology and Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
- Faculté de Médecine Necker, INSERM U1151, Université de Paris, Paris, France
| | - Dominique Prié
- Department of Physiology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
- Faculté de Médecine Necker, INSERM U1151, Université de Paris, Paris, France
| | - Frank Bienaimé
- Department of Physiology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
- Faculté de Médecine Necker, INSERM U1151, Université de Paris, Paris, France
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3
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Afsar B, Afsar RE, Caliskan Y, Lentine KL. Brain natriuretic peptide and N-terminal pro b-type natriuretic peptide in kidney transplantation: More than just cardiac markers. Transplant Rev (Orlando) 2024; 38:100869. [PMID: 38909518 DOI: 10.1016/j.trre.2024.100869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/15/2024] [Accepted: 06/16/2024] [Indexed: 06/25/2024]
Abstract
Although kidney transplantation (KT) is the best treatment option for most patients with end-stage kidney disease (ESKD) due to reduced mortality, morbidity and increased quality of life, long- term complications such as chronic kidney allograft dysfunction (CKAD) and increased cardiovascular disease burden are still major challenges. Thus, routine screening of KT recipients (KTRs) is very important to identify and quantify risks and guide preventative measures. However, no screening parameter has perfect sensitivity and specificity, and there is unmet need for new markers. In this review, we evaluate brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) as promising markers for risk stratification in the kidney transplant recipients (KTRs). The usefulness of these markers are already proven in heart failure, hypertension, coronary artery disease. In the context of KT, evidence is emerging. BNP and NT-proBNP has shown to be associated with kidney function, graft failure, echocardiographic parameters, major cardiovascular events and mortality but the underlying mechanisms are not known. Although BNP and NT-proBNP interact with immune system, renin angiotensin system and sympathetic system; it is not known whether these interactions are responsible for the clinical findings observed in KTRs. Future studies are needed whether these biomarkers show clinical efficacy, especially with regard to hard outcomes such as major adverse cardiovascular events and graft dysfunction and whether routine implementation of these markers are cost effective in KTRs.
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Affiliation(s)
- Baris Afsar
- Suleyman Demirel University, School of Medicine, Department of Nephrology, Turkey; Saint Louis University Transplant Center, SSM Health Saint Louis University Hospital, St. Louis, MO, USA.
| | - Rengin Elsurer Afsar
- Suleyman Demirel University, School of Medicine, Department of Nephrology, Turkey; Saint Louis University Transplant Center, SSM Health Saint Louis University Hospital, St. Louis, MO, USA
| | - Yasar Caliskan
- Saint Louis University Transplant Center, SSM Health Saint Louis University Hospital, St. Louis, MO, USA
| | - Krista L Lentine
- Saint Louis University Transplant Center, SSM Health Saint Louis University Hospital, St. Louis, MO, USA
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Kim HJ, Kim KW, Joo YS, Ryu J, Jung HY, Jeong KH, Kim MG, Ju MK, Han S, Lee JS, Kang KP, Ro H, Lee KW, Huh KH, Kim MS, Kim BS, Yang J. Impact of Blood Pressure on Allograft Function and Survival in Kidney Transplant Recipients. Transpl Int 2024; 37:12574. [PMID: 39170864 PMCID: PMC11336573 DOI: 10.3389/ti.2024.12574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 07/22/2024] [Indexed: 08/23/2024]
Abstract
The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.
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Affiliation(s)
- Hyo Jeong Kim
- Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea
| | - Kyung Won Kim
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young Su Joo
- Department of Internal Medicine, College of Medicine, Yongin Severance Hospital, Yonsei University, Yongin, Republic of Korea
| | - Junghwa Ryu
- Department of Internal Medicine, Seoul Hospital, Ewha Womans University, Seoul, Republic of Korea
| | - Hee-Yeon Jung
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Kyung Hwan Jeong
- Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Myung-Gyu Kim
- Department of Internal Medicine, College of Medicine, Anam Hospital, Korea University, Seoul, Republic of Korea
| | - Man Ki Ju
- Department of Surgery, College of Medicine, Gangnam Severance Hospital, Yonsei University, Seoul, Republic of Korea
| | - Seungyeup Han
- Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea
| | - Jong Soo Lee
- Department of Internal Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Kyung Pyo Kang
- Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Han Ro
- Department of Internal Medicine, Gil Hospital, Gachon University, Incheon, Republic of Korea
| | - Kyo Won Lee
- Department of Surgery, Seoul Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, College of Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, College of Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea
| | - Beom Seok Kim
- Department of Internal Medicine, College of Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, College of Medicine, Severance Hospital, Yonsei University, Seoul, Republic of Korea
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5
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Afsar B, Afsar RE, Caliskan Y, Lentine KL. A holistic review of sodium intake in kidney transplant patients: More questions than answers. Transplant Rev (Orlando) 2024; 38:100859. [PMID: 38749098 DOI: 10.1016/j.trre.2024.100859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 06/16/2024]
Abstract
Kidney transplantation (KT) is the best treatment option for end-stage kidney disease (ESKD). Acute rejection rates have decreased drastically in recent years but chronic kidney allograft disease (CKAD) is still an important cause of allograft failure and return to dialysis. Thus, there is unmet need to identify and reverse the cause of CKAD. Additionally, cardiovascular events after KT are still leading causes of morbidity and mortality. One overlooked potential contributor to CKAD and adverse cardiovascular events is increased sodium/salt intake in kidney transplant recipients (KTRs). In general population, the adverse effects of high sodium intake are well known but in KTRs, there is a paucity of evidence despite decades of experience with KT. Limited research showed that sodium intake is high in most KTRs. Moreover, excess sodium intake is associated with elevated blood pressure and albuminuria in some studies involving KTRs. There is also experimental evidence suggesting that increased sodium intake is associated with histologic graft damage. Critical knowledge gaps still remain, including the exact amount of sodium restriction needed in KTRs to optimize outcomes and allograft survival. Additionally, best methods to measure sodium intake and practices to follow-up are not clarified in KTRs. To meet these deficits, prospective long term studies are warranted in KTRs. Moreover, preventive measures must be determined and implemented both at individual and societal levels to achieve sodium restriction in KTRs.
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Affiliation(s)
- Baris Afsar
- Suleyman Demirel University, School of Medicine, Department of Nephrology, 32260, Cunur, Isparta, Türkiye; Saint Louis University, School of Medicine, Division of Nephrology, St. Louis, MO, USA.
| | - Rengin Elsurer Afsar
- Suleyman Demirel University, School of Medicine, Department of Nephrology, 32260, Cunur, Isparta, Türkiye; Saint Louis University, School of Medicine, Division of Nephrology, St. Louis, MO, USA
| | - Yasar Caliskan
- Saint Louis University, School of Medicine, Division of Nephrology, St. Louis, MO, USA
| | - Krista L Lentine
- Saint Louis University, School of Medicine, Division of Nephrology, St. Louis, MO, USA
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Hinrichs GR, Nielsen JR, Birn H, Bistrup C, Jensen BL. Amiloride evokes significant natriuresis and weight loss in kidney transplant recipients with and without albuminuria. Am J Physiol Renal Physiol 2023; 325:F426-F435. [PMID: 37560772 DOI: 10.1152/ajprenal.00108.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 07/14/2023] [Accepted: 08/03/2023] [Indexed: 08/11/2023] Open
Abstract
Albuminuria in kidney transplant recipients (KTRs) is associated with hypertension and aberrant glomerular filtration of serine proteases that may proteolytically activate the epithelial Na+ channel (ENaC). The present nonrandomized, pharmacodynamic intervention study aimed to investigate if inhibition of ENaC increases Na+ excretion and reduces extracellular volume in KTRs dependent on the presence of albuminuria. KTRs with and without albuminuria (albumin-to-creatinine ratio > 300 mg/g, n = 7, and <30 mg/g, n = 7, respectively) were included and ingested a diet with fixed Na+ content (150 mmol/day) for 5 days. On the last day, amiloride at 10 mg was administered twice. Body weight, 24-h urine electrolyte excretion, body water content, and ambulatory blood pressure as well as plasma renin, angiotensin II, and aldosterone concentrations were determined before and after amiloride. Amiloride led to a significant decrease in body weight, increase in 24-h urinary Na+ excretion, and decrease in 24-h urinary K+ excretion in both groups. Urine output increased in the nonalbuminuric group only. There was no change in plasma renin, aldosterone, and angiotensin II concentrations after amiloride, whereas a significant decrease in nocturnal systolic blood pressure and increase in 24-h urine aldosterone excretion was observed in albuminuric KTRs only. There was a significant correlation between 24-h urinary albumin excretion and amiloride-induced 24-h urinary Na+ excretion. In conclusion, ENaC activity contributes to Na+ and water retention in KTRs with and without albuminuria. ENaC is a relevant pharmacological target in KTRs; however, larger and long-term studies are needed to evaluate whether the magnitude of this effect depends on the presence of albuminuria.NEW & NOTEWORTHY Amiloride has a significant natriuretic effect in kidney transplant recipients (KTRs) that relates to urinary albumin excretion. The epithelial Na+ channel may be a relevant direct pharmacological target to counter Na+ retention and hypertension in KTRs. Epithelial Na+ channel blockers should be further investigated as a mean to mitigate Na+ and water retention and to potentially obtain optimal blood pressure control in KTRs.
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Affiliation(s)
- Gitte Rye Hinrichs
- Department of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
- Department of Nephrology, Odense University Hospital, Odense, Denmark
- Department of Nephrology, University Hospital of Southern Denmark, Esbjerg, Denmark
| | | | - Henrik Birn
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Claus Bistrup
- Department of Nephrology, Odense University Hospital, Odense, Denmark
- Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Boye Lagerbon Jensen
- Department of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark
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Perioperative fluid management and associated complications in children receiving kidney transplants in the UK. Pediatr Nephrol 2023; 38:1299-1307. [PMID: 35972538 PMCID: PMC9925477 DOI: 10.1007/s00467-022-05690-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. METHODS Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. RESULTS Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. CONCLUSIONS This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Alexandrou ME, Ferro CJ, Boletis I, Papagianni A, Sarafidis P. Hypertension in kidney transplant recipients. World J Transplant 2022; 12:211-222. [PMID: 36159073 PMCID: PMC9453294 DOI: 10.5500/wjt.v12.i8.211] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/07/2022] [Accepted: 08/06/2022] [Indexed: 02/05/2023] Open
Abstract
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.
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Affiliation(s)
- Maria-Eleni Alexandrou
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Charles J Ferro
- Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2WB, United Kingdom
| | - Ioannis Boletis
- Department of Nephrology, Laiko General Hospital, National and Kapodistrian University, Athens 11527, Greece
| | - Aikaterini Papagianni
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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9
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Nassar M, Nso N, Lakhdar S, Kondaveeti R, Buttar C, Bhangoo H, Awad M, Sheikh NS, Soliman KM, Munira MS, Radparvar F, Rizzo V, Daoud A. New onset hypertension after transplantation. World J Transplant 2022; 12:42-54. [PMID: 35433331 PMCID: PMC8968475 DOI: 10.5500/wjt.v12.i3.42] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/14/2021] [Accepted: 02/19/2022] [Indexed: 02/06/2023] Open
Abstract
It has been reported that up to 90% of organ transplant recipients have suboptimal blood pressure control. Uncontrolled hypertension is a well-known culprit of cardiovascular and overall morbidity and mortality. In addition, rigorous control of hypertension after organ transplantation is a crucial factor in prolonging graft survival. Nevertheless, hypertension after organ transplantation encompasses a broader range of causes than those identified in non-organ transplant patients. Hence, specific management awareness of those factors is mandated. An in-depth understanding of hypertension after organ transplantation remains a debatable issue that necessitates further clarification. This article provides a comprehensive review of the prevalence, risk factors, etiology, complications, prevention, and management of hypertension after organ transplantation.
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Affiliation(s)
- Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Sofia Lakhdar
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Ravali Kondaveeti
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Chandan Buttar
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Harangad Bhangoo
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Mahmoud Awad
- Department of Medicine, The Memorial Souad Kafafi University Hospital, 6th of October - Giza 0000, Egypt
| | - Naveen Siddique Sheikh
- Department of Physiology, CMH Lahore Medical College and Institute of Dentistry, Lahore - Punjab 0000, Pakistan
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Most Sirajum Munira
- Division of Cardiology, Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Farshid Radparvar
- Division of Cardiology, Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Vincent Rizzo
- Department of Medicine, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Queens), New York, NY 11432, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11211, Egypt
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Keller N, Monnier A, Caillard S, Cognard N, Geny B, Moulin B, Talha S. High-flow arteriovenous fistula and hemodynamic consequences at 1 year after kidney transplantation. Semin Dial 2021; 35:171-180. [PMID: 34726295 DOI: 10.1111/sdi.13028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 08/18/2021] [Accepted: 09/24/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION There are only scarce data regarding the cardiovascular impact of arteriovenous fistula after kidney transplantation depending on fistula flow. METHODS We performed a single-center, prospective, cohort study including 49 patients with a functional fistula at 1 year from kidney transplantation. Patients were convened for a clinical work-up, a biological analysis, a fistula's Doppler ultrasonography and an echocardiography. Main judgment criterion was comparison of echocardiography parameters between patients with relative (fistula flow >1 L/min and a fistula flow/cardiac output ratio >20%), absolute high-flow fistula (fistula flow >2 L/min) and normal-flow fistula. RESULTS High-flow fistula frequency was 69%. Significantly higher left ventricular end-diastolic and systolic diameters were observed in this group compared with the normal-flow fistula group (53 ± 6 vs. 48 ± 7 mm; p = 0.04 and 33 ± 6 vs. 28 ± 8 mm; p = 0.02) and between the absolute and relative high-flow fistula subgroups (56 ± 6 vs. 51 ± 6 mm; p = 0.009 and 35 ± 6 vs. 31 ± 5 mm; p = 0.01). The study showed no other significant differences. CONCLUSIONS This study showed a significantly higher but not pathological left ventricular end-diastolic and systolic diameters values in patients with high-flow fistula compared with patients with normal-flow fistula and between patients with respectively absolute and relative high-flow fistula.
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Affiliation(s)
- Nicolas Keller
- Department of Nephrology and Transplantation, Nouvel Hôpital Civil, Strasbourg, France
| | - Alexandra Monnier
- Medical Intensive Care Unit, Nouvel Hôpital Civil, Strasbourg, France
| | - Sophie Caillard
- Department of Nephrology and Transplantation, Nouvel Hôpital Civil, Strasbourg, France
| | - Noëlle Cognard
- Department of Nephrology and Transplantation, Nouvel Hôpital Civil, Strasbourg, France
| | - Bernard Geny
- Department of Physiology and Functional Explorations, Nouvel Hôpital Civil, Strasbourg, France
| | - Bruno Moulin
- Department of Nephrology and Transplantation, Nouvel Hôpital Civil, Strasbourg, France
| | - Samy Talha
- Department of Physiology and Functional Explorations, Nouvel Hôpital Civil, Strasbourg, France
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11
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Loutradis C, Sarafidis P, Marinaki S, Berry M, Borrows R, Sharif A, Ferro CJ. Role of hypertension in kidney transplant recipients. J Hum Hypertens 2021; 35:958-969. [PMID: 33947943 DOI: 10.1038/s41371-021-00540-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/24/2021] [Accepted: 04/09/2021] [Indexed: 02/03/2023]
Abstract
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.
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Affiliation(s)
- Charalampos Loutradis
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK.,Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Smaragdi Marinaki
- Department of Nephrology, Laiko General Hospital, National and Kapodistrian University, Athens, Greece
| | - Miriam Berry
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK
| | - Richard Borrows
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK
| | - Adnan Sharif
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK
| | - Charles J Ferro
- Department of Renal Medicine, University Hospitals Birmingham, Birmingham, UK. .,Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
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12
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Zoccali C, Roumeliotis S, Mallamaci F. Sleep Apnea as a Cardiorenal Risk Factor in CKD and Renal Transplant Patients. Blood Purif 2021; 50:642-648. [PMID: 33588408 DOI: 10.1159/000513424] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/27/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a public health priority of increasing concern worldwide. Sleep apnea (SA) of moderate-to-severe degree has a 3-9% prevalence in women and 10-17% in men in the general population. SUMMARY In CKD patients, the prevalence of SA parallels the decline of the GFR being 27% in CKD patients with a GFR of >60 mL/min/1.73 m2 and 57% in patients with end-stage kidney disease (ESKD). In the early CKD stages, fluid overload is probably the sole risk factor for SA in this population. At more severe CKD stages, disturbed central and peripheral chemosensitivity and the accumulation of uremic toxins might contribute to SA. Still, there is no direct evidence supporting this hypothesis in human studies. Observational studies coherently show that SA is a risk factor for CKD incidence and CKD progression as well as for cardiovascular disease and death in this population. However, there is no randomized clinical trial testing continuous positive airway pressure or other interventions documenting that attenuation of SA may have a favorable effect on renal and cardiovascular outcomes in CKD and ESKD patients. However, most likely, the causal nature of the association between SA and cardiorenal outcomes remains unproven. Renal transplantation is the most effective treatment of SA in patients with ESKD, but this disturbance re-emerges on long-term observation in this population. However, after renal transplantation, SA does not seem to be a predictor of adverse health outcomes.
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Affiliation(s)
- Carmine Zoccali
- CNR-IFC, Clinical Epidemiology of Renal Disease and Hypertension, Reggio Cal, Italy,
| | - Stefanos Roumeliotis
- Division of Nephrology and Hypertension, 1st Department of Internal Medicine, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Francesca Mallamaci
- CNR-IFC, Clinical Epidemiology of Renal Disease and Hypertension, Reggio Cal, Italy.,Nephrology, Dialysis and Renal Transplantation Unit, Grande Ospedale Metropolitano di Reggio Cal, Reggio Cal, Italy
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13
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Tantisattamo E, Molnar MZ, Ho BT, Reddy UG, Dafoe DC, Ichii H, Ferrey AJ, Hanna RM, Kalantar-Zadeh K, Amin A. Approach and Management of Hypertension After Kidney Transplantation. Front Med (Lausanne) 2020; 7:229. [PMID: 32613001 PMCID: PMC7310511 DOI: 10.3389/fmed.2020.00229] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 05/04/2020] [Indexed: 12/14/2022] Open
Abstract
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation. It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients. Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation. Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation. Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation. During late post-transplant period, chronic renal allograft dysfunction becomes an additional cause of hypertension. As these patients develop more substantial chronic kidney disease affecting their allografts, fibroblast growth factor 23 (FGF23) increases and is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients. The exact relationship between increased FGF23 and post-transplant hypertension remains poorly understood. Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment and should be individualized. Until strong evidence in the kidney transplant population exists, a BP of <130/80 mmHg is a reasonable target. Similar to complete renal denervation in non-transplant patients, bilateral native nephrectomy is another treatment option for resistant post-transplant hypertension. Native renal denervation offers promising outcomes for controlling resistant hypertension with no significant procedure-related complications. This review addresses the epidemiology, pathogenesis, and specific etiologies of post-transplant hypertension including TRAS, calcineurin inhibitor effects, OSA, and failed native kidney. The cardiovascular and survival outcomes related to post-transplant hypertension and the utility of 24-h blood pressure monitoring will be briefly discussed. Antihypertensive medications and their mechanism of actions relevant to kidney transplantation will be highlighted. A summary of guidelines from different professional societies for BP targets and antihypertensive medications as well as non-pharmacological interventions, including bilateral native nephrectomy and native renal denervation, will be reviewed.
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Affiliation(s)
- Ekamol Tantisattamo
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States.,Section of Nephrology, Department of Internal Medicine, Multi-Organ Transplant Center, William Beaumont Hospital, Oakland University William Beaumont School of Medicine, Royal Oak, MI, United States
| | - Miklos Z Molnar
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, United States.,Methodist University Hospital Transplant Institute, Memphis, TN, United States.,Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Bing T Ho
- Division of Nephrology and Hypertension, Department of Medicine, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Uttam G Reddy
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Donald C Dafoe
- Division of Transplantation, Department of Surgery, University of California Irvine School of Medicine, Orange, CA, United States
| | - Hirohito Ichii
- Division of Transplantation, Department of Surgery, University of California Irvine School of Medicine, Orange, CA, United States
| | - Antoney J Ferrey
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Ramy M Hanna
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Alpesh Amin
- Department of Medicine, University of California Irvine School of Medicine, Orange, CA, United States
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14
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Mallamaci F, Tripepi R, D’Arrigo G, Porto G, Versace MC, Marino C, Sanguedolce MC, Tripepi G, Zoccali C. Long-Term Changes in Sleep Disordered Breathing in Renal Transplant Patients: Relevance of the BMI. J Clin Med 2020; 9:E1739. [PMID: 32512816 PMCID: PMC7355565 DOI: 10.3390/jcm9061739] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/28/2020] [Accepted: 06/01/2020] [Indexed: 01/06/2023] Open
Abstract
Sleep disordered breathing (SDB), as defined by the Apnea Hypopnea Index (AHI), is a highly prevalent disturbance in end stage kidney disease. SDB improves early on after renal transplantation but long-term changes in AHI in these patients have not been studied. We studied the long-term changes in AHI in a series of 221 renal transplant patients (mean age: 47 ± 12 years; 70% males) over a median follow up of 35 months. Data analysis was made by the generalized estimating equations method (GEE). On longitudinal observation, the median AHI rose from 1.8 (Interquartile range: 0.6-5.0) to 2.9 (IQR: 1.0-6.6) and to 3.6 (IQR: 1.7-10.4) at the second and third visit, respectively (p = 0.009 by the GEE model and the proportion of patients with moderate to severe SDB rose from 8% to 20%. Longitudinal changes in minimum oxygen saturation (minSaO2) mirrored those in the AHI. In adjusted analyses, repeated measurements of BMI (p < 0.009) emerged as the strongest independent longitudinal correlate of AHI and MinSaO2. The AHI worsens over time in renal transplant patients and longitudinal changes of this biomarker are directly related to simultaneous changes in BMI. Overweight/obesity, a potentially modifiable risk factor, is an important factor underlying the risk of SDB in this population.
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Affiliation(s)
- Francesca Mallamaci
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
- Department of Medicine, Division of Nephrology and Transplantation, Ospedali Riuniti, 89124 Reggio Calabria, Italy
| | - Rocco Tripepi
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Graziella D’Arrigo
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Gaetana Porto
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Maria Carmela Versace
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Carmela Marino
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Maria Cristina Sanguedolce
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Giovanni Tripepi
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
| | - Carmine Zoccali
- CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension Unit, Center of Clinical Physiology, National Research Council of Italy, Reggio Cal., c/o Ospedali Riuniti, 89124 Reggio Calabaria, Italy; (F.M.); (R.T.); (G.D.); (G.P.); (M.C.V.); (C.M.); (M.C.S.); (G.T.)
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15
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Jaroszyński A, Furmaga J, Zapolski T, Zaborowski T, Rudzki S, Dąbrowski W. The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis. BMC Nephrol 2019; 20:441. [PMID: 31791259 PMCID: PMC6889434 DOI: 10.1186/s12882-019-1624-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 11/13/2019] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs). METHODS Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT. RESULTS An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement. CONCLUSIONS RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.
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Affiliation(s)
- Andrzej Jaroszyński
- Institute of Medical Sciences, Jan Kochanowski University in Kielce, Al. IX Wieków Kielc 19A, 25-317 Kielce, Poland
- Department of Family Medicine, Medical University of Lublin, Lublin, Poland
| | - Jacek Furmaga
- Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, Lublin, Poland
| | - Tomasz Zapolski
- Department of Cardiology, Medical University of Lublin, Lublin, Poland
| | - Tomasz Zaborowski
- Department of Anesthesiology and Intensive Care, Medical University of Lublin, Lublin, Poland
| | - Sławomir Rudzki
- Department of General and Transplant Surgery and Nutritional Treatment, Medical University of Lublin, Lublin, Poland
| | - Wojciech Dąbrowski
- Department of Anesthesiology and Intensive Care, Medical University of Lublin, Lublin, Poland
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16
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Fujii H, Watanabe S, Kono K, Watanabe K, Goto S, Ishimura T, Fujisawa M, Nishi S. One-Year Impact of Kidney Transplantation on Cardiac Abnormalities and Blood Pressure in Hemodialysis Patients. Ther Apher Dial 2019; 23:529-533. [PMID: 30941871 DOI: 10.1111/1744-9987.12808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 02/25/2019] [Accepted: 04/01/2019] [Indexed: 11/29/2022]
Abstract
Cardiac abnormalities, including left ventricular hypertrophy and systolic dysfunction, are frequently observed among patients with CKD, including kidney transplant recipients; they are closely linked to cardiovascular disease and mortality. Although several studies have been performed for elucidating changes and mechanisms of cardiac abnormalities after kidney transplantation, details remain unclear. This study included 43 consecutive patients who underwent HD and received kidney transplantation between 2008 and 2012 at our institution. All subjects underwent echocardiography before and 1 year after kidney transplantation. One year after kidney transplantation, left ventricular mass index, cardiac chamber sizes, BP, and the number of antihypertensive agents were reduced. Although the percentage of patients with concentric hypertrophy did not change, the percentage of those with eccentric hypertrophy significantly decreased after kidney transplantation. Volume reduction due to the recovery of kidney function may be primarily attributed to the improvement of cardiac abnormalities, including left ventricular hypertrophy.
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Affiliation(s)
- Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shuhei Watanabe
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kentaro Watanabe
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takeshi Ishimura
- Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masato Fujisawa
- Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
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17
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Hinrichs GR, Michelsen JS, Zachar R, Friis UG, Svenningsen P, Birn H, Bistrup C, Jensen BL. Albuminuria in kidney transplant recipients is associated with increased urinary serine proteases and activation of the epithelial sodium channel. Am J Physiol Renal Physiol 2018; 315:F151-F160. [PMID: 29363322 DOI: 10.1152/ajprenal.00545.2017] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Albuminuria predicts adverse renal outcome in kidney transplant recipients. The present study addressed the hypothesis that albuminuria is associated with increased urine serine proteases with the ability to activate the epithelial sodium channel (ENaC) and with greater extracellular volume and higher blood pressure. In a cross-sectional design, kidney transplant recipients with ( n = 18) and without ( n = 19) albuminuria were included for office blood pressure measurements, estimation of volume status by bioimpedance, and collection of spot urine and plasma samples. Urine was analyzed for serine proteases and for the ability to activate ENaC current in vitro. Urine exosome protein was immunoblotted for prostasin and γ-ENaC protein. In the present study, it was found that, compared with nonalbuminuria (8.8 mg/g creatinine), albuminuric (1,722 mg/g creatinine) kidney transplant recipients had a higher systolic and diastolic blood pressure, despite receiving significantly more antihypertensives, and a greater urinary total plasminogen, active plasmin, active urokinase-type plasminogen activator, and prostasin protein abundance, which correlated significantly with u-albumin. Fluid overload correlated with systolic blood pressure, urinary albumin/creatinine, and plasminogen/creatinine. Urine from albuminuric kidney transplant recipients evoked a greater amiloride- and aprotinin-sensitive inward current in single collecting duct cells (murine cell line M1). γENaC subunits at 50 and 75 kDa showed increased abundance in urine exosomes from albuminuric kidney transplant recipients when compared with controls. These findings show that albuminuria in kidney transplant recipients is associated with hypertension, ability of urine to proteolytically activate ENaC current, and increased abundance of γENaC. ENaC activity could contribute to hypertension and adverse outcome in posttransplant proteinuria.
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Affiliation(s)
- Gitte R Hinrichs
- Department of Cardiovascular and Renal Research, University of Southern Denmark , Odense , Denmark
| | | | - Rikke Zachar
- Department of Cardiovascular and Renal Research, University of Southern Denmark , Odense , Denmark
| | - Ulla G Friis
- Department of Cardiovascular and Renal Research, University of Southern Denmark , Odense , Denmark
| | - Per Svenningsen
- Department of Cardiovascular and Renal Research, University of Southern Denmark , Odense , Denmark
| | - Henrik Birn
- Department of Biomedicine, Aarhus University , Aarhus , Denmark.,Department of Renal Medicine, Aarhus University Hospital , Aarhus , Denmark
| | - Claus Bistrup
- Odense University Hospital, Department of Nephrology , Odense , Denmark
| | - Boye L Jensen
- Department of Cardiovascular and Renal Research, University of Southern Denmark , Odense , Denmark
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18
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Fu S, Ping P, Wang F, Luo L. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. J Biol Eng 2018; 12:2. [PMID: 29344085 PMCID: PMC5766980 DOI: 10.1186/s13036-017-0093-0] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 12/21/2017] [Indexed: 12/11/2022] Open
Abstract
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.
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Affiliation(s)
- Shihui Fu
- Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, 100853 China
- Department of Cardiology and Hainan Branch, Chinese People’s Liberation Army, General Hospital, Beijing, China
| | - Ping Ping
- Department of Pharmaceutical Care, Chinese People’s, Liberation Army General Hospital, Beijing, China
| | - Fengqi Wang
- Department of Cardiology and Hainan Branch, Chinese People’s Liberation Army, General Hospital, Beijing, China
| | - Leiming Luo
- Department of Geriatric Cardiology, Chinese People’s Liberation Army General Hospital, Beijing, 100853 China
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Canet E, Zafrani L, Azoulay É. The Critically Ill Kidney Transplant Recipient: A Narrative Review. Chest 2016; 149:1546-55. [PMID: 26836919 DOI: 10.1016/j.chest.2016.01.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 12/11/2015] [Accepted: 01/03/2016] [Indexed: 12/20/2022] Open
Abstract
Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (≥ 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments.
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Affiliation(s)
- Emmanuel Canet
- Medical Intensive Care Unit Department, Saint-Louis University Hospital, Paris, France.
| | - Lara Zafrani
- Medical Intensive Care Unit Department, Saint-Louis University Hospital, Paris, France; Paris Diderot University, Sorbonne Paris Cité Paris, France
| | - Élie Azoulay
- Medical Intensive Care Unit Department, Saint-Louis University Hospital, Paris, France; Paris Diderot University, Sorbonne Paris Cité Paris, France
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Santos-Araújo C, Leite-Moreira A, Pestana M. Clinical value of natriuretic peptides in chronic kidney disease. Nefrologia 2015; 35:227-33. [PMID: 26299165 DOI: 10.1016/j.nefro.2015.03.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 03/09/2015] [Indexed: 11/26/2022] Open
Abstract
According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure.
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Affiliation(s)
- Carla Santos-Araújo
- Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Center and Nephrology and Infectious Diseases Research and Development Group, INEB (I3S) Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Adelino Leite-Moreira
- Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Center, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Manuel Pestana
- Nephrology and Infectious Diseases Research and Development Group, INEB (I3S) and Department of Renal, Urologic and Infectious Diseases, Faculty of Medicine, University of Porto, Porto, Portugal
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