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Aboghanem A, Prasad GVR. Disorders of potassium homeostasis after kidney transplantation. World J Transplant 2024; 14:95905. [PMID: 39295980 PMCID: PMC11317851 DOI: 10.5500/wjt.v14.i3.95905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/29/2024] [Accepted: 06/26/2024] [Indexed: 07/31/2024] Open
Abstract
Disturbances of potassium balance are often encountered when managing kidney transplant recipients (KTR). Both hyperkalemia and hypokalemia may present either as medical emergencies or chronic outpatient abnormalities. Despite the high incidence of hyperkalemia and its potential life-threatening implications, consensus on its management in KTR is lacking. Hypokalemia in KTR is also well-described, although it is given less attention by clinicians compared to hyperkalemia. This article discusses the etiology, pathophysiology and management of both types of potassium disorders in KTR. Once any emergent situation has been corrected, treatment approaches include correcting insulin deficiency if present, adjusting non-immunosuppressive and immunosuppressive medications, eliminating or supplementing potassium as needed, and dietary counselling. Although commonly of multifactorial etiology, ascertaining the specific cause in a particular patient will help guide successful management. Monitoring KTR through regular laboratory testing is essential to detect serious disturbances in potassium balance since patients are often asymptomatic.
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Affiliation(s)
| | - G V Ramesh Prasad
- School of Medicine, University of Toronto, Toronto M5C 2T2, Ontario, Canada
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
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Liu X, Shen J, Yan H, Hu J, Liao G, Liu D, Zhou S, Zhang J, Liao J, Guo Z, Li Y, Yang S, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Luo P, Zhao M, Liu Y. Posttransplant complications: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2024; 5:e669. [PMID: 39224537 PMCID: PMC11366828 DOI: 10.1002/mco2.669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.
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Affiliation(s)
- Xiaoyou Liu
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Junyi Shen
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hongyan Yan
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jianmin Hu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Guorong Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ding Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Song Zhou
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jie Zhang
- Department of Organ transplantationThe First Affiliated Hospital, Guangzhou Medical UniversityGuangzhouChina
| | - Jun Liao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Zefeng Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yuzhu Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Siqiang Yang
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Shichao Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Hua Chen
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ying Guo
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Min Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Lipei Fan
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Liuyang Li
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Peng Luo
- Department of OncologyZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Ming Zhao
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
| | - Yongguang Liu
- Department of Organ transplantationZhujiang HospitalSouthern Medical UniversityGuangzhouChina
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Van Laecke S. Thiazides in kidney transplant recipients: skin in the game. Nat Rev Nephrol 2024; 20:351-352. [PMID: 38632382 DOI: 10.1038/s41581-024-00839-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024]
Affiliation(s)
- Steven Van Laecke
- Renal Division, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
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Low JK, Crawford K, Lai J, Manias E. Factors associated with readmission in chronic kidney disease: Systematic review and meta-analysis. J Ren Care 2023; 49:229-242. [PMID: 35809061 DOI: 10.1111/jorc.12437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 05/14/2022] [Accepted: 06/05/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Risk factors associated with all-cause hospital readmission are poorly characterised in patients with chronic kidney disease. OBJECTIVE A systematic review and meta-analysis were conducted to identify risk factors and protectors of hospital readmission in chronic kidney disease. DESIGN, PARTICIPANTS & MEASUREMENTS Studies involving adult patients were identified from four databases from inception to 31/03/2020. Random-effects meta-analyses were conducted to determine factors associated with all-cause 30-day hospital readmission in general chronic kidney disease, in dialysis and in kidney transplant recipient groups. RESULTS Eighty relevant studies (chronic kidney disease, n = 14 studies; dialysis, n = 34 studies; and transplant, n = 32 studies) were identified. Meta-analysis revealed that in both chronic kidney disease and transplant groups, increasing age in years and days spent at the hospital during the initial stay were associated with a higher risk of 30-day readmission. Other risk factors identified included increasing body mass index (kg/m2 ) in the transplant group, and functional impairment and discharge destination in the dialysis group. Within the chronic kidney disease group, having an outpatient follow-up appointment with a nephrologist within 14 days of discharge was protective against readmission but this was not protective if provided by a primary care provider or a cardiologist. CONCLUSION Risk-reduction interventions that can be implemented include a nephrologist appointment within 14 days of hospital discharge, rehabilitation programme for functional improvement in the dialysis group and meal plans in the transplant group. Future risk analysis should focus on modifiable factors to ensure that strategies can be tested and implemented in those who are more at risk.
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Affiliation(s)
- Jac Kee Low
- School of Nursing and Midwifery, Centre for Quality and Patient Safety Research, Institute for Health Transformation, Deakin University, Melbourne, Victoria, Australia
| | - Kimberley Crawford
- Monash Nursing and Midwifery, Monash University, Clayton, Victoria, Australia
| | - Jerry Lai
- eSolution, Deakin University, Geelong, Victoria, Australia
- Intersect Australia, Sydney, New South Wales, Australia
| | - Elizabeth Manias
- School of Nursing and Midwifery, Centre for Quality and Patient Safety Research, Institute for Health Transformation, Deakin University, Melbourne, Victoria, Australia
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Cardiovascular Risk after Kidney Transplantation: Causes and Current Approaches to a Relevant Burden. J Pers Med 2022; 12:jpm12081200. [PMID: 35893294 PMCID: PMC9329988 DOI: 10.3390/jpm12081200] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/11/2022] [Accepted: 07/20/2022] [Indexed: 11/17/2022] Open
Abstract
Background. Cardiovascular disease is a frequent complication after kidney transplantation and represents the leading cause of mortality in this population. Material and Methods. We searched for the relevant articles in the National Institutes of Health library of medicine, transplant, cardiologic and nephrological journals. Results. The pathogenesis of cardiovascular disease in kidney transplant is multifactorial. Apart from non-modifiable risk factors, such as age, gender, genetic predisposition and ethnicity, several traditional and non-traditional modifiable risk factors contribute to its development. Traditional factors, such as diabetes, hypertension and dyslipidemia, may be present before and may worsen after transplantation. Immunosuppressants and impaired graft function may strongly influence the exacerbation of these comorbidities. However, in the last years, several studies showed that many other cardiovascular risk factors may be involved in kidney transplantation, including hyperuricemia, inflammation, low klotho and elevated Fibroblast Growth Factor 23 levels, deficient levels of vitamin D, vascular calcifications, anemia and poor physical activity and quality of life. Conclusions. The timely and effective treatment of time-honored and recently discovered modifiable risk factors represent the basis of the prevention of cardiovascular complications in kidney transplantation. Reduction of cardiovascular risk can improve the life expectancy, the quality of life and the allograft function and survival.
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Hartleif S, Baier H, Kumpf M, Handgretinger R, Königsrainer A, Nadalin S, Sturm E. Targeting Calcineurin Inhibitor-Induced Arterial Hypertension in Liver Transplanted Children Using Hydrochlorothiazide. J Pediatr Pharmacol Ther 2022; 27:428-435. [PMID: 35845561 PMCID: PMC9268114 DOI: 10.5863/1551-6776-27.5.428] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 09/30/2021] [Indexed: 09/16/2023]
Abstract
OBJECTIVE Arterial hypertension (AH) is the most common toxic effect of calcineurin inhibitor (CNI)-based immunosuppression in children after liver transplantation (LT). Activation of the renal sodium chloride cotransporter (NCC) by CNIs has been described as a major cause of CNI-induced AH. Thiazides, for example, hydrochlorothiazide (HCTZ), can selectively block the NCC and may ameliorate CNI-induced AH after pediatric LT. METHODS From 2005 thru 2015 we conducted a retrospective, single-center analysis of blood pressure in 2 pediatric cohorts (each n = 33) with or without HCTZ in their first year after LT. All patients received CNI-based immunosuppression. According to AAP guidelines, AH was defined as stage 1 and stage 2. Cohort 1 received an HCTZ-containing regimen to target the CNI-induced effect on the NCC, leading to AH. Cohort 2 received standard antihypertensive therapy without HCTZ. RESULTS In children who have undergone LT and been treated with CNI, AH overall was observed less frequently in cohort 1 vs cohort 2 (31% vs 44%; ns). Moreover, severe AH (stage 2) was significantly lower in cohort 1 vs 2 (1% vs 18%; p < 0.001). Multivariate analysis revealed HCTZ as the only significant factor with a protective effect on occurrence of severe stage 2 AH. While monitoring safety and tolerability, mild asymptomatic hypokalemia was the only adverse effect observed more frequently in cohort 1 vs 2 (27% vs 3%; p = 0.013). CONCLUSIONS Targeting NCC by HCTZ significantly improved control of severe CNI-induced AH and was well tolerated in children who underwent LT. This effect may reduce the risk of long-term end-organ damage and improve quality of life.
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Affiliation(s)
- Steffen Hartleif
- Pediatric Gastroenterology and Hepatology (SH, HB, ES), University Hospital Tübingen, Tübingen, Germany
| | - Hannah Baier
- Pediatric Gastroenterology and Hepatology (SH, HB, ES), University Hospital Tübingen, Tübingen, Germany
| | - Matthias Kumpf
- Pediatric Cardiology, Pulmonology and Pediatric Intensive Care Medicine (MK), University Hospital Tübingen, Tübingen, Germany
| | - Rupert Handgretinger
- Pediatric Hematology and Oncology (RH), University Hospital Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery (AK, SN), University Hospital Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery (AK, SN), University Hospital Tübingen, Tübingen, Germany
| | - Ekkehard Sturm
- Pediatric Gastroenterology and Hepatology (SH, HB, ES), University Hospital Tübingen, Tübingen, Germany
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Sokooti S, Klont F, Tye SC, Kremer D, Douwes RM, Hopfgartner G, Dullaart RPF, Heerspink HJL, Bakker SJL. Association of diuretic use with increased risk for long-term post-transplantation diabetes mellitus in kidney transplant recipients. Nephrol Dial Transplant 2022; 37:1375-1383. [PMID: 35092430 PMCID: PMC9217635 DOI: 10.1093/ndt/gfac012] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background Post-transplantation diabetes mellitus (PTDM) is a major clinical problem in kidney transplant recipients (KTRs). Diuretic-induced hyperglycaemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in KTRs. Methods We included 486 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Participants were classified as diuretic users and non-users based on their medication use verified by medical records. Results At the baseline study, 168 (35%) KTRs used a diuretic (thiazide, n = 74; loop diuretic, n = 76; others, n = 18) and 318 KTRs did not use a diuretic. After 5.2 years [interquartile range (IQR) 4.0‒5.9] of follow up, 54 (11%) KTRs developed PTDM. In Cox regression analyses, diuretic use was associated with incident PTDM, independent of age, sex, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) {hazard ratio [HR] 3.28 [95% confidence interval (CI) 1.84–5.83]; P <0.001}. Further adjustment for potential confounders, including lifestyle, family history of cardiovascular disease, use of other medication, kidney function, transplantation-specific parameters, BMI, lipids and blood pressure did not materially change the association. Moreover, in Cox regression analyses, both thiazide and loop diuretics associated with the development of PTDM, independent of age, sex, FPG and HbA1c [HR 2.70 (95% CI 1.24–5.29); P = 0.012 and HR 5.08 (95% CI 2.49–10.34); P <0.001), respectively]. Conclusions This study demonstrates that diuretics overall are associated with an increased risk of developing PTDM in KTRs, independent of established risk factors for PTDM development. The association was present for both thiazide and loop diuretics.
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Affiliation(s)
- Sara Sokooti
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Frank Klont
- Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Geneva, Switzerland
| | - Sok Cin Tye
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Daan Kremer
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Rianne M Douwes
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Gérard Hopfgartner
- Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Geneva, Switzerland
| | - Robin P F Dullaart
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Rizk JG, Lazo JG, Quan D, Gabardi S, Rizk Y, Streja E, Kovesdy CP, Kalantar-Zadeh K. Mechanisms and management of drug-induced hyperkalemia in kidney transplant patients. Rev Endocr Metab Disord 2021; 22:1157-1170. [PMID: 34292479 DOI: 10.1007/s11154-021-09677-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/16/2021] [Indexed: 10/20/2022]
Abstract
Hyperkalemia is a common and potentially life-threatening complication following kidney transplantation that can be caused by a composite of factors such as medications, delayed graft function, and possibly potassium intake. Managing hyperkalemia after kidney transplantation is associated with increased morbidity and healthcare costs, and can be a cause of multiple hospital admissions and barriers to patient discharge. Medications used routinely after kidney transplantation are considered the most frequent culprit for post-transplant hyperkalemia in recipients with a well-functioning graft. These include calcineurin inhibitors (CNIs), pneumocystis pneumonia (PCP) prophylactic agents, and antihypertensives (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers). CNIs can cause hyperkalemic renal tubular acidosis. When hyperkalemia develops following transplantation, the potential offending medication may be discontinued, switched to another agent, or dose-reduced. Belatacept and mTOR inhibitors offer an alternative to calcineurin inhibitors in the event of hyperkalemia, however should be prescribed in the appropriate patient. While trimethoprim/sulfamethoxazole (TMP/SMX) remains the gold standard for prevention of PCP, alternative agents (e.g. dapsone, atovaquone) have been studied and can be recommend in place of TMP/SMX. Antihypertensives that act on the Renin-Angiotensin-Aldosterone System are generally avoided early after transplant but may be indicated later in the transplant course for patients with comorbidities. In cases of mild to moderate hyperkalemia, medical management can be used to normalize serum potassium levels and allow the transplant team additional time to evaluate the function of the graft. In the immediate post-operative setting following kidney transplantation, a rapidly rising potassium refractory to medical therapy can be an indication for dialysis. Patiromer and sodium zirconium cyclosilicate (ZS-9) may play an important role in the management of chronic hyperkalemia in kidney transplant patients, although additional long-term studies are necessary to confirm these effects.
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Affiliation(s)
- John G Rizk
- Arizona State University, Edson College, Phoenix, AZ, USA.
| | - Jose G Lazo
- UCSF Medical Center, University of California San Francisco, San Francisco, CA, USA
| | - David Quan
- UCSF Medical Center, University of California San Francisco, San Francisco, CA, USA
| | - Steven Gabardi
- Department of Transplant Surgery, Brigham and Women's Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Youssef Rizk
- Department of Internal Medicine, Division of Family Medicine, Lebanese American University Medical Center - St. John's Hospital, Beirut, Lebanon
| | - Elani Streja
- Department of Medicine, Division of Nephrology, Hypertension and Kidney Transplantation, School of Medicine, University of California, CA, Irvine, Orange, USA
| | - Csaba P Kovesdy
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Kamyar Kalantar-Zadeh
- Department of Medicine, Division of Nephrology, Hypertension and Kidney Transplantation, School of Medicine, University of California, CA, Irvine, Orange, USA
- Department of Epidemiology, University of California, UCLA Fielding School of Public Health, Los Angeles, CA, USA
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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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Gilewski W, Banach J, Rogowicz D, Wołowiec Ł, Sielski S, Grześk G. Treatment of Hypertension Because of Immunosuppressive Therapy After Solid Organ Transplantation-Pharmacological Approach. J Cardiovasc Pharmacol 2021; 77:735-744. [PMID: 34001720 DOI: 10.1097/fjc.0000000000001009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 02/09/2021] [Indexed: 01/18/2023]
Abstract
ABSTRACT Solid organs transplantation procedures have been performed for more than half a century. Growing knowledge of immune response and development of new immunosuppressive regimens guarantee more and more successful outcomes. However, many of the applied drugs lead to cardiovascular complications, the most frequent of which is hypertension. This article describes epidemiology, pathogenetic mechanisms, and treatment of hypertension induced by immunosuppressive medication. The main impact is focused on drugs belonging to the following groups: calcineurin inhibitors, the inhibitors of the mammalian target of rapamycin, and glucocorticosteroids. We analyze the mechanism of action of the main hypertensive drugs and their influence on the reversing hypertonic action of the immunosuppressive agents. In the absence of current guidelines addressing this problem, this article is an attempt to fill the gap, helping clinicians to choose proper medication.
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Affiliation(s)
- Wojciech Gilewski
- Department of Cardiology and Clinical Pharmacology, Nicolaus Copernicus University in Toruń Ludwik Rydygier Collegium Medicum in Bydgoszcz, Faculty of Health Sciences
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Almalki B, Cunningham K, Kapugi M, Kane C, Agrawal A. Management of hyperkalemia: A focus on kidney transplant recipients. Transplant Rev (Orlando) 2021; 35:100611. [PMID: 33711778 DOI: 10.1016/j.trre.2021.100611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/19/2021] [Accepted: 02/23/2021] [Indexed: 11/15/2022]
Abstract
Hyperkalemia is a frequent complication among kidney transplant recipients that can lead to fatal arrhythmias. The causes of hyperkalemia post kidney transplant are multifactorial and often are drug-induced, and include decreased glomerular filtration rate, tubular dysfunction, and impaired sodium delivery in the distal nephron. This review will discuss pathophysiology and recent updates in the management of both acute and chronic hyperkalemia with a focus on kidney transplant recipients.
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Affiliation(s)
- Bassem Almalki
- Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, United States.
| | - Kathleen Cunningham
- Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, United States
| | - Michelle Kapugi
- Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, United States
| | - Clare Kane
- Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, United States
| | - Akansha Agrawal
- Department of Nephrology, Northwestern Memorial Hospital, Chicago, IL, United States
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12
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Letellier T, Le Borgne F, Kerleau C, Gaultier A, Dantal J, Ville S. Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients. Clin J Am Soc Nephrol 2020; 15:1804-1813. [PMID: 33172936 PMCID: PMC7769023 DOI: 10.2215/cjn.02560220] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 09/28/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND OBJECTIVES Keratinocyte cancers, which primarily comprise squamous cell carcinomas and basal cell carcinomas, represent a major concern and potential risk for kidney transplant recipients. Hydrochlorothiazide, a diuretic widely used to treat hypertension, has been implicated in skin photosensitivity reaction. Recent studies conducted in the general population have found that hydrochlorothiazide use is associated with a higher risk of keratinocyte cancer, especially squamous cell carcinomas. High-risk groups, however, including transplant recipients were excluded from these. Our aim was to investigate whether hydrochlorothiazide use was associated with keratinocyte cancer in kidney transplant recipients on immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a single-center cohort of kidney (n=2155), combined kidney-pancreas (n=282), and pancreas (n=59) transplant recipients from the Données Informatisées VAlidées Transplantation (DIVAT) database transplanted between 2000 and 2017 in Nantes, France, we evaluated the association between hydrochlorothiazide exposure and keratinocyte cancers. Multivariable cause-specific, time-varying Cox models were used to estimate the relationship between hydrochlorothiazide exposure and the hazard of squamous cell carcinoma and basal cell carcinoma, with hydrochlorothiazide designated as the time-dependent variable. RESULTS Among the participants, 279 of 2496 (11%) were exposed to hydrochlorothiazide after the transplantation. Cumulative incidence rates of keratinocyte cancer by 10 and 15 years were 7% and 9% for squamous cell carcinomas, respectively, and 8% and 11% for basal cell carcinomas, respectively. We found a relationship between exposure to hydrochlorothiazide and the risk of squamous cell carcinomas (hazard ratio, 2.04; 95% confidence interval, 1.27 to 3.28). In contrast, we found no association between hydrochlorothiazide exposure and basal cell carcinomas (hazard ratio, 0.63; 95% confidence interval, 0.35 to 1.15). CONCLUSIONS In a single-center cohort of kidney, combined kidney-pancreas, and pancreas transplant recipients, exposure to hydrochlorothiazide was associated with a two-fold higher risk of squamous cell carcinoma and no higher risk of basal cell carcinoma.
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Affiliation(s)
- Thibault Letellier
- Department of Nephrology and Urology, Institut de Transplantation Urologie Néphrologie, Centre Hospitalo-Universitaire Nantes, Nantes, France
| | - Florent Le Borgne
- Institut National de la Santé Et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1246-methodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Nantes University, Nantes, France.,Informatique et Données Biomédicales à la Carte (iDBC), Pacé, France
| | - Clarisse Kerleau
- Department of Nephrology and Urology, Institut de Transplantation Urologie Néphrologie, Centre Hospitalo-Universitaire Nantes, Nantes, France
| | - Aurélie Gaultier
- Department of Research, Centre Hospitalo-Universitaire de Nantes, Direction de la recherche, Plateforme de Méthodologie et Biostatistique, Nantes, France
| | - Jacques Dantal
- Department of Nephrology and Urology, Institut de Transplantation Urologie Néphrologie, Centre Hospitalo-Universitaire Nantes, Nantes, France.,Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
| | - Simon Ville
- Department of Nephrology and Urology, Institut de Transplantation Urologie Néphrologie, Centre Hospitalo-Universitaire Nantes, Nantes, France .,Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France
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McGillicuddy J, Chandler J, Sox L, Mueller M, Nemeth L, Baliga P, Treiber F. "Smartphone Medication Adherence Saves Kidneys" for Kidney Transplantation Recipients: Protocol for a Randomized Controlled Trial. JMIR Res Protoc 2019; 8:e13351. [PMID: 31228175 PMCID: PMC6611329 DOI: 10.2196/13351] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 04/17/2019] [Accepted: 05/02/2019] [Indexed: 12/31/2022] Open
Abstract
Background Kidney 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). Objective Our 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. Methods This 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. Results The 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. Conclusions This 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
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Affiliation(s)
- John McGillicuddy
- College of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Jessica Chandler
- College of Nursing, Medical University of South Carolina, Charleston, SC, United States
| | - Luke Sox
- College of Nursing, Medical University of South Carolina, Charleston, SC, United States
| | - Martina Mueller
- College of Nursing, Medical University of South Carolina, Charleston, SC, United States
| | - Lynne Nemeth
- College of Nursing, Medical University of South Carolina, Charleston, SC, United States
| | - Prabhakar Baliga
- College of Medicine, Medical University of South Carolina, Charleston, SC, United States
| | - Frank Treiber
- College of Nursing, Medical University of South Carolina, Charleston, SC, United States
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Aziz F, Clark D, Garg N, Mandelbrot D, Djamali A. Hypertension guidelines: How do they apply to kidney transplant recipients. Transplant Rev (Orlando) 2018; 32:225-233. [DOI: 10.1016/j.trre.2018.06.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/05/2018] [Accepted: 06/17/2018] [Indexed: 12/28/2022]
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15
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McGillicuddy JW, Taber DJ, Mueller M, Patel S, Baliga PK, Chavin KD, Sox L, Favela AP, Brunner-Jackson BM, Treiber FA. Sustainability of improvements in medication adherence through a mobile health intervention. Prog Transplant 2018; 25:217-23. [PMID: 26308780 DOI: 10.7182/pit2015975] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Context-Very few patient-centered, theory-guided programs for medication adherence and blood pressure control have been conducted in kidney transplant recipients. Objective-To evaluate preliminary indications of sustainability of improved blood pressure in kidney transplant recipients 12 months after completion of a 3-month randomized controlled trial of a mobile health pilot program to improve blood pressure and medication adherence. Participants and Design-A total of 18 of the 19 trial participants were contacted and all consented to inclusion in the retrospective analysis of their medical records showing their clinic-recorded systolic blood pressures at 3, 6, and 12 months following participation in the 3-month trial of a medical regimen self-management intervention. Results-A significant group difference in systolic blood pressure was observed longitudinally, indicating that the intervention group, as compared with the standard-care group, exhibited lower clinic-measured systolic blood pressures at the 12-month posttrial follow-up visit (P= .01). At 12-month follow-up, success in establishing and sustaining control of systolic blood pressure (<131 mm Hg) was greater in the intervention group (50%) than in the control group (11%). Conclusion-Patients in the intervention group continued to exhibit lower systolic blood pressure than did patients in the control group 12 months after the trial ended, suggesting that the intervention may have a durable impact on blood pressure control that most likely reflects sustained medication adherence. These findings will aid in the development of an adequately powered randomized controlled trial to address the sustainable impact of the intervention program on medication adherence and blood pressure control.
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Affiliation(s)
- John W McGillicuddy
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - David J Taber
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Martina Mueller
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Sachin Patel
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Prabhakar K Baliga
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Kenneth D Chavin
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Luke Sox
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - April P Favela
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Brenda M Brunner-Jackson
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
| | - Frank A Treiber
- Medical University of South Carolina (JWM, DT, MM, SP, PKB, KDC, LS, AF, BB-J, FAT), College of Charleston (LS, AF), Charleston, South Carolina
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16
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Moes AD, Hesselink DA, van den Meiracker AH, Zietse R, Hoorn EJ. Chlorthalidone Versus Amlodipine for Hypertension in Kidney Transplant Recipients Treated With Tacrolimus: A Randomized Crossover Trial. Am J Kidney Dis 2017; 69:796-804. [PMID: 28259499 DOI: 10.1053/j.ajkd.2016.12.017] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 12/19/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND 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. STUDY DESIGN Randomized noninferiority crossover trial (noninferiority margin, -2.8mmHg). SETTING & PARTICIPANTS 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). INTERVENTION Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) for 8 weeks (separated by 2-week washout). OUTCOMES Average daytime (9 am to 9 pm) ambulatory SBP. MEASUREMENTS Blood pressure and laboratory parameters. RESULTS 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. LIMITATIONS Open-label design, short follow-up, per-protocol analysis. CONCLUSIONS Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation.
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Affiliation(s)
- Arthur D Moes
- Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Dennis A Hesselink
- Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - Robert Zietse
- Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Ewout J Hoorn
- Division of Nephrology & Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
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Blowey DL. Diuretics in the treatment of hypertension. Pediatr Nephrol 2016; 31:2223-2233. [PMID: 26983630 DOI: 10.1007/s00467-016-3334-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 01/11/2016] [Accepted: 01/12/2016] [Indexed: 01/12/2023]
Abstract
Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.
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Affiliation(s)
- Douglas L Blowey
- Pediatrics and Pharmacology, Division of Pediatric Nephrology, Children's Mercy Hospital, University of Missouri, 2401 Gillham Road, Kansas City, MO, 64108, USA.
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Thomas B, Weir MR. The Evaluation and Therapeutic Management of Hypertension in the Transplant Patient. Curr Cardiol Rep 2015; 17:95. [DOI: 10.1007/s11886-015-0647-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Rojas-Vega L, Jiménez-Vega AR, Bazúa-Valenti S, Arroyo-Garza I, Jiménez JV, Gómez-Ocádiz R, Carrillo-Pérez DL, Moreno E, Morales-Buenrostro LE, Alberú J, Gamba G. Increased phosphorylation of the renal Na+-Cl- cotransporter in male kidney transplant recipient patients with hypertension: a prospective cohort. Am J Physiol Renal Physiol 2015; 309:F836-42. [PMID: 26336164 DOI: 10.1152/ajprenal.00326.2015] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 08/27/2015] [Indexed: 11/22/2022] Open
Abstract
Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7±0.19) than normotensive (1±0.13) (P=0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57±0.16 vs. 1±0.07; P=0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension.
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Affiliation(s)
- Lorena Rojas-Vega
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Aldo R Jiménez-Vega
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Silvana Bazúa-Valenti
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Isidora Arroyo-Garza
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José Victor Jiménez
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Ruy Gómez-Ocádiz
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Diego Luis Carrillo-Pérez
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Erika Moreno
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luis E Morales-Buenrostro
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Josefina Alberú
- Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; and
| | - Gerardo Gamba
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Moes AD, Hesselink DA, Zietse R, van Schaik RHN, van Gelder T, Hoorn EJ. Calcineurin inhibitors and hypertension: a role for pharmacogenetics? Pharmacogenomics 2014; 15:1243-51. [DOI: 10.2217/pgs.14.87] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns.
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Affiliation(s)
- Arthur D Moes
- Department of Internal Medicine, Nephrology & Transplantation, Erasmus Medical Center, PO Box 2040 – Room H-438, 3000 CA Rotterdam, The Netherlands
| | - Dennis A Hesselink
- Department of Internal Medicine, Nephrology & Transplantation, Erasmus Medical Center, PO Box 2040 – Room H-438, 3000 CA Rotterdam, The Netherlands
| | - Robert Zietse
- Department of Internal Medicine, Nephrology & Transplantation, Erasmus Medical Center, PO Box 2040 – Room H-438, 3000 CA Rotterdam, The Netherlands
| | - Ron HN van Schaik
- Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Teun van Gelder
- Department of Internal Medicine, Nephrology & Transplantation, Erasmus Medical Center, PO Box 2040 – Room H-438, 3000 CA Rotterdam, The Netherlands
- Department of Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Ewout J Hoorn
- Department of Internal Medicine, Nephrology & Transplantation, Erasmus Medical Center, PO Box 2040 – Room H-438, 3000 CA Rotterdam, The Netherlands
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