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Farkona S, Kotlyar M, Burns K, Knoll G, Brinc D, Jurisica I, Konvalinka A. Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial. J Proteome Res 2025; 24:2040-2052. [PMID: 40111290 DOI: 10.1021/acs.jproteome.4c01100] [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] [Indexed: 03/22/2025]
Abstract
The renin-angiotensin system (RAS) is involved in kidney fibrosis. We previously identified six RAS-regulated proteins (RHOB, BST1, LYPA1, GLNA, TSP1, and LAMB2) that were increased in the urine of patients with kidney allograft fibrosis, compared to patients without fibrosis. We hypothesized that these urinary RAS-regulated proteins predicted primary outcomes in kidney transplant recipients enrolled in the largest RAS inhibitor randomized controlled trial. Urine excretion of 10 peptides corresponding to the six RAS-regulated proteins was quantified using parallel reaction monitoring mass spectrometry assays (normalized by urine creatinine) in a subset of patients in the trial. Machine learning models predicting outcomes based on urine peptide excretion rates were developed and evaluated. Urine samples (n = 111) from 56 patients were collected at 0, 6, 12, and 24 months. Twenty-four primary outcomes (doubling of serum creatinine, graft loss, or death) occurred in 17 patients. Logistic regression utilizing eight peptides of TSP1, BST1, LAMB2, LYPA1, and RHOB, from the last urine sample prior to outcomes, predicted a graft loss with an AUC of 0.78 (p = 0.00001). A random forest classifier utilizing BST1 and LYPA1 peptides predicted death with an AUC of 0.80 (p = 0.0016). Urine measurements of RAS-regulated proteins may predict outcomes in kidney transplant recipients, although further prospective studies are required.
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Affiliation(s)
- Sofia Farkona
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2N2, Canada
| | - Max Kotlyar
- Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health, Toronto, ON M5T 0S8, Canada
| | - Kevin Burns
- Division of Nephrology, Department of Medicine and Kidney Research Centre, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | - Greg Knoll
- Division of Nephrology, Department of Medicine and Kidney Research Centre, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Department of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Kidney Research Centre, Ottawa Hospital Research Institute and University of Ottawa, Ottawa, ON K1H 8L6, Canada
| | - Davor Brinc
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada
- Division of Clinical Biochemistry, Laboratory Medicine Program, University Health Network, Toronto, Ontario M5S 3K3, Canada
| | - Igor Jurisica
- Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health, Toronto, ON M5T 0S8, Canada
- Departments of Medical Biophysics and Computer Science and Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1L7, Canada
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava 845 10, Slovakia
| | - Ana Konvalinka
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2N2, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 3K3, Canada
- Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 2N2, Canada
- Department of Medicine, Division of Nephrology, University Health Network, Toronto, ON M5G 2N2, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON M5S 3K3, Canada
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Beaudrey T, Bedo D, Weschler C, Caillard S, Florens N. From Risk Assessment to Management: Cardiovascular Complications in Pre- and Post-Kidney Transplant Recipients: A Narrative Review. Diagnostics (Basel) 2025; 15:802. [PMID: 40218153 PMCID: PMC11988545 DOI: 10.3390/diagnostics15070802] [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: 02/14/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.
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Affiliation(s)
- Thomas Beaudrey
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Dimitri Bedo
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Célia Weschler
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
| | - Sophie Caillard
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, 67000 Strasbourg, France
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Paccagnella C, Andreola S, Gambaro A, Gambaro G, Caletti C. Immunosuppressive Therapy-Related Cardiovascular Risk Factors in Renal Transplantation: A Narrative Review. Cardiorenal Med 2025; 15:209-228. [PMID: 39956105 DOI: 10.1159/000542378] [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] [Received: 01/24/2024] [Accepted: 10/24/2024] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Kidney transplantation is the best treatment for patients with chronic renal failure, capable of improving life expectancy and the risk of death from all causes, which, however, remains higher than in the general population. The leading cause of death in transplant patients is cardiovascular events, burdened by a significant impact brought about by anti-rejection therapy. Experimental and clinical studies to date show that in kidney transplant recipients, traditional cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, tobacco, etc.) may be exacerbated or worsened by the dysmetabolic effects of immunosuppressive drugs, which may also result in additional risk factors such as proteinuria, anemia, and arterial stiffness. The aim of this review was to provide an in-depth evaluation of the effect of immunosuppressive treatments on cardiovascular risk factors. SUMMARY We have investigated and described the main cardiovascular risk factors related to immunosuppressive drugs. We searched for relevant scientific articles in medicine, transplant, cardiologic, and nephrological journals in major medical science libraries. KEY MESSAGES Immunosuppressive drugs allow graft survival and successful bunking of the transplant; however, they are not without significant side effects and should always be prescribed weighing the risk/benefit ratio and the individual patient's therapeutic needs.
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Affiliation(s)
- Chiara Paccagnella
- Nephrology Postgraduate School, Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Stefano Andreola
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Alessia Gambaro
- Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy
| | - Giovanni Gambaro
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| | - Chiara Caletti
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
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Kanbay M, Copur S, Mizrak B, Mallamaci F, Zoccali C. Mineralocorticoid receptor antagonists in kidney transplantation. Eur J Clin Invest 2024; 54:e14206. [PMID: 38578116 DOI: 10.1111/eci.14206] [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] [Received: 02/05/2024] [Revised: 03/16/2024] [Accepted: 03/19/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. RESULTS The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia-reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. CONCLUSION Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Berk Mizrak
- Department of Internal Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit Azienda Ospedaliera "Bianchi-Melacrino-Morelli" & CNR-IFC, Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Reggio Calabria, Italy
| | - Carmine Zoccali
- Renal Research Institute, New York, New York, USA
- Associazione Ipertensione Nefrologia Trapianto Renal (IPNET), Reggio Calabria, Italy
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Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev 2024; 7:CD003598. [PMID: 39082471 PMCID: PMC11290053 DOI: 10.1002/14651858.cd003598.pub3] [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] [Indexed: 08/03/2024]
Abstract
BACKGROUND The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review. OBJECTIVES To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients. SEARCH METHODS We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible. DATA COLLECTION AND ANALYSIS Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. MAIN RESULTS Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation. AUTHORS' CONCLUSIONS For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.
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Affiliation(s)
- Patrizia Natale
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
| | - Pamela Kl Mooi
- Department of Nephrology, Christchurch Hospital, Te Whatu Ora Waitaha Canterbury, Christchurch, New Zealand
| | - Suetonia C Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Nicholas B Cross
- Department of Nephrology, Christchurch Hospital, Te Whatu Ora Waitaha Canterbury, Christchurch, New Zealand
- New Zealand Clinical Research, 3/264 Antigua St, Christchurch, New Zealand
| | - Tess E Cooper
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Angela C Webster
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Westmead Applied Research Centre, The University of Sydney at Westmead, Westmead, Australia
- Department of Transplant and Renal Medicine, Westmead Hospital, Westmead, Australia
| | - Philip Masson
- Department of Renal Medicine, Royal Free London NHS Foundation Trust, London, UK
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Giovanni Fm Strippoli
- Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, Bari, Italy
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
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Grewal HS, Thaniyavarn T, Arcasoy SM, Goldberg HJ. Common Noninfectious Complications Following Lung Transplantation. Clin Chest Med 2023; 44:179-190. [PMID: 36774163 DOI: 10.1016/j.ccm.2022.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
According to the Scientific Registry of Transplant Recipients, both transplant volume and survival among lung transplant recipients are improving over time. However, the outcomes of lung transplantation remain challenged by multiple thoracic and extrathoracic complications. With improving lung transplant survival, patients experience prolonged exposure to chronic immunosuppressive agents that can lead to multiple infectious and noninfectious complications. This article focuses on most common noninfectious complications with significant clinical impact.
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Affiliation(s)
- Harpreet Singh Grewal
- Lung Transplant Program, Columbia University, Irving Medical Center, 622 West 168th Street, PH 14E, Suite 104, New York, NY 10032, USA.
| | - Tany Thaniyavarn
- Lung Transplant Program, Brigham and Women's Hospital, 75 Francis Street, PBB Clinic 3, Boston, MA 02115, USA
| | - Selim M Arcasoy
- Lung Transplant Program, Columbia University, Irving Medical Center, 622 West 168th Street, PH 14E, Suite 104, New York, NY 10032, USA
| | - Hilary J Goldberg
- Lung Transplant Program, Brigham and Women's Hospital, 75 Francis Street, PBB Clinic 3, Boston, MA 02115, USA
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Sridhar VS, Ambinathan JPN, Gillard P, Mathieu C, Cherney DZI, Lytvyn Y, Singh SK. Cardiometabolic and Kidney Protection in Kidney Transplant Recipients With Diabetes: Mechanisms, Clinical Applications, and Summary of Clinical Trials. Transplantation 2022; 106:734-748. [PMID: 34381005 DOI: 10.1097/tp.0000000000003919] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the therapy of choice for patients with end-stage renal disease. Preexisting diabetes is highly prevalent in kidney transplant recipients (KTR), and the development of posttransplant diabetes is common because of a number of transplant-specific risk factors such as the use of diabetogenic immunosuppressive medications and posttransplant weight gain. The presence of pretransplant and posttransplant diabetes in KTR significantly and variably affect the risk of graft failure, cardiovascular disease (CVD), and death. Among the many available therapies for diabetes, there are little data to determine the glucose-lowering agent(s) of choice in KTR. Furthermore, despite the high burden of graft loss and CVD among KTR with diabetes, evidence for strategies offering cardiovascular and kidney protection is lacking. Recent accumulating evidence convincingly shows glucose-independent cardiorenal protective effects in non-KTR with glucose-lowering agents, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Therefore, our aim was to review cardiorenal protective strategies, including the evidence, mechanisms, and rationale for the use of these glucose-lowering agents in KTR with diabetes.
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Affiliation(s)
- Vikas S Sridhar
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Jaya Prakash N Ambinathan
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Pieter Gillard
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - Chantal Mathieu
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - David Z I Cherney
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Yuliya Lytvyn
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Sunita K Singh
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Measurement of the Surface Area of the Renal Sinus Fat Using MDCT: Correlation with Presence and Severity of Essential Hypertension and Body Mass Index. J Belg Soc Radiol 2022; 106:91. [PMID: 36304908 PMCID: PMC9541188 DOI: 10.5334/jbsr.2776] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 08/27/2022] [Indexed: 11/07/2022] Open
Abstract
Objectives: Essential hypertension remains a major modifiable risk factor for cardiovascular disease. Excess visceral adipose tissue is associated with the presence of adverse metabolic risk factors. Our study aims to measure the surface area of the renal sinus fat using MDCT and correlate the renal sinus surface area with the presence and grading of essential hypertension as well as body mass index. Materials and Methods: This cross-sectional study included two groups; the patients’ group including 40 cases presented with a history of primary essential hypertension and the control group including 40 cases. The average of the surface area of the two kidneys as well as the average of the surface area of sinus fat was measured in the control and patient subgroups and was correlated with the presence and grading of essential hypertension as well as body mass index. Results: There was a significant correlation between the presence and grading of essential hypertension with prominent renal sinus fat. There was a significant correlation between the average surface area of kidneys and surface area of sinus fat in overweight and obese groups than in the control group (P < 0.01). Conclusion: Obesity is now recognized as a risk factor for the development of renal dysfunction. There was a significant correlation between the surface area of renal sinus fat measured using MDCT and the presence as well as grading of essential hypertension, suggesting that renal sinus fat may promote cardiovascular events.
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Update on Treatment of Hypertension After Renal Transplantation. Curr Hypertens Rep 2021; 23:25. [PMID: 33961145 DOI: 10.1007/s11906-021-01151-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW To incorporate novel findings on pathophysiology and treatment of posttransplant hypertension. RECENT FINDINGS (1) The sodium retaining effects of CNIs are mediated by stimulation of the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule and in this regard chlorthalidone was proven to be an effective antihypertensive drug in renal transplantation. (2) Local and not systemic activation of the renin-angiotensin-aldosterone system plays a crucial role in the pathogenesis of posttransplant hypertension. (3) Recent randomized controlled trials failed to prove the presumed superiority of renin-angiotensin blockers in kidney transplantation. (4) Steroid-free and mammalian target of rapamycin-based immunosuppressive drug combinations did not show favorable effects on blood pressure control. (5) In a recent report the risk of non-melanoma skin cancer was higher with thiazide diuretics. But the increased cancer risk in transplant recipients is mainly attributed to comorbidities, such as diabetes and hypertension and of course to the transplantation condition itself or the obligatory application of immunosuppression, and has little to do with the antihypertensive medication Actual recommendations about BP targets in adult renal transplant recipients are coming from a post hoc analysis of a large randomized trial with another primary endpoint. Unless convincing studies on treatment of hypertension after renal transplantation are available, the ESC/ESH Guidelines 2018 should apply for these patients.
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Should ACE inhibitors or calcium channel blockers be used for post-transplant hypertension? Pediatr Nephrol 2021; 36:539-549. [PMID: 32060819 DOI: 10.1007/s00467-020-04485-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 01/14/2020] [Accepted: 01/17/2020] [Indexed: 10/25/2022]
Abstract
Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.
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11
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Jehn U, Schütte-Nütgen K, Strauss M, Kunert J, Pavenstädt H, Thölking G, Suwelack B, Reuter S. Antihypertensive Treatment in Kidney Transplant Recipients-A Current Single Center Experience. J Clin Med 2020; 9:jcm9123969. [PMID: 33297518 PMCID: PMC7762385 DOI: 10.3390/jcm9123969] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 11/20/2020] [Accepted: 12/03/2020] [Indexed: 12/11/2022] Open
Abstract
Arterial hypertension affects the survival of the kidney graft and the cardiovascular morbidity and mortality of the recipient after kidney transplantation (KTx). Thus, antihypertensive treatment is necessary for a vast majority of these patients. Long-term data on antihypertensive drugs and their effects on allograft function after KTx is still limited, and further investigation is required. We retrospectively analyzed a cohort of 854 recipients who received a kidney transplant at our transplant center between 2007 and 2015 with regard to antihypertensive treatment and its influence on graft function and survival. 1-y after KTx, 95.3% patients were treated with antihypertensive therapy. Of these, 38.6% received mono- or dual-drug therapy, 38.0% received three to four drugs and 8.1% were on a regimen of ≥5 drugs. Beta-blockers were the most frequently used antihypertensive agents (68.1%). Neither the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (51.9%) and calcium channel blockers (51.5%), nor the use the use of loop diuretics (38.7%) affected allograft survival. Arterial hypertension and the number of antihypertensive agents were associated with unfavorable allograft outcomes (each p < 0.001). In addition to the well-known risk factors of cold ischemic time and acute rejection episodes, the number of antihypertensive drugs after one year, which reflects the severity of hypertension, is a strong predictor of unfavorable allograft survival.
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Affiliation(s)
- Ulrich Jehn
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Katharina Schütte-Nütgen
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Markus Strauss
- Department of Medicine C, Division of Cardiology and Angiology, University Hospital of Münster, 48149 Münster, Germany;
| | - Jan Kunert
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Hermann Pavenstädt
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Gerold Thölking
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Barbara Suwelack
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
| | - Stefan Reuter
- Department of Medicine D, Division of General Internal Medicine, Nephrology and Rheumatology, University Hospital of Münster, 48149 Münster, Germany; (U.J.); (K.S.-N.); (J.K.); (H.P.); (G.T.); (B.S.)
- Correspondence: ; Tel.: +49-251-83-47540; Fax: +49-251-83-56973
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12
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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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13
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Rangaswami J, Mathew RO, Parasuraman R, Tantisattamo E, Lubetzky M, Rao S, Yaqub MS, Birdwell KA, Bennett W, Dalal P, Kapoor R, Lerma EV, Lerman M, McCormick N, Bangalore S, McCullough PA, Dadhania DM. Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies. Nephrol Dial Transplant 2020; 34:760-773. [PMID: 30984976 DOI: 10.1093/ndt/gfz053] [Citation(s) in RCA: 123] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Indexed: 12/19/2022] Open
Abstract
Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint 'cardio-nephrology' clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.
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Affiliation(s)
- Janani Rangaswami
- Einstein Medical Center, Philadelphia, PA, USA.,Sidney Kimmel College of Thomas Jefferson University, Philadelphia, PA, USA
| | - Roy O Mathew
- Columbia Veterans Affairs Health Care System, Columbia, SC, USA
| | | | | | - Michelle Lubetzky
- Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY, USA
| | - Swati Rao
- University of Virginia, Charlottesville, VA, USA
| | | | | | | | | | - Rajan Kapoor
- Augusta University Medical Center, Augusta, GA, USA
| | - Edgar V Lerma
- UIC/Advocate Christ Medical Center, Oak Lawn, IL, USA
| | - Mark Lerman
- Medical City Dallas Hospital, Dallas, TX, USA
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14
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Abstract
ZusammenfassungErhöhter Blutdruck bleibt eine Hauptursache von kardiovaskulären Erkrankungen, Behinderung und frühzeitiger Sterblichkeit in Österreich, wobei die Raten an Diagnose, Behandlung und Kontrolle auch in rezenten Studien suboptimal sind. Das Management von Bluthochdruck ist eine häufige Herausforderung für Ärztinnen und Ärzte vieler Fachrichtungen. In einem Versuch, diagnostische und therapeutische Strategien zu standardisieren und letztendlich die Rate an gut kontrollierten Hypertoniker/innen zu erhöhen und dadurch kardiovaskuläre Erkrankungen zu verhindern, haben 13 österreichische medizinische Fachgesellschaften die vorhandene Evidenz zur Prävention, Diagnose, Abklärung, Therapie und Konsequenzen erhöhten Blutdrucks gesichtet. Das hier vorgestellte Ergebnis ist der erste Österreichische Blutdruckkonsens. Die Autoren und die beteiligten Fachgesellschaften sind davon überzeugt, daß es einer gemeinsamen nationalen Anstrengung bedarf, die Blutdruck-assoziierte Morbidität und Mortalität in unserem Land zu verringern.
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Abstract
Untoward side effects of pharmaceuticals can result in considerable morbidity and expense to the health care system. There is likely a sizable fraction of the hypertensive population with disease either induced or exacerbated by polypharmacy. The elevation of blood pressure in drug-induced hypertension occurs through a variety of mechanisms, most notably, sodium and fluid retention, activation of the renin-angiotensin-aldosterone system, alteration of vascular tone, or a combination of these pathways. Recognition of common medications causing drug-induced hypertension is important to effectively control blood pressure. The epidemiology, pathophysiology, and management of these agents are discussed.
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Affiliation(s)
- Matthew C Foy
- Division of Nephrology, Louisiana State University Health Science Center, 5246 Brittany Dr, Baton Rouge, LA 70808, USA
| | - Joban Vaishnav
- Division of Cardiology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA
| | - Christopher John Sperati
- Division of Nephrology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 416, Baltimore, MD 21287, USA.
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16
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Aronow WS. Implications of the New 2017 American College of Cardiology/American Heart Association Guidelines for Hypertension. Minerva Cardioangiol 2019; 67:399-410. [PMID: 31220914 DOI: 10.23736/s0026-4725.19.04965-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Automated validated devices should be used for measuring blood pressure (BP). The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines recommend that a systolic BP between 120-129 mmHg with a diastolic BP less than 80 mmHg should be treated with lifestyle measures. These guidelines recommend treatment with lifestyle measures plus BP lowering drugs for secondary prevention of cardiovascular events in persons with clinical cardiovascular disease and an average systolic BP of ≥130 mmHg or an average diastolic BP≥80 mmHg. These guidelines recommend treatment with lifestyle measures plus BP lowering drugs for primary prevention of cardiovascular disease in persons with an estimated 10-year risk of atherosclerotic cardiovascular disease ≥ 10% and an average systolic BP ≥130 mmHg or an average diastolic BP ≥80 mmHg. These guidelines recommend treatment with lifestyle measures plus BP lowering drugs for primary prevention of cardiovascular disease in persons with an estimated 10-year risk of atherosclerotic cardiovascular disease of < 10% and an average systolic BP ≥140 mmHg or an average diastolic BP ≥ 90 mmHg. These guidelines recommend initiating antihypertensive drug therapy with 2 first-line drugs from different classes either as separate agents or in a fixed-dose combination in persons with a BP ≥140/90 mmHg or with a BP > 20/10 mmHg above their BP target. White coat hypertension must be excluded before starting treatment with antihypertensive drugs in persons with hypertension at low risk for atherosclerotic cardiovascular disease. Antihypertensive drug treatment for different disorders is discussed.
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Affiliation(s)
- Wilbert S Aronow
- Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA -
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17
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Dose-Response Relationship Between Diltiazem and Tacrolimus and Its Safety in Renal Transplant Recipients. Transplant Proc 2018; 50:2515-2520. [DOI: 10.1016/j.transproceed.2018.04.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 03/26/2018] [Accepted: 04/09/2018] [Indexed: 11/17/2022]
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18
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19
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Abstract
The 2017 American College of Cardiology/American Heart Association hypertension guidelines diagnose hypertension if systolic blood pressure (SBP) is ≥ 130 mmHg or diastolic blood pressure (DBP) is ≥ 80 mmHg. Increased BP is SBP 120-129 mmHg with DBP < 80 mmHg. Lifestyle measures should be used to treat individuals with increased BP. Lifestyle measures plus BP-lowering drugs should be used for secondary prevention of recurrent cardiovascular events in individuals with clinical cardiovascular disease (coronary heart disease, congestive heart failure, or stroke) and an average SBP ≥ 130 mmHg or an average DBP ≥ 80 mmHg. Lifestyle measures plus BP-lowering drugs should be used for primary prevention of cardiovascular disease in individuals with an estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD) ≥ 10% and an average SBP ≥ 130 mmHg or an average DBP ≥ 80 mmHg. Lifestyle measures plus BP-lowering drugs should be used for primary prevention of cardiovascular disease in individuals with an estimated 10-year risk of ASCVD < 10% and an average SBP ≥ 140 mmHg or an average DBP ≥ 90 mmHg. White coat hypertension must be excluded before starting antihypertensive drug treatment in individuals with hypertension with a low risk for ASCVD. BP should be lowered to < 130/80 mmHg in patients with coronary heart disease, heart failure, or chronic kidney disease; after renal transplantation; for secondary stroke prevention; in lacunar stroke, peripheral arterial disease, and diabetes mellitus; and in ambulatory community-dwelling adults aged > 65 years. The selection of antihypertensive drug treatment is discussed.
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Affiliation(s)
- Wilbert S Aronow
- Cardiology Division and the Department of Medicine, Westchester Medical Center and New York Medical College, Macy Pavilion, Room 141, Valhalla, NY, 10595, USA.
| | - William H Frishman
- Cardiology Division and the Department of Medicine, Westchester Medical Center and New York Medical College, Macy Pavilion, Room 141, Valhalla, NY, 10595, USA
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20
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Aronow WS. Antihypertensive drug therapy. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:123. [PMID: 29955583 PMCID: PMC6015954 DOI: 10.21037/atm.2018.01.26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 01/19/2018] [Indexed: 08/29/2023]
Affiliation(s)
- Wilbert S Aronow
- Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
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21
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Abstract
Automated validated devices should be used for measuring blood pressure (BP). A systolic BP between 120 and 129 mm Hg with a diastolic BP < 80 mm Hg should be treated by lifestyle measures. Lifestyle measures plus BP lowering drugs should be used for secondary prevention of recurrent cardiovascular disease (CVD) events in persons with clinical CVD (coronary heart disease, congestive heart failure, and stroke) and an average systolic BP of ≥130 mm Hg or an average diastolic BP ≥ 80 mm Hg. Lifestyle measures plus BP lowering drugs should be used for primary prevention of CVD in persons with an estimated 10-year risk of atherosclerotic CVD ≥ 10% and an average systolic BP ≥130 mm Hg or an average diastolic BP ≥ 80 mm Hg. Lifestyle measures plus BP lowering drugs should be used for primary prevention of CVD in persons with an estimated 10-year risk of atherosclerotic CVD of <10% and an average systolic BP ≥ 140 mm Hg or an average diastolic BP ≥ 90 mm Hg. Initiate antihypertensive drug therapy with 2 first-line drugs from different classes either as separate agents or in a fixed-dose combination in persons with a BP ≥ 140/90 mm Hg or with a BP > 20/10 mm Hg above their BP target. White coat hypertension must be excluded before initiating treatment with antihypertensive drugs in persons with hypertension at low risk for atherosclerotic CVD. Antihypertensive drug treatment for different disorders is discussed.
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Affiliation(s)
- Wilbert S Aronow
- From the Department of Medicine, Cardiology Division, Westchester Medical Center and New York Medical College, Valhalla, NY
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22
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CKD complications in kidney-transplanted patients going back to dialysis: impact on patients outcomes. J Nephrol 2017; 31:147-155. [DOI: 10.1007/s40620-017-0449-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 10/13/2017] [Indexed: 01/07/2023]
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23
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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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24
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Liao RX, Lyu XF, Tang WJ, Gao K. Short- and long-term outcomes with renin-angiotensin-aldosterone inhibitors in renal transplant recipients: A meta-analysis of randomized controlled trials. Clin Transplant 2017; 31. [PMID: 28186357 DOI: 10.1111/ctr.12917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2017] [Indexed: 02/05/2023]
Affiliation(s)
- Ruo-xi Liao
- Department of Nephrology; West China Hospital; Sichuan University; Chengdu China
| | - Xia-fei Lyu
- Department of Radiology; West China Hospital; Sichuan University; Chengdu China
| | - Wen-jiao Tang
- Department of Hematology; West China Hospital; Sichuan University; Chengdu China
| | - Kai Gao
- Department of Computer Science and Technology; Tsinghua University; Beijing China
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25
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Renin-angiotensin system inhibitors in kidney transplantation: a benefit-risk assessment. J Nephrol 2017; 30:155-157. [PMID: 28211033 DOI: 10.1007/s40620-017-0378-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 01/02/2017] [Indexed: 10/20/2022]
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26
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Deletion of mineralocorticoid receptors in smooth muscle cells blunts renal vascular resistance following acute cyclosporine administration. Kidney Int 2017; 89:354-62. [PMID: 26422501 DOI: 10.1038/ki.2015.312] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 08/13/2015] [Accepted: 08/20/2015] [Indexed: 12/23/2022]
Abstract
Calcineurin inhibitors such as cyclosporine A (CsA) are still commonly used after renal transplantation, despite CsA--induced nephrotoxicity (CIN), which is partly related to vasoactive mechanisms. The mineralocorticoid receptor (MR) is now recognized as a key player in the control of vascular tone, and both endothelial cell- and vascular smooth muscle cell (SMC)-MR modulate the vasoactive responses to vasodilators and vasoconstrictors. Here we tested whether vascular MR is involved in renal hemodynamic changes induced by CsA. The relative contribution of vascular MR in acute CsA treatment was evaluated using mouse models with targeted deletion of MR in endothelial cell or SMC. Results indicate that MR expressed in SMC, but not in endothelium, contributes to the increase of plasma urea and creatinine, the appearance of isometric tubular vacuolization, and overexpression of a kidney injury biomarker (neutrophil gelatinase--associated lipocalin) after CsA treatment. Inactivation of MR in SMC blunted CsA--induced phosphorylation of contractile proteins. Finally, the in vivo increase of renal vascular resistance induced by CsA was blunted when MR was deleted from SMC cells, and this was associated with decreased L-type Ca2D channel activity. Thus, our study provides new insights into the role of vascular MR in renal hemodynamics during acute CIN, and provides rationale for clinical studies of MR antagonism to manage the side effects of calcineurin inhibitors.
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27
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Charnaya O, Moudgil A. Hypertension in the Pediatric Kidney Transplant Recipient. Front Pediatr 2017; 5:86. [PMID: 28507980 PMCID: PMC5410589 DOI: 10.3389/fped.2017.00086] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Accepted: 04/07/2017] [Indexed: 12/14/2022] Open
Abstract
Hypertension after kidney transplant is a frequent occurrence in pediatric patients. It is a risk factor for graft loss and contributes to the significant burden of cardiovascular disease (CVD) in this population. The etiology of posttransplant hypertension is multifactorial including donor factors, recipient factors, medications, and lifestyle factors similar to those prevalent in the general population. Ambulatory blood pressure monitoring has emerged as the most reliable method for measuring hypertension in pediatric transplant recipients, and many consider it to be essential in the care of these patients. Recent technological advances including measurement of carotid intima-media thickness, pulse wave velocity, and myocardial strain using specked echocardiography and cardiac magnetic resonance imaging have improved our ability to assess CVD burden. Since hypertension remains underrecognized and inadequately treated, an early diagnosis and an appropriate control should be the focus of therapy to help improve patient and graft survival.
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Affiliation(s)
- Olga Charnaya
- Division of Pediatric Nephrology, Children's National Health System, Washington, DC, USA
| | - Asha Moudgil
- Division of Pediatric Nephrology, Children's National Health System, Washington, DC, USA
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Ozkul F, Kasim Arik M, Erbiş H, Akbaş A, Yilmaz VT, Barutcu A, Ali Osmanoğlu I, Kocak H. Left ventricle ejection fraction may predict mortality in renal transplant patients. Ren Fail 2016; 38:1622-1625. [PMID: 27841080 DOI: 10.1080/0886022x.2016.1194162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
PURPOSE Mortality is a major problem in renal transplant patients, and appropriate preoperative evaluation is very important. We retrospectively reviewed the left ventricle ejection fraction (LVEF) of renal transplant patients. MATERIAL AND METHODS The clinical records of 1763 patients who had preoperative LVEF results and who underwent renal transplantation at Akdeniz University Faculty of Medicine during the years 2004-2014 were studied. The LVEF limit was set at 55%. LVEF, age, gender, diabetes mellitus, hypertension, type of dialysis were assessed by linear multiple regression analysis on survival. RESULTS There were a total of 1763 renal transplant patients. Those with LVEF of <55% were identified as having left ventricular dysfunction. The mean LVEF was 59.4 ± 9.1 in the 43 patients who died after renal transplantation, while it was 62.6 ± 7.4 in the survivors (p = 0.02). The mortality rate in the LVEF < 55% group was 6.8% (11/162 patients), while mortality in the LVEF ≥ 55% group was 2% (32/1601 patients, p < 0.001). LVEF was found to be the most powerful variable on survival by the linear multiple regression analysis, R2 = 0.05, p < 0.001. CONCLUSION LVEF may predict mortality in renal transplant patients. LVEF is known to be lower in patients with high cardiac mortality, who may require greater modifications of the postoperative risks.
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Affiliation(s)
- Faruk Ozkul
- a Department of General Surgery, Faculty of Medicine , Çanakkale Onsekiz Mart University , Çanakkale , Turkey
| | - Muhammmet Kasim Arik
- a Department of General Surgery, Faculty of Medicine , Çanakkale Onsekiz Mart University , Çanakkale , Turkey
| | - Halil Erbiş
- b Department of General Surgery, School of Medicine , Akdeniz University , Antalya , Turkey
| | - Alpaslan Akbaş
- c Department of Urology, Faculty of Medicine , Çanakkale Onsekiz Mart University , Çanakkale , Turkey
| | - Vural Taner Yilmaz
- d Department of Internal Medicine, Division of Nephrology, School of Medicine , Akdeniz University , Antalya , Turkey
| | - Ahmet Barutcu
- e Department of Cardiology, Faculty of Medicine , Çanakkale Onsekiz Mart University , Çanakkale , Turkey
| | - Ibrahim Ali Osmanoğlu
- b Department of General Surgery, School of Medicine , Akdeniz University , Antalya , Turkey
| | - Hüseyin Kocak
- d Department of Internal Medicine, Division of Nephrology, School of Medicine , Akdeniz University , Antalya , Turkey
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Unique Considerations When Managing Hypertension in the Transplant Patient. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2016. [PMID: 27815930 DOI: 10.1007/5584_2016_87] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Abstract
For the select fortunate recipients of organ transplants, transplantation affords the rare opportunity for a new life. Given the scarcity of organs for transplantation, it is imperative that the health of transplant recipients be optimized in order to fully benefit from this gift of life. Unfortunately, hypertension is highly prevalent in the transplant population and it is considered a major cardiovascular risk factor contributing to mortality and morbidity in this population. In this chapter, we expound on the epidemiology, unique pathophysiology, evaluation, and management of hypertension as it pertains to the solid organ transplant recipient. In addition, a brief commentary is made on the subject of hypertension following living kidney donation, and practical aspects of management of hypertension in the solid organ recipient are summarized at the end of the chapter.
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Malachias MVB, Amodeo C, Paula RB, Cordeiro AC, Magalhães LBNC, Bodanese LC. 7th Brazilian Guideline of Arterial Hypertension: Chapter 8 - Hypertension and Associated Clinical Conditions. Arq Bras Cardiol 2016; 107:44-48. [PMID: 27819387 PMCID: PMC5319465 DOI: 10.5935/abc.20160158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
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Cheungpasitporn W, Thongprayoon C, Mao MA, Kittanamongkolchai W, Sathick IJJ, Erickson SB. The Effect of Renin-angiotensin System Inhibitors on Kidney Allograft Survival: A Systematic Review and Meta-analysis. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2016; 8:291-6. [PMID: 27583237 PMCID: PMC4982358 DOI: 10.4103/1947-2714.187141] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Background: The use of renin-angiotensin system (RAS) inhibitors in patients with chronic kidney disease, and especially in diabetic kidney disease, has been shown to provide renoprotective effects and slow progression to end-stage renal disease. However, this protective effect in kidney transplant patient populations is unclear. Aim: The objective of this systematic review and meta-analysis was to evaluate the effect of RAS inhibitors on kidney allograft survival. Materials and Methods: A literature search for randomized controlled trials (RCTs) was performed from inception through February 2016. Studies that reported relative risks or hazard ratios comparing the risks of renal graft loss in renal transplant recipients who received RAS inhibitors vs. controls were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Results: Five studies (3 RCTs and 2 cohort studies) with 20024 kidney transplant patients were included in the meta-analysis. Pooled RR of allograft failure in recipients who received RAS inhibitors was 0.73 (95% CI: 0.45–1.21). When meta-analysis was limited only to RCTs, the pooled RR of allograft failure in patients using RAS inhibitors was 0.59 (95%: CI 0.20–1.69). The risk for mortality (RR: 1.13 [95% CI: 0.62–2.07]) in patients using RAS inhibitors compared to controls was not significantly reduced. Conclusion: This meta-analysis demonstrated insignificant reduced risks of renal graft loss among renal transplant recipients who received RAS inhibitors. Future studies assessing the potential benefits of RAS inhibitors on allograft survival in specific kidney transplant patient populations are needed.
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Affiliation(s)
| | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael A Mao
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Insara J J Sathick
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephen B Erickson
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
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de Vries LV, Dobrowolski LC, van den Bosch JJ, Riphagen IJ, Krediet CP, Bemelman FJ, Bakker SJ, Navis G. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial. Am J Kidney Dis 2016; 67:936-44. [DOI: 10.1053/j.ajkd.2015.11.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 11/30/2015] [Indexed: 01/13/2023]
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Abstract
Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.
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Affiliation(s)
- Mrudula R Munagala
- Department of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Avenue, Suite # L4, Newark, NJ 07112, USA.
| | - Anita Phancao
- Integris Baptist Medical Center, 3400 Northwest Expressway, Building C, Suite 200, Oklahoma City, OK 73112, USA
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Knoll GA, Fergusson D, Chassé M, Hebert P, Wells G, Tibbles LA, Treleaven D, Holland D, White C, Muirhead N, Cantarovich M, Paquet M, Kiberd B, Gourishankar S, Shapiro J, Prasad R, Cole E, Pilmore H, Cronin V, Hogan D, Ramsay T, Gill J. Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol 2016; 4:318-26. [PMID: 26608067 DOI: 10.1016/s2213-8587(15)00368-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 09/14/2015] [Accepted: 09/15/2015] [Indexed: 01/13/2023]
Abstract
BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of end-stage renal disease and death in non-transplant patients with proteinuria. We examined whether ramipril would have a similar beneficial effect on important clinical outcomes in kidney transplant recipients with proteinuria. METHODS In this double-blind, placebo-controlled, randomised trial, conducted at 14 centres in Canada and New Zealand, we enrolled adult renal transplant recipients at least 3-months post-transplant with an estimated glomerular filtration rate (GFR) of 20 mL/min/1·73m(2) or greater and proteinuria 0·2 g per day or greater and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years. Patients completing the final 4-year study visit were invited to participate in a trial extension phase. Treatment was assigned by centrally generated randomisation with permuted variable blocks of 2 and 4, stratified by centre and estimated GFR (above or below 40 mL/min/1·73 m(2)). The primary outcome was a composite consisting of doubling of serum creatinine, end-stage renal disease, or death in the intention-to-treat population. The principal secondary outcome was the change in measured GFR. We ascertained whether any component of the primary outcome had occurred at each study visit (1 month and 6 months post-randomisation, then every 6 months thereafter). This trial is registered with ISRCTN, number 78129473. FINDINGS Between Aug 23, 2006, and March 28, 2012, 213 patients were randomised. 109 were allocated to placebo and 104 were allocated to ramipril, of whom 109 patients in the placebo group and 103 patients in the ramipril group were analysed and the trial is now complete. The intention to treat population (placebo n=109, ramipril n=103) was used for the primary analysis and the trial extension phase analysis. The primary outcome occurred in 19 (17%) of 109 patients in the placebo group and 14 (14%) of 103 patients in the ramipril group (hazard ratio [HR] 0·76 [95% CI 0·38-1·51]; absolute risk difference -3·8% [95% CI -13·6 to 6·1]). With extended follow-up (mean 48 months), the primary outcome occurred in 27 patients (25%) in the placebo group and 25 (24%) patients in the ramipril group (HR 0·96 [95% CI 0·55-1·65]); absolute risk difference: -0·5% (95% CI -12·0 to 11·1). There was no significant difference in the rate of measured GFR decline between the two groups (mean difference per 6-month interval: -0·16 mL/min/1·73m(2) (SE 0·24); p=0·49). 14 (14%) of patients died in the ramipril group and 11 (10%) in the placebo group, but the difference between groups was not statistically significant (HR 1·45 [95% CI 0·66 to 3·21]). Adverse events were more common in the ramipril group (39 [38%]) than in the placebo group (24 [22%]; p=0·02). INTERPRETATION Treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population. FUNDING Canadian Institutes of Health Research.
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Affiliation(s)
- Greg A Knoll
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada; Kidney Research Centre, Ottawa Hospital Research Institute and University of Ottawa, Ottawa, ON, Canada.
| | - Dean Fergusson
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Michaël Chassé
- Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Paul Hebert
- Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
| | - George Wells
- Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Lee Anne Tibbles
- Division of Nephrology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Darin Treleaven
- Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - David Holland
- Division of Nephrology, Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Christine White
- Division of Nephrology, Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Norman Muirhead
- Division of Nephrology, Department of Medicine, Western University, London, ON, Canada
| | - Marcelo Cantarovich
- Division of Nephrology, Department of Medicine, McGill University, Montreal, QC, Canada
| | - Michel Paquet
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
| | - Bryce Kiberd
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sita Gourishankar
- Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Jean Shapiro
- Division of Nephrology, Department of Medicine, Vancouver General Hospital, Vancouver, BC, Canada
| | - Ramesh Prasad
- Division of Nephrology, Department of Medicine, St Michael's Hospital, Toronto, ON, Canada
| | - Edward Cole
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, ON, Canada
| | - Helen Pilmore
- Department of Renal Medicine, Auckland City Hospital and Department of Medicine, Auckland University, Auckland, New Zealand
| | - Valerie Cronin
- Kidney Research Centre, Ottawa Hospital Research Institute and University of Ottawa, Ottawa, ON, Canada
| | - Debora Hogan
- Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Tim Ramsay
- Clinical Epidemiology Program, Ottawa Hospital Research Institute and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada
| | - John Gill
- Division of Nephrology, Department of Medicine, St Paul's Hospital, Vancouver, BC, Canada
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Pathophysiologic and treatment strategies for cardiovascular disease in end-stage renal disease and kidney transplantations. Cardiol Rev 2016; 23:109-18. [PMID: 25420053 DOI: 10.1097/crd.0000000000000044] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The inextricable link between the heart and the kidneys predestines that significant cardiovascular disease ensues in the face of end-stage renal disease (ESRD). As a point of fact, the leading cause of mortality of patients on dialysis is still from cardiovascular etiologies, albeit differing in particular types of disease from the general population. For example, sudden cardiac death outnumbers coronary artery disease in patients with ESRD, which is the reverse for the general population. In this review, we will focus on the pathophysiology and treatment options of important traditional and nontraditional risk factors for cardiovascular disease in ESRD patients such as hypertension, anemia, vascular calcification, hyperparathyroidism, uremia, and oxidative stress. The evidence of erythropoietin-stimulating agents, phosphate binders, calcimimetics, and dialysis modalities will be presented. We will then discuss how these risk factors may be changed and perhaps exacerbated after renal transplantation. This is largely due to the immunosuppressive agents that are both crucial yet potentially detrimental in the posttransplant state. Calcineurin inhibitors, corticosteroids, and mammalian target of rapamycin inhibitors, the mainstay of transplant immunosuppression, are all known to increase the risks of developing new onset diabetes as well as the metabolic syndrome. Thus, we need to carefully negotiate between patients' cardiovascular profile and their risks of rejection. Finally, we end by considering strategies by which we may minimize cardiovascular disease in the transplant population, as this modality still confers the highest chance of survival in patients with ESRD.
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Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant 2015; 5:183-95. [PMID: 26722646 PMCID: PMC4689929 DOI: 10.5500/wjt.v5.i4.183] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 08/19/2015] [Accepted: 09/25/2015] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.
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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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Trachtman H, Frymoyer A, Lewandowski A, Greenbaum LA, Feig DI, Gipson DS, Warady BA, Goebel JW, Schwartz GJ, Lewis K, Anand R, Patel UD. Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection. Clin Pharmacol Ther 2015; 98:25-33. [PMID: 25807932 PMCID: PMC4536255 DOI: 10.1002/cpt.127] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 03/19/2015] [Indexed: 12/24/2022]
Abstract
Hypertension in pediatric kidney transplant recipients contributes to long-term graft loss, yet treatment options--including angiotensin-converting enzyme inhibitors--are poorly characterized in this vulnerable population. We conducted a multicenter, open-label pharmacokinetic (PK) study of daily oral lisinopril in 22 children (ages 7-17 years) with stable kidney transplant function. Standard noncompartmental PK analyses were performed at steady state. Effects on blood pressure were examined in lisinopril-naïve patients (n = 13). Oral clearance declined in proportion to underlying kidney function; however, in patients with low estimated glomerular filtration rate (30-59 ml/min per 1.73m(2)), exposure (standardized to 0.1 mg/kg/day dose) was within the range reported previously in children without a kidney transplant. In lisinopril-naïve patients, 85% and 77% had a ≥ 6 mmHg reduction in systolic and diastolic blood pressure, respectively. Lisinopril was well tolerated. Our study provides initial insight on lisinopril use in children with a kidney transplant, including starting dose considerations.
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Affiliation(s)
- Howard Trachtman
- Department of Pediatrics, New York University, New York, NY, USA
| | - Adam Frymoyer
- Department of Pediatrics, Stanford University, Palo Alto, CA, USA
| | | | | | - Daniel I. Feig
- Division of Pediatric Nephrology, University of Alabama, Birmingham, AL, USA
| | - Debbie S. Gipson
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Bradley A. Warady
- Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA
| | - Jens W. Goebel
- Division of Nephrology and Hypertension, Cincinnati Children’s Hospital, Cincinnati, OH, USA
| | - George J. Schwartz
- Division of Pediatric Nephrology, University of Rochester, Rochester, NY, USA
| | | | | | - Uptal D. Patel
- Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
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Veličković-Radovanović RM, Janković SM, Milovanović JR, Catić-Đorđević AK, Spasić AA, Stefanović NZ, Džodić PL, Šmelcerović AA, Cvetković TP. Variability of mycophenolic acid elimination in the renal transplant recipients – population pharmacokinetic approach. Ren Fail 2015; 37:652-658. [PMID: 25707517 DOI: 10.3109/0886022x.2015.1010442] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.33 kg) using nonlinear mixed-effect modeling (NONMEM). Characteristics of patients screened for influence on the pharmacokinetic parameters were gender, age, body weight, time after transplantation, whether the patient was diagnosed as having diabetes mellitus, organ source (living or deceased donor), biochemical parameters and co-therapy (tacrolimus, cyclosporine, prednisolone, omeprazole, bisoprolol, carvedilol, nifedipine). A validation set of 25 renal transplant recipients was used to estimate the predictive performance of population pharmacokinetic model. Typical mean value of MPA oral clearance, estimated by base model (without covariates) was 0.741 L h(-1). During population modeling, the full model showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy. In the final model, clearance of MPA was reported to be significantly influenced by age, total daily dose of MPA and thenifedipine co-therapy. The derived model describes adequately MPA clearance in terms of characteristics of our patients, offering basis for individual pharmacotherapy approach.
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Rossi AP, Vella JP. Hypertension, living kidney donors, and transplantation: where are we today? Adv Chronic Kidney Dis 2015; 22:154-64. [PMID: 25704353 DOI: 10.1053/j.ackd.2015.01.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 01/05/2015] [Indexed: 02/08/2023]
Abstract
Hypertension is a prevalent problem in kidney transplant recipients that is known to be a "traditional" risk factor for atherosclerotic cardiovascular disease leading to premature allograft failure and death. Donor, peritransplant, and recipient factors affect hypertension risk. Blood pressure control after transplantation is inversely associated with glomerular filtration rate (GFR). Calcineurin inhibitors, the most commonly used class of immunosuppressives, cause endothelial dysfunction, increase vascular tone, and sodium retention via the renin-angiotensin-aldosterone system resulting in systemic hypertension. Steroid withdrawal seems to have little impact on blood pressure control. Newer agents like belatacept appear to be associated with less hypertension. Transplant renal artery stenosis is an important, potentially treatable cause of hypertension. Dihydropyridine calcium channel blockers mitigate calcineurin inhibitor nephrotoxicity and may be associated with improved estimated GFR. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not recommended in the first 3 to 6 months given their effects on reduced estimated GFR, anemia, and hyperkalemia. The use of ß-blockers may be associated with improved patient survival, even for patients without cardiovascular disease. Living donation may increase blood pressure by 5 mm Hg or more. Some transplant centers accept Caucasian living donors with well-controlled hypertension on a single agent if they agree to close follow-up.
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Houri I, Tzukert K, Levi IMY, Aharon M, Bloch A, Gotsman O, Backenroth R, Levi R, Dov IB, Rubinger D, Elhalel MD. Implementation of guidelines for metabolic syndrome control in kidney transplant recipients: results at a single center. Diabetol Metab Syndr 2015; 7:90. [PMID: 26478748 PMCID: PMC4609158 DOI: 10.1186/s13098-015-0083-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 10/01/2015] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Cardiovascular disease is a leading cause of death among kidney transplant recipients. Metabolic syndrome increases the risk for cardiovascular events and decreases graft survival. Lately, guidelines for management of the metabolic syndrome, primarily hypertension, diabetes mellitus (DM) and hypercholesterolemia have dramatically changed in an attempt to decrease cardiovascular risks among kidney transplant recipients. In the present study we examined whether these guideline changes had impact on our management of post-transplantation patients and the subsequent treatment outcomes for these diseases. METHODS Data were obtained from kidney transplant clinic files from two follow-up (FU) periods-between 1994-1997 and between 2008-2011. Demographic data, monitoring and screening frequency for cardiovascular risk factors, immunosuppression regimen, treatment for hypertension, diabetes and hyperlipidemia, treatment outcomes and graft function changes were compared between the two follow-up periods. RESULTS There was a significant increase in the percentage of patients undergoing transplantation due to renal failure secondary to diabetes and/or hypertension. Patient monitoring and screening during the second FU period were less frequent, but more targeted, reflecting changes in clinic routines. Blood pressure was better controlled in the second FU period (p < 0.01), as was hypercholesterolemia (p < 0.001). High fasting glucose levels were more prevalent among patients in the second group (p < 0.005), although more patients received treatment for DM (p < 0.001). Significantly, fewer patients experienced deterioration of kidney functions during the second FU period (p < 0.001). CONCLUSIONS We found that guideline changes had impact on clinical practice, which translated to better control of the metabolic syndrome. DM control is challenging. Overall, stability of kidney function improved.
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Affiliation(s)
- Inbal Houri
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Keren Tzukert
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Irit Mor-Yosef Levi
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Michal Aharon
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Aharon Bloch
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Olga Gotsman
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Rebecca Backenroth
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Ronen Levi
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Iddo Ben Dov
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Dvora Rubinger
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
| | - Michal Dranitzki Elhalel
- Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
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Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int 2014; 28:10-21. [PMID: 25081992 DOI: 10.1111/tri.12413] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 07/28/2014] [Indexed: 12/14/2022]
Abstract
Kidney transplantation is the optimal treatment for patients with end stage renal disease (ESRD) who would otherwise require dialysis. Patients with ESRD are at dramatically increased cardiovascular (CV) risk compared with the general population. As well as improving quality of life, successful transplantation accords major benefits by reducing CV risk in these patients. Worldwide, cardiovascular disease remains the leading cause of death with a functioning graft and therefore is a leading cause of graft failure. This review focuses on the mechanisms underpinning excess CV morbidity and mortality and current evidence for improving CV risk in kidney transplant recipients. Conventional CV risk factors such as hypertension, diabetes mellitus, dyslipidaemia and pre-existing ischaemic heart disease are all highly prevalent in this group. In addition, kidney transplant recipients exhibit a number of risk factors associated with pre-existing renal disease. Furthermore, complications specific to transplantation may ensue including reduced graft function, side effects of immunosuppression and post-transplantation diabetes mellitus. Strategies to improve CV outcomes post-transplantation may include pharmacological intervention including lipid-lowering or antihypertensive therapy, optimization of graft function, lifestyle intervention and personalizing immunosuppression to the individual patients risk profile.
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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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Thomas B, Taber DJ, Srinivas TR. Hypertension after kidney transplantation: a pathophysiologic approach. Curr Hypertens Rep 2014; 15:458-69. [PMID: 23933793 DOI: 10.1007/s11906-013-0381-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.
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Affiliation(s)
- Beje Thomas
- Division of Nephrology, Medical University of South Carolina, 96 Jonathan Lucas Street CSB 829, Charleston, SC, 29425, USA,
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Lentine KL, Anyaegbu E, Gleisner A, Schnitzler MA, Axelrod D, Brennan DC, Dharnidharka VR, Abraham E, Tuttle-Newhall JE. Understanding medical care of transplant recipients through integrated registry and pharmacy claims data. Am J Nephrol 2013; 38:420-9. [PMID: 24216747 DOI: 10.1159/000356092] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 09/29/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND Limited data exist on medication use aside from immunosuppression among large samples of kidney transplant recipients. METHODS We examined a novel database wherein Organ Procurement and Transplantation Network (OPTN) registry data were linked to records from a US pharmaceutical claims clearinghouse (2005-2010 claims) to examine pharmaceutical care at the first transplant anniversary (n = 16,157). We quantified the use of the following medication types within ±60 days of the first-year OPTN report according to estimated glomerular filtration rate (eGFR): antihypertensives, lipid-lowering, bone and mineral, and anemia treatments. Adjusted associations of medication use with eGFR and other clinical factors were quantified by multivariate logistic regression. RESULTS Requirements for multiple antihypertensive agents rose with lower eGFR, with β-blockers comprising the most commonly used antihypertensive agent. The adjusted likelihood of vitamin D (adjusted odds ratio (aOR) 2.07, 95% CI 1.19-3.59) and especially erythrocyte-stimulating agents (aOR 19.94, 95% CI 7.01-56.00) rose in a graded manner to peak with eGFR <15 versus >90, whereas statin use was most common with eGFR 30-59 ml/min/1.73 m(2). Black race was independently associated with increased use of all classes of antihypertensives and vitamin D, but lower adjusted statin use. Rapamycin-based immunosuppression was associated with increased use of statins and erythrocyte-stimulating agents. CONCLUSIONS Integrated registry and pharmacy fill data provide a novel tool for pharmacoepidemiologic investigations of delivered post-transplant care. Transplant recipients with reduced renal function have increased requirements for pharmaceutical care of comorbidities. Causes of racial variation in medication fills warrant further investigation.
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Affiliation(s)
- Krista L Lentine
- Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, Mo., USA
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Oblak M, Kandus A, Mlinšek G, Buturović-Ponikvar J, Arnol M. Increase in Proteinuria After Acute Kidney Graft Rejection is Associated With Decreased Graft Function and Survival. Transplant Proc 2013; 45:1453-7. [DOI: 10.1016/j.transproceed.2013.02.106] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 02/08/2013] [Accepted: 02/27/2013] [Indexed: 01/21/2023]
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Abstract
PURPOSE OF REVIEW After renal transplantation, cardiovascular disease (CVD) is the leading cause of death with a functioning graft. Guidelines for prevention of CVD are mainly based on data from the general population. The purpose of this review is to give a practical approach on prevention of CVD in renal transplant recipients. RECENT FINDINGS New epidemiological data have shown that in addition to traditional risk factors for CVD, other risk factors may influence cardiovascular risk in renal transplant recipients. Recently, a specific risk calculator for CVD in renal transplant recipients has been developed. Prevention of CVD in renal transplant recipients should include lifestyle modifications, such as prevention of overweight, smoking cessation and physical exercise. Optimal treatment of hypertension, lipid disturbances and posttransplant diabetes should be encouraged. Accumulating evidence indicates that declining graft function and graft loss are potentially modifiable risk factors in this population, which make strategies for preserving graft function important. This situation may include individual tailoring of immunosuppression and use of new immunosuppressive medications with a more favorable effect on cardiovascular risk factors and graft function. SUMMARY To prevent CVD in renal transplant recipients, cardiovascular risk assessment should be performed regularly. Prevention should include both lifestyle modifications, optimal treatment of cardiovascular risk factors and strategies to preserve graft function.
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