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Thongprayoon C, Hansrivijit P, Leeaphorn N, Acharya P, Torres-Ortiz A, Kaewput W, Kovvuru K, Kanduri SR, Bathini T, Cheungpasitporn W. Recent Advances and Clinical Outcomes of Kidney Transplantation. J Clin Med 2020; 9:1193. [PMID: 32331309 PMCID: PMC7230851 DOI: 10.3390/jcm9041193] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.
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Affiliation(s)
- Charat Thongprayoon
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | - Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA 17105, USA;
| | - Napat Leeaphorn
- Department of Nephrology, Department of Medicine, Saint Luke’s Health System, Kansas City, MO 64111, USA;
| | - Prakrati Acharya
- Division of Nephrology, Department of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA;
| | - Aldo Torres-Ortiz
- Department of Medicine, Ochsner Medical Center, New Orleans, LA 70121, USA;
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand;
| | - Karthik Kovvuru
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
| | - Swetha R. Kanduri
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
| | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85724, USA;
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.)
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Abstract
Advancement in kidney transplantation has led to prolonged survival in our population with kidney disease. Newer agents of immunosuppression have made this possible with less rejections and lesser opportunistic infections and transplant related deaths. Preventative care like timely vaccines, cancer screenings, aggressive blood pressure, blood sugar, lipid control, timely referral to consultants is required in these patient population to provide quality care and to prolong their survival. Primary care physicians are the best advocate for our transplant populations. To care for these complex transplant patients, it is vital for primary care physicians to be familiar with the overall approach on our patients.
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Affiliation(s)
- Kavitha Ramaswamy
- Thomas Jefferson University Hospital, Division of Nephrology, 833 Chestnut St, Suite 700, Philadelphia, PA 19107, USA.
| | - Hector M Madariaga
- Good Samaritan Medical Center, Department of Medicine, 235N Pearl St, Brockton, MA 02301, USA
| | - Beje S Thomas
- Georgetown University Medical Center, MedStar Georgetown Transplant Institute, 3800 Reservoir Road, Washington, DC 20007 USA
| | - Edgar V Lerma
- University of Illinois at Chicago College of Medicine/ Advocate Christ Medical Center, Oak Lawn, IL, USA
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The consequences of pediatric renal transplantation on bone metabolism and growth. Curr Opin Organ Transplant 2015; 18:555-62. [PMID: 23995376 DOI: 10.1097/mot.0b013e3283651b21] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. RECENT FINDINGS In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. SUMMARY In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).
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Pandya V, Rao A, Chaudhary K. Lipid abnormalities in kidney disease and management strategies. World J Nephrol 2015; 4:83-91. [PMID: 25664249 PMCID: PMC4317631 DOI: 10.5527/wjn.v4.i1.83] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 10/10/2014] [Accepted: 11/03/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with kidney diseases continue to experience significant cardiovascular disease (CVD) morbidity and mortality. Although there are many important risk factors playing a role in the pathogenesis of CVD in chronic kidney disease (CKD) patients, dyslipidemia (elevated triglycerides, elevated oxidized low-density lipoprotein and low/dysfunctional low high-density) represents one of the modifiable risk factors. Renal failure patients have unique lipid abnormalities which not only have complex role in pathogenesis of CVD but also cause relative resistance to usual interventions. Most of the randomized trials have been in hemodialysis population and data from CKD non-dialysis, peritoneal dialysis and renal transplant populations is extremely limited. Compared to general population, evidence of mortality benefit of lipid lowering medications in CKD population is scarce. Future research should be directed towards establishing long term benefits and side effects of lipid lowering medications, through randomized trials, in CKD population.
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Murakami N, Riella LV, Funakoshi T. Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis. Am J Transplant 2014; 14:2317-27. [PMID: 25146383 DOI: 10.1111/ajt.12852] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 05/14/2014] [Accepted: 05/28/2014] [Indexed: 01/25/2023]
Abstract
Mammalian target of rapamycin (mTOR) inhibitors have been used in transplantation with the hope of minimizing calcineurin inhibitor (CNI)-induced nephrotoxicity. However, mTOR inhibitors are also associated with a range of side effects, including metabolic complications. We aimed to determine the risks of metabolic complications after the conversion from CNI to mTOR inhibitor postkidney transplant. A systematic search in PubMed up to September 2013 identified nine relevant trials (a total of 2323 patients). The primary end points were the relative risks (RRs) of new-onset diabetes after transplant (NODAT) and hypercholesterolemia. The overall RRs of NODAT and hypercholesterolemia associated with mTOR inhibitors were 1.32 (95% confidence interval [CI] 0.92-1.87) and 2.15 (95% CI 1.35-3.41), respectively, compared with CNI-based regimen. Subgroup analyses revealed no differences in the incidence of NODAT or hypercholesterolemia between sirolimus- versus everolimus-based regimen, or between early versus late conversion. Analyses of secondary outcomes revealed a higher risk of acute rejection, proteinuria and anemia, but no difference in the risk of opportunistic infections after mTOR inhibitor conversion. In conclusion, the conversion from CNI to mTOR inhibitor in low-to-moderate risk kidney transplant recipients was associated with nonsignificant trend toward increased risk of NODAT and significant increase in hypercholesterolemia, acute rejection, proteinuria and anemia.
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Affiliation(s)
- N Murakami
- Department of Medicine, Beth Israel Medical Center, New York, NY
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Holdaas H, Holme I, Schmieder RE, Jardine AG, Zannad F, Norby GE, Fellström BC. Rosuvastatin in diabetic hemodialysis patients. J Am Soc Nephrol 2011; 22:1335-41. [PMID: 21566054 DOI: 10.1681/asn.2010090987] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
A randomized, placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint, but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk. Because the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial included patients with and without diabetes, we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis. Among the 731 participants with diabetes, traditional risk factors such as LDL-C, smoking, and BP did not associate with cardiac events (cardiac death and nonfatal myocardial infarction). At baseline, only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events. Assignment to rosuvastatin associated with a nonsignificant 16.2% reduction in risk for the AURORA trial's composite primary endpoint of cardiac death, nonfatal MI, or fatal or nonfatal stroke (HR 0.84; 95% CI 0.65 to 1.07). There was no difference in overall stroke, but the rosuvastatin group had more hemorrhagic strokes than the placebo group (12 versus two strokes, respectively; HR, 5.21; 95% CI 1.17 to 23.27). Rosuvastatin treatment significantly reduced the rates of cardiac events by 32% among patients with diabetes (HR 0.68; 95% CI 0.51 to 0.90). In conclusion, among hemodialysis patients with diabetes mellitus, rosuvastatin might reduce the risk of fatal and nonfatal cardiac events.
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Affiliation(s)
- Hallvard Holdaas
- Department of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Sognsvannsveien 22, 0072 Oslo, Norway.
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Vivek V, Bhandari S. Prevalence of modifiable cardiovascular risk factors in long-term renal transplant patients. Int J Nephrol Renovasc Dis 2010; 3:175-82. [PMID: 21694943 PMCID: PMC3108770 DOI: 10.2147/ijnrd.s13866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Indexed: 12/14/2022] Open
Abstract
Background: Cardiovascular disease accounts for the majority of morbidity and mortality in renal transplant patients. This relates to a number of modifiable and nonmodifiable risk factors, including new onset diabetes after transplantation (NODAT). We examined the prevalence of these risk factors in a cohort of 126 renal transplant patients. Methods: A retrospective cross-sectional study of 94 nondiabetic post-transplant (ND) patients (mean age 45.7 ± 13.5 years) and 32 NODAT patients (55.2 ± 9.6 years) was performed. Univariate linear regression analysis was used to identify potential factors that affected cardiovascular events. Multivariable analysis was performed on those factors found to achieve a P value of less than 0.20 after univariate analysis to test for significance in relation to cardiovascular risk as the primary factor. Results: Mean serum creatinine levels were 131.1 ± 4.3 μmol/L and 135.2 ± 4.9 μmol/L at 96.9 ± 8.7 and 79.4 ± 14.1 months post-transplantation, respectively. Systolic pressure and pulse pressure were significantly higher in NODAT patients (P = 0.016 and P < 0.005). Adequate target blood pressures were obtained in 80% of patients. Low-density lipoprotein and high-density lipoprotein cholesterol were reduced in NODAT (P = 0.04 and P = 0.005). Homocysteine was similarly elevated in both groups (17.5 and 15.6 μmol/L, respectively). Coronary events and/or coronary disease were present in 19.1% of ND and 37.5% of NODAT patients (P < 0.05). Cardiac deaths were three-fold more common (25% versus 7.4%) in patients with NODAT. Univariate analysis revealed diabetes and age, and subsequent multivariable analysis revealed age only, as being significantly associated with cardiovascular outcomes. Conclusions: Cardiac events are more common in patients with NODAT. Age is an important determinant of cardiovascular risk.
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Affiliation(s)
- Vadamalai Vivek
- Department of Renal Medicine, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, East Yorkshire, UK
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Toms TE, Smith JP, Panoulas VF, Douglas KMJ, Saratzis AN, Kitas GD. Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients. Musculoskeletal Care 2010; 8:2-9. [PMID: 19642078 DOI: 10.1002/msc.160] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVES Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (SLCO1B1). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in RA. METHODS A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS Almost 80% of RA patients had one or more risk factor (range 1-5) for the development of statin-induced myopathy. Of the 74 RA patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. CONCLUSIONS RA patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients.
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Affiliation(s)
- Tracey E Toms
- Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, West Midlands, UK
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Wiesbauer F, Heinze G, Mitterbauer C, Harnoncourt F, Hörl WH, Oberbauer R. Statin use is associated with prolonged survival of renal transplant recipients. J Am Soc Nephrol 2008; 19:2211-8. [PMID: 18650477 PMCID: PMC2573011 DOI: 10.1681/asn.2008010101] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2008] [Accepted: 06/10/2008] [Indexed: 11/03/2022] Open
Abstract
The efficacy of statins for the prevention of cardiovascular events is well established in the general population but remains unknown in renal transplant recipients. In this study, the association of statin use with patient and graft survival was investigated in a cohort of 2041 first-time recipients of renal allografts between 1990 and 2003. Multivariable Cox regression demonstrated that statin use was independently associated with lower mortality rates. Twelve-year survival rates were 73% for statin users and 64% for nonusers (P = 0.055). The adjusted hazard ratio for all-cause mortality associated with statin use was 0.64 (95% confidence interval 0.48 to 0.86). Graft survival rates during the same time period were 76% for statin users and 70% for nonusers (P = 0.055). The adjusted hazard ratio for graft survival associated with statin use was 0.76 (95% confidence interval 0.55 to 1.04). Results from marginal structural models were virtually identical. In summary, statin use was associated with prolonged patient survival, but no difference in graft survival was detected. Although these results are encouraging, a definitive causal relationship can be determined only from randomized clinical trials.
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Affiliation(s)
- Franz Wiesbauer
- Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
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Gluhovschi G, Gluhovschi C, Bob F, Velciov S, Trandafirescu V, Petrica L, Bozdog G. Multiorgan-protective actions of blockers of the renin-angiotensin system, statins and erythropoietin: common pleiotropic effects in reno-, cardio- and neuroprotection. Acta Clin Belg 2008; 63:152-69. [PMID: 18714846 DOI: 10.1179/acb.2008.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Renal diseases induce nephroprotective measures that may affect the heart, brain and other organs. In addition, many cardiovascular and neurological diseases are accompanied by renal lesions. For these reasons, multiorgan-protective measures, including cardio-, reno- and neuro-protective measures, are necessary to treat these diseases. The drugs used in nephrology are often pleiotropic. Although they usually address a single organ or tissue, many of them have complex actions that may provide multiorgan-protection. The present paper aims to review 3 classes of drugs that are commonly prescribed in nephrological practice: statins, RAS blockers (such as ACEIs and ARBs) and erythropoietin (EPO). This paper highlights the renoprotective actions, as well as those that are protective of the heart, brain and other organs, of these drugs at the cellular and molecular level. Their protective actions are attributable to their main effects and pleiotropic effects. The protective pleiotropic actions of these drugs may be exerted on multiple organs, making them multiorgan-protective. Another objective is to analyse the shared multiorgan-protective pleiotropic effects of RAS blockers (ACEIs and ARBs), statins and erythropoietin. This will allow for the practical association of the main renoprotective drugs with multiorgan protection.
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Affiliation(s)
- G Gluhovschi
- Nephrology Department, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania.
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Khella S, Bleicher MB. Stroke and its prevention in chronic kidney disease. Clin J Am Soc Nephrol 2007; 2:1343-51. [PMID: 17942760 DOI: 10.2215/cjn.04341206] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This is a review of stroke mechanisms and management. The concept of stroke and transient ischemic attack and the recently proposed revision in definitions and controversies are discussed. We also discuss the use of antiplatelet and anticoagulant drugs for stroke due to carotid and cardiac disease.
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Affiliation(s)
- Sami Khella
- Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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Webster AC, Craig JC, Simpson JM, Jones MP, Chapman JR. Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: a cohort study of 15,183 recipients. Am J Transplant 2007; 7:2140-51. [PMID: 17640312 DOI: 10.1111/j.1600-6143.2007.01908.x] [Citation(s) in RCA: 212] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Transplant recipients have increased cancer risk, but data on risk variation across different patient groups are sparse. Rates and standardized rate ratios (SRR) of cancer (all sites, excluding nonmelanocytic skin and lip cancer) compared to the general population were calculated, using Australia and New Zealand Dialysis and Transplant Registry data. Within the transplant population, risk factors were identified (hazard ratios: HR; 95% CI) and absolute risk estimated for recipient groups. A total of 1642 (10.8%) of 15 183 recipients developed cancer. Risk was inversely related to age (SRR 15-30 children, 2 if >65 years). Females aged 25-29 had rates equivalent to women aged 55-59 from the general population. Age trend for lymphoma, colorectal and breast risk was similar; melanoma showed less variability across ages, prostate showed no risk increase. Within the transplanted population, risk was affected by age differently for each sex (p = 0.007), elevated by prior malignancy (HR 1.40; 1.03-1.89), white race (HR 1.36; 1.12-1.89), but reduced by diabetic end-stage kidney disease (ESKD) (HR 0.67; 0.50-0.89). Cancer rates in kidney recipients are similar to nontransplanted people 20-30 years older, but absolute risk differs across patient groups. Men aged 45-54 surviving 10 years have cancer risks varying from 1 in 13 (non-white, no prior cancer, diabetic ESKD) to 1 in 5 (white, prior cancer, other ESKD).
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Affiliation(s)
- A C Webster
- NHMRC Centre for Clinical Research Excellence in Renal Medicine, Children's Hospital at Westmead, NSW, Australia.
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Abstract
As survival increases after liver transplantation, common issues that arise involve immunosuppression-related complications and primary health care. Proper emphasis on the prevention and treatment of post-liver transplant complications, such as diabetes mellitus, dyslipidemia, renal dysfunction, osteoporosis, and obesity, requires careful screening and long-term surveillance to minimize the progression of these complications. Active involvement by internists and subspecialists is necessary and a multidisciplinary approach should be undertaken. Liver transplantation should be viewed as a lifelong commitment by both patient and physician.
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Affiliation(s)
- Lawrence U Liu
- Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1104, New York, NY 10029, USA.
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Holdaas H, Fellström B, Cole E, Nyberg G, Olsson AG, Pedersen TR, Madsen S, Grönhagen-Riska C, Neumayer HH, Maes B, Ambühl P, Hartmann A, Staffler B, Jardine AG. Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant 2005; 5:2929-36. [PMID: 16303007 DOI: 10.1111/j.1600-6143.2005.01105.x] [Citation(s) in RCA: 227] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Renal transplant recipients (RTR) have an increased risk of premature cardiovascular disease. The ALERT study is the first trial to evaluate the effect of statin therapy on cardiac outcomes following renal transplantation. Patients initially randomized to fluvastatin or placebo in the 5-6 year ALERT study were offered open-label fluvastatin XL 80 mg/day in a 2-year extension to the original study. The primary endpoint was time to first major adverse cardiac event (MACE). Of 1787 patients who completed ALERT, 1652 (92%) were followed in the extension. Mean total follow-up was 6.7 years. Mean LDL-cholesterol was 98 mg/dL (2.5 mmol/L) at last follow-up compared to a pre-study level of 159 mg/dL (4.1 mmol/L). Patients randomized to fluvastatin had a reduced risk of MACE (hazards ratio [HR] 0.79, 95% CI 0.63-0.99, p = 0.036), and a 29% reduction in cardiac death or definite non-fatal MI (HR 0.71, 95% CI 0.55-0.93, p = 0.014). Total mortality and graft loss did not differ significantly between groups. Fluvastatin produces a safe and effective reduction in LDL-cholesterol associated with reduced risk of MACE in RTR. The lipid-lowering and cardiovascular benefits of fluvastatin are comparable to those of statins in other patient groups, and support use of fluvastatin in RTR.
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Abstract
1. Yearly screening of liver recipients with serum cholesterol, triglycerides, and lipoproteins, and assessment for risk factors for atherosclerotic cardiovascular disease, is an important component of comprehensive post transplant care. 2. Revised guidelines and target levels of LDL-cholesterol levels specific for moderate and high cardiovascular risk patients have been recently revised. 3. Transplant physicians should be aware of advances in the management of post transplant arterial hypertension, diabetes mellitus, obesity, and nicotine dependence.
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Affiliation(s)
- Santiago J Muñoz
- Center for Liver Disease, Division of Hepatology, Albert Einstein Medical Center, Philadelphia, PA 19141, USA.
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