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Vitamin K and Kidney Transplantation.
Fusaro, M, Cosmai, L, Evenepoel, P, Nickolas, TL, Cheung, AM, Aghi, A, Tripepi, G, Plebani, M, Iervasi, G, Vettor, R, et al
Nutrients. 2020;(9)
Abstract
The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.
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Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical Practice.
Garg, AX, Levey, AS, Kasiske, BL, Cheung, M, Lentine, KL, ,
Clinical journal of the American Society of Nephrology : CJASN. 2020;(6):896-905
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Abstract
The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 "Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors" was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a "proof-of-concept" risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate's profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.
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Treatment of dyslipidemia in kidney transplantation.
Ponticelli, C, Arnaboldi, L, Moroni, G, Corsini, A
Expert opinion on drug safety. 2020;(3):257-267
Abstract
Introduction: Lipid disorders are frequent after kidney transplantation (KT) and KT recipients are considered at high- or very-high cardiovascular risk. Among many concurring factors, a major role is played by immunosuppressants.Areas covered: General measures to manage lipid disorders first include physical activity and diet counseling. Modulating the doses of immunosuppressants also improves dyslipidemia. When lipid-lowering drugs are necessary to control elevated plasma cholesterol and/or triglycerides, statins are the cornerstone for managing hypercholesterolemia. However, side-effects (e.g. myopathy, new-onset diabetes, and kidney graft dysfunction) may occur. In these cases, ezetimibe (which does not affect kidney function) alone or on top of statins for the severe cases, is suggested by the most recent Guidelines. Proprotein convertase subtilisin/kexin type9 inhibitors are promising but expensive and their use in KT is still limited.Expert opinion: In KT recipients, statins should be used cautiously. Rather than using high-dose statin in difficult patients, an association with ezetimibe is suggested. While fibrates, niacin, and resins do not play a relevant role due to their erratic efficacy and common side-effects, new lipid-lowering drugs are emerging but their safety and efficacy in KT patients still need to be assessed.
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[Post-transplantation diabetes in kidney transplant: from the diabetologist point of view].
Pauchet, A, Schwotzer, N, Lamine, F, Perrottet, N, Zanchi, A, Golshayan, D, Wojtusciszyn, A
Revue medicale suisse. 2020;(697):1200-1205
Abstract
Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients.
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Post-transplantation Outcomes in Patients with PA or MMA: A Review of the Literature.
Yap, S, Vara, R, Morais, A
Advances in therapy. 2020;(5):1866-1896
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Abstract
INTRODUCTION Liver transplantation is recognised as a treatment option for patients with propionic acidemia (PA) and those with methylmalonic acidemia (MMA) without renal impairment. In patients with MMA and moderate-to-severe renal impairment, combined liver-kidney transplantation is indicated. However, clinical experience of these transplantation options in patients with PA and MMA remains limited and fragmented. We undertook an overview of post-transplantation outcomes in patients with PA and MMA using the current available evidence. METHODS A literature search identified publications on the use of transplantation in patients with PA and MMA. Publications were considered if they presented adequate demographic and outcome data from patients with PA or MMA. Publications that did not report any specific outcomes for patients or provided insufficient data were excluded. RESULTS Seventy publications were identified of which 38 were full papers. A total of 373 patients underwent liver/kidney/combined liver-kidney transplantation for PA or MMA. The most typical reason for transplantation was recurrent metabolic decompensation. A total of 27 post-transplant deaths were reported in patients with PA [14.0% (27/194)]. For patients with MMA, 18 post-transplant deaths were reported [11% (18/167)]. A total of 62 complications were reported in 115 patients with PA (54%) with cardiomyopathy (n = 12), hepatic arterial thrombosis (HAT; n = 14) and viral infections (n = 12) being the most commonly reported. A total of 52 complications were reported in 106 patients with MMA (49%) with viral infections (n = 14) and renal failure/impairment (n = 10) being the most commonly reported. CONCLUSIONS Liver transplantation and combined liver-kidney transplantation appears to benefit some patients with PA or MMA, respectively, but this approach does not provide complete correction of the metabolic defect and some patients remain at risk from disease-related and transplantation-related complications, including death. Thus, all treatment avenues should be exhausted before consideration of organ transplantation and the benefits of this approach must be weighed against the risk of perioperative complications on an individual basis.
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Mycophenolates: The latest modern and potent immunosuppressive drugs in adult kidney transplantation: What we should know about them?
Bentata, Y
Artificial organs. 2020;(6):561-576
Abstract
Introduced in 1995, mycophenolate mofetil (MMF) would become the most powerful antiproliferative agent in the field of organ transplantation, thereby supplanting azathioprine, the first antiproliferative agent introduced in the early 1960s. Its association with tacrolimus greatly improved kidney transplant (KT) prognosis by significantly reducing the incidence of posttransplant acute rejection. MMF is also reputed to be a safe medication, but the frequency of the gastrointestinal complications associated with it, even minor ones, has induced the marketing of a second molecule called enteric-coated mycophenolate sodium. This late form of mycophenolate was supposed to be better tolerated thanks to its pharmacokinetic properties but the studies did not show significant differences between the two molecules. Otherwise, the combination of MMF with tacrolimus has significantly increased the risk of infections, particularly viral, and of neoplasia. To reduce this risk and avoid any situation of under or overexposure while remaining effective, only a strict and long-term monitoring of MMF allows the maintenance of already established therapeutic targets within the predefined ranges. In KT, individualizing the prescription and targets of MMF according to immunologic risk, global immunosuppression, and posttransplant period, as for other immunosuppressants, is open to discussion and may be beneficial.
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New treatments for cytomegalovirus in transplant patients.
Coppock, GM, Blumberg, E
Current opinion in nephrology and hypertension. 2019;(6):587-592
Abstract
PURPOSE OF REVIEW The purpose of this review is to highlight novel advances in prophylaxis against and treatment of CMV in kidney transplant recipients. Current options include intravenous ganciclovir and oral valganciclovir, but use of these agents is limited by side effects, such as myelosuppression as well as evolving resistance in CMV strains. RECENT FINDINGS Advances in the field include novel drugs that have shown promise in preliminary studies and are now being tested in large-scale clinical trials. Moreover, there is a developing focus in enhancing host immune responses to better protect against viral infection using anti-CMV vaccines. Studying host immune responses to CMV has also led to improved monitoring strategies, such as the QuantiFERON assay, which will allow for improved risk stratification and targeted therapies in transplant recipients. SUMMARY In summary, although options for prophylaxis and treatment against CMV have been somewhat limited to date, a number of new strategies are currently under development with several drugs in phase 3 trials. Therefore, the landscape of CMV management in kidney transplant recipients will be changing significantly in the coming years with the ultimate goal of safer and more effective therapies to combat CMV.
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Management of Diabetes Mellitus in Normal Renal Function, Renal Dysfunction and Renal Transplant Recipients, Focusing on Glucagon-Like Peptide-1 Agonist: A Review Based upon Current Evidence.
Tsai, SF, Chen, CH
International journal of molecular sciences. 2019;(13)
Abstract
Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug-drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired β-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.
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Immunosuppression and Reproductive Health After Kidney Transplantation.
Chandra, A, Midtvedt, K, Åsberg, A, Eide, IA
Transplantation. 2019;(11):e325-e333
Abstract
Following successful kidney transplantation, recipients usually regain fertility. Post-engraftment pregnancies should be planned and the teratogenic mycophenolic acid should be replaced with azathioprine before conception. To avoid unintentional pregnancies, pre-conception counseling is mandatory in women of reproductive age who are scheduled for a kidney transplant. Counseling should be repeated after transplantation. Female recipients should receive advice to use long-acting reversible contraception and avoid pregnancy for a minimum of 1 year following transplantation. Conception should be deferred even longer in female recipients with moderate to severe proteinuria, uncontrolled hypertension or reduced graft function and be very carefully discussed in highly HLA-sensitized patients. The recipient wishes, values and acceptance of pregnancy-related risk should receive attention. Assisted fertilization increases the risk of pre-eclampsia, but still result in live births. Pregnancy management in kidney transplant recipients should be provided by a multidisciplinary team consisting of a nephrologist, a midwife and an obstetrician with expertise in high-risk pregnancies. Until measurement of unbound fraction of calcineurin inhibitors becomes clinically available, we recommend to adjust calcineurin inhibitor dose according to whole blood trough level, even though it overestimates the effective drug concentration during pregnancy. If nephrotoxicity is suspected, the calcineurin inhibitor dose should be reduced. Breastfeeding should be accepted after kidney transplantation since infant immunosuppressive drug exposure via breastmilk is extremely low. The prevalence of congenital malformations in children fathered by male recipients, including patients on mycophenolic acid therapy at the time of conception, is at level with the general population.
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Role of Diabetes Education Program in Controlling Posttransplant Diabetes in a Recent Renal Transplant Bodybuilder: Case Report and Review of the Literature.
Othman, N, Gheith, O, Al-Otaibi, T, Abdou, H, Halim, MA, Mahmoud, T, Nair, P, Yagan, J, Maher, A, Dahab, M, et al
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2019;(Suppl 1):169-171
Abstract
Posttransplant diabetes is a common complication of solid-organ transplantation. We present the possible role of diabetes education in improvement of posttransplant diabetes in a 36-year-old bodybuilder who was a kidney transplant recipient. The patient had been abusing some medications to help in bodybuilding. He underwent living unrelated-donor renal transplant with thymoglobulin induction and was maintained on steroids, tacrolimus, and mycophenolate mofetil. Posttransplant diabetes was confirmed by blood tests. His blood sugar was partially controlled by 3 oral agents. The patient participated in our structured diabetes education program. This program was created to cover different items related to diabetes control, including diet, proper exercise, blood sugar monitoring, sick day management, and pathophysiologic roles of diabetes medications. Within 4 months of participation in this program, the patient's blood sugar became well controlled and his diabetes medications started to be minimized. He presently has stable graft function with hemoglobin A1c level around 5.6% on only diet management. Bodybuilders are at risk of deterioration of their kidney function. A proper diabetes education program is recommended to help renal transplant recipients with early posttransplant diabetes mellitus to control their disease. Success requires close evaluation and a multidisciplinary approach.