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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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2.
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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3.
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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4.
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.
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5.
Epitope matching in kidney transplantation: recent advances and current limitations.
Larkins, NG, Wong, G, Taverniti, A, Lim, WH
Current opinion in organ transplantation. 2019;(4):370-377
Abstract
PURPOSE OF REVIEW Evolution of human leukocyte antigen (HLA) molecular typing techniques has progressively enabled more accurate determination of the three-dimensional building blocks that form the antibody accessibility and binding sites of each HLA allele. These immunogenic HLA regions known as epitopes are composed of polymorphic sequences of amino acid residues termed eplets. This review provides a critical appraisal of the current understanding of epitope compatibility in kidney transplantation. RECENT FINDINGS There is a tendency to suggest that epitope matching is likely to be superior to broad antigen HLA matching such that the allocation of donor kidneys to patients with a more favorable epitope compatibility profile may lead to better allograft outcomes. A growing body of work has highlighted the association between a greater number of eplet mismatches and adverse allograft outcomes, and approaches using eplet matching have been successfully implemented in organ allocation programs. However, our understanding of epitope compatibility remains in its infancy, requiring further and more in-depth evaluation. Critically, it remains unclear how best to translate findings derived at the population level to the care of individual patients. Questions that need to be answered include a lack of consensus in the definition and interpretation of epitope compatibility, are class I and II compatibility of similar clinical importance, how best to define predetermined mismatch thresholds for utilization in organ allocation, and whether other properties such as differences in electrostatic potential between donor and recipient HLA alleles are also important in determining immunological compatibility. SUMMARY Epitope matching likely represents a valid progression in understanding donor-recipient HLA compatibility. However, more clinical data and a better understanding about differences in methods to determine epitope compatibility are required before the approach can be widely applied in clinical practice.
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6.
Recurrent urinary tract infections caused by Raoultella planticola after kidney transplant.
Harmon, SL, Nadeem, I
Transplant infectious disease : an official journal of the Transplantation Society. 2019;(6):e13196
Abstract
Recurrent urinary tract infections are difficult to manage in patients with a history of kidney transplant and may contribute to graft loss. Few cases describe recurrent urinary tract infections due to Raoultella planticola in this population. We describe the management of recurrent urinary tract infections due to R planticola in a kidney transplant recipient and review other case reports of urinary tract infections due to this organism.
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7.
Management of Post-transplant Hyperparathyroidism and Bone Disease.
Delos Santos, R, Rossi, A, Coyne, D, Maw, TT
Drugs. 2019;(5):501-513
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Abstract
Significant advances in immunosuppressive therapies have been made in renal transplantation, leading to increased allograft and patient survival. Despite improvement in overall patient survival, patients continue to require management of persistent post-transplant hyperparathyroidism. Medications that treat persistent hyperparathyroidism include vitamin D, vitamin D analogues, and calcimimetics. Medication side effects such as hypocalcemia or hypercalcemia, and adynamic bone disease, may lead to a decrease in the drugs. When medical management fails to control persistent post-transplant hyperparathyroidism, treatment is a parathyroidectomy. Surgical techniques are not uniform between centers and surgeons. Undergoing the surgery may include a subtotal technique or a technique including total parathyroid gland resection with partial heterotopic gland reimplantation. In addition, there are possible post-surgical complications. The ideal treatment for persistent post-transplant hyperparathyroidism is the treatment and prevention of the condition while patients are being managed for their late-stage chronic kidney disease and end-stage renal disease.
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TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.
Rosado-Canto, R, Carrillo-Pérez, DL, Jiménez, JV, Cuellar-Rodríguez, J, Parra-Avila, I, Alberú, J, Morales-Buenrostro, LE
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2019;(4):265-274
Abstract
BACKGROUND There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.
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Calciphylaxis in end-stage liver and renal disease patients before and after transplant.
Couri, T, Stier, M, Mikolajczyk, A, Aronsohn, A
Clinical transplantation. 2018;(6):e13272
Abstract
Calciphylaxis is a rare vascular disorder characterized by calcification of arterioles which causes tissue inflammation and necrosis. It is associated with the metabolic disturbances seen in end-stage renal disease (ESRD) and has also been described in patients with cirrhosis with preserved kidney function. Characteristic calciphylaxis lesions are black eschars surrounded by retiform purpura, and the gold standard for diagnosis is skin biopsy. Reported 1-year mortality rates range between 45% and 80%. No treatment modality has been evaluated in a prospective randomized trial, and reports of treatment efficacy vary. Kidney transplant has been reported as a successful therapy for calciphylaxis; however, cases exist of the initial onset of calciphylaxis following kidney transplant as well as simultaneous liver-kidney (SLK) transplant. The decision to maintain a patient with end-stage renal and liver disease on the waiting list for SLK transplant following the onset of calciphylaxis must consider the high 1-year mortality associated with this condition. More research is necessary to understand how to allocate donor allografts to manage patients with calciphylaxis and ESRD and/or cirrhosis effectively.
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10.
Hypertension guidelines: How do they apply to kidney transplant recipients.
Aziz, F, Clark, D, Garg, N, Mandelbrot, D, Djamali, A
Transplantation reviews (Orlando, Fla.). 2018;(4):225-233
Abstract
Hypertension is common among kidney transplant recipients and may result from traditional risk factors or transplant specific variables, which commonly include donor associated causes, immunosuppression, or transplant renal artery stenosis. Uncontrolled blood pressure in this patient population is associated with increased cardiovascular mortality and morbidity, and decreased graft survival. Despite these negative associations, there are no randomized controlled trials looking at the optimal blood pressure targets and identifying the best antihypertensive regimen for this special patient population. Multiple hypertension guidelines have been published in the last 10 years, but the Kidney Disease: Improving Global Outcomes (KDIGO) and American Society of Transplantation (AST) guidelines are the only to recommended a target blood pressure in kidney transplant recipients. In this manuscript, we will review the available evidence based on randomized clinical trials and large observational studies in kidney transplant recipients. Pending new interventional trials, we believe that: a) a blood pressure target of ≤130/80 is a reasonable goal as suggested by KDIGO; b) the choice of antihypertensive agent should be based on the patients' other comorbidities; and c) achieving good blood pressure control is more important than the choice of the antihypertensive agent; however, the initial choice of antihypertensive medications should be calcium channel blockers, beta-blockers, diuretics, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers as they have all been shown to reduce cardiovascular events in the general population.