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Early Post-Renal Transplant Hyperglycemia.
Iqbal, A, Zhou, K, Kashyap, SR, Lansang, MC
The Journal of clinical endocrinology and metabolism. 2022;(2):549-562
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Abstract
CONTEXT Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post-renal transplant hyperglycemia (EPTH) (< 45 days) similarly puts kidney transplant recipients at risk of infections, rehospitalizations, and graft failure and is not emphasized much in the literature. Proactive screening and management of EPTH is required given these consequences. OBJECTIVE The aim of this article is to promote recognition of early post-renal transplant hyperglycemia, and to summarize available information on its pathophysiology, adverse effects, and management. METHODS A PubMed search was conducted for "early post-renal transplant hyperglycemia," "immediate posttransplant hyperglycemia," "post-renal transplant diabetes," "renal transplant," "diabetes," and combinations of these terms. EPTH is associated with significant complications including acute graft failure, rehospitalizations, cardiovascular events, PTDM, and infections. CONCLUSION Patients with diabetes experience better glycemic control in end-stage renal disease (ESRD), with resurgence of hyperglycemia after kidney transplant. Patients with and without known diabetes are at risk of EPTH. Risk factors include elevated pretransplant fasting glucose, diabetes, glucocorticoids, chronic infections, and posttransplant infections. We find that EPTH increases risk of re-hospitalizations from infections (cytomegalovirus, possibly COVID-19), acute graft rejections, cardiovascular events, and PTDM. It is essential, therefore, to provide diabetes education to patients before discharge. Insulin remains the standard of care while inpatient. Close follow-up after discharge is recommended for insulin adjustment. Some agents like dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have shown promise. The tenuous kidney function in the early posttransplant period and lack of data limit the use of sodium-glucose cotransporter 2 inhibitors. There is a need for studies assessing noninsulin agents for EPTH to decrease risk of hypoglycemia associated with insulin and long-term complications of EPTH.
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Post-renal transplant malignancies: Opportunities for prevention and early screening.
Turshudzhyan, A
Cancer treatment and research communications. 2021;:100283
Abstract
GOAL OF THE REVIEW While transplant recipients are aware of increased malignancy risk, there is little consensus on the preventative measures. The goal of this review is to bring available preventative measures to light and prompt more research to be done with ultimate goal of developing an individualized prevention plan for each patient based on risk factors and available screening tools. INTRODUCTION Transplant surgery offers patients with end-stage renal disease a longer life expectancy with help of immunosuppressive therapies. Nonetheless, life-long immunosuppression comes at a cost of post-renal transplant malignancies, which have become the leading cause of morbidity in this patient group. DISCUSSION Post-renal transplant cancers can develop through either de novo, by donor-related transmission, or recurrence of recipient's pre-transplant cancer. While immunosuppressive therapy is considered to be the leading cause, weakened immunosurveillance of neoplastic cells and inadequate immune response against oncogenic viruses also plays an important role. The most common cancers seen in renal transplant patients are skin cancers and post-transplant lymphoproliferative disorder (PTLD). Risk factors for skin cancers have are ultraviolet light, human papilloma virus infection, and use of cyclosporin and azathioprine. Numerous viral infections have been associated with transplant-related malignancies post-transplant. CONCLUSION While lowering of immunosuppressive therapy remains the treatment of choice, it may lead to graft failure. Given some of the presented malignancies have modifiable risk factors and options for screening, clinical outcomes can be improved. Limiting skin exposure, dermatologic screening, and prophylactic retinoids can help lower the incidence rate of skin malignancy. Endoscopic screening for renal transplant patients can help identify gastric adenocarcinoma early and improve survival rates. Some of the post-transplant malignancies have been responsive to anti-viral treatment.
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Sodium-glucose cotransporter 2 inhibitors for diabetes mellitus control after kidney transplantation: Review of the current evidence.
Kanbay, M, Demiray, A, Afsar, B, Karakus, KE, Ortiz, A, Hornum, M, Covic, A, Sarafidis, P, Rossing, P
Nephrology (Carlton, Vic.). 2021;(12):1007-1017
Abstract
Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are promising drugs to treat chronic kidney disease patients with or without diabetes mellitus (DM). Besides improving glycemic control, SGLT2i are cardioprotective and kidney protective and decrease bodyweight, serum uric acid, blood pressure, albuminuria and glomerular hyperfiltration. These effects may benefit graft function and survival in kidney transplant (KT) patients. In this review, we evaluate data on the efficacy and safety of SGLT2i for KT patients with DM. Eleven studies with 214 diabetic KT patients treated with SGLT2i have been reported. SGLT2i lowered haemoglobin A1c and bodyweight. While glomerular filtration rate may be reduced in the short-term, it remained similar to baseline after 3-12 months. In two studies, blood pressure decreased and remained unchanged in the others. There were no significant changes in urine protein to creatinine ratio. Regarding safety, 23 patients had urinary tract infections, 2 patients had a genital yeast infection, one had acute kidney injury, and one had mild hypoglycaemia. No cases of ketoacidosis or acute rejection were reported. In conclusion, the limited experience so far suggests that SGLT2i are safe in KT patients with DM, decrease bodyweight and improve glycemic control. However, some of the benefits observed in larger studies in the non-KT population have yet to be demonstrated in KT recipients, including preservation of kidney function, reduction in blood pressure and decreased proteinuria.
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A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation.
Lentine, KL, Pastan, S, Mohan, S, Reese, PP, Leichtman, A, Delmonico, FL, Danovitch, GM, Larsen, CP, Harshman, L, Wiseman, A, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(3):319-332
Abstract
Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.
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Cardiac evaluation of the kidney or liver transplant candidate.
Levy, PE, Khan, SS, VanWagner, LB
Current opinion in organ transplantation. 2021;(1):77-84
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PURPOSE OF REVIEW As the field of transplant has advanced, cardiac events have become the leading cause of morbidity and mortality after liver and kidney transplantation ahead of graft failure and infection. This trend has been bolstered by the transplantation of older and sicker patients who have a higher burden of cardiovascular risk factors, accentuating the need to determine which patients should undergo more extensive cardiac evaluation prior to transplantation. RECENT FINDINGS Computed tomography coronary angiography with or without coronary artery calcium scoring is now preferred over stress imaging in most transplant candidates for assessment of coronary artery disease. Assessment of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended, particularly in liver transplant candidates who are at high risk of cirrhotic cardiomyopathy, for which new diagnostic criteria were recently published in 2019. SUMMARY Cardiac evaluation of liver and kidney transplant candidates requires a global assessment for both short and long-term risk for cardiac events. Imaging of cardiac structure and function using transthoracic echocardiography with tissue doppler imaging and strain imaging is recommended. Risk stratification should consider both the anatomic and functional consequences of coronary artery disease in transplant candidates. VIDEO ABSTRACT http://links.lww.com/MOT/A27.
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Hypercalcemia associated with Pneumocystis jirovecii pneumonia in renal transplant recipients: case report and literature review.
Coche, S, Cornet, G, Morelle, J, Labriola, L, Kanaan, N, Demoulin, N
Acta clinica Belgica. 2021;(1):75-78
Abstract
Background: Pneumocystis jirovecii associated pneumonia is a potentially life-threatening opportunistic infection, occurring most frequently in the first year after renal transplantation, and may be associated with hypercalcemia. Clinical presentation:We report the case of a renal transplant recipient presenting with Pneumocystis jirovecii associated pneumonia and hypercalcemia due to ectopic production of 1,25-dihydroxyvitamin D, 6 years after renal transplantation. Calcemia and 1-25 hydroxyvitamin D levels normalized after our patient was treated by trimethoprim-sulfamethoxazole. Discussion: We review similar cases to delineate the clinical and biological profile of patients with Pneumocystis jirovecii pneumonia associated hypercalcemia. Conclusion:Physicians should evoke this diagnosis in renal transplant recipients presenting with pulmonary infection associated with hypercalcemia.
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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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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 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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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.