scholarly journals Recent Advances and Clinical Outcomes of Kidney Transplantation

2020 ◽  
Vol 9 (4) ◽  
pp. 1193 ◽  
Author(s):  
Charat Thongprayoon ◽  
Panupong Hansrivijit ◽  
Napat Leeaphorn ◽  
Prakrati Acharya ◽  
Aldo Torres-Ortiz ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Molecular Techniques ◽  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Recent Advances ◽  
Monitoring Protocols

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.

scholarly journals Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Magdalena Krajewska ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Kamińska ◽  
Marcelina Żabińska ◽  
Marta Myszka-Kozłowska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Transplant Outcome ◽  
Kidney Allograft ◽  
Transcriptional Pattern ◽  
Treg Population ◽  
Allograft Function

Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9±2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28− lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28− population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.

scholarly journals Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation

2020 ◽  
Vol 32 (5) ◽  
pp. 335-346 ◽  
Author(s):  
Haruka Higuchi ◽  
Daisuke Kamimura ◽  
Jing-Jing Jiang ◽  
Toru Atsumi ◽  
Daiki Iwami ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Therapeutic Target ◽  
Allograft Rejection ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Tubular Cells ◽  
Chronic Allograft Rejection ◽  
Antibody Mediated Rejection

Abstract Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection.

scholarly journals Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

2020 ◽  
Vol 9 (6) ◽  
pp. 1911 ◽  
Author(s):  
Camilo G. Sotomayor ◽  
Charlotte A. te Velde-Keyzer ◽  
Martin H. de Borst ◽  
Gerjan J. Navis ◽  
Stephan J.L. Bakker
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
Vascular Calcification ◽  
Graft Failure ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes

After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

scholarly journals Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 413
Author(s):  
Theerawut Klangjareonchai ◽  
Natsuki Eguchi ◽  
Ekamol Tantisattamo ◽  
Antoney J. Ferrey ◽  
Uttam Reddy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Pharmacological Intervention ◽  
Diabetic Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kidney Allograft ◽  
Post Transplant ◽  
Glucose Management

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

scholarly journals The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients

2019 ◽  
Vol 316 (1) ◽  
pp. F9-F19 ◽  
Author(s):  
Alice Doreille ◽  
Mélanie Dieudé ◽  
Heloise Cardinal
Keyword(s):  
Kidney Disease ◽  
Kidney Transplant ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Hla Antibodies ◽  
Microvascular Injury ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries

Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of profibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts, as well as modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the two main etiologies of microvascular damage in kidney transplant recipients. The presence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies, histological findings, such as diffuse C4d staining in peritubular capillaries, and the extent and severity of peritubular capillaritis, are commonly used clinically to provide both diagnostic and prognostic information. Complement-dependent assays, circulating non-HLA antibodies, or evaluation of the microvasculature with novel imaging techniques are the subject of ongoing studies.

scholarly journals Living Donor Kidney Transplantation Improves Graft and Recipient Survival in Patients with Multiple Kidney Transplants

2020 ◽  
Vol 9 (7) ◽  
pp. 2118 ◽  
Author(s):  
Maria Irene Bellini ◽  
Aisling E Courtney ◽  
Jennifer A McCaughan
Keyword(s):  
Kidney Transplantation ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Living Donor ◽  
Patient Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients’ factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor’s pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. Methods: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. Results: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). Conclusions: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival—in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients.

MANAGEMENT OF HYPERPARATHYROIDISM IN KIDNEY TRANSPLANTATION CANDIDATES: A NEED FOR CONSENSUS

2020 ◽  
Vol 26 (3) ◽  
pp. 299-304 ◽  
Author(s):  
Hubert Golingan ◽  
Shenae K. Samuels ◽  
Pauline Camacho ◽  
Darshana M. Dadhania ◽  
Fernando E. Pedraza-Taborda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Kidney Transplant ◽  
American Association ◽  
The United States ◽  
Standards Of Care ◽  
Endocrine Surgery ◽  
Transplant Candidates

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates. Methods: An 11-question, Institutional Review Board–approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019. Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates. Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates. Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease–mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography

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