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Infections, Complications and Management of Kidney Transplantation
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Infections, Complications and Management of Kidney Transplantation

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (5 April 2022) | Viewed by 32381

Special Issue Editors

Prof. Francesc Moreso

E-Mail Website
Guest Editor
Department of Nephrology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Interests: kidney transplantation; bacterial and viral infection; posttransplant diabetes; rejection; cancer; cardiovascular complications; immunosuppression
Prof. Daniel Serón

E-Mail Website
Guest Editor
Department of Nephrology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Interests: kidney transplantation; bacterial and viral infection; posttransplant diabetes; rejection; cancer; cardiovascular complications; immunosuppression

Special Issue Information

Dear Colleagues,

Renal transplantation is the best treatment for end-stage renal disease patients and it is widely delivered in developed countries. However, there are a large number of complications that arise after transplantation hampering its short- and long-term outcomes. The quality of the transplanted graft (living, standard criteria and expanded criteria donors including donors after circulatory death), the recipient characteristics (age and comorbidities) and the immunological risk (HLA or ABO barriers) aids clinicians to define the proper immunosuppressive regimen for each patient. However, despite the wide experience of clinicians managing renal transplants, patient and graft survival have not substantially improved during recent years. Short-term complications include bacterial and viral infections, posttransplant diabetes mellitus and clinical/subclinical rejection. Long-term complications include patient’s death mainly related with cardiovascular events and cancer and graft loss due to chronic rejection or recurrence of the primary disease. Despite the big effort to include new biomarkers to improve renal transplant outcomes, only monitoring of HLA donor-specific antibodies and nuclear acid testing for some viruses (cytomegalovirus and polyoma BK virus) have been incorporated into the clinical routine.

In the present Special Issue of the Journal of Clinical Medicine, we aim to collect a number of reviews and original articles that highlight significant advances in the management of renal transplants and its complications. As complications directly impact on the health and the outcome of transplant recipients, this Special Issue should increase the awareness as well as the knowledge of transplant physicians and researchers in these issues.

Potential topics include but are not limited to the following:

  • Donor quality and graft outcome;
  • Antibody-mediated and cellular clinical and subclinical rejection;
  • Monitoring and management of cytomegalovirus infection;
  • Monitoring and management polyoma BK virus;
  • Bacterial infections after transplantation;
  • Posttransplant diabetes mellitus;
  • Skin and non-skin cancer in renal transplants;
  • Cardiovascular risk and complications in transplant candidates and transplant recipients;
  • New biomarkers to monitor renal transplants;
  • Tailored immunosuppression;
  • Monitoring of immunosuppression.

Prof. Francesc Moreso
Prof. Daniel Serón
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • kidney transplantation
  • bacterial and viral infection
  • posttransplant diabetes
  • rejection
  • cancer
  • cardiovascular complications
  • immunosuppression

Published Papers (16 papers)

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10 pages, 723 KiB  
Article
Effect of Sirolimus vs. Everolimus on CMV-Infections after Kidney Transplantation—A Network Meta-Analysis
by Sebastian Wolf, Verena S. Hoffmann, Florian Sommer, Matthias Schrempf, Mingming Li, Martin Ryll, Ulrich Wirth, Matthias Ilmer, Jens Werner and Joachim Andrassy
J. Clin. Med. 2022, 11(14), 4216; https://doi.org/10.3390/jcm11144216 - 20 Jul 2022
Cited by 6 | Viewed by 1832
Abstract
(1) Background: Following renal transplantation, infection with cytomegalovirus (CMV) is a common and feared complication. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with calcineurininhibitors (CNIs), significantly reduces the CMV incidence after organ transplantation. As of now, there is no information on which [...] Read more.
(1) Background: Following renal transplantation, infection with cytomegalovirus (CMV) is a common and feared complication. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with calcineurininhibitors (CNIs), significantly reduces the CMV incidence after organ transplantation. As of now, there is no information on which mTOR-I, sirolimus (SIR) or everolimus (ERL), has a stronger anti-CMV effect. (2) Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 1164 trials screened, of which 27 could be included (11,655 pts.). We performed a network meta-analysis to analyze the relative risk of different types of mTOR-I treatment on CMV infection 12 months after transplantation compared to CNI treatment. (3) Results: Four different types of mTOR-I treatment were analyzed in network meta-analyses—SIR mono, ERL mono, SIR with CNI, ERL with CNI. The mTOR-I treatment with the strongest anti-CMV effect compared to a regular CNI treatment was ERL in combination with a CNI (relative risk (RR) 0.27, confidence interval (CI) 0.22–0.32, p < 0.0001). The other mTOR-I therapy groups showed a slightly decreased anti-CMV efficacy (SIR monotherapy (mono): RR 0.35, CI 0.22–0.57, p < 0.001; SIR with CNI: RR 0.43, CI 0.29–0.64, p < 0.0001; ERL mono: RR 0.46, CI 0.22–0.93, p = 0.031). (4) Conclusions: The anti-CMV effect of both mTOR-Is (SRL and ERL) is highly effective, irrespective of the combination with other immunosuppressive drugs. Certain differences with respect to the potency against the CMV could be found between SRL and ERL. Data gained from this analysis seem to support that a combination of ERL and CNI has the most potent anti-CMV efficacy. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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13 pages, 292 KiB  
Article
Risk Factors and Outcomes of Acute Graft Pyelonephritis with Bacteremia Due to Multidrug-Resistant Gram-Negative Bacilli among Kidney Transplant Recipients
by Núria Sabé, Marta Maristany, Manel Tuells, Alexandre Favà, Edoardo Melilli, Fe Tubau, Josep Maria Cruzado and Jordi Carratalà
J. Clin. Med. 2022, 11(11), 3165; https://doi.org/10.3390/jcm11113165 - 2 Jun 2022
Cited by 4 | Viewed by 1407
Abstract
Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, [...] Read more.
Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, and outcomes of AGP with bacteremia due to MDR Gram-negative bacilli. Overall, 278 episodes of AGP with bacteremia due to MDR Gram-negative and non-MDR Gram-negative bacilli were identified and compared in 214 KT recipients; MDR Gram-negative bacilli were the cause in 28.4%. Overall 30-day mortality was low (1.1%). Risk factors independently associated with AGP due to MDR Gram-negative bacilli were male sex (OR 3.08; 95%CI 1.60–5.93), previous episode of bacteremic AGP (OR 2.11, 95%CI 1.09–4.09), prior antibiotic therapy in the preceding month (OR 2.47, 95%CI 1.33–4.57), and nosocomial acquisition (OR 2.03, 95%CI 1.14–3.62). Forty-three percent of MDR Gram-negative episodes received inappropriate empirical antibiotic therapy. The risk factors identified in this study may help physicians when selecting empirical antibiotic treatment for AGP. Previous antibiotic use was the main modifiable factor. Its presence highlights the importance of avoiding unnecessary antibiotics in order to bring down the high rates of MDR Gram-negative bacilli infections in this population. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
8 pages, 357 KiB  
Article
Kidney Transplant Outcomes after Prolonged Delayed Graft Function
by Cullan V. Donnelly, Maria Keller and Liise Kayler
J. Clin. Med. 2022, 11(6), 1535; https://doi.org/10.3390/jcm11061535 - 11 Mar 2022
Cited by 2 | Viewed by 1815
Abstract
Background: The protracted recovery of renal function may be an actionable marker of post-transplant adverse events, but a paucity of data are available to determine if the duration of graft recovery serves to stratify risk. Materials and Methods: Single-center data of adult-isolated deceased-donor [...] Read more.
Background: The protracted recovery of renal function may be an actionable marker of post-transplant adverse events, but a paucity of data are available to determine if the duration of graft recovery serves to stratify risk. Materials and Methods: Single-center data of adult-isolated deceased-donor kidney transplant (KTX) recipients between 1 July 2015 and 31 December 2018 were stratified by delayed graft function (DGF) duration, defined as time to serum creatinine < 3.0 mg/dL. Results: Of 355 kidney transplants, the time to creatinine < 3.0 mg/dL was 0–3 days among 96 cases (DGF ≤ 3), 4–10 days among 85 cases (DGF4-10), 11–20 days among 93 cases (DGF11-20), and ≥21 days for 81 cases (DGF ≥ 21). DGF ≥ 21 recipients were significantly more likely to be male, non-sensitized, and receive kidneys from donors that were older, with donation after circulatory death, non-mandatory share, hypertensive, higher KDPI, higher terminal creatinine, and longer cold and warm ischemia time. On multivariate analysis, DGF ≥ 21 was associated with a 5.73-fold increased odds of 12-month eGFR < 40 mL/min compared to DGF ≤ 3. Lesser degrees of DGF had similar outcomes. Conclusions: Prolonged DGF lasting over 20 days signifies a substantially higher risk for reduced eGFR at 1 year compared to lesser degrees of DGF, thus serving as a threshold indicator of increased risk. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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13 pages, 847 KiB  
Article
Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship?
by Jens Strohaeker, Victoria Aschke, Alfred Koenigsrainer, Silvio Nadalin and Robert Bachmann
J. Clin. Med. 2022, 11(1), 226; https://doi.org/10.3390/jcm11010226 - 31 Dec 2021
Cited by 7 | Viewed by 2364
Abstract
(1) Background: Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were [...] Read more.
(1) Background: Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT). After the recent recommendation to avoid them in these patients, however, alternative treatment strategies need to be investigated (2) Methods: We retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. (3) Results: Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001). The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both, bacterial resistance was more common in the study cohort than in the control group. (4) Conclusions: Urinary tract infections appear to be linked to worse graft functions. Thus, prevention and treatment should be accompanied by antibiotic stewardship teams. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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11 pages, 12165 KiB  
Article
Early Hypertransaminasemia after Kidney Transplantation: Significance and Evolution According to Donor Type
by Eulàlia Solà-Porta, Dolores Redondo-Pachón, Carlos Arias-Cabrales, Diego Navazo, Anna Buxeda, Carla Burballa, Marta Crespo, Montserrat García-Retortillo, Julio Pascual and María José Pérez-Sáez
J. Clin. Med. 2021, 10(21), 5168; https://doi.org/10.3390/jcm10215168 - 4 Nov 2021
Cited by 1 | Viewed by 2263
Abstract
Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the [...] Read more.
Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the increase in serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) during the first three months post-KT in 151 recipients who received thymoglobulin as induction therapy, either from brain-death donors (DBD, n = 75), controlled circulatory death donors (cDCD, n = 33), or uncontrolled DCD (uDCD, n = 43). Eighty-five KT recipients from DBD who received basiliximab were included as controls. From KT recipients who received thymoglobulin, 33.6/43.4% presented with an increase in AST/ALT at 72 h post-KT, respectively. Regarding donor type, the percentage of recipients who experienced 72 h post-KT hypertransaminasemia was higher in uDCD group (65.1/83.7% vs. 20.3/26% in DBD and 20.7/27.6% in cDCD, p < 0.001). Within the control group, 9.4/12.9% of patients presented with AST/ALT elevation. One month after transplant, AST/ALT values returned to baseline in all groups. The multivariate analysis showed that uDCD recipients had 6- to 12-fold higher risk of developing early post-KT hypertransaminasemia. Early post-KT hypertransaminasemia is a frequent and transient event related to the kidney donor type, being more frequent in uDCD recipients. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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12 pages, 1693 KiB  
Article
Comparative Long-Term Renal Allograft Outcomes of Recurrent Immunoglobulin A with Severe Activity in Kidney Transplant Recipients with and without Rituximab: An Observational Cohort Study
by Wiwat Chancharoenthana, Asada Leelahavanichkul, Wassawon Ariyanon, Somratai Vadcharavivad and Weerapong Phumratanaprapin
J. Clin. Med. 2021, 10(17), 3939; https://doi.org/10.3390/jcm10173939 - 31 Aug 2021
Cited by 3 | Viewed by 1890
Abstract
Recurrent IgA nephropathy (IgAN) remains an important cause of allograft loss in renal transplantation. Due to the limited efficacy of corticosteroid in the treatment of recurrent glomerulonephritis, rituximab was used in kidney transplant (KT) recipients with severe recurrent IgAN. A retrospective cohort study [...] Read more.
Recurrent IgA nephropathy (IgAN) remains an important cause of allograft loss in renal transplantation. Due to the limited efficacy of corticosteroid in the treatment of recurrent glomerulonephritis, rituximab was used in kidney transplant (KT) recipients with severe recurrent IgAN. A retrospective cohort study was conducted between January 2015 and December 2020. Accordingly, there were 64 KT recipients with biopsy-proven recurrent IgAN with similar baseline characteristics that were treated with the conventional standard therapy alone (controls, n = 43) or together with rituximab (cases, n = 21). All of the recipients had glomerular endocapillary hypercellularity and proteinuria (>1 g/d) with creatinine clearance (CrCl) > 30 mL/min/1.73 m2 and well-controlled blood pressure using renin–angiotensin–aldosterone blockers. The treatment outcomes were renal allograft survival rate, proteinuria, and post-treatment allograft pathology. During 3.8 years of follow-up, the rituximab-based regimen rapidly decreased proteinuria within 12 months after rituximab administration and maintained renal allograft function—the primary endpoint—for approximately 3 years. There were eight recipients in the case group (38%), and none in the control group reached a complete remission (proteinuria < 250 mg/d) at 12 months after treatment. Notably, renal allograft histopathology from patients with rituximab-based regimen showed the less severe endocapillary hypercellularity despite the remaining strong IgA deposition. In conclusion, adjunctive treatment with rituximab potentially demonstrated favorable outcomes for treatment of recurrent severe IgAN post-KT as demonstrated by proteinuria reduction and renal allograft function in our cohort. Further in-depth mechanistic studies with the longer follow-up periods are recommended. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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10 pages, 898 KiB  
Article
The Association between Peri-Transplant RBC Transfusion and Graft Failure after Kidney Transplantation: A Nationwide Cohort Study
by Kyungho Lee, Seohee Lee, Eun Jin Jang, Ga Hee Kim, Seokha Yoo, Minkyoo Lee, Hye Ryoun Jang and Ho Geol Ryu
J. Clin. Med. 2021, 10(16), 3750; https://doi.org/10.3390/jcm10163750 - 23 Aug 2021
Cited by 7 | Viewed by 2224
Abstract
Background: Patients undergoing kidney transplantation (KT) often receive red blood cell (RBC) transfusion during admission for KT which may increase the risk of allosensitization. The association between peri-transplant RBC transfusion and graft survival was evaluated using a nationwide cohort. Methods: This retrospective study [...] Read more.
Background: Patients undergoing kidney transplantation (KT) often receive red blood cell (RBC) transfusion during admission for KT which may increase the risk of allosensitization. The association between peri-transplant RBC transfusion and graft survival was evaluated using a nationwide cohort. Methods: This retrospective study analyzed 13,871 patients who underwent KT in Korea between 2007 and 2015. The outcomes were graft failure rate and overall patient survival depending on the amount of RBC transfusion. Results: The overall graft failure rate was 15.5%. Compared to the graft failure rate of 13.5% in the no transfusion group, the graft failure rate was 15.4% in the 1–2 units group (sHR 1.06 (95% CI 0.97–1.17), p = 0.216), 21.4% in the 3–5 units group (sHR 1.39 (1.21–1.61), p < 0.001), and 35.3% in the 6 or more units group (sHR 2.20 (1.70–2.85), p < 0.001). The overall survival rate was 97.5% in the no transfusion group, compared to 95.9% in the 1–2 units group (HR 1.50 (1.22–1.83), p < 0.001), 92.0% in the 3–5 units group (HR 2.43 (1.87–3.15), p < 0.001), and 67.5% in the 6 or more units group (HR 6.81 (5.03–9.22), p < 0.001). Conclusions: Peri-transplant RBC transfusion was independently associated with the increased risk of renal allograft failure and death in KT patients. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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14 pages, 1846 KiB  
Article
Protocol Biopsies on de novo Renal-Transplants at 3 Months after Surgery: Impact on 5-Year Transplant Survival
by Florian Terrec, Johan Noble, Hamza Naciri-Bennani, Paolo Malvezzi, Bénédicte Janbon, Camille Emprou, Diane Giovannini, Lionel Rostaing and Thomas Jouve
J. Clin. Med. 2021, 10(16), 3635; https://doi.org/10.3390/jcm10163635 - 17 Aug 2021
Cited by 7 | Viewed by 1890
Abstract
Background: In many centers, a protocol kidney biopsy (PKB) is performed at 3 months post-transplantation (M3), without a demonstrated benefit on death-censored graft survival (DCGS). In this study, we compared DCGS between kidney transplant recipients undergoing a PKB or without such biopsy while [...] Read more.
Background: In many centers, a protocol kidney biopsy (PKB) is performed at 3 months post-transplantation (M3), without a demonstrated benefit on death-censored graft survival (DCGS). In this study, we compared DCGS between kidney transplant recipients undergoing a PKB or without such biopsy while accounting for the obvious indication bias. Methods: In this retrospective, single-center study conducted between 2007 and 2013, we compared DCGS with respect to the availability and features of a PKB. We built a propensity score (PS) to account for PKB indication likelihood and adjusted the DCGS analysis on PKB availability and the PS. Results: A total of 615 patients were included: 333 had a PKB, 282 did not. In bivariate Kaplan–Meier survival analysis, adjusting for the availability of a PKB and for the PS, a PKB was associated with a better 5-year DCGS independently of the PS (p < 0.001). Among the PKB+ patients, 87 recipients (26%) had IF/TA > 0. Patients with an IF/TA score of 3 had the worst survival. A total of 144 patients (44%) showed cv lesions. Patients with cv2 and cv3 lesions had the worst 5-year DCGS. Conclusions: A M3 PKB was associated with improved graft survival independently of potential confounders. These results could be explained by the early treatment of subclinical immunological events. It could be due to better management of the immunosuppressive regimen. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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12 pages, 2354 KiB  
Article
De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017
by Boyeon Kim, Minjin Kang, Yoonjung Kim, Hyung Soon Lee, Banseok Kim, Jung Jun Lee, Yongjung Park and Kyung-A Lee
J. Clin. Med. 2021, 10(16), 3530; https://doi.org/10.3390/jcm10163530 - 11 Aug 2021
Cited by 7 | Viewed by 1761
Abstract
Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from [...] Read more.
Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi’s sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients’ age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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9 pages, 646 KiB  
Article
The Framingham Risk Score Is Associated with Chronic Graft Failure in Renal Transplant Recipients
by Josephine L. C. Anderson, Margot L. Poot, Hannah L. M. Steffen, Daan Kremer, Stephan J. L. Bakker and Uwe J. F. Tietge
J. Clin. Med. 2021, 10(15), 3287; https://doi.org/10.3390/jcm10153287 - 26 Jul 2021
Viewed by 1491
Abstract
Predicting chronic graft failure in renal transplant recipients (RTR) is an unmet clinical need. Chronic graft failure is often accompanied by transplant vasculopathy, the formation of de novo atherosclerosis in the transplanted kidney. Therefore, we determined whether the 10-year Framingham risk score (FRS), [...] Read more.
Predicting chronic graft failure in renal transplant recipients (RTR) is an unmet clinical need. Chronic graft failure is often accompanied by transplant vasculopathy, the formation of de novo atherosclerosis in the transplanted kidney. Therefore, we determined whether the 10-year Framingham risk score (FRS), an established atherosclerotic cardiovascular disease prediction module, is associated with chronic graft failure in RTR. In this prospective longitudinal study, 600 well-characterised RTR were followed for 10 years. The association with death-censored chronic graft failure (n = 81, 13.5%) was computed. An extended Cox model showed that each one percent increase of the FRS significantly increased the risk of chronic graft failure by 4% (HR: 1.04, p < 0.001). This association remained significant after adjustment for potential confounders, including eGFR (HR: 1.03, p = 0.014). Adding the FRS to eGFR resulted in a higher AUC in a receiver operating curve (AUC = 0.79, p < 0.001) than eGFR alone (AUC = 0.75, p < 0.001), and an improvement in the model likelihood ratio statistic (67.60 to 88.39, p < 0.001). These results suggest that a combination of the FRS and eGFR improves risk prediction. The easy to determine and widely available FRS has clinical potential to predict chronic graft failure in RTR. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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14 pages, 964 KiB  
Article
Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis
by Felix Becker, Anne-Sophie Mehdorn, Vasilios Getsopulos, Katharina Schütte-Nütgen, Stefan Reuter, Barbara Suwelack, Andreas Pascher, Jens G. Brockmann and Ralf Bahde
J. Clin. Med. 2021, 10(11), 2349; https://doi.org/10.3390/jcm10112349 - 27 May 2021
Cited by 1 | Viewed by 1559
Abstract
Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on [...] Read more.
Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce. A retrospective double case control matched pair analysis (60 months follow-up) was carried out and RTx-recipients were stratified for history of PTM. First, PTM-RTx recipients were matched according to age, sex and duration of immunosuppressive therapy. Next, PTM-RTx recipients were matched 1:1 for age, sex and cause of end-stage renal disease. Five-year patient and graft survival as well as oncological outcomes were analyzed. A total of 65 PTM-RTx recipients were identified. Post-RTx recurrence rate was 5%, while 20% developed second de novo malignancy, comparable to 14% in the control group. PTM-RTx recipients had a noticeable lower five-year death-censored as well as overall graft survival and Cox proportional hazard modeling showed a correlation between PTM and inferior graft survival. Although underlying reasons remain not fully understood, this study is the first to show inferior graft survival in PTM-RTx recipients and advocates necessity to focus on more meticulous graft monitoring in PTM recipients in addition to heightened surveillance for cancer recurrence. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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9 pages, 2663 KiB  
Article
A Specific Tubular ApoA-I Distribution Is Associated to FSGS Recurrence after Kidney Transplantation
by Conxita Jacobs-Cachá, Natàlia Puig-Gay, Ander Vergara, Maria-Alejandra Gabaldon, Joana Sellarés, Yolanda Villena-Ortiz, Irene Agraz, Francesc Moreso, Maria José Soler, Daniel Serón and Joan López-Hellín
J. Clin. Med. 2021, 10(10), 2174; https://doi.org/10.3390/jcm10102174 - 18 May 2021
Cited by 2 | Viewed by 1894
Abstract
A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear [...] Read more.
A major complication of primary focal segmental glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens in 30 to 40% of the patients. The diagnosis of these relapses is not always easy as the histological lesions are not highly specific and appear after the proteinuria increase. Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, specifically present in the urine of recurrent FSGS patients after kidney transplantation. Aberrant forms of ApoA-I have also been described in the urine of native primary FSGS patients; this feature has been associated with prominent staining of ApoA-I at the apical membrane of the tubular cells. In this study, we aim to analyze the ApoA-I distribution in kidney allograft biopsies of recurrent FSGS patients. We detected ApoA-I by immunohistochemistry in kidney allograft biopsies of patients with FSGS relapse after kidney transplantation and in kidney allograft biopsies of patients with a disease different from FSGS in the native kidney (non-FSGS). In recurrent FSGS patients, ApoA-I was prominently localized at the brush border of the tubular cells, while in the non-FSGS patients, ApoA-I was found along the cytoplasm of the tubular cells. The localization of ApoA-I at the brush border of the tubular cells is a specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly specific tubular distribution. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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10 pages, 417 KiB  
Article
Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19
by Marta Bodro, Frederic Cofan, Jose Ríos, Sabina Herrera, Laura Linares, María Angeles Marcos, Alex Soriano, Asunción Moreno and Fritz Diekmann
J. Clin. Med. 2021, 10(8), 1551; https://doi.org/10.3390/jcm10081551 - 7 Apr 2021
Cited by 9 | Viewed by 2126
Abstract
In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which [...] Read more.
In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
12 pages, 994 KiB  
Article
Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates
by Marina de Cos Gomez, Adalberto Benito Hernandez, Maria Teresa Garcia Unzueta, Jaime Mazon Ruiz, Covadonga Lopez del Moral Cuesta, Jose Luis Perez Canga, David San Segundo Arribas, Rosalia Valero San Cecilio, Juan Carlos Ruiz San Millan and Emilio Rodrigo Calabia
J. Clin. Med. 2020, 9(12), 4112; https://doi.org/10.3390/jcm9124112 - 20 Dec 2020
Cited by 4 | Viewed by 1793
Abstract
Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the [...] Read more.
Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49–16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2–8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65–11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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Review

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28 pages, 394 KiB  
Review
Belatacept Use after Kidney Transplantation and Its Effects on Risk of Infection and COVID-19 Vaccine Response
by Florian Terrec, Thomas Jouve, Paolo Malvezzi, Bénédicte Janbon, Hamza Naciri Bennani, Lionel Rostaing and Johan Noble
J. Clin. Med. 2021, 10(21), 5159; https://doi.org/10.3390/jcm10215159 - 3 Nov 2021
Cited by 13 | Viewed by 2839
Abstract
Introduction: Belatacept is a common immunosuppressive therapy used after kidney transplantation (KT) to avoid calcineurin-inhibitor (CNI) use and its related toxicities. It is unclear whether its use exposes KT recipients (KTx) to a greater risk of infection or a poorer response to vaccines. [...] Read more.
Introduction: Belatacept is a common immunosuppressive therapy used after kidney transplantation (KT) to avoid calcineurin-inhibitor (CNI) use and its related toxicities. It is unclear whether its use exposes KT recipients (KTx) to a greater risk of infection or a poorer response to vaccines. Areas covered: We reviewed PubMed and the Cochrane database. We then summarized the mechanisms and impacts of belatacept use on the risk of infection, particularly opportunistic, in two settings, i.e., de novo KTx and conversion from CNIs. We also focused on COVID-19 infection risk and response to SARS-CoV-2 vaccination in patients whose maintenance immunosuppression relies on belatacept. Expert opinion: When belatacept is used de novo, or after drug conversion the safety profile regarding the risk of infection remains good. However, there is an increased risk of opportunistic infections, mainly CMV disease and Pneumocystis pneumonia, particularly in those with a low eGFR, in older people, in those receiving steroid-based therapy, or those that have an early conversion from CNI to belatacept (i.e., <six months post-transplantation). Thus, we recommend, if possible, delaying conversion from CNI to belatacept until at least six months post-transplantation. Optimal timing seems to be eight months post-transplantation. In addition, KTx receiving belatacept respond poorly to SARS-CoV-2 vaccination. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)

Other

Jump to: Research, Review

8 pages, 666 KiB  
Brief Report
Association between Long-Term Change in Arterial Stiffness and Cardiovascular Outcomes in Kidney Transplant Recipients: Insights from the TRANSARTE Study
by Madonna Salib, Arnaud Simon, Nicolas Girerd, Anna Kearney-Schwartz, Patrick Rossignol, Athanase Benetos, Luc Frimat and Sophie Girerd
J. Clin. Med. 2022, 11(5), 1410; https://doi.org/10.3390/jcm11051410 - 4 Mar 2022
Cited by 4 | Viewed by 1608
Abstract
(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in [...] Read more.
(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in the early post-transplant period, followed by a potential re-worsening in the late period. In a cohort of KT patients, we evaluated the associations of pulse-wave velocity (PWV) measured at different time-points (pre-transplant, and early and late post-transplant periods) with CV morbi-mortality, as well as the evolution between these measurements with CV morbi-mortality. (2) Methods: Forty KT recipients with a 10-year follow-up were included. The association of PWV with CV events was assessed with multivariable cox analysis. Backward linear regressions were conducted to identify the determinants of PWV at 1 year and those of the long-term evolution of PWV after KT (delta PWV at 1 year—latest PWV). (3) Results: The absence of arterial stiffening during the long-term follow-up after KT is associated with a lower CV outcome rate (HR for the delta PWV = 0.76 (0.58–0.98), p = 0.036). Age at KT is associated with the worsening of arterial stiffness in the late post-transplantation period (β for the delta PWV = −0.104, p = 0.031). A high PWV at 1 year was associated with a potential for recovery during follow-up (β = 0.744, p < 0.0001). (4) Conclusions: The absence of PWV worsening in the late post-transplantation period was significantly associated with a lower risk of CV events, whereas early changes in PWV were not. Finding an intervention capable of reducing long-term PWV could improve the prognosis of KT recipients. Full article
(This article belongs to the Special Issue Infections, Complications and Management of Kidney Transplantation)
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