Chronic Allograft Dysfunction

2017 ◽  
Author(s):  
Juliya Hemmett ◽  
Anthony M Jevnikar ◽  
Lakshman Gunaratnam

Premature renal allograft failure is a major problem in kidney transplantation as it is associated with high morbidity, mortality, and health care costs as patients return to dialysis. The most common cause of graft loss the first year after transplantation is death with a functioning graft, closely followed by what is now termed chronic allograft dysfunction (CAD). Development of donor-specific antibodies and chronic antibody rejection are emerging as the major pathophysiologic mechanisms responsible for this entity. There are currently no validated therapies for CAD, but improving adherence and reducing risk factors for CAD may improve outcomes. This review summarizes current understanding of the epidemiology, diagnosis, and pathophysiology of CAD, as well as potential treatment strategies. This review contains 3 figures and 133 references  

Acta Medica ◽  
2021 ◽  
pp. 1-10
Author(s):  
Göksel Güven ◽  
Şeref Rahmi Yılmaz ◽  
Tolga Yıldırım ◽  
Fazıl Tuncay Akı ◽  
Yunus Erdem

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients. Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively. Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p<0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p<0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p<0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002). Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.


Author(s):  
Lorna K. Henderson ◽  
Brian J. Nankivell ◽  
Jeremy R. Chapman

Despite improvements in short-term renal allograft survival, long-term survival has not appreciably changed. Excepting death with a functioning graft, most late graft loss results from chronic allograft dysfunction. Immune and non-immune-mediated injuries contribute to graft dysfunction over time, ultimately leading to a non-specific and irreversible histological end-point of fibrosis, tubular atrophy, and glomerulosclerosis. Screening and early identification of pathology is crucial to allow timely intervention in order to prevent permanent nephron damage and graft loss. This chapter outlines assessment of renal dysfunction following transplantation, defines the causes of chronic allograft failure, and their pathophysiology, and evaluates current therapeutic strategies used to improve or stabilize chronic allograft dysfunction.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  

Background: Kidney transplant recipients (KTRs) are exposed to a high risk of BK polyomavirus (BKPyV) replication, which in turn may lead to graft loss. Although the microRNAs (miRNAs) bkv-miR-B1-3p and bkv-miR-B1-5p are produced during the viral cycle, their putative value as markers of viral replication has yet to be established. In KTRs, the clinical relevance of the changes over time in BKPyV miRNA levels has not been determined. Methods: In a retrospective study, we analyzed 186 urine samples and 120 plasma samples collected from 67 KTRs during the first year post-transplantation. Using a reproducible, standardized, quantitative RT-PCR assay, we measured the levels of bkv-miR-B1-3p and bkv-miR-B1-5p (relative to the BKPyV DNA load). Results: Detection of the two miRNAs had low diagnostic value for identifying patients with DNAemia or for predicting DNAuria during follow-up. Seven of the 14 KTRs with a sustained BKPyV infection within the first year post-transplantation showed a progressive reduction in the DNA load and then a rapid disappearance of the miRNAs. DNA and miRNA loads were stable in the other seven KTRs. Conclusions: After the DNA-based diagnosis of BKPyV infection in KTRs, bkv-miR-B1-3p and bkv-miR-B1-5p levels in the urine might be valuable markers for viral replication monitoring and thus might help physicians to avoid an excessive reduction in the immunosuppressive regimen.


2021 ◽  
Vol 6 (2) ◽  
pp. 91
Author(s):  
Pier Francesco Indelli ◽  
Stefano Ghirardelli ◽  
Ferdinando Iannotti ◽  
Alessia Maria Indelli ◽  
Gennaro Pipino

Background: Periprosthetic joint infection (PJI) represents a devastating consequence of total joint arthroplasty (TJA) because of its high morbidity and its high impact on patient quality of life. The lack of standardized preventive and treatment strategies is a major challenge for arthroplasty surgeons. The purpose of this article was to explore the potential and future uses of nanotechnology as a tool for the prevention and treatment of PJI. Methods: Multiple review articles from the PubMed, Scopus and Google Scholar databases were reviewed in order to establish the current efficacy of nanotechnology in PJI preventive or therapeutic scenarios. Results: As a prevention tool, anti-biofilm implants equipped with nanoparticles (silver, silk fibroin, poly nanofibers, nanophase selenium) have shown promising antibacterial functionality. As a therapeutic tool, drug-loaded nanomolecules have been created and a wide variety of carrier materials (chitosan, titanium, calcium phosphate) have shown precise drug targeting and efficient control of drug release. Other nanotechnology-based antibiotic carriers (lipid nanoparticles, silica, clay nanotubes), when added to common bone cements, enhanced prolonged drug delivery, making this technology promising for the creation of antibiotic-added cement joint spacers. Conclusion: Although still in its infancy, nanotechnology has the potential to revolutionize prevention and treatment protocols of PJI. Nevertheless, extensive basic science and clinical research will be needed to investigate the potential toxicities of nanoparticles.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aziza Ajlan ◽  
Hassan Aleid ◽  
Tariq Zulfiquar Ali ◽  
Hala Joharji ◽  
Khalid Almeshari ◽  
...  

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.


2005 ◽  
Vol 24 (9) ◽  
pp. 1260-1268 ◽  
Author(s):  
Smita Sakha Pakhale ◽  
Denis Hadjiliadis ◽  
David N. Howell ◽  
Scott M. Palmer ◽  
Carlos Gutierrez ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document