Evaluation of antibodies directed against two GPCRs, anti-AT1R and anti-ETAR, on kidney transplant outcome: Own experience and review of the topic

2021 ◽  
Vol 22 ◽  
Author(s):  
El Kaaoui El Band J ◽  
S. Llorente ◽  
P Martinez-Garcia ◽  
R Alfaro ◽  
V Jimenez-Coll ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Graft Loss ◽  
Autoimmune Response ◽  
Vascular Lesions ◽  
Kidney Graft ◽  
Post Transplantation ◽  
High Association ◽  
Graft Outcome ◽  
Stage Renal Disease ◽  
Self Antigens

Background: The role of an alloimmune response against non-self-antigens is established in organ transplantation. The main actors of this recognition are the HLA incompatibilities between donor and recipient, but may also involve reactivity against other alloantigens expressed on the allograft and result from an autoimmune response developed against self-antigens. Objective: Our study aimed to determine the presence of non-anti-HLA antibodies (anti-AT1R and anti-ETAR) in sera from patients with end-stage renal disease who underwent kidney transplantation in pre-and post-transplantation samples and study their influence on the development and evolution of acute humoral rejections and DSAs. Method: In this sense, antibodies (Abs) against two G protein-coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR), have been detected in the sera of transplant recipients who experience allograft dysfunction, patients with coronary heart disease, marginal hypertension and refractory, vascular lesions, myocardial hypertrophy and chronic inflammatory diseases such as atherosclerosis or sclerosis. Results: In our own experience, kidney graft recipients were monitored for anti-ETAR, -AT1R, and -HLA Abs in pre-and post-transplant evolution, and anti-AT1R and/or -ETAR Abs were detected in 24% of recipients (22.4% with anti-AT1R Abs and 9.8% with anti-ETAR Abs). Due to acute humoral rejection, Graft loss was detected in 6.4% of patients with anti-GPCRs non-HLA Abs, and 3.2% had DSA anti-HLA Abs. In this research and review paper, we bring together our own experience, also how to function the anti-GPCRs autoAbs and how these Abs that activate GPCRs could influence graft outcome. Conclusion. Therefore, in conclusion, there is a high association of non-HLA anti-GPCRs Abs levels with reduced kidney function after transplantation, especially in the presence of DSA anti-HLA Abs. Although more studies are needed, anti-AT1R and anti-ETAR antibodies may be helpful biomarkers that allow the risk of graft loss to be assessed.

scholarly journals Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 60 ◽  
Author(s):  
Adriana Franco-Acevedo ◽  
Zesergio Melo ◽  
Raquel Echavarria
Keyword(s):  
Large Scale ◽  
Expression Profiles ◽  
Graft Loss ◽  
Large Body ◽  
Public Health Problem ◽  
Molecular Data ◽  
Data Generation ◽  
Post Transplantation ◽  
Protein Coding ◽  
Stage Renal Disease

End-stage renal disease is a public health problem responsible for millions of deaths worldwide each year. Although transplantation is the preferred treatment for patients in need of renal replacement therapy, long-term allograft survival remains challenging. Advances in high-throughput methods for large-scale molecular data generation and computational analysis are promising to overcome the current limitations posed by conventional diagnostic and disease classifications post-transplantation. Non-coding RNAs (ncRNAs) are RNA molecules that, despite lacking protein-coding potential, are essential in the regulation of epigenetic, transcriptional, and post-translational mechanisms involved in both health and disease. A large body of evidence suggests that ncRNAs can act as biomarkers of renal injury and graft loss after transplantation. Hence, the focus of this review is to discuss the existing molecular signatures of non-coding transcripts and their value to improve diagnosis, predict the risk of rejection, and guide therapeutic choices post-transplantation.

scholarly journals Individual and Combined Impact of Oxygen and Oxygen Transporter Supplementation during Kidney Machine Preservation in a Porcine Preclinical Kidney Transplantation Model

2019 ◽  
Vol 20 (8) ◽  
pp. 1992 ◽  
Author(s):  
Abdelsalam Kasil ◽  
Sebastien Giraud ◽  
Pierre Couturier ◽  
Akbar Amiri ◽  
Jerome Danion ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Fractional Excretion ◽  
Blood Levels ◽  
Kidney Graft ◽  
Post Transplantation ◽  
Kidney Fibrosis ◽  
Graft Outcome ◽  
Lower Blood ◽  
Fractional Excretion Of Sodium ◽  
Anti Oxidant

Marginal kidney graft preservation in machine perfusion (MP) is well-established. However, this method requires improvement in order to mitigate oxidative stress during ischemia-reperfusion, by using oxygenation or an O2 carrier with anti-oxidant capacities (hemoglobin of the marine worm; M101). In our preclinical porcine (pig related) model, kidneys were submitted to 1h-warm ischemia, followed by 23 h hypothermic preservation in Waves® MP before auto-transplantation. Four groups were studied: W (MP without 100%-O2), W-O2 (MP with 100%-O2; also called hyperoxia), W-M101 (MP without 100%-O2 + M101 2 g/L), W-O2 + M101 (MP with 100%-O2 + M101 2 g/L) (n = 6/group). Results: Kidneys preserved in the W-M101 group showed lower resistance, compared to our W group. During the first week post-transplantation, W-O2 and W-M101 groups showed a lower blood creatinine and better glomerular filtration rate. KIM-1 and IL-18 blood levels were lower in the W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, fractional excretion of sodium and the proteinuria/creatinuria ratio remained higher in the W group, creatininemia was lower in the W-M101 group, and kidney fibrosis was lower in M101 groups. We concluded that supplementation with M101 associated with or without 100% O2 improved the Waves® MP effect upon kidney recovery and late graft outcome.

scholarly journals Histological Evaluation of Extended Criteria Donors: Donor’s Kidney Biopsy and Graft Outcome after 5 Years of Transplantation

2020 ◽  
Vol 4 (2) ◽  
pp. 61-66
Author(s):  
Paolo Carta ◽  
Emma Bartaletti ◽  
Giulia Ghiandai ◽  
Leonardo Caroti ◽  
Aida Larti ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Graft Loss ◽  
Histological Evaluation ◽  
Kidney Graft ◽  
Graft Outcome ◽  
Histological Score ◽  
Transplant Kidney ◽  
Single Kidney ◽  
Marginal Donors

Pre-transplant kidney biopsy is routinely used to decide whether kidneys from marginal donors should be transplanted as single or double trans-plantation. This is a 5-year extension of the follow-up of a previous study. In that study, graft outcomes were compared retrospectively between a group of 44 recipients of a single kidney graft from an extended criteria donor and a Karpinski histological score of 3 or less, and another group of 56 recipients of a single transplant with a Karpinski histological score of 4 or 5. After 5 years of transplantation, there was no difference between the two groups in terms of recipient’s serum creatinine levels (1.8 ± 0.5 vs 1.9 ± 0.6 mg/dL, P = 0.5), creatinine clearance (53 ± 23 vs 49 ± 27.0 mL/min, P = 0.6), or the rates of graft loss (41% vs 49%,P = 0.5). Therefore, the choice between single and double transplant should not be made only on the basis of histological score but should be done together with the evaluation of donor’s clinical parameters, especially the renal function.

scholarly journals BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 351
Author(s):  
Baptiste Demey ◽  
Véronique Descamps ◽  
Claire Presne ◽  
Francois Helle ◽  
Catherine Francois ◽  
...  
Keyword(s):  
Viral Replication ◽  
Kidney Transplant ◽  
Clinical Relevance ◽  
Graft Loss ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplantation ◽  
Bk Polyomavirus ◽  
Micro Rnas

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.

scholarly journals Effects of renal transplantation on erectile dysfunction: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Irham Arif Rahman ◽  
Nur Rasyid ◽  
Ponco Birowo ◽  
Widi Atmoko
Keyword(s):  
Systematic Review ◽  
Erectile Dysfunction ◽  
Kidney Transplantation ◽  
Renal Transplantation ◽  
End Stage Renal Disease ◽  
Erectile Function ◽  
Meta Analysis ◽  
Post Transplantation ◽  
Stage Renal Disease ◽  
End Stage

AbstractErectile dysfunction (ED) is a major global health burden commonly observed in patients with end-stage renal disease (ESRD). Although renal transplantation improves the problem in some patients, it persists in ≈20–50% of recipients. Studies regarding the effects of kidney transplantation on ED present contradictory findings. We performed a systematic review to summarise the effects of kidney transplantation on ED. A systematic literature search was performed across PubMed, Cochrane, and Scopus databases in April 2020. We included all prospective studies that investigated the pre and posttransplant international index of erectile function (IIEF-5) scores in recipients with ED. Data search in PubMed and Google Scholar produced 1326 articles; eight were systematically reviewed with a total of 448 subjects. Meta-analysis of IIEF-5 scores showed significant improvements between pre and post transplantation. Our findings confirm that renal transplantation improves erectile function. Furthermore, transplantation also increases testosterone level. However, the evidence is limited because of the small number of studies. Further studies are required to investigate the effects of renal transplantation on erectile function.

scholarly journals Clinical impact of serum bilirubin levels on kidney transplant outcomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juhan Lee ◽  
Eun Jin Kim ◽  
Jae Geun Lee ◽  
Beom Seok Kim ◽  
Kyu Ha Huh ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Serum Bilirubin ◽  
Graft Loss ◽  
Multivariable Analysis ◽  
Post Transplantation ◽  
Transplant Outcomes ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Kidney Transplantations

AbstractSerum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3–12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.64, 95% CI 1.67–4.18, P < 0.001), death-censored graft failure (HR 2.97, 95% CI 1.63–5.42, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01–4.22, P = 0.046). Patients with lower serum bilirubin were also at greater risk of rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.

scholarly journals Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas–Kidney Transplantation (SPKT)—A Landmark Analysis

2021 ◽  
Vol 10 (15) ◽  
pp. 3237
Author(s):  
Lukas Johannes Lehner ◽  
Robert Öllinger ◽  
Brigitta Globke ◽  
Marcel G. Naik ◽  
Klemens Budde ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Type I ◽  
Kidney Graft ◽  
Landmark Analysis ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

(1) Background: Simultaneous pancreas–kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Alport syndrome: HLA association and kidney graft outcome

2004 ◽  
Vol 31 (3) ◽  
pp. 115-119 ◽  
Author(s):  
S. Barocci ◽  
S. Fiordoro ◽  
G. Santori ◽  
U. Valente ◽  
M. Mossa ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Kidney Graft ◽  
Hla Association ◽  
Graft Outcome

scholarly journals Calcium Metabolism following Renal Transplantation

1994 ◽  
Vol 31 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Anne M Straffen ◽  
DJS Carmichael ◽  
Angela Fairney ◽  
B Hulme ◽  
M Snell
Keyword(s):  
Renal Transplantation ◽  
Calcium Homeostasis ◽  
End Stage Renal Disease ◽  
Post Transplantation ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Transplant Patients ◽  
The Status ◽  
Stage Renal Disease ◽  
End Stage

Abnormalities of calcium homeostasis are a recognized feature of end-stage renal disease. The treatment of choice is renal transplantation, but this does not always result in normalization of the biochemical profile. Persistent hypercalcaemia is well documented and our study was undertaken to investigate the status of the calcium regulating hormones in renal patients post-transplantation. Serum calcium, parathyroid hormone, 1,25-dihydroxyvitamin D (1,25(OH)2D) and osteocalcin concentrations were measured in post-transplant patients. Twenty per cent of the patients had subnormal 1,25(OH)2D concentrations while 55% had biochemical evidence of hyperparathyroidism but only 5% were hypercalcaemic. Time elapsed since transplantation was not correlated with any of the analytes investigated and there was no relationship between persistent impairment of renal function and abnormalities of calcium homeostasis.

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