scholarly journals Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

2020 ◽  
Vol 21 (15) ◽  
pp. 5404 ◽  
Author(s):  
Marco Quaglia ◽  
Guido Merlotti ◽  
Gabriele Guglielmetti ◽  
Giuseppe Castellano ◽  
Vincenzo Cantaluppi
Keyword(s):  
Graft Survival ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Graft Function ◽  
Kidney Graft ◽  
Graft Dysfunction ◽  
Prognostic Information ◽  
Management Of Complications ◽  
Wide Range ◽  
New Biomarkers

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes

2021 ◽  
pp. CJN.03290321
Author(s):  
Simon Ville ◽  
Marine Lorent ◽  
Clarisse Kerleau ◽  
Anders Asberg ◽  
Christophe Legendre ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Ischemia Reperfusion ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Deceased Donor ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Heart Beating ◽  
Deceased Donor Kidney Transplant

BackgroundThe recognition that metabolism and immune function are regulated by an endogenous molecular clock generating circadian rhythms suggests that the magnitude of ischemia-reperfusion and subsequent inflammation on kidney transplantation, could be affected by the time of the day. MethodsAccordingly, we evaluated 5026 first kidney transplant recipients from deceased heart-beating donors. In a cause-specific multivariable analysis, we compare delayed graft function (DGF) and graft survival according to the time of kidney clamping and declamping. Participants were divided into clamping between midnight and noon (AM clamping group, 65%) or clamping between noon and midnight (PM clamping group, 35%), and similarly, AM declamping or PM declamping (25% / 75%). ResultsDGF occurred among 550 participants (27%) with AM clamping and 339 (34%) with PM clamping (adjusted OR = 0.81, 95%CI: 0.67 to 0.98, p= 0.03). No significant association of clamping time with overall death censored graft survival was observed (HR = 0.92, 95%CI: 0.77 to 1.10, p= 0.37). No significant association of declamping time with DGF or graft survival was observed. ConclusionsClamping between midnight and noon was associated with a lower incidence of DGF whilst the declamping time was not associated with kidney graft outcomes.

scholarly journals Low-Fouling Substrates for Plasmonic Sensing of Circulating Biomarkers in Biological Fluids

Biosensors ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 63
Author(s):  
Elba Mauriz
Keyword(s):  
Biological Fluids ◽  
Point Of Care ◽  
Disease Onset ◽  
Screening Tools ◽  
Circulating Biomarkers ◽  
Prognostic Information ◽  
Wide Range ◽  
Biomarker Analysis ◽  
Surface Enhanced Raman ◽  
The Impact

The monitoring of biomarkers in body fluids provides valuable prognostic information regarding disease onset and progression. Most biosensing approaches use noninvasive screening tools and are conducted in order to improve early clinical diagnosis. However, biofouling of the sensing surface may disturb the quantification of circulating biomarkers in complex biological fluids. Thus, there is a great need for antifouling interfaces to be designed in order to reduce nonspecific adsorption and prevent inactivation of biological receptors and loss of sensitivity. To address these limitations and enable their application in clinical practice, a variety of plasmonic platforms have been recently developed for biomarker analysis in easily accessible biological fluids. This review presents an overview of the latest advances in the design of antifouling strategies for the detection of clinically relevant biomarkers on the basis of the characteristics of biological samples. The impact of nanoplasmonic biosensors as point-of-care devices has been examined for a wide range of biomarkers associated with cancer, inflammatory, infectious and neurodegenerative diseases. Clinical applications in readily obtainable biofluids such as blood, saliva, urine, tears and cerebrospinal and synovial fluids, covering almost the whole range of plasmonic applications, from surface plasmon resonance (SPR) to surface-enhanced Raman scattering (SERS), are also discussed.

scholarly journals Monocyte-Derived Dendritic Cells Impair Early Graft Function following Allogeneic Islet Transplantation

2017 ◽  
Vol 26 (2) ◽  
pp. 319-326 ◽  
Author(s):  
Kevin V. Chow ◽  
Emma M. Carrington ◽  
Yifan Zhan ◽  
Andrew M. Lew ◽  
Robyn M. Sutherland
Keyword(s):  
Dendritic Cells ◽  
Graft Survival ◽  
Islet Transplantation ◽  
Graft Function ◽  
Saline Control ◽  
Graft Dysfunction ◽  
Adaptive Immune ◽  
Early Graft ◽  
Early Graft Dysfunction

Islet transplantation can cure type 1 diabetes but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte-derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2. DTR recipients (H-2b) treated with either saline (control) or diphtheria toxin (DT) to deplete moDCs. Graft function was assessed by blood glucose (BG) measurement. DT treatment resulted in specific depletion of graft site moDCs posttransplant. Despite equivalent pretransplant BG levels [27.0 ± 1.3 vs. 29.6 ± 1.1 mM, not significant (ns)], DT recipients achieved lower posttransplant BG levels and better rates of normoglycemia than control recipients (11.0 ± 1.9 vs. 19.1 ± 1.4 mM, p = 0.004) at 1 day posttransplant in diabetic recipients. When a suboptimal donor dose of 200 islets was transplanted, DT-induced moDC depletion resulted in normoglycemia in 78% compared to 25% of control recipients ( p = 0.03). As well as amelioration of graft dysfunction in the immediate peritransplant period, prolonged DT administration (15 days posttransplant) resulted in improved graft survival (21 vs. 11 days, p = 0.005). moDCs impair early graft function post-allogeneic islet transplantation. moDC depletion may allow for improved early graft function, permit transplantation with lower islet masses, and enhance graft survival.

Kidney graft function before pregnancy as a predictor of graft, maternal and fetal outcomes in pregnant renal transplant recipients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Filipe S. Mira ◽  
Joana Oliveira ◽  
Filipa Sousa ◽  
Dora Antunes ◽  
Ana Carolina Figueiredo ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Adverse Outcomes ◽  
Hypertensive Disorder ◽  
Renal Transplant Recipients ◽  
Kidney Graft ◽  
Transplant Recipients ◽  
Graft Dysfunction ◽  
Kidney Transplant Recipients

Abstract Objectives Maternal and fetal complications can occur in pregnant kidney transplant recipients. Since these are high-risk pregnancies, they require a multidisciplinary follow-up to prematurely detect adverse events. Identifying factors that would affect fetal, maternal and graft outcomes is essential to further stratify the risk of pregnant kidney transplant recipients. Methods All pregnancies in kidney transplant recipients followed in a single center for 30 years were included. Data included previous transplant information and blood and urine tests performed before pregnancy. Impact of graft function on fetal, maternal and graft outcomes was evaluated. Results There were 41 pregnancies among 34 patients. Mean gestational age of 35 ± 3 weeks. Caesarean section was performed in 69.4% of patients. Five pregnancies were unsuccessful (12.2%). Four patients suffered an acute graft dysfunction (9.8%) and 12 (29.3%) had a serious maternal hypertensive disorder (preeclampsia, eclampsia or HELLP syndrome). Graft function before pregnancy showed significant correlation with adverse outcomes. Conclusions A proteinuria >669 mg/g, serum creatinine >1.75 mg/dL and glomerular filtration rate <36.2 mL/min/1.73 m2 before pregnancy were correlated to graft dysfunction during pregnancy. Similar values of proteinuria were also associated with a risk of maternal hypertensive disorders and pregnancy failure. Therefore, in patients with proteinuria and graft dysfunction, follow-up should be stricter to quickly detect complications.

scholarly journals Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Robert G. Wallace ◽  
Laura C. Twomey ◽  
Marc-Antoine Custaud ◽  
Niall Moyna ◽  
Philip M. Cummins ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Cell Types ◽  
Lifestyle Changes ◽  
The Body ◽  
Direct Function ◽  
Disease States ◽  
Markers Of Inflammation ◽  
Wide Range ◽  
Alternative Means ◽  
New Biomarkers

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

scholarly journals Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hengcheng Zhang ◽  
Zijie Wang ◽  
Jiayi Zhang ◽  
Zeping Gui ◽  
Zhijian Han ◽  
...  
Keyword(s):  
Immune Response ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Serum Creatinine ◽  
Graft Survival ◽  
Rat Kidney ◽  
Combined Therapy ◽  
Graft Function ◽  
Kidney Graft ◽  
Term Survival

BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and MethodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

MO942PREDICTORS OF DELAYED GRAFT FUNCTION IN KIDNEY TRANSPLANT RECIPIENTS THROUGHOUT 3 DECADES: A SINGLE-CENTER EXPERIENCE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Carolina Figueiredo ◽  
Mariana Fernandes ◽  
Filipe Mira ◽  
Clara Pardinhas ◽  
Rita Leal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Survival ◽  
Univariate Analysis ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Kidney Graft ◽  
Cold Ischemia Time ◽  
Cold Ischemia ◽  
Ischemia Time ◽  
The Impact

Abstract Background and Aims Delayed graft function (DGF), defined as the need for dialysis within one week post-transplantation, is associated with poorer kidney graft survival. We aimed to identify risk factors for DGF throughout 3 decades and evaluate their effect on graft survival. Method Retrospective study including 3081 kidney transplants performed at our transplantation unit between January 1st, 1989 and December 31st, 2018, split in 3 decades (1: 1989-1998; 2: 1999-2008; 3: 2009-2018). Data regarding donor and recipient demographics, time on dialysis, immunization, cold ischemia time, hemodynamic parameters and immunosuppression were collected from our prospectively maintained data base. Results Main donor, recipient and perioperative characteristics are summarized in table 1. There were clear differences in these characteristics between the decades, standing out more adverse features from both recipients and donors. Overall incidence rate of DGF was 16% (n=493): 14% in decade 1; 19.3% in decade 2 and 15% in decade 3. On univariate analysis, most studied variables included in table 1 were statistically significant as predictors of DGF. However, on multivariate analysis, we found that in the first decade the predominant risk factors for DGF were pre-transplant dialysis time and cold-ischemia time, whilst in the following decades donor characteristics, as well as recipient’s weight became more relevant (table 2). Conclusion The observed shift from donor-unrelated variables in the first decade into donor-related variables in the second and third decades as the main determinants of DGF highlights the impact of expanding donor’s acceptance criteria. Nevertheless, the increase in expanded criteria donors did not translate into poorer overall results, probable contributors being shorter cold-ischemia times and stronger immunosuppression.

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