scholarly journals Elevated plasma free thiols are associated with early and one-year graft function in renal transplant recipients

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255930
Author(s):  
Marie B. Nielsen ◽  
Bente Jespersen ◽  
Henrik Birn ◽  
Nicoline V. Krogstrup ◽  
Arno R. Bourgonje ◽  
...  

Background Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR. Methods Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation. Results Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF. Conclusion Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors. Trial registration ClinicalTrials.gov Identifier: NCT01395719.

2018 ◽  
Vol 90 (2) ◽  
pp. 28-33 ◽  
Author(s):  
Piotr Hogendorf ◽  
Anna Suska ◽  
Aleksander Skulimowski ◽  
Joanna Rut ◽  
Monika Grochowska ◽  
...  

Background Delayed graft function (DGF) is a common complication following kidney transplantation and is associated with ischemia-reperfusion injury (IRI). Lymphocytes contribute to the pathogenesis of IRI and ischemia-reperfusion related delayed graft function Materials and Methods 135 Caucasian patients received a kidney graft from deceased heart-beating organ donors. We divided patients into 2 groups- patients with the eGFR>=30 on the 21st day post-transplantation (n=36) and patients with the eGFR<30 on the 21st day post-transplantation (n=99) to assess kidney graft function. We measured the serum creatinine levels on 1st and 2nd post-transplant day and preoperative levels of monocytes, lymphocytes, platelets and neutrophils and their ratios. Results We have found statistically significant differences between the eGFR<30 and the eGFR>=30 groups in the average lnLymphocytes (0,36 +/-0,6 vs -0,016 +/-0,74 respectively p=0,004) lnNLR ( 1,27 +/-0,92 vs. 1,73+/-1,08 p=0,016) lnLMR (1,01 +/-0,57 vs. 0,73 +/-0,64 p=0,02), lnPLR (4,97 +/-0,55 vs. 5,26 +/- 0,67 p=0,023) and CCR2% (-20,20 +/- 21,55 vs. -4,29 +/- 29,62 p=0,004 . On univariate analysis, factors of lnLymphocytes >=0,22 (OR=0,331 95%CI 0,151-0,728 p=0,006), lnLMR>=1,4 (OR=0,255 95%CI 0,072-0,903 p=0,034) were associated with worse graft function while lnNLR>=1,05 (OR=2,653 95%CI 1,158-6,078 p=0,021), lnPLR>=5,15 (OR=2,536 95%CI 1,155-5,566 p=0,02) and CRR2 (OR=3,286 95% CI 1,359-7,944 p=0,008) indicated better graft function Conclusion Higher absolute lymphocyte count (lnLymphocytes) and lnLMR as well as lower lnNLR and lnPLR were associated with lower eGFR on the 21st day after kidney transplantation. On multivariate analysis CRR2 in combination with either lnLymphocytes, lnNLR or lnPLR improved the accuracy of detecting patients with poor graft function.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65613 ◽  
Author(s):  
Rui Ding ◽  
Xiangmei Chen ◽  
Di Wu ◽  
Ribao Wei ◽  
Quan Hong ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Krzysztof Letachowicz ◽  
Mirosław Banasik ◽  
Anna Królicka ◽  
Oktawia Mazanowska ◽  
Tomasz Gołębiowski ◽  
...  

Introduction: More attention has been paid to the influence of arteriovenous fistula (AVF) on the cardiovascular system. In renal transplant recipients, some beneficial effect of an elective vascular access (VA) ligation was observed in patients with a high AVF flow. However, this strategy is not widely accepted and is in contradiction to the rule of vasculature preservation for possible future access. The aim of our study is to elucidate the vascular access function and VA perspective in the kidney transplantation (KTx) population.Materials and Methods: KTx patients with a stable graft function were recruited to participate in this single center observational study (NCT04478968). The measurement of VA flow and vessel mapping for future vascular access was performed by a color Doppler ultrasound. The study group included 99 (63%) males and 58 (37%) females; the median age was 57 (IQR 48–64) years. The median time from the transplantation to the baseline visit was 94 (IQR 61–149) months. Median serum creatinine concentration was 1.36 (IQR 1.13–1.67) mg/dl.Results: Functioning VA was found in 83 out of 157 (52.9%) patients. The sites were as follows: snuffbox in six (7.2%), wrist in 41 (49.4%), distal forearm in 18 (21.7%), middle or proximal forearm in eight (9.6%), upper-arm AV graft in one (1.2%), and upper-arm AVFs in nine (10.8%) patients, respectively. Blood flow ranged from 248 to 7,830 ml/min; the median was 1,134 ml/min. From the transplantation to the study visit, 66 (44.6%) patients experienced access loss. Spontaneous thrombosis was the most common, and it occurred in 60 (90.9%) patients. The surgical closure of VA was performed only in six (4%) patients of the study group with a functioning VA at the time of transplantation. Access loss occurred within the 1st year after KTx in 33 (50%) patients. Majority (50 out of 83, 60.2%) of the patients with an active VA had options to create a snuffbox or wrist AVF on the contralateral extremity. In a group of 74 patients without a functioning VA, the creation of a snuffbox or wrist AVF on the non-dominant and dominant extremity was possible in seven (9.2%) and 40 (52.6%) patients, respectively. In 10 (13.1%) patients, the possibilities were limited only to the upper-arm or proximal forearm VA on both sides. Access ligation was considered by 15 out of 83 (18.1%) patients with a patent VA.Conclusions: In the majority of the patients, vascular access blood flow was below the threshold of the negative cardiovascular effect of vascular access. Creation of a distal AVF is a protective measure to avoid a high flow and preserve the vessels for future access. The approach to VA should be individualized and adjusted to the patient's profile.


2008 ◽  
Vol 86 (Supplement) ◽  
pp. 696
Author(s):  
R Ruiz ◽  
B Fischbach ◽  
N Onaca ◽  
G McKenna ◽  
H Randall ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irina Larina ◽  
Anastasia Severina ◽  
Minara Shamhalova ◽  
Marina Shestakova ◽  
Larisa Nikankina ◽  
...  

Abstract Background and Aims To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT). Method The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy. Results SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE & creatinine (R=0.50, p=0.02), RAGE & KIM-1 (R=0.43, p=0.047), 3-NT& eGFR (R= - 0.40, p=0.046), IL-18 & SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE & HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline & RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”. Conclusion SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.


2020 ◽  
Vol 5 (3) ◽  
pp. S144
Author(s):  
Z. Heleniak PhD ◽  
S. Illersberger ◽  
S. Brakemeier ◽  
A. Dębska-Ślizień ◽  
K. Budde ◽  
...  

2019 ◽  
Vol 8 (11) ◽  
pp. 1899 ◽  
Author(s):  
Shadi Katou ◽  
Brigitta Globke ◽  
M. Haluk Morgul ◽  
Thomas Vogel ◽  
Benjamin Struecker ◽  
...  

The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Rao Chen ◽  
Haifeng Wang ◽  
Lei Song ◽  
Jianfei Hou ◽  
Jiawei Peng ◽  
...  

Abstract Background Delayed graft function (DGF) is closely associated with the use of marginal donated kidneys due to deficits during transplantation and in recipients. We aimed to predict the incidence of DGF and evaluate its effect on graft survival. Methods This retrospective study on kidney transplantation was conducted from January 1, 2018, to December 31, 2019, at the Second Xiangya Hospital of Central South University. We classified recipients whose operations were performed in different years into training and validation cohorts and used data from the training cohort to analyze predictors of DGF. A nomogram was then constructed to predict the likelihood of DGF based on these predictors. Results The incidence rate of DGF was 16.92%. Binary logistic regression analysis showed correlations between the incidence of DGF and cold ischemic time (CIT), warm ischemic time (WIT), terminal serum creatine (Scr) concentration, duration of pretransplant dialysis, primary cause of donor death, and usage of LifePort. The internal accuracy of the nomogram was 83.12%. One-year graft survival rates were 93.59 and 99.74%, respectively, for the groups with and without DGF (P < 0.05). Conclusion The nomogram established in this study showed good accuracy in predicting DGF after deceased donor kidney transplantation; additionally, DGF decreased one-year graft survival.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Vladimir Hanzal ◽  
Janka Slatinska ◽  
Petra Hruba ◽  
Ondrej Viklicky

Abstract Background and Aims Cytomegalovirus (CMV) disease and infection negatively influence outcome of kidney transplantation. The aim of this retrospective study was to analyze risk factors for CMV disease and its influence on kidney graft function and survival. Method 1050 patients underwent kidney transplantation from January 2014 to December 2018 and received calcineurin inhibitor, mycophenolate mofetil and steroid-based immunosuppression. Recipients with PRA&gt;20% received rATG while others had received basiliximab as induction. 825 out of 1050 patients (78.6%) received CMV prophylaxis (D+/R-, n=173; R+, n=652). Patients were followed up to 71 months /median 38 months/. Results CMV tissue invasive disease occurred in 49 out of 1050 patients (4.7%), while CMV infection in 87 patients (8.3%). CMV disease, but not CMV infection, had significant negative influence on graft survival at 5 years post transplantation (p=0.0029). Patients with CMV disease had significantly worse graft function at 4 years post transplantation (p&lt;0.0001). CMV disease occurred in 31 out of 173 patients (17.9%) in D+/R- group vs. 18 out of 652 patients (2.8%) in R+ group. Incidence of CMV infection was 30/173 patients (17.3%) in D+/R- group vs. 57/652 patients (8.7%) with induction therapy. Shortening of CMV prophylaxis was found in 82 patients (9.9%). Leukopenia (≤ 2.0 x 109/L) was observed in 97 (11.7%) patients from those who received CMV prophylaxis, Its shortening significantly increased risk for both CMV infection (20,7% vs. 7.2%, p&lt;0,0001) and CMV disease (8,5% vs. 4,2%, p=0,04). Among most significant risk factors for CMV disease in univariable analysis were CMV mismatch (OR 11, 95% CI: 5,9-20,4; p&lt;0,0001), delayed graft function (OR 2,8, 95% CI: 1,6-5,1; p&lt;0,0001, cadaveric donor (OR 6, 95% CI: 1,5-25,1; p=0,00013) and shortening of CMV prophylaxis (OR 2.1, 95% CI: 0,91-4,86; p=0,08). Multivariable analysis revealed as independent significant predictors of CMV disease DGF (OR 2,29, 95% CI: 1,2-4,3; p=0,01) and CMV mismatch (OR 10,8, 95% CI: 5,7-20,6; p&lt;0.0001) in a model adjusted for type of donor, prophylaxis shortening and leukopenia. Conclusion CMV mismatch is the main independent predictor of CMV disease after kidney transplantation in multivariable analysis.


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