scholarly journals Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Thomas Verissimo ◽  
Anna Faivre ◽  
Sebastian Sgardello ◽  
Maarten Naesens ◽  
Sophie de Seigneux ◽  
...  
Keyword(s):  
Renal Function ◽  
Learning Algorithm ◽  
Standard Procedure ◽  
Graft Function ◽  
Training Dataset ◽  
Kidney Graft ◽  
Kidney Recipients ◽  
Protocol Biopsies ◽  
Patients At Risk ◽  
One Year

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

scholarly journals Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts

2019 ◽  
Vol 8 (11) ◽  
pp. 1899 ◽  
Author(s):  
Shadi Katou ◽  
Brigitta Globke ◽  
M. Haluk Morgul ◽  
Thomas Vogel ◽  
Benjamin Struecker ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Function ◽  
Rejection Sensitivity ◽  
Deceased Donor ◽  
Urine Samples ◽  
Kidney Graft ◽  
Donor Kidney ◽  
Kidney Recipients ◽  
Deceased Donor Kidney ◽  
Brain Dead

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.

A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant

2020 ◽  
Vol 30 (4) ◽  
pp. 342-348
Author(s):  
Fahad Aziz ◽  
Ali Gardezi ◽  
Brenda Muth ◽  
Justin Blazel ◽  
Neetika Garg ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Kidney Graft ◽  
Kidney Allograft ◽  
Risk Of Death ◽  
Kidney Recipients ◽  
Allograft Failure ◽  
Liver And Kidney ◽  
Multiple Variables

Background: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. Methods: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. Results: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. Conclusion: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

scholarly journals P1643TORQUE TENO VIRUS FOR RISK STRATIFICATION OF SUBCLINICAL GRAFT REJECTION AFTER KIDNEY TRANSPLANTATION- A PROSPECTIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Konstantin Doberer ◽  
Georg A Böhmig ◽  
Elisabeth Puchhammer-Stöckl ◽  
Gregor Bond
Keyword(s):  
Kidney Transplantation ◽  
Graft Rejection ◽  
Graft Function ◽  
Type I ◽  
Kidney Graft ◽  
Protocol Biopsy ◽  
Patients At Risk ◽  
Subclinical Rejection ◽  
High Level ◽  
A Prospective Study

Abstract Background and Aims Non-invasive monitoring strategies are insufficient to detect patients at risk for subclinical graft rejection after kidney transplantation. The highly prevalent and non-pathogenic Torque Teno virus (TTV) reflects the immunocompetence of its host: high level viraemia indicates strong and low level viraemia weak immunosuppression, respectively. Thus TTV replication might serve as a candidate for immunologic monitoring. Method To analyze the association between TTV and subclinical kidney graft rejection, an interim analysis of the prospective “TTV POET” cohort study (DRKS00012335) was performed including data available until 31/01/2019. All consecutive kidney graft recipients transplanted at the Medical University Vienna since 01/12/2016 (n=308) with a protocol biopsy 12 months after transplantation (n=47; median 12.4 months) and stable graft function were included. Biopsy results according to current BANFF classification were analyzed in the context of peripheral blood TTV levels quantified by PCR. Results Graft function was excellent (median eGFR MDRD: 57 ml/min/1.73m2, urinary PKR: 92 mg/g). Twenty recipients (43%) had subclinical rejection (borderline TCMR, n=16; ABMR, n=3; TCMR type I, n=1). TTV level quantified at the date of biopsy was lower in recipients with rejection compared to recipients without rejection. The risk for rejection increased by 11% with each log level decrease in TTV copies/ml (RR 0.89, 95% CI 0.85-0.93; p&lt;0.001). Differences in TTV levels were evident not only at the date of biopsy, but already 6 weeks earlier. Patients with biopsies showing chronic leasons, suggesting ongoing allo-reactivity, had a longer period of time with TTV levels &lt;1x106 copies/ml. Conclusion Our data suggests an association between TTV level and subclinical graft rejection at 12 months after kidney transplantation. Future clinical trials are necessary to test the potential of TTV guided immunosuppression to reduce subclinical rejection.

scholarly journals P1601COMPLEMENT MEMBRANE ATTACK COMPLEX DURING THE FIRST WEEK AFTER KIDNEY TRANSPLANTATION AS SEVERITY BIOMARKER TO DELAYED GRAFT FUNCTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carlos Arias-Cabrales ◽  
Marta Riera ◽  
Maria José Pérez-Sáez ◽  
Javier Gimeno ◽  
Carla Burballa ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Complement Activation ◽  
Graft Function ◽  
Membrane Attack Complex ◽  
Factor H ◽  
Delayed Graft Function ◽  
Positive Staining ◽  
Complement Factor ◽  
Protocol Biopsies

Abstract Background and Aims Ischemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available about the expression of the complement cascade final component -membrane attack complex (MAC)- and I/R injury in KT patients. We studied the dynamics of membrane attack complex (MAC) as plasma fraction (pMAC) and the histological deposit pattern of C3b, complement factor H (FH) and MAC in DGF patients. Method We evaluated pMAC levels in 59 recipients, 38 with immediate graft function and 21 without serum creatinine decreased at day 7 (DGF). pMAC was measured at admission for KT (day 0) and 7 days after KT (day 7). Sandwich ELISAs were used to measure MAC. Additionally, we performed imunohistoquimical stained for MAC, C3b and kidney biopsies (KB) with DGF (n=12) and a control group of one-year protocol biopsies without damage (n=4) Results Patients in the DGF group were older, more frequently diabetics and received kidneys from older donors and more frequently controlled cardio-circulatory death type. Day0 and day7 post-KT pMAC levels were similar in non-DGF patients 5902±3049 mAu/L vs 6178±2882 mAu/L; p=0.686). However, patients with DGF showed a significant increase of pMAC levels between day0 and day7 (6621±2202 mAu/L vs 9625±4142 mAu/L; p=0.006. Figure 1 Percentage pMAC levels increase (Δ0-7 pMAC%) discriminative assessment analyzed by ROC curve showed a good discriminative value for DGF with an AUC of 0.78; p&lt;0.001 (sensitivity 81%, specificity 66% by cut-off point of 5%). In patients with DGF longer than ten days, we found more frequently patients with a Δ0-7 pMAC &gt;5% (83% vs 17% Δ0-7 pMAC &lt;5% ; p=0.003).Patients with DGF showed renal function at 3 and 6 months, but worse renal function 1 year after KT (serum creatinine 1.78±0.61 vs 1.35±0.30 mg/dl in non-DGF patients). DGF patients with Δ0-7 pMAC &gt;5% displayed worse renal function 1 and 2 year after KT compared to DGF patients with Δ0-7 pMAC &lt;5%. MAC, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed more frequently high-intensity stain for MAC and FH than controls, without differences to C3b stain. DGF-kidney biopsies also showed a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for MAC, C3b and FH than the controls. Figure 2. Among the 12 patients with DGF-biopsies, three (25%) never recovered renal function, all of them presented Δ0-7 pMAC &gt;5% and intense, diffuse and positive staining in more than 50% of tubular perimeter for MAC, FH and C3b Conclusion Complement activation during peritrasplant period could be related with the severity of graft injury and the presence of DGF. Therefore, the determination of MAC levels could be useful to identify patients with possible complement dependent graft injury that might benefit from complement inhibitor therapies

A joint transition model for evaluating eGFR as biomarker for rejection after kidney transplantation

2021 ◽  
pp. 1471082X2110486
Author(s):  
Maarten Coemans ◽  
Geert Verbeke ◽  
Maarten Naesens
Keyword(s):  
Estimated Glomerular Filtration Rate ◽  
Graft Function ◽  
Diagnostic Value ◽  
Transition Model ◽  
Kidney Graft ◽  
University Hospitals ◽  
Protocol Biopsies ◽  
The Mean ◽  
Transition Models ◽  
Carry Over

The estimated glomerular filtration rate (eGFR) quantifies kidney graft function and is measured repeatedly after transplantation. Kidney graft rejection is diagnosed by performing biopsies on a regular basis (protocol biopsies at time of stable eGFR) or by performing biopsies due to clinical cause (indication biopsies at time of declining eGFR). The diagnostic value of the eGFR evolution as biomarker for rejection is not well established. To this end, we built a joint model which combines characteristics of transition models and shared parameter models to carry over information from one biopsy to the next, taking into account the longitudinal information of eGFR collected in between. From our model, applied to data of University Hospitals Leuven (870 transplantations, 2 635 biopsies), we conclude that a negative deviation from the mean eGFR slope increases the probability of rejection in indication biopsies, but that, on top of the biopsy history, there is little benefit in using the eGFR profile for diagnosing rejection. Methodologically, our model fills a gap in the biomarker literature by relating a frequently (repeatedly) measured continuous outcome with a less frequently (repeatedly) measured binary indicator. The developed joint transition model is flexible and applicable to multiple other research settings.

scholarly journals P1772CONVERSION TO BELATACEPT IMPROVES RENAL GRAFT FUNCTION OF PATIENTS WITH SEVERE HISTOLOGICAL AND FUNCTIONAL INVOLVEMENT. LONG-TERM UNICENTRIC EXPERIENCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Ovidia Lopez-Oliva ◽  
Laura Alvarez Garcia ◽  
Tamara Perez Robles ◽  
Marco Antonio Vaca Gallardo ◽  
Santacruz Juan ◽  
...  
Keyword(s):  
Renal Function ◽  
Acute Rejection ◽  
De Novo ◽  
Graft Function ◽  
Vascular Lesions ◽  
Kidney Graft ◽  
Contralateral Kidney ◽  
Renal Graft ◽  
Functional Involvement

Abstract Background and Aims Belatacept selectively blocks the costimulation signal of T cells. Its use, both de novo and in conversion, is associated with a better renal graft function compared to the regimens that include a calcineurin inhibitor (CNI). We expose our experience with belatacept as a rescue therapy in patients who present moderate-severe dysfunction after renal transplantation and compare the evolution with those patients who received the contralateral kidney graft without change to belatacept. Method Adult kidney transplanted patients, with graft dysfunction and renal biopsy with CNI toxicity or chronic vascular lesions who are changed from CNI to belatacept were included. Efficacy (creatinine, proteinuria, TFGe, acute rejection tested by biopsy, anti HLA) and safety (adverse events, tumors or infections) variables were recorded before and after the change. Results 11 patients were included. The change to belatacept was made at a median of 13 months from the transplant (range 1-62 months) and the duration of the treatment ranged between 6 and 74 months. Renal function improved from a mean creatinine of 3.04±1.34 mg/dl before the change to 1.9±0.3 mg/dl at 6 and 12 months after conversion (p = 0.016), being the last average creatinine (December 2019) of 1.7±0.3 mg/dl. Belatacept was withdrawn in one case, at one year, due to the development of specific donor antibodies without evidence of acute rejection. There were no cases of post-transplant lymphoproliferative syndrome. Two patients developed VBK replication controlled with immunosuppression modification and three patients developed CMV infection controlled with valganciclovir. There was no episode of acute rejection after conversion. In 5 cases the contralateral kidney graft was not implanted, while in 6 cases it was implanted in another recipient who was not given belatacept and was taken on CNI therapy. The last average creatinine (December 2019) of patients without belatacept was 3.3±1.6 mg/dl vs. 1.6±0.2 mg/dl in patients with belatacept (p = 0.03). Conclusion The change to belatacept improves the renal function of all patients, even in those with severe histological and functional involvement. The improvement of renal function remains stable in the medium/long term and is significantly better than the renal function of patients with CNI.

scholarly journals Latent Abnormal Pathology Affects Long-Term Graft Function in Elder Living Renal Allograft Recipients

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Linlin Ma ◽  
Lei Zhang ◽  
Yu Du ◽  
Zelin Xie ◽  
Yawang Tang ◽  
...  
Keyword(s):  
Renal Function ◽  
Living Donor ◽  
Graft Function ◽  
Kidney Graft ◽  
Donor Kidney ◽  
Time Zero ◽  
Arterial Lesions ◽  
Abnormal Pathology ◽  
Living Donor Kidney

Objective. This study evaluated the long-term effects and clinical significance of latent abnormal pathology on elder living donor kidney graft function after renal transplantation in China. Methods. One-hundred and thirty-eight living donor renal transplantations have been carried out at our hospital in recent years. Of these, 72 Time-Zero biopsies were performed and used in this analysis. Clinical data were retrospectively measured at 3, 6, 12, and 24 months after renal transplants. Relationships and effects from biopsy results taken from implanted donor kidney grafts were analyzed. Results. Time-Zero biopsy pathology results from donor kidneys showed that 48.61% of donor kidneys had latent abnormal changes; arterial lesions of donor kidneys had significant effects on the renal function of grafts after 2 years' transplantation; correlations between donor age and arterial lesions were significant; and Time-Zero biopsy pathology results could help predict the long-term function of a renal graft. Conclusions. Existing latent pathological changes of an elder living donor kidney before transplantation could affect long-term renal function. Whether a senior donor is used should be very carefully considered.

scholarly journals P0295IMPROVED LEFT VENTRICULAR FUNCTION EVALUATION AFTER KIDNEY TRANSPLANT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Milagros Melissa Flores Fonseca ◽  
Viridiana Rodriguez Ugarte ◽  
Priscila Berenice Villalvazo Osoria ◽  
Norma Cecilia Ruiz Cruz ◽  
Sandra Fabiola Velasco Ramirez ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Transplant ◽  
Graft Function ◽  
Left Ventricular ◽  
Structure And Function ◽  
Wilcoxon Test ◽  
Categorical Variables ◽  
Kidney Graft ◽  
Echocardiographic Evaluation ◽  
And Function

Abstract Background and Aims Chronic kidney disease (CKD) represents a major risk factor for cardiovascular (CV) disease. CKD pro inflammatory state evokes structural and functional cardiac and vascular changes, such as chronic dysregulation of nitric oxide in vascular muscle, results in left ventricular hypertrophy (LVH), LV dilatation, LV systolic and diastolic dysfunction, endothelial dysfunction and atherosclerosis. Recent advances in echocardiographic methods allows to evaluate changes in cardiac structure and function after KT. The aim of this study was to assess changes in LV structure and function after renal transplantation in patients with end-stage renal disease (ESRD). Method All subjects were prospectively recruited prior to kidney transplantation in our center at Centro Medico Nacional de Occidente, Jalisco, Mexico. Demographics, echocardiographic evaluation, clinical and biochemical studies were performed before and after KT. Patients with transplant failure after KT were excluded. Thirty patients were included in the final analysis. Statistical analysis: Results are expressed as means and standard deviation (SD). Accordingly, paired T test or Wilcoxon test were used for comparison of paired observations. Categorical variables were compared using chi-square test or Fisher’s exact probability test, as appropriate. Multivariate logistic regression models including the variables changes in LVEF, LV systolic and diastolic function and LV mass index. Statistical analyses were performed using SPSS v26.0 (IBM Corporation, NY, USA); p &lt; 0.05 was considered statistically significant. Results Mean age was 31.99 ± 11.28 years, and 65% were women. Before transplant, LVEF was 58% and pulmonary arterial pressure was 32 mmHg. Ventricular dysfunction was associated with unclamping donor renal vessels at 107.8 ± 7.96mmHg, and lower perioperative hemodynamics values. The LVEF group increased from 25% to 72.5%, and serum creatinine decrease from 2.25 ± 3.76 mg/dl to 1.98± 2.65 mg/dl (p&lt;0.001) by 6 months after kidney transplant. The best set of predictors in multiple regression analysis of renal function were the onset of diuresis and the use of diuretics (R2 = 0.4; p &lt; 0.001). Conclusion We observed a significant reversal of LV dysfunction. This was accompanied by a significant improvement on kidney graft function. These findings highlight the dynamics between cardiac and renal function, and support the application of adequate echocardiographic evaluation on CKD patients with low LVEF undergoing KT.

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