SP763PROGNOSTIC ROLE OF THE KIDNEY GRAFT VASCULOPATHY ON THE GRAFT FUNCTION FIVE YEARS POST-TRANSPLANT

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Marko Pražetina ◽  
NIKOLA ZAGOREC ◽  
Mira Knežić ◽  
Karlo Mihovilović ◽  
Danica Galešić Ljubanović ◽  
...  
2015 ◽  
Author(s):  
Laurent Mesnard ◽  
Thangamani Muthukumar ◽  
Maren Burbach ◽  
Carol Li ◽  
Huimin Shang ◽  
...  

BACKGROUND: Kidney transplantation is the treatment of choice for most patients with end-stage renal disease and existing data suggest that post transplant graft function is a predictor of kidney graft failure. METHODS: Exome sequencing of DNA from kidney graft recipients and their donors was used to determine recipient and donor mismatches at the amino acid level. The number of mismatches that are more likely to induce an immune response in the recipient was computationally estimated and designated the allogenomics mismatch score. The relationship between the allogenomics score and post transplant kidney allograft function was examined using linear regression. RESULTS: A significant inverse correlation between the allogenomics mismatch score and kidney graft function at 36 months post transplantation was observed in a discovery cohort of kidney recipient-donor pairs (r2>=0.57, P<0.05, the score vs. level of serum creatinine or estimated glomerular filtration rate). This relationship was confirmed in an independent validation cohort of kidney recipient-donor pairs. We observed that the strength of the correlation increased with time post-transplantation. This inverse correlation remained after excluding HLA loci from the calculation of the score. Exome sequencing yielded allogenomics scores with stronger correlations with graft function than simulations of genotyping assays which measure common polymorphisms only. CONCLUSIONS: The allogenomics mismatch score, derived by exome sequencing of recipient-donor pairs, facilitates quantification of histoincompatibility between the organ donor and recipient impacting long-term post transplant graft function. The allogenomics mismatch score, by serving as a prognostic biomarker, may help identify patients at risk for graft failure.


2009 ◽  
Vol 9 (4) ◽  
pp. 307-312 ◽  
Author(s):  
Goran Imamović ◽  
Enver Zerem ◽  
Safet Omerović ◽  
Enes Osmanović ◽  
Emir Hodžić

Delayed kidney graft function and acute rejection in the early post-transplant period affect both short and long-term allograft survival. Allograft rejection, as an inflammatory state, results in increased eryth-ropoietin resistance, which leads to decreased haemoglobin (Hb) level. We conducted this study to evaluate whether inflammation in the early post-transplant period could predict later anemia.This is a retrospective cohort study based on the analysis of 64 existing clinical records. Predictor. White blood cells (WBC) count obtained by the end of the first week post-transplant (W1). Covariates. Donor’s age, recipient’s age and sex. Outcome. Anemia identified at 12 months (M12) post engraftment.Median WBC count at W1 was 9,5 x103^L (5th - 95th percentile 5,2 x103^L -17,8 x 103/μΚ). Mean Hb values at M12 were 129,9 ± 20,3 g/L, in males 136,2 ± 20,1 g/L and in females 119,4 ± 16,2 g/L. The significant correlation was found between WBC at W1 and Hb at M12. Pearson coefficient of correlation r was -0,26, and 95% confidence interval (CI) for r was -0,47 to -0,015 (p=0,03). Univariate logistic regression showed significant association between WBC at W1 and Hb at M12 (OR 1,20; 95% CI 1,04 to 1,39, p=0,01). After the adjustment for donor’s and recipient’s age by transplantation and recipient’s sex, multiple regression showed that WBC count remained predictive of anemia at M12 (OR 1,17; 95% CI 1,01 to 1,36, p=0,03).Early post-transplant inflammatory response predicts later anemia in kidney transplant recipients. An increase in WBC count in the first week post-transplant by 109/L increases the risk for anemia after twelve months by 17%.


2021 ◽  
Vol 10 (11) ◽  
pp. 2322
Author(s):  
David Montaigne ◽  
Nasser Alhawajri ◽  
Mathilde Jacquelinet ◽  
Amandine Coppin ◽  
Marie Frimat ◽  
...  

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR= 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR= 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (>15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.


2011 ◽  
Vol 80 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Miklos Z. Molnar ◽  
Csaba P. Kovesdy ◽  
Istvan Mucsi ◽  
Suphamai Bunnapradist ◽  
Elani Streja ◽  
...  

2020 ◽  
Vol 36 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Phoebe Uhl ◽  
Andreas Heilos ◽  
Gregor Bond ◽  
Elias Meyer ◽  
Michael Böhm ◽  
...  

Abstract Background Chronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation. Methods TTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally. Results TTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor–based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found. Conclusions TTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections—common consequences of insufficient or too intense IS.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guoqiang Zhang ◽  
Hayato Iwase ◽  
Qi Li ◽  
Takayuki Yamamoto ◽  
Abhijit Jagdale ◽  
...  

BackgroundIn pig-to-baboon transplantation models, there is increasing evidence of systemic inflammation in xenograft recipients (SIXR) associated with pig xenograft failure. We evaluated the relationship between systemic inflammatory factors and pig kidney xenograft failure.MethodsBaboons received kidney transplants from genetically engineered pigs (n=9), and received an anti-CD40mAb-based (n=4) or conventional (n=5) immunosuppressive regimen. The pig kidney grafts were monitored by measurements of serum creatinine, serum amyloid A (SAA), white blood cell (WBC) and platelet counts, plasma fibrinogen, and pro-inflammatory cytokines (baboon and pig IL-6, TNF-α, IL-1β).ResultsSix baboons were euthanized or died from rejection, and 3 were euthanized for infection. Changes in serum creatinine correlated with those of SAA (r=0.56, p&lt;0.01). Serum baboon IL-6 was increased significantly on day 1 after transplantation and at euthanasia (both p&lt;0.05) and correlated with serum creatinine and SAA (r=0.59, p&lt;0.001, r=0.58, p&lt;0.01; respectively). but no difference was observed between rejection and infection. Levels of serum pig IL-6, TNF-α, IL-1β were also significantly increased on day 1 and at euthanasia, and serum pig IL-6 and IL-1β correlated with serum creatinine and SAA. The level of serum baboon IL-6 correlated with the expression of IL-6 and amyloid A in the baboon liver (r=0.93, p&lt;0.01, r=0.79, p&lt;0.05; respectively).ConclusionEarly upregulation of SAA and serum IL-6 may indicate the development of rejection or infection, and are associated with impaired kidney graft function. Detection and prevention of systemic inflammation may be required to prevent pig kidney xenograft failure after xenotransplantation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Maria Ivanova ◽  
Olga Vetchinnikova ◽  
Andrey Vatazin

Abstract Background and Aims The normalization of the function of the parathyroid glands after successful kidney transplantation does not occur in all patients. The aim of our study was to determine of parathyroid function, patient factors that would be predictive of achieving a normal serum PTH in the first months after surgery and prevalence of hyperparathyroidism (HPT) in patients after kidney transplantation (KT) at various stages of the post-transplant period. Method The observational cross-retrospective study included 230 kidney graft recipients. Inclusion criteria: the duration of the post-transplant period is more than 12 months and stable kidney transplant function for 6 months. The median of the pre-transplant stage was 18 months (Q1-Q3: 9; 35), post-transplant period - 42 months (Q1-Q3: 21; 73). Serum concentrations of parathyroid hormone (PTH), calcium, phosphorus, total alkaline phosphatase activity, albumin, and creatinine were determined using standard methods. HPT was diagnosed with PTH&gt;130 pg/ml. Retrospective analysis of parameters in three months after surgery it was performed in 197 patients. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula, stratification of chronic kidney disease (CKD) stages was carried out according to the eGFR. Results Patients had different kidney transplant function: eGFR 117-15 ml/min, median 51 (Q1-Q3: 39;65): CKD 1(КT) st. was in 3.5%, CKD 2(КT) st. - in 33.9%, CKD 3(КT) st. - in 49.1% and CKD 4(КT) st. – in 13.5% patients. Serum PTH levels were 27-670 pg/ml, median 120 pg/ml (Q1-Q3: 87; 182). The median PTH of blood in patients was 99 pg/ml (Q1-Q3: 76; 120), 98 pg/ml (Q1-Q3: 79; 123), 120 pg/ml (Q1-Q3: 89; 180) and 267 pg/ml (Q1-Q3: 170; 328), respectively, with CKD 1(КT), CKD 2(КT), CKD 3(T) and CKD 4(КT) st. The frequency of HPT was 38.7%: 19.8% in patients with eGFR≥60 ml/min, 38.1% and 93.5% in patients with CKD 3(КT) and CKD 4(КT) st. (p&lt;0.001) (Fig. 1). HPT was equally frequently diagnosed in the second, third, fourth and fifth years after kidney transplantation and amounted to 30.3% in the first five years. In patients with a post-transplant period of more than 5 years, HPT was 54.7% (p&lt;0.001). In the same group, the proportion of patients with eGFR&lt;60 ml/min was also higher - 55.5% (p=0.002) (Fig. 2). An inverse relationship was established between serum PTH and eGFR and a direct relationship between serum PTH and serum creatinine (p&lt;0.001). A retrospective analysis showed that 3 months after kidney transplantation, the median PTH was 178 pg/ml (Q1-Q3: 120; 250), HPT was recorded in 65.5% of patients. Serum PTH decreased by 6-92%, median 50%. Kidney graft function was worse in patients with a decrease in serum PTH ≤50% (n = 100) versus patients with a decrease in serum PTH &gt;50% (n = 97). Minimal blood creatinine was recorded in the early postoperative period, respectively, on (median) 7 and 5 days (p = 0.015), the median eGFR by the end of the third month was 59 and 63 ml/min, respectively (p=0.044). We found that preoperative PTH&gt;585 pg/ml (p&lt;0.0001 OR 2.93 95% CI 1.78; 5.05), delayed kidney graft function (p=0.005 OR 1.57 95% CI 1.58; 9.87), and eGFR&lt;60 ml/min (p&lt;0.0005 OR 2.01 95% CI 1.36; 3.09) were predictive of HPT in patients in the early stages after kidney transplantation. Conclusion Hyperparathyroidism in patients after kidney transplantation continues to be an ongoing problem. It occurs in a third of patients in the first five postoperative years and in half patients in subsequent years. Preoperative secondary hyperparathyroidism, delayed and suboptimal kidney graft function prevent the restoration of parathyroid glands function after kidney transplantation.


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