scholarly journals Over Ten-Year Kidney Graft Survival Determinants

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Anabela Malho Guedes ◽  
Jorge Malheiro ◽  
Isabel Fonseca ◽  
La Salete Martins ◽  
Sofia Pedroso ◽  
...  

Kidney graft survival has been mainly evaluated using an up to 10-year threshold. Instead, in this study our aim was to evaluate predictive variables that impact long-term kidney graft survival (≥10 years). We enrolled 892 patients in our analysis: 638 patients with functioning graft at 10 years PT and 254 patients with graft failure at 10 years PT (considering patient death with a functioning graft <10 years PT as graft failure). Between groups comparisons were done using Mann-Whitney and chi-square test. To determine independent predictive variables for long-term graft survival a multivariate-adjusted logistic regression was performed. Significant predictors of long term graft survival were lower 12-month PT creatinine (, ), lower donor age (, ), shorter time on dialysis (, ), recipient positive CMV IgG (, ), absence of AR episodes (, ), 0 to 1 (versus 2) HLA-B mismatch (, ), and recipients male gender (, ). Our results show that an early KT, younger donor age, and an optimal first year graft function are of paramount importance for long-term graft survival. Measures that address these issues (careful donor selection, preemptive KT, and effective immunosuppressive protocols) are still warranted.

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.


2015 ◽  
Author(s):  
Laurent Mesnard ◽  
Thangamani Muthukumar ◽  
Maren Burbach ◽  
Carol Li ◽  
Huimin Shang ◽  
...  

Current strategies to improve graft outcome following kidney transplantation consider information at the HLA loci. Here, we used exome sequencing of DNA from ABO compatible kidney graft recipients and their living donors to determine recipient and donor mismatches at the amino acid level over entire exomes. We estimated the number of amino acid mismatches in transmembrane proteins, more likely to be seen as foreign by the recipient’s immune system, and designated this tally as the allogenomics mismatch score (AMS). The AMS can be measured prior to transplantation with DNA for potential donor and recipient pairs. We examined the degree of relationship between the AMS and post-transplantation kidney allograft function by linear regression. In a discovery cohort, we found a significant inverse correlation between the AMS and kidney graft function at 36 months post-transplantation (n=10 recipient/donor pairs; 20 exomes) (r2>=0.57, P<0.05). The predictive ability of the AMS persists when the score is restricted to regions outside of the HLA loci. This relationship was validated using an independent cohort of 24 recipient donor pairs (n=48 exomes) (r2>=0.39, P<0.005). In an additional cohort of living and mostly intra-familial recipient/donor pairs (n=19, 38 exomes), we validated the association after controlling for donor age at time of transplantation. Finally, a model that controls for donor age, HLA mismatches and time post-transplantation yields a consistent AMS effect across these three independent cohorts (P<0.05). Taken together, these results show that the AMS is a strong predictor of long-term graft function in kidney transplant recipients.


2015 ◽  
Author(s):  
Laurent Mesnard ◽  
Thangamani Muthukumar ◽  
Maren Burbach ◽  
Carol Li ◽  
Huimin Shang ◽  
...  

Current strategies to improve graft outcome following kidney transplantation consider information at the HLA loci. Here, we used exome sequencing of DNA from ABO compatible kidney graft recipients and their living donors to determine recipient and donor mismatches at the amino acid level over entire exomes. We estimated the number of amino acid mismatches in transmembrane proteins, more likely to be seen as foreign by the recipient's immune system, and designated this tally as the allogenomics mismatch score (AMS). The AMS can be measured prior to transplantation with DNA for potential donor and recipient pairs. We examined the degree of relationship between the AMS and post-transplantation kidney allograft function by linear regression. In a discovery cohort, we found a significant inverse correlation between the AMS and kidney graft function at 36 months post-transplantation (n=10 recipient/donor pairs; 20 exomes) (r2>=0.57, P<0.05). The predictive ability of the AMS persists when the score is restricted to regions outside of the HLA loci. This relationship was validated using an independent cohort of 24 recipient donor pairs (n=48 exomes) (r2>=0.39, P<0.005). In an additional cohort of living and mostly intra-familial recipient/donor pairs (n=19, 38 exomes), we validated the association after controlling for donor age at time of transplantation. Finally, a model that controls for donor age, HLA mismatches and time post-transplantation yields a consistent AMS effect across these three independent cohorts (P<0.05). Taken together, these results show that the AMS is a strong predictor of long-term graft function in kidney transplant recipients.


2019 ◽  
Vol 34 (9) ◽  
pp. 1597-1604
Author(s):  
Arnaud Devresse ◽  
Lise Morin ◽  
Florence Aulagnon ◽  
Jean-Luc Taupin ◽  
Anne Scemla ◽  
...  

Abstract Background Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown. Methods Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study. Results An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P &lt; 0.001) than non-infectious diarrhoea. However, the non-infectious group had lower death-censored graft survival than the infectious group (Gehan–Wilcoxon test, P = 0.038). Multivariate analysis retained three independent predictors of graft failure after diarrhoea: diarrhoea occurring ≥5 years after KT [hazard ratio (HR) 4.82; P &lt; 0.001], re-transplantation (HR 2.38; P = 0.001) and baseline estimated glomerular filtration rate &lt;30 mL/min/1.73 m2 (HR 11.02; P &lt; 0.001). Conclusion Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea.


Author(s):  
Laurent Mesnard ◽  
Thangamani Muthukumar ◽  
Maren Burbach ◽  
Carol Li ◽  
Huimin Shang ◽  
...  

Current strategies to improve graft outcome following kidney transplantation consider information at the HLA loci. Here, we used exome sequencing of DNA from ABO compatible kidney graft recipients and their living donors to determine recipient and donor mismatches at the amino acid level over entire exomes. We estimated the number of amino acid mismatches in transmembrane proteins, more likely to be seen as foreign by the recipient’s immune system, and designated this tally as the allogenomics mismatch score (AMS). The AMS can be measured prior to transplantation with DNA for potential donor and recipient pairs. We examined the degree of relationship between the AMS and post-transplantation kidney allograft function by linear regression. In a discovery cohort, we found a significant inverse correlation between the AMS and kidney graft function at 36 months post-transplantation (n=10 recipient/donor pairs; 20 exomes) (r2>=0.57, P<0.05). The predictive ability of the AMS persists when the score is restricted to regions outside of the HLA loci. This relationship was validated using an independent cohort of 24 recipient donor pairs (n=48 exomes) (r2>=0.39, P<0.005). In an additional cohort of living and mostly intra-familial recipient/donor pairs (n=19, 38 exomes), we validated the association after controlling for donor age at time of transplantation. Finally, a model that controls for donor age, HLA mismatches and time post-transplantation yields a consistent AMS effect across these three independent cohorts (P<0.05). Taken together, these results show that the AMS is a strong predictor of long-term graft function in kidney transplant recipients.


2016 ◽  
Vol 30 (6) ◽  
pp. 869-875 ◽  
Author(s):  
María A. Ballesteros ◽  
Jorge Duerto Álvarez ◽  
Luis Martín-Penagos ◽  
Emilio Rodrigo ◽  
Manuel Arias ◽  
...  

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