Machine learning support for decision making in kidney transplantation: step-by-step development of a technological solution (Preprint)

2021 ◽  
Author(s):  
François-Xavier Paquette ◽  
Amir Ghassemi ◽  
Olga Bukhtiyarova ◽  
Moustapha Cisse ◽  
Natanael Gagnon ◽  
...  

BACKGROUND Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. To maximize patient and graft survival, the allocation of donor organs to potential recipients requires careful consideration. OBJECTIVE To develop an innovative technological solution to enable better prediction of kidney transplant survival for each potential donor-recipient pair. METHODS We used de-identified data on past organ donors, recipients and transplant outcomes in the United States from the Scientific Registry of Transplant Recipients (SRTR). To predict transplant outcomes for potential donor-recipient pairs, we used several survival analysis models, including regression analysis (Cox Proportional Hazards), Random Survival Forests (RSF) and several artificial neural networks (DeepSurv, DeepHit, Recurrent Neural Networks (RNN)). We evaluated the performance of each model on their ability to predict the probability of graft survival after kidney transplantation from deceased donors. Three metrics were employed: the C-index, the Integrated Brier Score and the Integrated Calibration Index (ICI), along with calibration plots. RESULTS Based on the C-index metrics, the neural network-based models (DeepSurv, DeepHit, RNN) had better discriminative ability than the Cox model and RSF (0.650, 0.661, 0.659 vs 0.646 and 0.644, correspondingly). The proposed RNN model offered a compromise between the good discriminative ability and calibration and was implemented in a technological solution of TRL-4. CONCLUSIONS Our technological solution based on RNN model can effectively predict kidney transplant survival and provide support for medical professionals and candidate recipients in determining the most optimal donor-recipient pair. CLINICALTRIAL Not applicable.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
...  

Introduction Improvement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exists about the effect of transforming growth factor beta 1 (TGF-beta1) on kidney transplant survival, since TGF-beta1 has profibrotic and protective effects. We therefore the impact of a recently discovered functional TGBF1 polymorphism on long term kidney graft survival. Methods We performed an observational cohort study analyzing recipient and donor DNA in 1,271-kidney transplant pairs from the University Medical Center Groningen in The Netherlands and associated a low-producing TGBF1 polymorphism (rs1800472 C>T) with 5, 10, and 15-year death-censored kidney graft survival. Results Donor genotype frequencies of s1800472 in TGBF1 differed significantly between patients with and without graft loss (P=0.042). Additionally, the low-producing TGBF1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (HR 2.13 for the T allele; 95%-CI 1.16-3.90; P=0.015). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 28.9% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGBF1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGBF1 polymorphism in the recipient and graft loss. Conclusion Kidney allografts possessing a low-producing TGBF1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGFbeta1 is beneficial, rather than harmful, for kidney transplant survival.


2020 ◽  
Vol 9 (7) ◽  
pp. 2118 ◽  
Author(s):  
Maria Irene Bellini ◽  
Aisling E Courtney ◽  
Jennifer A McCaughan

Background: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients’ factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor’s pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. Methods: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. Results: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). Conclusions: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival—in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients.


2020 ◽  
Vol 26 (3) ◽  
pp. 299-304 ◽  
Author(s):  
Hubert Golingan ◽  
Shenae K. Samuels ◽  
Pauline Camacho ◽  
Darshana M. Dadhania ◽  
Fernando E. Pedraza-Taborda ◽  
...  

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates. Methods: An 11-question, Institutional Review Board–approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019. Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates. Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates. Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease–mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.


Author(s):  
Rasoul Alimi ◽  
Maryam Hami ◽  
Monavar Afzalaghaee ◽  
Fatemeh Nazemian ◽  
Mahmood Mahmoodi ◽  
...  

Background: Graft and patient survival are of great importance after transplantation. This study aimed to determine the long-term survival rate of kidney transplantation and its effective factors among transplanted patients in Mashhad transplantation centers in northeastern Iran. Methods: Overall, 618 kidney transplant recipients were examined in different transplantation centers during the years from 2000 to 2015 in a historical cohort study. The Kaplan-Meier method and the Log-rank test were used to calculate the survival rate of the kidney transplant, and to check the difference between survival curves respectively. Modeling of effective factors in survival rate was performed using Cox regression model. Results: Overall, 1, 3, 5, 7, 10, and 15-year survival rate of kidney transplantation were 99%, 98%, 97%, 93%, 88 and 70% respectively. The adjusted hazard ratio indicated that variables such as recipient age >40 yr [HR=0.22, 95% CI=(0.071,0.691)], serum creatinine after transplantation >1.6 Mg/dl [HR=3.03, 95% CI=(1.284,7.125)], history of hypertension [HR=6.70, 95% CI=(2.746,16.348)], and BMI [HR (normal weight versus underweight)=0.26, 95% CI=(0.088,0.761), HR (over weight versus underweight)=0.13,95% CI=(0.038,0.442)] were significant factors on kidney transplant survival rate. Conclusion: The short-term transplant survival rate was good in transplant patients. What's more, through a consideration of variables such as age, creatinine serum after transplantation, history hypertension and body mass index, as well as proper planning to control their effect, it is possible to improve the long-term graft survival rate.


2019 ◽  
Vol 103 (10) ◽  
pp. 2183-2189
Author(s):  
Tanjala S. Purnell ◽  
Xun Luo ◽  
Deidra C. Crews ◽  
Sunjae Bae ◽  
Jessica M. Ruck ◽  
...  

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Diana Valeria Pastrana

ABSTRACT Diana V. Pastrana works in the field of DNA tumor virus biology. In this mSphere of Influence article, she reflects on how the two papers “Donor origin of BKV replication after kidney transplantation” (C. Schmitt, L. Raggub, S. Linnenweber-Held, O. Adams, et al., J Clin Virol 59:120–125, 2014, https://doi.org/10.1016/j.jcv.2013.11.009) and “Neutralizing antibody-mediated response and risk of BK virus-associated nephropathy” (M. Solis, A. Velay, R. Porcher, P. Domingo-Calap, et al., J Am Soc Nephrol 29:326–334, 2018, https://doi.org/10.1681/ASN.2017050532) reminded her of the importance of allowing data, and not adherence to dogma, to drive her research.


Author(s):  
Clarisse Grèze ◽  
Bruno Pereira ◽  
Yves Boirie ◽  
Laurent Guy ◽  
Clémentine Millet ◽  
...  

Abstract Background The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes. Methods We carried out a prospective cohort study using two French registries REIN and CRISTAL on 7 270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (Obese WL and Obese nWL). Results The mean BMI in our obese patients was 32 kg/m2. Graft survival was lower in obese patients than in non-obese patients (HR = 1.40, IC 95% [1.09; 1.78], P = 0.007) whereas patient survival was similar (HR = 0.94, IC 95% [0.73; 1.23], P = 0.66). Graft survival was significantly lower in Obese WL than in Obese nWL (HR = 2.17, CI 95% [1.02; 4.63], P = 0.045) whereas patient survival was similar in the two groups (HR = 0.79, IC 95% [0.35; 1.77], P = 0.56). Conclusion Grade I obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in this patients should not be essential for registration on waiting list.


Sign in / Sign up

Export Citation Format

Share Document