OBJECTIVE:The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome.
SUMMARY OF BACKGROUND DATA:Results from ...donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated.
METHODS:We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes.
RESULTS:A total of 49 (14.3%) caDBD were accepted for transplantation median CAT of 5.0 min (IQR 2.5–15.0). Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF OR 1.09 (95% CI, 1.01–1.17), and the duration of CPR discriminated for EGF AUC of 0.86 (95% CI, 0.74–0.98), with a sensitivity and specificity of 100% and 75% at a cutoff of 15 minutes. When evaluated separately, caDBD >15 min increased over 5 times the risk for EGF HR 5.80 (95% CI, 1.82–18.56); P = 0.003, and these presented fewer days on the ICU (1.0 vs 3.0 d).
CONCLUSION:CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.
The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population.
From April to October 2021, 481 KT ...recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351).
Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010).
COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.
Identifying a short‐term endpoint for use in clinical trials that accurately reflects the influence of specific immunosuppressive regimens on long‐term kidney graft survival is challenging. The ...number, timing, type (T‐cell‐mediated or antibody mediated), and severity of biopsy‐proven acute rejection (BPAR) episodes in terms of histological changes and functional impact are highly influential for graft prognosis, and a crude measure of overall acute rejection incidence alone is unlikely to be a robust predictor of graft outcome. A series of studies has shown remarkably consistent results in terms of the cutoff point for one‐yr renal function which predicts poor long‐term graft survival, indicating that a threshold of 50 mL/min/1.73 m2 is likely to be appropriate. Estimated glomerular filtration rate at one yr post‐transplant discriminates effectively among immunosuppressive regimens with regard to graft survival, primarily calcineurin inhibitor reduction strategies. Several other factors that can affect graft survival, such as pathological changes in the graft, may be partly influenced by the immunosuppressive regimen, but the contribution of drug therapy is difficult to define. A combined approach in which both treated BPAR and renal function at one yr are used to assess novel immunosuppressive regimens appears to be promising as the emphasis shifts toward sustaining kidney allograft survival over the long term.
Abstract
BACKGROUND AND AIMS
Graphical Abstract
In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate lesions inherited from the donor or acquired after ...transplantation. However, many centres worldwide do not perform those biopsies which remain invasive, costly and may delay the transplant procedure. We aimed to develop and validate a noninvasive virtual biopsy system.
METHOD
A total of 17 centres were included from Europe, North America and Australia from 2000 to 2019. Candidate predictors were assessed following a prespecified protocol. Outcome measures were the day-zero biopsy lesions (Banff classification) including CV, AH, IFTA scores and % of sclerotic glomeruli. Six machine learning models were developed and their performances were assessed.
RESULTS
A total of 12 992 day-zero biopsies were included. Eleven parameters were used to build the classifiers, including donor age, kidney function, hypertension, BMI, proteinuria, diabetes, sex, donor type, cause of death and Hep-C status. The ensemble models (random forests, neural networks, gradient boosting, extreme gradient boosting tree, linear discriminant analysis, and naive Bayes) showed multi-AUC of 0.738, 0.817 and 0.788 for prediction of CV, AH and IFTA scores, and a good performance for predicting glomerulosclerosis (mean absolute error, MAE = 4.766). We confirmed the robustness and generalizability in multiple clinical scenarios and subpopulations and built an online interface for clinicians: https://transplant-pred/Virtual_Biopsy.
CONCLUSION
We developed and validated the first virtual biopsy system that enables the prediction of day-zero biopsy, based on routinely collected parameters. This can assist clinicians in assessing allograft quality, discrimination of donor derived versus acquired lesions after transplantation and prevent overdiagnosis of calcineurin inhibitor (CNI) toxicity.
To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient's age.
The results at 5 years of post-transplant cardiovascular ...disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000-2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient's age: Group A: <40 years, Group B: 40-60 years and Group C: >60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids.
Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40-60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients <40 years old and death with functioning graft in the two remaining groups. In the multivariate analysis for graft survival, only elevated creatinine levels and proteinuria >1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups.
Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.
The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide ...(PINP), and beta-carboxyterminal telopeptide of type I collagen (beta-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4 h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, beta-CTX, and iPTH. Beta-CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and beta-CTX were the only markers which correlated with iPTH ( P << 0.05) and creatinine values ( P << 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: beta-CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and beta-CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.
In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not ...perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.
Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). ...The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed.
We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference.
Pancreas survival was similar between all groups, but inferior for PAldK when including only those with a functioning graft at day 90 post-transplantation (P = 0.004). Pancreas acute rejection was significantly increased in PAldK (67%; 1.8 ± 1.4 episodes/graft) when compared with PAddK (25%) and SPK (32%) (P < 0.05) patients. In a multivariate Cox regression model including known risk factors for pancreas rejection, PAldK was the only predictor of acute rejection (hazard ratio 6.82, 95% confidence interval 1.51-30.70, P < 0.05). No association was found between donor-recipient HLA mismatches and graft rejection. Repeated HLA mismatches between kidney and pancreas donors (0 versus 1-6) did not correlate with pancreas graft rejection or survival in either PAK transplantation group (P > 0.05).
Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.
Abstract
Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not ...widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is ‘solved’ by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020–2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true.
The introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side‐effects. An enteric‐coated ...formulation of mycophenolate sodium (EC‐MPS; myfortic®) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC‐MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral®) and corticosteroids, was assessed in 423 de novo kidney transplant patients recruited to a 12‐month, double‐blind study. Efficacy failure (biopsy‐proven acute rejection BPAR, graft loss, death or loss to follow up) at 6 months (EC‐MPS 25.8% vs. MMF 26.2%; 95% CI: −8.7, +8.0) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC‐MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC‐MPS and 9.8% with MMF (p = ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC‐MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p = ns). Enteric‐coated‐MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.
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