Kidney Function In Recipients Research Articles

#650 Predictive value of LKDPI on recipient's renal function one year after kidney transplantation: single-centre experience

Abstract Background and Aims The selection of the appropriate living kidney donor can be challenging, given the absence of a definitive method to determine the quality of the renal graft. This decision requires a delicate balance, weighing the recipient's benefits while prioritizing the safety of the donor. Recently, a tool known as the Living Kidney Donor Profile Index (LKDPI) was proposed to assess living donor kidneys, based on various donor characteristics, so as to predict the probability of recipient's graft loss; however, the validation of its effectiveness still needs to be proven. Method We evaluated retrospectively 147 stable living kidney donors, who donated between 01/2021 and 11/2023 and are currently attending the Living Donor Clinic of our Department. Our study aimed to assess the impact of the LKDPI on the recipient's estimated renal glomerular filtration rate (eGFR) (measured by the CKD-EPI) one-year posttransplant. Additionally, dialysis vintage, cause of CKD, comorbidities and medication were also determined in all recipients. Results The study comprised 147 stable kidney recipients (KTR), each with their respective living donor. Of these, 96 (65.3%) were males, with a mean age 44.02 ± 13.96 years and a mean dialysis vintage of 1.8 ± 2.3 years. In parallel, living kidney donors were predominantly females (70.7%), with a mean age of 59.08 ± 10.36 years and a mean eGFR prior to donation of 95 ± 13.11 ml/min/1.73 m². Furthermore, 20.1% of kidney transplantations were ABO incompatible and the mean LKDPI score was 34.6 ± 25.9%. Data analysis revealed a statistically significant negative correlation between LKDPI and the recipient's GFR one year after transplantation (p < 0.0001), suggesting that higher LKDPI scores were associated with lower renal function in recipients. In a post hoc analysis, KTRs who were on CKD stage 1, one-year post-transplantation, demonstrated no statistical difference in LKDPI values, compared to stage 2 (p = 0.35). Meanwhile recipients on stage 3 exhibited comparable LKDPI values to those on stage 4 (p = 0.821). The main statistical discrepancy was particularly evident between CKD stage 2 and 3, as recipients with a LKDPI surpassing 25.6, experienced a transition from stage 2 to stage 3 within the first year following transplantation (p < 0.0001). In addition, after multivariate analysis there were no correlations between KTR's eGFR and age difference between donor and recipient or recipient's smoking history or medication. Last, dialysis vintage or the number of previous transplantations did not affect recipient's kidney function. Conclusion LKDPI seems to be a promising tool for predicting the outcome of kidney transplantation, concerning the renal function of KTR particularly at the end of the first-year post-transplant However, it needs to be thoroughly evaluated before being considered as a decision-making factor in living kidney transplantations.

Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients.

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, we show that high pre-transplant anti-LG3 are associated with DGF when the kidney is transported on ice (odds ratio (OR): 1.75, 95% confidence interval 1.02-3.00), but not when placed on hypothermic perfusion pump (OR: 0.78, 95% CI 0.43-1.37). In patients with DGF, high pre-transplant anti-LG3 are associated with a higher risk of graft failure (subdistribution hazard ratio (SHR): 4.07, 95% CI: 1.80, 9.22), while this was not the case in patients with immediate graft function (SHR: 0.50, 95% CI 0.19, 1.29). High anti-LG3 levels are associated with a higher risk of DGF in kidneys exposed to cold storage, but not when hypothermic pump perfusion is used. High anti-LG3 are also associated with a higher risk of graft failure in patients who experience DGF, a clinical manifestation of severe IRI.

Hypothermia or Machine Perfusion in Kidney Donors

BackgroundTherapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation.MethodsAt six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group). The primary outcome was delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplantation). We also evaluated whether hypothermia alone was noninferior to machine perfusion alone and whether the combination of both methods was superior to each of the individual therapies. Secondary outcomes included graft survival at 1 year after transplantation.ResultsFrom 725 enrolled donors, 1349 kidneys were transplanted: 359 kidneys in the hypothermia group, 511 in the machine-perfusion group, and 479 in the combined-therapy group. Delayed graft function occurred in 109 patients (30%) in the hypothermia group, in 99 patients (19%) in the machine-perfusion group, and in 103 patients (22%) in the combination-therapy group. Adjusted risk ratios for delayed graft function were 1.72 (95% confidence interval [CI], 1.35 to 2.17) for hypothermia as compared with machine perfusion, 1.57 (95% CI, 1.26 to 1.96) for hypothermia as compared with combination therapy, and 1.09 (95% CI, 0.85 to 1.40) for combination therapy as compared with machine perfusion. At 1 year, the frequency of graft survival was similar in the three groups. A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction.ConclusionsAmong brain-dead organ donors, therapeutic hypothermia was inferior to machine perfusion of the kidney in reducing delayed graft function after transplantation. The combination of hypothermia and machine perfusion did not provide additional protection. (Funded by Arnold Ventures; ClinicalTrials.gov number, NCT02525510.)

Nonutilization of Kidneys From Donors After Circulatory Determinant of Death.

Background.The expansion of donation after circulatory determination of death (DCDD) programs and unmet demands for kidney transplantation indicate that there is a need to improve the efficiency and utilization of these organs.Methods.We studied all DCDD donors retrieved for kidney transplantation in Australia between 2014 and 2019 and determined the factors associated with nonutilization using least absolute shrinkage and selection operator and random forest models. Self-organizing maps were used to group these donors into clusters with similar characteristics and features associated with nonutilization were defined.Results.Of the 762 DCDD donors, 116 (15%) were not utilized for kidney transplantation. Of the 9 clusters derived from self-organizing map, 2 had the highest proportions of nonutilized kidneys. Factors for nonutilization (adjusted odds ratio [95% confidence interval], per SD increase) were duration from withdrawal of cardiorespiratory support till death (1.38 [1.16-1.64]), admission and terminal serum creatinine (1.43 [1.13-1.85]) and (1.41 [1.16-1.73]). Donor kidney function and duration of warm ischemia were the main factors for clinical decisions taken not to use kidneys from DCDD donors.Conclusions.Donor terminal kidney function and the duration of warm ischemia are the key factors for nonutilization of DCDD kidneys. Strategies to reduce the duration of warm ischemia and improve post-transplant recipient kidney function may reduce rates of nonutilization.

MO950: Living Donor Kidney Transplantation—Does Donor Sex Modify Recipient Outcomes?

Abstract BACKGROUND AND AIMS Living donor kidney transplantation (LDKT) provides the best outcomes of all renal replacement modalities, including survival and quality of life. Studies on the association between pre-donation estimated glomerular filtration rate (eGFR) and graft outcomes have yielded inconsistent results. Two eGFR thresholds are generally used to accept or deny a donor (respectively, ≥90 and <60 mL/min/1.73 m2), with 60–89 mL/min/1.73 m2 as an intermediate range in which the decision is based on other factors. In this study, we aimed to evaluate how donor's pre-donation eGFR, particularly when <90 mL/min/1.73 m2 impacts the recipient's kidney function and graft survival, and if these outcomes are modified by donor's sex. METHOD This is a unicentric retrospective observational study that included the LDKT pairs submitted to transplant between 2008 and 2017. We gathered clinical data, including donor's comorbidities, immunological features of the transplant, the occurrence of acute rejection episodes in the first year, and graft eGFR during the follow-up period. For statistical purposes, we split the donors in three groups: group 1, with eGFR ≥90 mL/min/1.73 m2; group 2, eGFR < 90mL/min/1.73 m2 and female sex; and group 3, eGFR <90 mL/min/1.73 m2 and male sex. The Kaplan–Meier curves and Cox proportional hazards multivariable regression were used for survival analysis, and linear mixed regression was used to evaluate the annual slope of the recipient's eGFR. RESULTS We studied 210 donor-recipient pairs. The average age at the time of transplant was 48.0 ± 10.6 years for donors and 41.3 ± 13.3 years for recipients. Pre-donation eGFR was 100.1 ± 14.2 mL/min/1.73 m2 and most donors (78%) were in group 1 (eGFR 105.9 ± 9.4 mL/min/1.73 m2). We found two independent predictors of death censored graft failure: the occurrence of rejection episode(s) during the first year (HR: 4.99, CI: 1.44–17.26, P = 0.011) and having a donor from group 3 (HR: 5.14, CI: 1.49–17.75, P < 0.010). The independent predictors of global graft loss were rejection episode(s) during the first year (HR: 4.002, CI: 1.224–13.086, P = 0.022), calculated PRA > 0% (HR: 3.802, CI: 1.387–10.489, P = 0.010) and donor from group 3 (HR: 3.514, CI: 1.087–11.355, P = 0.036). At 1-year after transplant, the recipients from group 1 had a significantly higher eGFR than patients from group 2, but did not differ from group 3 (respectively, 60.8 versus 54.4 [P < 0.05], versus 55.2 mL/min/1.73 m2 [P = 0.328]). However, when analyzing the slope of annual decline in the recipients’ eGFR beyond 1-year post-transplant, the groups 1 and 2 did not differ (decline rate of -1.0 mL/min/1.73 m2 in both groups, P = 0.978), but there was a statistical difference between groups 1 and 3 (decline rates of, respectively, −1.0 versus −2.7 mL/min/1.73 m2 P = 0.003). CONCLUSION This study suggests that in LDKT, when donors’ eGFR is borderline (<90 mL/min/1.73 m2), donors’ sex has an important impact on recipient outcomes. In fact, we observed that having a male donor is a strong predictor of graft failure (both death-censored and global) and that there is a steeper decline in the annual kidney function of these recipients after the first year. Thus, we suggest that donors’ eGFR should be clinically balanced with other determinants of kidney function, particularly in the presence of a male donor, with careful selection of both donors and recipients.

Starting at the Source: Donor Research, Done Right.

Transplant research needs to start at the source. Optimizing graft function to ameliorate ischemia-reperfusion needs to occur before the injury occurs to protect organs and prevent graft failure. The aim of donor management is to optimize perfusion and oxygen delivery to the grafts by maintaining favorable hemodynamics, intravascular volume, and metabolic states while averting the pathophysiological derangements that occur with death by neurological criteria. Defining specific donor management goals a priori and implementing standardized interventions to meet these goals improve organ yield1 and are widely put in practice by organ procurement organizations. Achieving the hemodynamic goals (usually mean arterial pressure between 60 and 110 mm Hg) to maintain organ perfusion is considered particularly important; however, it is controversial what interventions are best suited to reach that goal. The study by van Bakel et al2 studied almost 200 organ donors who were randomized to receive either high-dose methylprednisolone, levothyroxine, both, or neither before organ procurement. Although the study was not powered to detect a difference in organ yield or quality, the authors found that methylprednisolone either alone or in combination with levothyroxine (but not levothyroxine alone) reduced vasopressor requirements. Administration of methylprednisolone further reduced a number of inflammatory markers, specifically of interleukin-6, interleukin-12p40, and tumor necrosis factor-alpha, potentially an indication that the reduction of vasopressors may actually improve organ perfusion. Vasopressors are a double-edged sword that may—in the vasodilated state—restore vascular tone and organ perfusion and can also decrease graft perfusion and cause ischemia. Nevertheless, use of high-dose vasopressors in donors has consistently been associated with worse outcome, and reduction of vasopressor requirements should probably be considered beneficial. A number of studies have demonstrated that bundles of hormone replacement (steroids, thyroid hormone, vasopressin) improve organ yield and function,3 but which component of the bundle is beneficial has been unknown. Based on the results of the present study, administration of steroids should be considered part of donor management protocols. Unfortunately, this study was not powered to actually detect the difference in outcomes and therefore does not provide the conclusive, strong evidence needed to unequivocally support wide spread use of steroids in all donors. There is scant evidence for any donor interventions before procurement to a large degree because of the logistical difficulties of organ donor research. A landmark study by Niemann et al4 demonstrated the benefit of mild donor hypothermia to prevent delayed graft function in kidney recipients. More importantly, this study provided a blueprint on how to conduct large, randomized studies of transplant donors. Ethical considerations are real: studying donors who are dead by neurological criteria is not human subject research. But any (randomized) intervention applied to the donor can affect up to 8 solid organ recipients. True equipoise is essential for donor research to avoid biases and potential harm to recipients. Some interventions that may be favorable for 1 organ may harm others, and coordination of organ donor intervention research may be needed. The National Academies of Sciences, Engineering, and Medicine recognized the need for more donor research and provided a broad framework in their 2017 consensus study report “Opportunities for Organ Donor Intervention Research: Saving Lives by Improving the Quality and Quantity of Organs for Transplantation.”5 This report delineates a process to address the ethical concerns of donor research and recommends the institution of a single institutional review board, a Donor Research Oversight Committee, to coordinate different projects and data and the institution of safety monitoring boards to oversee the conduct of these studies. This is a great step in the right direction to create a scaffolding to support studies that further our knowledge about donor management and may help us improve organ yield, graft function, and outcomes after transplantation.

Vesicoureteral reflux treatment following kidney transplantation potentially prevents graft function deterioration and allows long-term graft survival.

The impact of vesicoureteral reflux post-kidney transplantation on graft survival remains unclear, and guidelines on appropriate vesicoureteral reflux management post-kidney transplantation are lacking. For this reason, we conducted a retrospective study on the impact of vesicoureteral reflux and its treatment on graft survival. We evaluated 347 consecutive kidney transplantation recipients, who also underwent a ureteroneocystostomy, between 1996 and 2012. Vesicoureteral reflux was diagnosed in 55 cases (15.9%), with a median post-kidney transplantation duration of 50 months (range 0-172 months). Among these, 22 were monitored, 17 underwent transurethral collagen injections, and 16 received a ureteroneocystostomy. The 10-year graft survival rate was significantly lower in recipients with vesicoureteral reflux (68.9%) than in those without vesicoureteral reflux (84.4%) (P = 0.0165). Moreover, among the vesicoureteral reflux recipients, the 10-year graft survival rate was significantly higher in those whose vesicoureteral reflux was cured (80.1%) than in those whose vesicoureteral reflux persisted (53.6%) (P = 0.0062). Multivariate analysis showed that vesicoureteral reflux was significantly associated with both overall and death-censored graft loss (odds ratio 3.737 and 3.685; P = 0.0015 and P = 0.0052, respectively). Lastly, the incidence of interstitial fibrosis and tubular atrophy was higher in recipients with vesicoureteral reflux than in those without vesicoureteral reflux (P = 0.0009). Post-kidney transplantation vesicoureteral reflux has a negative impact on long-term graft survival, and that treatment prevents graft deterioration. From the perspective of maintaining long-term graft function in kidney recipients, vesicoureteral reflux may be one of the most important complications to be addressed.

Fasting before living-kidney donation: effect on donor well-being and postoperative recovery: study protocol of a multicenter randomized controlled trial

BackgroundOne of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. CR/STF increases the expression of cytoprotective genes, increases immunomodulation via increased anti-inflammatory cytokine production, and decreases the expression of pro-inflammatory markers. As such, nutritional preconditioning by CR or STF represents a non-invasive and cost-effective method that could mitigate the effects of acute surgery-induced stress and postoperative fatigue. To investigate whether preoperative STF contributes to a reduction in fatigue after living-kidney donation, a randomized clinical trial is indicated.MethodsWe aim to determine whether 2.5 days of fasting reduces postoperative fatigue score in subjects undergoing living-kidney donation. In this randomized study, the intervention group will follow a preoperative fasting regime for 2.5 days with a low-dose laxative, while the control group will receive standard care. The main study endpoint is postoperative fatigue, 4 weeks after living-kidney donation. Secondary endpoints include the effect of preoperative fasting on postoperative hospital admission time, the feasibility of STF, and the postoperative recovery of donor and recipient kidney function. This study will provide us with knowledge of the feasibility of STF and confirm its effect on postoperative recovery.DiscussionOur study will provide clinically relevant information on the merits of caloric restriction for living-kidney donors and recipients. We expect to reduce the postoperative fatigue in living-kidney donors and improve the postoperative recovery of living-kidney recipients. It will provide evidence on the clinical merits and potential caveats of preoperative dietary interventions.Trial registrationNetherlands Trial Register NL9262. EudraCT 2020-005445-16. MEC Erasmus MC MEC-2020-0778. CCMO NL74623.078.21

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR)≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P= 0.01). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n=5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P<0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

Is Bigger Better? Living Donor Kidney Volume as Measured by the Donor CT Angiogram in Predicting Donor and Recipient eGFR after Living Donor Kidney Transplantation.

Background The role of kidney volume measurement in predicting the donor and recipient kidney function is not clear. Methods We measured kidney volume bilaterally in living kidney donors using CT angiography and assessed the association with the donor remaining kidney and recipient kidney (donated kidney) function at 1 year after kidney transplantation. Donor volume was categorized into tertiles based on lowest, middle, and highest volume. Results There were 166 living donor and recipient pairs. The mean donor age was 44.8 years (SD ± 10.8), and donor mean BMI was 25.5 (SD ± 2.9). The recipients of living donor kidneys were 64% male and had a mean age of 43.5 years (SD ± 13.3). Six percent of patients experienced an episode of cellular rejection and were maintained on dialysis for a mean of 18 months (13–32) prior to transplant. Kidney volume was divided into tertiles based on lowest, middle, and highest volume. Kidney volume median (range) in tertiles 1, 2, and 3 was 124 (89–135 ml), 155 (136–164 ml), and 184 (165–240 ml) with donor eGFR ml/min (adjusted for body surface area expressed as ml/min/1.73 m2) at the time of donation in each tertile, 109 (93–129), 110 (92–132), and 101 ml/min (84–117). The median (IQR) eGFR in tertiles 1 to 3 in kidney recipients at 1 year after donation was 54 (44–67), 62 (50–75), and 63 ml/min (58–79), respectively. The median (IQR) eGFR in tertiles 1 to 3 in the remaining kidney of donors at 1 year after donation was 59 (53–66), 65 (57–72), and 65 ml/min (56–73), respectively. Conclusion Bigger kidney volume was associated with better eGFR at 1 year after transplant in the recipient and marginally in the donor remaining kidney.

Analysis of Factors Influencing Kidney Function of Recipients After Renal Transplantation in Southwestern China: A Retrospective Study.

Background: Factors influencing the kidney function of patients after renal transplantation include both recipient-related factors and donor-related factors. To gain a better understanding of these factors and to improve clinical decision-making, we performed a retrospective study of southwestern Chinese people receiving kidney transplantation.Methods: In this retrospective analysis, a total of 2,462 recipients receiving allogeneic kidney transplantation in West China Hospital of Sichuan University from December 13, 2008 to January 10, 2018 were included. Data on recipient and donor characteristics were extracted from the Transplant Center Database and stratified by discrete time points after kidney transplantation. Univariate and multivariate logistic regression analyses were carried out on the study variables, and kidney function of postoperative patients was monitored using cystatin C (CysC) as the outcome indicator.Results: From the univariate analysis, several factors showed statistically significant short-term impact on kidney function based on CysC after kidney transplantation, including age, ethnicity, body mass index (BMI), and HLA A-B-DR-DQ loci mismatch. Gender of recipients and gender-consistency between donors and recipients revealed both short-term and long-term influence. Younger donors had significantly better medium-and-long-term influence on kidney function. From the multivariate logistic regression analysis, recipient gender, ethnicity, BMI, and donor age were independent factors affecting postoperative CysC recovery at discrete time points.Conclusion: Several factors of recipients related to renal function after kidney transplantation, such as gender, ethnicity, BMI and donor's age should be paid more attention to. Moreover, female and non-Han recipients decreased the risk of poor outcome during postoperative kidney function recovery while large BMI of recipients and higher donor age increased the risk. It is useful to predict the postoperative renal function earlier according to corresponding factors, and improve the patient's quality of life.

MP59-04 SYSTEMIC VASCULAR FUNCTION OF KIDNEY DONOR INFLUENCES SHORT-TERM RENAL PERFORMANCE OF RECEPTOR

INTRODUCTION AND OBJECTIVE: Renal function is highly dependent on adequate vascular function. This is especially relevant when considering the increasing use of older and marginal kidney donors to overcome organ unavailability. Our aim was to evaluate the influence of donor’s vascular function at different vascular beds on renal function in kidney recipients. METHODS: Aorta, mesenteric microvessels (MM) and corpus cavernosum (CC) specimens were obtained at the time of kidney explant for transplantation and vascular function was ex vivo determined by evaluating adrenergic contractions to norepinephrine and endothelium-dependent vasodilations to bradykinin (BK, MM) or acetylcholine (ACh, CC). RESULTS: Vascular function in each donor (n=38) was correlated with serum creatinine levels (SC) and glomerular filtration rate (GFR) in each receptor(s) (n=49). Endothelium-dependent vasodilation of donor MM (pEC50 for BK) was significantly and negatively associated with SC (r2=0.245, p=0.003) while positively with GFR (r2=0.267, p=0.002) at 3 months after transplantation but significance was lost at 6 months (SC: r2=0.114, p=0.092; GFR: r2=0.131, p=0.069). Receptor’s GFR was also positively associated with endothelium-dependent relaxation (pEC50 for ACh) in CC from male donors (r2=0.310;p=0.006) and negatively with adrenergic contraction in aorta (r2=0.289, p=0.001) at 3 months. These associations were also lost at 6 months after transplantation. Moreover, receptors with GFR≥60 ml/min at 3 months received the kidney from donors displaying a significantly better endothelial vasodilation in MM (pEC50 for BK 7.60±0.25 vs. 6.71±0.15, p=0.004). Conversely, donors in the highest tertile of endothelium-dependent relaxation in MM or CC displayed lower SC and higher GFR at 3 and 6 months after transplantation. CONCLUSIONS: Systemic vascular function of kidney donor is a determinant for renal function in the receptor at short-term but the influence of receptor condition on renal performance probably prevails at later time. Source of Funding: No

CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy.

Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n=178) or mycophenolate sodium (n=97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results:CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p<0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR=0.07; 95% CI=0.03-0.18 and OR=0.45; 95% CI=0.20-0.99, respectively, p<0.05). Conclusion: The CYP3A5*3 variant is associated with increased early exposure to TAC. Living donor and CYP2C8*3 variant seem to be protective factors for delayed graft function in kidney recipients.

Retrospective Investigation of Grafted Kidney Function After Reversal of Neuromuscular Blockade Using Neostigmine or Sugammadex

IntroductionSugammadex has the steroid-encapsulating effect that reverses neuromuscular block induced by aminosteroid neuromuscular-blocking agents. Sugammadex can interact with other drugs that have the same steroidal structure with rocuronium, such as corticosteroids. Corticosteroids play a crucial role in the immunosuppression of kidney transplantation. The purpose of this study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation when sugammadex or neostigmine is given to the recipient. MethodsThe study included 42 recipients of kidney transplant, with complete, readable medical charts and anesthetic records. Fourteen recipients’ neuromuscular block was reversed with sugammadex (group S) and 28 recipients’ neuromuscular block was reversed with neostigmine (group N). We tested noninferiority for serum creatinine during the preoperative period and 5 days after transplantation. Short-term (28 days) outcomes of kidney transplantations were assessed by the incidence of acute rejection episodes, graft failure, length of stay at hospital, and mortality. ResultsThere were no significant differences in demographic characteristics, serum creatinine values, short-term outcomes, and graft survival rates at 28 days’ postoperatively between group S and group N (P > .05). ConclusionsOur data showed no difference in risk of serious adverse effects on short-term graft functions in patients who underwent kidney transplantation. However, considering the sugammadex-corticosteroids interaction, the immunosuppression and long-term effects on grafted kidney functions, current safety experience is insufficient to support the recommendation of routine sugammadex use in this population. These results need to be confirmed by sufficiently powered, controlled, pharmacokinetic, and pharmacodynamic studies on larger patient populations.

Reliability of computed tomography-based renal cortex volume to determine split renal function in preoperative living kidney donors.

Objective:The purpose of this study was to assess the utility of CT-based renal cortex volume to estimate split renal function (SRF) in pre-transplant living kidney donors and to evaluate its reliability to predict graft function in the recipients.Methods:Our study recruited all adult potential donors who had both Tc-99m-diethylenetriamine pentacetate (DTPA) scintigraphy and CT angiography of the abdominal aorta done before donating their kidney. We compared the correlation between CT-based renal cortex volume combined with kidney function and DTPA scan as well as post-donation kidney function in the recipients.Results:The correlation between CT-based split cortex volume and DTPA-measured SRF before transplantation was strong (intraclass correlation coefficient = 0.954–0.968). The inter-rater reliability of two radiologists also showed substantial agreement (intraclass correlation coefficient = 0.97, p < 0.001). In contrast, the correlations between renal cortical volume of donated kidney adjusted to recipient body weight and recipient kidney function was poor at both 2 week and 2 year follow-up.Conclusion:CT-based renal cortex volume combined with pre-operative kidney function appears to be precise and reproducible to evaluate pre-transplant SRF. Nevertheless, the prediction of recipient graft function needs to be further investigated to ensure a good outcome.Advances in knowledge:This method is practicable for all potential donors who undergo kidney transplantation in terms of streamline donor workup without compromising information.

Chronic Kidney Disease After Liver Transplantation: Impact of Extended Criteria Grafts.

The use of extended criteria donor (ECD) grafts has been associated with acute kidney injury (AKI) after liver transplantation. However, the relation between graft quality and development of chronic kidney disease (CKD) remains unknown. Therefore, the aim of this study was to analyze the impact of ECD grafts for CKD after liver transplantation. All patients (2007-2015) transplanted for end-stage liver disease at our center were assessed. Longterm kidney function was divided into 4 groups: no CKD (estimated glomerular filtration rate [eGFR], ≥60 mL/minute/1.73 m2 ), mild CKD (eGFR, 30-59 mL/minute/1.73 m2 ), severe CKD (eGFR, 15-29 mL/minute/1.73 m2 ), and end-stage renal disease (ESRD). Marginal donation after brain death (DBD) grafts (donor age, >70 years; body mass index, >35 kg/m2 ; cold storage, >12 hours) and donation after circulatory death (DCD) grafts were considered ECD grafts. Overall, 926 patients were included, and 43% received an ECD graft (15% marginal DBD; 28% DCD). After 5 years, 35% developed CKD; severe CKD and ESRD occurred in only 2% and 1%, respectively. CKD rates were comparable for all 3 graft groups (standard group, 36%; marginal DBD group, 29%; DCD group, 35%; standard versus marginal DBD groups, P=0.16; standard versus DCD group, P=0.80). None of the ECD criteria were identified as independent risk factors in a Cox regression model for CKD. Risk factors included recipient age, female sex, and preoperative kidney function. Furthermore, recipients who had severe acute kidney injury (AKI; Kidney Disease: Improving Global Outcomes stages 2 and 3) had a 1.8-fold increased risk for CKD. Longterm kidney function of recipients with severe AKI depended on the recovery of kidney function in the first postoperative week. In conclusion, there is no direct relation between the use of ECD grafts and CKD after liver transplantation. However, caution should be taken in recipients who experience severe AKI, regardless of graft type.

Preserved insulin secretion and kidney function in recipients with functional pancreas grafts 1 year after transplantation: a single-center prospective observational study

Successful simultaneous pancreas and kidney transplantation (SPK) or pancreas transplantation alone (PTA) restores glycemic control. Diabetes and impaired kidney function are common side effects of immunosuppressive therapy. This study addresses glucometabolic parameters and kidney function during the first year. We examined 67 patients with functioning grafts (SPK n = 30, PTA n = 37) transplanted between September 2011 and November 2016 who underwent repeated oral glucose tolerance tests (OGTTs) 8 and 52 weeks after transplantation. Another 19 patients lost their graft the first year post-transplant and 28 patients did not undergo repeated OGTTs and could not be studied. All patients received ATG induction therapy plus tacrolimus, mycophenolate and prednisolone. Glomerular filtration rate was measured before and 8 and 52 weeks after transplantation by serum clearance methods. From week 8 to 52 after transplantation, mean fasting glucose decreased (SPK: 5.4 ± 0.7 to 5.1 ± 0.8 mmol/L, PTA: 5.4 ± 0.6 to 5.2 ± 0.7 mmol/L; both P < 0.05), and also 120-min post-OGTT glucose (SPK: 6.9 ± 2.9 to 5.7 ± 2.2 mmol/L; P = 0.07, PTA: 6.5 ± 1.7 to 5.7 ± 1.2 mmol/L; P < 0.05). Fasting C-peptide levels also decreased (SPK: 1500 ± 573 to 1078 ± 357 pmol/L, PTA: 1210 ± 487 to 1021 ± 434 pmol/L, both P < 0.005). Measured GFR decreased from enlistment to 8 weeks post transplant in PTA patients (94 ± 22 to 78 ± 19 mL/min/1.73 m2; P < 0.005), but did not deteriorate from week 8 to week 52 (SPK: 55.0 ± 15.1 vs 59.7 ± 11.3 ml/min/1.73 m²; P = 0.19, PTA: 76 ± 19 vs 77 ± 19 mL/min/1.73 m²; P = 0.74). Glycemic control and kidney function remain preserved in recipients with functioning SPK and PTA grafts 1 year after transplantation.

State of the Science in Deceased Organ Donor Management

Research in deceased organ donor management offers an opportunity to increase the quantity and quality of organs available for transplantation. This article aims to appraise the current literature with a focus on reviewing deceased donor intervention trials. Aggressive critical care management after determination of brain death resulting in meeting of a donor management goal bundle has consistently demonstrated an association with significantly more organs transplanted per donor as well as improved graft outcomes. Although there is a dearth of experience with randomized donor intervention studies, dopamine and targeted mild therapeutic hypothermia have been found to significantly reduce delayed graft function in kidney recipients. Progress in understanding the ethical, legal, regulatory, policy, and organizational elements of organ donor research has provided a mechanism that allows for the endorsement of potentially impactful donor management studies. Ongoing trials should incorporate methods to ensure safety to all organs donated from donors enrolled in interventional trials.

A dynamic model for predicting graft function in kidney recipients’ upcoming follow up visits: A clinical application of artificial neural network

BackgroundPredicting the function of transplanted kidneys would help clinicians in individualized medical interventions. We aimed to develop and validate a predictive tool for a future value of estimated glomerular filtration rate (eGFR) at upcoming visits. MethodsWe used static and time-dependent covariates as inputs of artificial neural network based prediction models for predicting an eGFR value for an upcoming visit. We included 675 kidney recipients, who received transplant in the Urmia kidney transplant center in 2001–2013 and were longitudinally cared for in 2001–2017. The first 75% of records of longitudinal data of each patient were used to develop the prediction models and the remaining last 25% for evaluating its performance. Models’ performances were evaluated by Mean Square Error (MSE) and Mean Absolute Error (MAE). ResultsThe development and validation datasets included 18,773 and 7038 records of historical data, respectively. The most accurate model included 3 static covariates of recipients’ gender and donors’ age and gender as well as 11 dynamic covariates of recipients including current age, time since transplant, serum creatinine, fasting blood sugar, weight and blood pressures available at each visit time. The performance of prediction models in the validation cohort was improved when history window of time dependent variables’ recent values was increased from 1 to 10 (an MSE decline from 161 to 99). ConclusionsOur best performed model is able to dynamically predict a future eGFR value for kidney recipients’ upcoming visits. Integrating such a clinical tool into daily workflow of outpatient clinics can potentially support clinicians in optimal and individualized decision makings.

Kidney Transplantation From Old Deceased Donors: Impact of Uric Acid Level—A Quarter-Century of Experience in One Transplant Center

BackgroundThe long-term burden of higher donor age on graft function and survival after kidney transplantation remains uncertain. Because both recipient and donor characteristics have evolved and the general population age is on the increase, we looked at the causes of kidney graft outcome. AimThe aim of this study was to evaluate the impact of different clinical parameters on long-term outcome of older-donor kidney transplantation. This retrospective study included 345 adult patients (58 patients received kidney from donors at least 55 years old) transplanted between January 1993 and December 2005 and were followed in one center throughout the post-transplant course (median, 9.4 years). Data included recipient and donor age, cold ischemia time, delayed graft function, panel reactive antibodies, HLA mismatch, time on dialysis, graft function at different time points, uric acid level, proteinuria, immunosuppression, and biopsy-proven rejection. ResultsImprovement of estimated glomerular filtration rate at 36 months after transplantation was a good prognostic factor for long-term kidney function. Higher donor age decreased the chance for improvement of kidney function by 2.8% per year of life (P = .0244). Hyperuricemia was found in 46% of the study population; estimated glomerular filtration rate less than 50 mL/min/1.72 m2 was associated with hyperuricaemia. A higher uric acid level was associated with inferior kidney function in recipient of older kidneys. Graft failure occurred late (median, 6.3 years post-transplantation) in 26 (44.8%) of older-donor recipients and in 87 (30.3%) of the remaining patients. ConclusionsOur results suggest an important association between older donor age and decreased allograft function in kidney recipients with elevated uric acid level. Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.