Recipient eGFR Research Articles

Analyzing body composition in living kidney donors: impact on post-transplant kidney function.

Living donor kidney transplantation boasts superior patient and graft survival rates compared to deceased donor kidney transplantation. However, the impact of living donor body composition (BC) on post-transplant kidney function remains uncertain. In a cohort of 293 living kidney donor-recipients pairs, we utilized linear mixed model analyses, adjusted for time and including a multiplicative interaction term of time with the donor body composition measure, and found no significant associations between any donor BC measure and the annual change in recipient post-transplantation estimated glomerular filtration rate (eGFR) [donor body mass index (BMI): B=-0.01, 95%CI -0.13; 0.11, p=0.88; donor waist circumference: B=0.02, 95%CI -0.02; 0.06, p=0.38; donor skeletal muscle index: B=-0.02, 95%CI -0.07; 0.04, p=0.63; donor skeletal muscle radiation attenuation: B=-0.002, 95%CI -0.06; 0.06, p=0.96; donor visceral adipose tissue index: B=-0.001, 95%CI -0.02; 0.02, p=0.93; donor subcutaneous adipose tissue index: B=-0.001, 95%CI -0.02; 0.02, p=0.94; donor intramuscular adipose tissue index: B=-0.12, 95%CI -0.29; 0.06, p=0.19; donor total abdominal adipose tissue index: B=-0.001, 95%CI -0.01; 0.01, p=0.89]. Our study suggests that pre-donation BC does not affect post-transplantation recipient eGFR in donor populations with a BMI below 35 kg/m2.

Comparison of Short-Term Outcomes in Kidney Transplant Recipients from SARS-CoV-2-Infected versus Noninfected Deceased Donors.

Acceptable post-transplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease 2019 (COVID-19); however, there are no comparative studies with well-matched controls. This multicenter, prospective observational study, which included three transplant centers in the United States, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics in the same transplant centers to compare 6-month eGFR. Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and noninfected donor groups (55±21 and 57±25 ml/min per 1.73 m 2 , respectively; P = 0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died of reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 ml/min per 1.73 m 2 , respectively; P = 0.51). However, recipients from donors who died of COVID-19 had significantly lower 6-month eGFR than those from SARS-CoV-2-negative donors (46±17 and 58±27 ml/min per 1.73 m 2 , respectively; P = 0.03). No donor-to-recipient SARS-CoV-2 transmission was observed. Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and noninfected donors. However, those receiving kidneys from donors who died of COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed.

423.8: Live Donated Kidneys Don’t Behave Like the One Left Behind

Introduction: Following live kidney donation (LD), the donor glomerular filtration rate (GFR) increases for the initial 5 years1, especially in younger donors. We queried whether the recipients of younger LD kidneys would have a similar eGFR increase. Methods: The medical records of primary LD and DD adult kidney alone recipients at a single center performed between 1/1/10-6/30/21 were analyzed. 62,371 eGFR calculations (CKD-EPI) were available between 3-36 months post-transplant for 1186 recipients. Restricted cubic splines were used to analyze the trajectory of eGFR from 3-36 months post-transplant recipients of kidneys from donors 18-35, 35-55 and >55 years. Slopes were constructed separately from 3-9, 9-21 and 21-36 months. A mixed effects model was utilized to calculate predicted eGFR for donor type/age group, separately for male and female donors (21 additional recipients excluded due to lack of donor gender data). An analysis adjusting for BSA was completed with similar results. Model results are presented in Table 1. All analyses were performed in R, ver. 4.1.1. Results: The eGFR varied by donor age and gender. Kidneys (DD and LD) from women on aggregate provided lesser eGFR than male donors (Table 1). However, predicted eGFR change was similar when grouped by gender and age of DD and LD kidneys. Compared to recipients of LD aged 35-55, DD kidneys 18-35 years had an eGFR +10.339 mL/min/1.73m2 from female donors and +8.423 mL/min/1.73m2 difference from males. For DD 35-55 years, -2.333 mL/min/1.73m2 difference from females and -2.092 mL/min/1.73m2 from males, with a larger difference in the LD >55 year age group -5.478 mL/min/1.73m2 difference with females and -5.479 mL/min/1.73m2 difference with males. In a separate analysis, no observed differences in the rate of eGFR change was noted from recipient age, gender or race. The p-values (Table 1) are based on an eGFR difference from 0 mL/min/1.73m2, many p-values while statistically significant, may not be clinically significant.Gender is significant. Males tend to have more kidney mass and greater BSA. If the recipient is a female and the donor a male, a higher eGFR is expected, conversely in a male receiving a female kidney. 59.7% of the recipients of female kidneys were male. Of the recipients of male kidneys, 56.4% were male. Overall, a slightly higher eGFR in recipients of male kidneys at 3 months and 3 years was observed. Conclusion: The post-donation increase of eGFR observed after live kidney donation did not occur in the recipients of LD kidneys. The overall trajectory of LD and DD kidney transplant eGFR during the first 3 post-transplant years is similar within the age/donor type groups. Donor age and gender (more likely amount of renal mass) are important factors determining eGFR. 1.Matas AJ, Vock DM, Ibrahim HN. GFR ≤25 years postdonation in living kidney donors with (vs. without) a first-degree relative with ESRD. Am J Transplant. 2018;18:625–631.

MO954: Older Living Donors—is it A Feasible Alternative For Kidney Transplantation?

Abstract BACKGROUND AND AIMS Kidney transplantation (KT) improves survival and quality of life of patients with end-stage renal disease. However, there is still an unbalance between supply and demand for kidneys. To increase the number of available grafts and reduce the waiting list for transplantation, recruitment of older living donors has expanded. This approach remains controversial for several reasons, including the impact of kidney function decline on long-term graft and recipient survival. We aimed to evaluate the impact of living donor (LD) age on recipient graft survival and on graft function decline over time. METHOD This is a Unicenter retrospective observational study that included kidney transplants of LD between 2008 and 2017. Several clinical data were analyzed, including donors’ comorbidities, immunological features of the transplant, induction immunosuppression, number of acute rejections (AR) at the first year, and the graft glomerular filtration rate (eGFR) during the follow-up period. The eGFR was calculated using the CKD-EPI equation. The LDs were classified as young (<60 years) and old (≥60 years) for analysis purposes. 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 recipient eGFR, comparing both groups. RESULTS We observed 210 LD kidney transplants: 86% (n = 181) from young (D < 60) and 14% (n = 29) from old donors (D ≥60). The average age was 41.3 ± 13.3 years for recipients and 48.0 ± 10.6 years for donors. The pre-donation eGFR was significantly higher in D < 60 than D ≥60 (101.7 ± 14.0 versus 90.2 ± 11.0 mL/min/1.73 m2; P < 0.001). There was no significant difference in AR in the first year between both groups. (Table 1) The censored recipient graft survival was similar for D < 60 and D ≥60 (86% versus 84%, P = 0.144) (Figure 1) and the older donors’ age was not a predictor of censored graft failure [hazard ratio (HR): 2.689 (95% CI: 0.832–8.690; P = 0.098)]. Although not statistically significant, the overall recipient graft survival was lower in D ≥60 (67% versus 86%, P = 0.071) (Figure 1) and donors’ age ≥60 years was an independent predictor of global recipient graft failure (HR: 3.303, 95% CI: 1.102–9.899; P = 0.033). Linear mixed regression showed that recipient eGFR from D ≥60 was lower than D < 60 at 12 months [46.5 mL/min/1.73 m2 (95% CI: 41.4–51.5) versus 58.6 mL/min/1.73 m2 (95% CI: 56.4–60.8); P = 0.026] and, beyond 1-year, eGFR slope annual decline was steeper in older donor recipients by −1.4 mL/min/1.73 m2 each year [95% CI: (−2.4) to (−0.4); P = 0.005] than in those from younger donors. CONCLUSION Although the greater eGFR graft decline in the first 12 months and beyond, we demonstrated that kidneys from older living donors did not significantly compromise the censored recipient graft survival. We did not evaluate the age match between donor and recipient, as has been done in other studies, but even so, these results support the importance of increasingly encouraging KT from older living donors. It can improve the quality of life, compared to the time on dialysis and, especially for old candidates, can be the only chance to get transplanted.

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.

Extracellular Vesicles From Kidney Allografts Express miR-218-5p and Alter Th17/Treg Ratios.

Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen. KP-EV from kidneys that experience DGF increase the T-helper 17 (Th17) to T-regulatory (Treg) ratio in third party peripheral blood mononuclear cells to a greater degree than those from kidneys with immediate function. We report miR-218-5p upregulation in KP-EV of kidney transplant recipients with DGF. Levels of miR-218-5p in KP-EV inversely correlated with recipient eGFR at multiple time points following transplantation. Additionally, the degree of increase in Th17/Treg ratio by KP-EV positively correlated with miR-218-5p expression in KP-EV samples. Taken together, these data provide evidence that KP-EV may contribute to modulating immune responses in transplant recipients. This could lead to novel intervention strategies to inhibit DGF in order to improve graft function and survival.

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients.

Objectives: We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.Methods: We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.Results: Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m2. After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313), P = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051), P = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR (Pinteraction = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702), P = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204), P = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened (Ptrend = 0.011).Conclusion: Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

Changes in glomerular filtration rate in liver recipients after reduced exposure to calcineurin inhibitors with concomitant everolimus administration within the first year after immunosuppression conversion

Objective: to compare changes in estimated glomerular filtration rate (eGFR) in liver recipients with initially normal and impaired eGFR within the first year after immunosuppression conversion.Materials and methods. Enrolled in the study were 215 recipients of deceased-donor livers from February 2009 to February 2020, who received everolimus with dose reduction or complete withdrawal of calcineurin inhibitors (immunosuppression conversion, ISxC) for varying periods of time. GFR was measured using the MDRD-4 formula immediately before ISxC, then 3, 6, and 12 months after orthotopic liver transplantation (LTx). One month was considered an acceptable temporary deviation from the corresponding point.Results. At the time of ISxC, 32 (15%) of 215 recipients had normal renal function. Chronic kidney disease (CKD) increased in 60% of the recipients with normal eGFR by the end of the first year following ISxC; the fall in eGFR was particularly pronounced in older recipients. In the group with a baseline eGFR of 60–89 mL/min/1.73 m2, eGFR normalized in 62% of cases within 12 months; 28% of cases had no changes in renal function. In the subgroup with a pronounced decrease in eGFR at the time of ISxC, increased eGFR was observed as early as 1 month after ISxC, and the maximum was recorded after 3–6 months. The mean eGFR relative to baseline by month 3 after eGFR were higher for ISxC that was done in the first 2 months after LTx (19.7 ± 15.7 ml/minute/1.73 m2) than for ISxC done in the long-term period after LTx (10.1 ± 8.7 ml/minute/1.73 m2, p < 0.05).Conclusion. Changes in eGFR in liver recipients receiving EVR plus low-dose calcineurin inhibitor (CNI) depend on baseline eGFR and are multidirectional. The use of ISxC in the early post-LTx period led to a more pronounced improvement in eGFR. Maximal changes in eGFR were observed by 3–6 months after ISxC.

Impact of the Mayo Adhesive Probability Score on Donor and Recipient Outcomes After Living-donor Kidney Transplantation: A Retrospective, Single-center Study of 782 Transplants.

This study was performed to assess the impact of the Mayo Adhesive Probability (MAP) score on donor and recipient outcomes after living-donor kidney transplantation (LDKT). We retrospectively analyzed 782 transplants involving LDKT between February 2008 and October 2019 to assess the correlation between the MAP score and outcome after LDKT. We divided the transplants into 2 groups according to the donor MAP score: 0 (MAP0) and 1-5 (MAP1-5). Compared with the MAP0 group, donors in the MAP1-5 group were significantly older, had higher body mass index, and were more likely to be men. The prevalences of hypertension, hyperlipidemia, and diabetes were also higher among donors in the MAP1-5 group than among donors in the MAP0 group. Operative time, estimated blood loss during donor nephrectomy, and percentage of glomerular sclerosis were significantly greater in the MAP1-5 group than in the MAP0 group. Donor and recipient perioperative complications were comparable between the 2 groups; death-censored graft survival rates also did not significantly differ between groups. Although the recipient mean estimated glomerular filtration rate (eGFR) from postoperative d 1 to 7 was significantly higher in the MAP0 group than in the MAP1-5 group (P = 0.007), eGFR reductions within 5 y after transplantation were similar between groups. There were no significant differences between groups in recipient mortality and biopsy-proven acute rejection episodes within 1 y after transplantation. Additionally, multivariate analysis showed that the only factors affecting recipient eGFR at postoperative d 7 were donor age, recipient age, and female sex (P < 0.001, <0.001, and =0.004, respectively). The MAP score did not influence surgical complications or graft survival; therefore, it should not affect donor selection.

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.

Association of Admission, Nadir, and Terminal Donor Creatinine With Kidney Transplantation Outcomes

IntroductionWhen assessing deceased kidney donors, a key factor in organ acceptance and allocation is donor kidney function. It is unclear whether terminal, admission, or the highest of terminal and admission donor estimated glomerular filtration rate (eGFR) most predicts recipient outcomes.MethodsWe examined which measurement best predicts outcomes. Using data from the Australia and New Zealand Organ Donation and Dialysis and Transplant Registries, we included adult recipients of deceased donor kidney-only transplants over 2003 to 2019. We compared the 3 different exposure variables of admission, terminal, or highest eGFR. We created logistic regression models for delayed graft function (DGF), multilinear regression models for 6- and 12-month eGFR, and Cox proportional hazards models for graft loss, death censored graft failure and patient death.ResultsA total of 8971 transplant recipients were included. There was strong evidence of an association between terminal, admission, and highest donor eGFR and DGF and recipient eGFR at 6 and 12 months. The eGFR was a strong predictor of graft and death censored graft failure, but not patient death. Terminal was a better predictor than admission and highest eGFR particularly for more contemporaneous outcomes.ConclusionIn assessing kidney donors, terminal eGFR were marginally better than admission and highest at predicting outcomes. Terminal eGFR should be used in risk equations to predict hard clinical endpoints.

Performance of the various serum creatinine-based GFR estimating equations in pediatric kidney transplant recipients, stratified by age and CKD staging.

Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II-V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents.

Role of Prior Split Renal Function for Living Kidney Transplantation in Recipients and Donors

PurposeThe purpose of this study was to determine the relationship between pre-operative donor split renal function (SRF) and the renal function outcome of donors and recipients after kidney transplantation (KT). MethodsA total of 217 living KT cases were investigated. The estimated glomerular filtration rate (eGFR) change of recipients and donors, as well as graft survival, were analyzed based on the donor SRF. The difference in SRF (dSRF) in a donor was defined as follows: the SRF of the donated kidney minus the SRF of the remaining kidney determined by pre-operative 99mTc-diethylenetriaminepentaacetic acid in the donors. The dSRF was categorized into tertiles. ResultsThe dSRF was not associated with the eGFR in recipients in any tertile at 6 or 12 months post-KT. The overall graft and patient survival did not differ significantly among tertiles. Donors in the high tertile, who donated kidneys with a higher SRF, showed a greater reduction in eGFR than did donors in the low and middle tertile after adjustment for function of the not-donated kidney (−34 ± 1.9 vs −28 ± 2.2, and −27 ± 1.3 mL/min/1.73 m2, P < .05). ConclusionsThe dSRF did not affect the post-KT renal function or graft survival in recipients. However, the donors who donated the better functioning kidney had a poorer renal function after donation.

P1665STUDY OF CORRELATION OF DONOR KIDNEY VOLUME AND WEIGHT WITH GRAFT OUTCOMES FOLLOWING LIVE DONOR KIDNEY TRANSPLANTATION

Abstract Background Impact of organ quality in long-term graft function in living kidney transplantation is less well understood. Potential markers of donor organ quality in living kidney donation may include donor kidney volume and weight. There have been some studies done which correlated individually graft volume with its outcome. Trials have also explored in the fact that graft mass also influences the recipient eGFR. But no study so far has combined these two variables and correlated with the graft outcome. Aims To study the association between baseline graft kidney volume and weight matched with recipient body surface area and graft function by serum creatinine. Secondarily the association with proteinuria, graft survival at 1 year and episodes of acute rejection was also studied. Method Prospective observational single centre study conducted at our centre. Total 60 live donor renal transplants from period of October 2018 to December 2018 were assessed for the donor kidney volume and its weight and then correlated with creatinine at post-transplant day 7 and 1 year after transplant. Cadaveric, paediatric and second transplants were excluded. Whole renal parenchymal volume was obtained from the delayed phase CT data excluding the renal sinus fat using Syngo Volume Calculation. According to common procedure recommendations, kidney grafts were prepared first then weighed by the surgeon. Results 45 were female donors and 15 were male donors. Mean donor age was 46.60 +/- 12.04 years with minimum donor age of 19 years and maximum donor age of 75 years. The donated graft GFR was 48.86 ml/min/1.73 m2 with a S.D. of 42.77 ml/min/1.73 m2. .Mean transplanted graft volume (donated kidney volume X 1.73 m2/ recipient BSA) was 137.49 mm3/1.73m2 with a S.D. of 28.34 mm3/1.73m2 (Minimum 95 mm3/1.73 m2 and maximum 227.23 mm3 /1.73 m2). Mean total kidney volumes of females was 254.45 +/- 46.57 mm3 and males was 293.37 +/- 42.99 mm3 (p value &amp;lt; 0.05). Donor kidney volume and donor age showed negative co-relation (r-0.25) (p-0.08.) Donor kidney volume and donor GFR showed a positive co-relation (r 0.38) and it was statistically significant p &amp;lt; 0.001. Graft volume and serum creatinine on post-transplant day 7 had negative co-relation (r=-0.19), not statistically significant. Graft volume had negative co-relation with creatinine at 1 year (r= -0.49), statistically significant (p &amp;lt; 0.01). Hence lower the graft volume, higher the creatinine. Mean transplanted graft weight was 170 grams (+/- 34 grams)- Minimum 119.5grams, maximum 204 grams. Donor kidney weight showed a positive correlation with the donor’s body surface area. No correlation with age was seen. Donor kidney weight and donor GFR showed a positive correlation (r 0.26). Graft weight and serum creatinine on post-transplant at 7 day showed negative co-relation(r=-0.25) but it was not statistically significant. Graft weight and creatinine at 1 year (r= -0.49) had negative co-relation and it was statistically significant (p &amp;lt; 0.01). Hence higher the transplanted graft volume and weight, better is the e-GFR at one year post-transplant. No significant association was found with proteinuria at 1 year with either graft volume or weight (p-0.07). In present study 3 patients had an acute cellular rejection. There was no statistically significant co-relation found between kidney volume and acute cellular rejection. None of the patients had an acute humoral rejection till 1 year of follow up period. None of the patients had graft loss till 1 year follow up. Conclusion The present study shows that during pre-operative donor evaluation, the donor kidney volume and weight estimation helps us in predicting the outcome of the renal transplant. Better kidney volumes matched to the body surface area of recipient predict better outcomes. Hence kidneys with higher graft volume and weight that is matched to recipient have better e-GFR at 1year post-transplant. This will help us in finding the suitable donors wherever feasible.

P1715CORRELATION OF DONATED KIDNEY MASS AND GRAFT FUNCTION IN RECIPIENTS OF LIVING DONOR KIDNEY TRANSPLANTATION

Abstract Background and Aims Kidney volume has been proven to be a surrogate marker of nephron mass and renal function in living donors. Although many studies correlate the kidney mass with renal donors’ function after donation, few studies have compared the donated kidney mass with estimated glomerular filtration rate (eGFR) in the kidneýs recipients. The purpose of this study is to examine the relationship between donor kidney volume and post-transplantation graft function by using computerized tomography to obtain renal volumes. Method Clinical data off all donor and recipient pairs undergoing live donor kidney transplantation (KT) at our institution between January 2008 and December 2017 (n=195) were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software and correlate to transplant recipient eGFR. Results All metrics of donor kidney volume (DKV): DKV alone, ADK adjusted for weight, body mass index (BMI) or body surface area (BSA), correlated significantly with eGFR (all with p&amp;lt;0,001) at 1 year after KT, with DKV/BSA having the highest correlation (r=0,431). Hence, recipients were divided into terciles according their DKV/BSA (cm3/m2): tercile 1 (DKV/BSA between 49,7-77,5, n=64), tercile 2 (78-95,2, n=63) and tercile 3 (95,4-176, n=63). eGFR differences between groups at each time point were all significant (P&amp;lt;0.05), except for the comparison between T1 and T2 at month 6 (figure 1) Significant risk factors for eGFR&amp;lt;60 ml/min at 1-year were: acute rejection (AR) at 1-year (OR=4.116, P=0.018); calculated PRA&amp;gt;0% (OR=2.075, P=0.039); higher donor age (OR per unit=1.033, P=0.047); and peritoneal dialysis modality (in comparison with preemptive KT: OR=3.232, P=0.013). Higher (T3) DKV/BSA tercile (in comparison with T1: OR=0.306, P=0.004) was protective of this outcome. Patients that experienced AR at 1-year had significantly lower DKV/BSA, particularly those with acute cellular rejection (ACR). The median follow-up was 4,8 years (IQR: 3.2-7.5). The censored graft survival by DKV/BSA terciles at 10 years were 59,3% for group 1, 91.3% for group 2 and 91.1% for group 3 (figure 3). Conclusion Our study demonstrates that transplantation of donor-recipient pairs with lower DKV/BSA ratio were associated with significantly worse graft function and higher incidence of AR. This data suggests that a larger mass of nephrons remaining adjusted to recipient’s weight seems to predict a better long-term eGFR. This method can be useful in order to identify patients at risk for a low eGFR after KT and, in cases of multiple potential donors, optimize donor selection.

Living Kidney Transplantation From Marginal Donors Presents Feasible Donor Renal Function Despite Inferior Recipient Renal Function

IntroductionKidney transplantation from marginal donors is an important solution for organ shortage problems. In this study, we evaluated the safety and effectiveness of living kidney transplantation from marginal donors at our hospitals. MethodsBetween June 2006 and April 2019, 107 patients underwent living kidney transplantation at our hospitals. Marginal donors were defined as those with 1. age >70 years, 2. hypertension, 3. creatinine clearance <80 mL/min, 4. body mass index >30 kg/m2, or 5. hemoglobin A1c >6.2%. We retrospectively compared renal function and its chronological changes between marginal and standard donors. We also compared graft survival and recipient renal function between the groups. ResultsThirty-one (29%) donors were defined as marginal. The primary reason for being defined as marginal was hypertension (74%). The mean age of the marginal donors (62 ± 10 years) was higher than that of standard donors (52 ± 12 years, P < .001). The estimated glomerular filtration rate (eGFR) before and after transplantation was lower in the marginal group, whereas the decline ratio of eGFR was not different between the marginal and standard donors. Five-year graft survival of transplantations from marginal donors (89%) was not significantly inferior to that from standard donors (95%). Meanwhile, recipient eGFR was lower in transplantation from marginal donors than standard donors from 1 month through 5 years after transplantation. ConclusionsNo significant differences were observed between the groups regarding the decline ratios of donor eGFR and graft survival. Thus, transplantation from marginal donors may be a feasible solution for donor shortage problems.

Determinants of the intercept and slope of glomerular filtration rate in recipients of alive donor kidney transplant.

SummaryBackgroundDonor kidney function is considered a critical determinant of allograft survival after live donor (LD) kidney transplantation, but its independent impact on the evolution of graft function is less well defined. The objective of this study was to dissect the relative contribution of LD kidney function to baseline estimated glomerular filtration rate (eGFR) of recipients and its decline.MethodsIn this study 91 LD kidney transplantations performed between 2007 and 2015 were included. The eGFR of donated kidneys (eGFR-dk) was calculated from total LD eGFR (eGFR-dt) based on the results of isotope nephrography. Recipient eGFR (eGFR-r) determined 6‑monthly until 36 months posttransplantation served as dependent variable in mixed linear models estimating changes in baseline allograft function (intercept) and eGFR‑r slope. Models were adjusted either for eGFR-dk or eGFR-dt, in addition to other potential confounders.ResultsOverall, unadjusted mean eGFR‑r at baseline (6 months) and its annual decline in allograft function were 56.5 mL/min/1.73 m2 and −0.2 mL/min/1.73 m2, respectively. In multivariate analysis, eGFR-dk impacted on baseline eGFR‑r (0.6 mL/min/1.73 m2 mean estimated increase per unit; P = 0.02) but not on its slope. In the eGFR-dt-adjusted model, a marginal effect was observed for LD age (P = 0.05). Both models identified antibody-mediated rejection (ABMR) as the strongest risk factor of accelerated loss of allograft function (eGFR‑r slope: approximately −6 mL/min/1.73 m2 per year; P ≤ 0.02).ConclusionDonor-related characteristics, most prominently the function of donated kidneys and LD age, were predictive of eGFR at baseline. The ABMR was identified as the cardinal cause of progressive deterioration of allograft function.

Increased circulating Tfh to Tfr ratio in chronic renal allograft dysfunction: a pilot study

BackgroundT follicular helper (Tfh) cells play a control role in contribution of B cell differentiation and antibody production. T follicular regulatory (Tfr) cells inhibit Tfh-B cell interaction.MethodsTo identify whether circulating Tfh (cTfh) and Tfr (cTfr) cells contribute to chronic renal allograft dysfunction (CAD), 67 kidney transplant recipients (34 recipients with CAD, 33 recipients with stable function) were enrolled. The frequency of cTfh and cTfr cells, the level of serum CXCL13 were measured.ResultsThe frequency of cTfr cells in CAD group was significantly lower than that in stable group (0.31% vs 0.68%, P = 0.002). The cTfh to cTfr ratio in CAD group was significantly higher than that in stable group (55.4 vs 25.3, P = 0.013). Serum CXCL13 in CAD group was significantly higher than stable group (30.4 vs 21.9 ng/ml, P = 0.025). After linear regression analysis, the cTfh to cTfr ratio was an independent risk factor for estimated glomerular filtration rate (eGFR) in recipients (standardized coefficient = − 0.420, P = 0.012). After logistic regression analysis, the cTfh to cTfr ratio was an independent risk factor for CAD (OR = 1.043, 95%CI = 1.004–1.085, P = 0.031).ConclusionThe imbalance between cTfh and cTfr cells contribute to the development of CAD.

MiR-200c in extracellular vesicles as a circulating biomarker of EGFR-TKI response and a mediator of EGFR-TKI sensitivity in heterogeneous NSCLC.

e20547 Background: Through intercellular transfer of EV(extracellular vesicles) miRNA, tumor cells can confer drug resistance to each other and contribute to tumor heterogeneity. However, the mechanisms why EGFR-TKI can be effective in heterogeneous NSCLC with low abundances of EGFR mutations remain unknown. The aim of the study is to investigate the significance of EV miRNA in mediating the efficacy of EGFR-TKI in heterogeneous NSCLC and serving as the biomarker of response to EGFR-TKI. Methods: We first evaluate if EVs from EGFR mutant cell (PC9) can affect EGFR-TKI sensitivity of EGFR wild type cell (CL1-5, H1299) in vitro co-culture system and i n vivo. We then identified the differential miRNA panel by comparing EVs from PC9 to those from CL1-5. Finally, we verified if the expressions level of these miRNA are different in blood EVs from patient with good response compared to those with poor response to EGFR-TKI. Results: We first verified that CL1-5 can take up labelled EVs from PC9 under time-lapse microscope and EGFR mutant DNA can be detected in recipient EGFR wild-type cell using digital PCR. We found EVs from PC9 enhanced gefitinib sensitivity of CL1-5. And co-culturing PC9 with CL1-5 enhanced CL1-5 gefitinib sensitivity which was reversed by adding GW4789, the inhibitor of exosome secretion. In subcutaneous CL1-5 animal model, in comparison to treating with gefitinib or PC9 EVs alone, only the combination treatment with gefitinib and PC9 EVs delayed cancer growth. Using small RNA sequencing, we identified a unique miRNA profile allowing discriminating EV from PC9 cells to those from CL1-5; MiRNA 200 family including 200a, 200b, 200c and mir429 were up-regulated significantly in PC9 EV. From Aug 2015 to Sep 2017, sixteen patients with good response (PFS &gt; 12M) or poor response (PFS &lt; 6M) to EGFR-TKI were enrolled and blood were collected for EV miRNA isolation. Ten of these blood samples were qualified for miRNA analysis and mir200a and 200c were found up-regulated in good responder to EGFR-TKI. The transfection of mir200c in CL1-5 cells not only inhibited the oncogenic pathway contributing to EGFR-TKI resistance including Stat3, Akt, EMT and BIM pathway but also enhanced gefitinib sensitivity of CL1-5 cells. Conclusions: Our data suggested mir200c from blood EV serve as a biomarker of response to EGFR-TKI and mir200c may mediate EGFR-TKI sensitivity in heterogenous EGFR mutant NSCLC.

Young donors with severe acute kidney injury offer an opportunity to expand the donor pool

BackgroundThis study assessed our experience transplanting kidneys from young donors with severe acute kidney injury. MethodsWe performed a single center retrospective analysis of 315 kidney transplants between 1/1/2014-12/31/2016. Donor kidneys were classified according to the Acute Kidney Injury Network (AKIN) criteria. A case-matched cohort was created using recipient age, history of diabetes, donor specific antibody, donor age and donor after cardiac death. Primary endpoints were graft function measured by eGFR at 90 days and at 1-year. ResultsStage 3 AKIN recipients had significantly greater eGFR at one year (63.9 ml/min v. 51.2 ml/min, p < 0.001) compared to those with Stage 0 AKIN. This difference was abrogated when compared to a case matched cohort (eGFR at 90 days or 1 year; p > 0.05). Donor and recipient characteristics on eGFR at 1 year were analyzed using linear and logistic regression. Only donor age had a significant impact on recipient eGFR. ConclusionsDonor kidneys with severe acute injury can achieve optimal 1-year outcomes. Donor age is the most significant predictor of eGFR >45 ml/min after transplant.