Telemedicine for Kidney Transplant Recipients: Current State, Advantages, and Barriers.

Telemedicine is defined as the use of electronic information and communication technologies to provide and support healthcare at a distance. In kidney transplantation, telemedicine is limited but is expected to grow markedly in the coming y. Current experience shows that it is possible to provide transplant care at a distance, with benefits for patients like reduced travel time and costs, better adherence to medication and appointment visits, more self-sufficiency, and more reliable blood pressure values. However, multiple barriers in different areas need to be overcome for successful implementation, such as recipients' preferences, willingness, skills, and digital literacy. Moreover, in many countries, limited digital infrastructure, legislation, local policy, costs, and reimbursement issues could be barriers to the implementation of telemedicine. Finally, telemedicine changes the way transplant professionals provide care, and this transition needs time, training, willingness, and acceptance. This review discusses the current state and benefits of telemedicine in kidney transplantation, with the aforementioned barriers, and provides an overview of future directions on telemedicine in kidney transplantation.

Imlifidase Desensitization in HLA-incompatible Kidney Transplantation: Finding the Sweet Spot.

Imlifidase, derived from a Streptococcus pyogenes enzyme, cleaves the entire immunoglobulin G pool within hours after administration in fully cleaved antigen-binding and crystallizable fragments. These cleaved fragments can no longer exert their antibody-dependent cytotoxic functions, thereby creating a window to permit HLA-incompatible kidney transplantation. Imlifidase is labeled, in Europe only, for deceased donor kidney transplantation in highly sensitized patients, whose chances for an HLA-compatible transplant are negligible. This review discusses outcomes of preclinical and clinical studies on imlifidase and describes the phase III desensitization trials that are currently enrolling patients. A comparison is made with other desensitization methods. The review discusses the immunological work-up of imlifidase candidates and especially the "delisting strategy" of antigens that shift from unacceptable to acceptable with imlifidase desensitization. Other considerations for clinical implementation, such as adaptation of induction protocols, are also discussed. Imlifidase cleaves most of the currently used induction agents except for horse antithymocyte globulin, and rebound of donor-specific antibodies should be managed. Another consideration is the timing and interpretation of (virtual) crossmatches when bringing this novel desensitization agent into the clinic.

Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation: A retrospective cohort study.

AIMS: Pregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole-blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model. METHODS: Data of pregnant women using a twice-daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness-of-fit plots, visual predictive checks and a bootstrap analysis. RESULTS: A total of 260 whole-blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance. CONCLUSIONS: Tacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole-blood tacrolimus predose concentrations during pregnancy, increasing the dose is required.

Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers.

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions. Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calculated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08-0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129-0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists' certainty about their decision.

Impact of Extraction Time During Donation After Circulatory Death Organ Procurement on Kidney Function After Transplantation in The Netherlands.

Background: In The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included. Methods: Between 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF. Results: In our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF. Conclusions: Considering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.

Long-Term Kidney and Maternal Outcomes After Pregnancy in Living Kidney Donors.

For counseling it is important to know if pregnancy after Living Kidney Donation (LKD) affects long-term outcomes of the mono-kidney and the mother. Therefore, we performed a retrospective multicenter study in women ≤45 years who donated their kidney between 1981 and 2017. Data was collected via questionnaires and medical records. eGFR of women with post-LKD pregnancies were compared to women with pre-LKD pregnancies or nulliparous. eGFR before and after pregnancy were compared in women with post-LKD pregnancies. Pregnancy outcomes post-LKD were compared with pre-LKD pregnancy outcomes. 234 women (499 pregnancies) were included, of which 20 with pre- and post-LKD pregnancies (68) and 26 with only post-LKD pregnancies (59). Multilevel analysis demonstrated that eGFR was not different between women with and without post-LKD pregnancies (p = 0.23). Furthermore, eGFR was not different before and after post-LKD pregnancy (p = 0.13). More hypertensive disorders of pregnancy (HDP) occurred in post-LKD pregnancies (p = 0.002). Adverse fetal outcomes did not differ. We conclude that, despite a higher incidence of HDP, eGFR was not affected by post-LKD pregnancy. In line with previous studies, we found an increased risk for HDP after LKD without affecting fetal outcome. Therefore, a pregnancy wish alone should not be a reason to exclude women for LKD.

Paving the way for solutions improving access to kidney transplantation: a qualitative study from a multistakeholder perspective.

OBJECTIVES: The aim of this study was to obtain an in-depth perspective from stakeholders involved in access to kidney transplantation to pave the way for solutions in improving access to kidney transplantation. This study qualitatively explored factors influencing optimal access to kidney transplantation from a broad stakeholder perspective. DESIGN: A qualitative study was performed using semistructured interviews both in focus groups and with individual participants. All interviews were recorded, transcribed and coded according to the principles of grounded theory. SETTING: Participants were healthcare providers (geographically spread), patients and (former living) kidney donors, policy-makers and insurers. PARTICIPANTS: Stakeholders (N=87) were interviewed regarding their perceptions, opinions and attitudes regarding access to kidney transplantation. RESULTS: The problems identified by stakeholders within the domains-policy, medical, psychological, social and economic-were acknowledged by all respondents. According to respondents, more efforts should be made to make healthcare providers and patients aware of the clinical guideline for kidney transplantation. The same opinion applied to differences in medical inclusion criteria used in the different transplantation centres. Stakeholders saw room for improvement based on psychological and social themes, especially regarding the provision of information. Many stakeholders described the need to rethink the current economic model to improve access to kidney transplantation. This discussion led to a definition of the most urgent problems for which, according to the respondents, a solution must be sought to optimise access to kidney transplantation. CONCLUSIONS: Stakeholders indicated a high sense of urgency to solve barriers in patient access to kidney transplantation. Moreover, it appears that some barriers are quite straightforward to overcome; according to stakeholders, it is striking that this process has not yet been overcome. Stakeholders involved in kidney transplantation have provided directions for future solutions, and now it is possible to search for solutions with them.

Increasing Kidney-Exchange Options Within the Existing Living Donor Pool With CIAT: A Pilot Implementation Study.

Computerized integration of alternative transplantation programs (CIAT) is a kidney-exchange program that allows AB0- and/or HLA-incompatible allocation to difficult-to-match patients, thereby increasing their chances. Altruistic donors make this available for waiting list patients as well. Strict criteria were defined for selected highly-immunized (sHI) and long waiting (LW) candidates. For LW patients AB0i allocation was allowed. sHI patients were given priority and AB0i and/or CDC cross-match negative HLAi allocations were allowed. A local pilot was established between 2017 and 2022. CIAT results were assessed against all other transplant programs available. In the period studied there were 131 incompatible couples; CIAT transplanted the highest number of couples (35%), compared to the other programs. There were 55 sHI patients; CIAT transplanted as many sHI patients as the Acceptable Mismatch program (18%); Other programs contributed less. There were 69 LW patients; 53% received deceased donor transplantations, 20% were transplanted via CIAT. In total, 72 CIAT transplants were performed: 66 compatible, 5 AB0i and 1 both AB0i and HLAi. CIAT increased opportunities for difficult-to-match patients, not by increasing pool size, but through prioritization and allowing AB0i and "low risk" HLAi allocation. CIAT is a powerful addition to the limited number of programs available for difficult-to-match patients.

A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.

Combined liver-kidney transplantation with delayed kidney implantation: A case report.

INTRODUCTION: In rare cases, patients require a combined liver-kidney transplant. However, the peri- and postoperative care of liver transplant recipients differs from kidney transplant recipients, which can lead to conflicts of interest. In the case of poor coagulation status and/or instable hemodynamics of the patient, liver transplantation, followed by delayed kidney transplantation can lead to better postoperative recovery. PRESENTATION OF CASE: In our case report, we present a 48-year old man with Alagille syndrome and IgA nephropathy with bilirubin-associated acute kidney injury, causing him to develop both end-stage liver and kidney disease. He underwent a combined liver-kidney transplant as the first patient in the Netherlands, in which the donor kidney was transplanted one day after the liver transplantation. One-year post-transplant patient is in good clinical condition, with normal liver function and an eGFR of 57 ml/min. CONCLUSION: Combined liver-kidney transplantation with delayed kidney implantation in a medical center with no previous experience with this technique is feasible and safe. This could be better for both the patient and the kidney graft.

Counselling on Conceiving: Attitudes and Factors Influencing Advice of Professionals in Transplantation.

Pregnancy after kidney transplantation (KT) conveys risks of adverse pregnancy outcomes (APO). Little is known about performance of pre-pregnancy counselling after KT. This study investigated perceptions of risk, attitudes towards pregnancy and factors influencing advice given at pre-pregnancy counselling after KT. A web-based vignette survey was conducted among nephrologists and gynaecologists between March 2020 and March 2021, consisting of five vignettes containing known risk factors for APO and general questions on pre-pregnancy counselling after KT. Per vignette, attitudes towards pregnancy and estimation of outcomes were examined. In total 52 nephrologists and 25 gynaecologists participated, 56% from university hospitals. One third had no experience with pregnancy after KT. All gave positive pregnancy advice in the vignette with ideal circumstances (V1), versus 83% in V2 (proteinuria), 81% in V3 (hypertension), 71% in V4 (eGFR 40 ml/min/1.73 m2). Only 2% was positive in V5 (worst-case scenario). Chance of preeclampsia was underestimated by 89% in V1. 63% and 98% overestimated risk for graft loss in V4 and V5. Professionals often incorrectly estimated risk of APO after KT. As experience with pregnancy after KT was limited among professionals, patients should be referred to specialised centres for multidisciplinary pre-pregnancy counselling to build experience and increase consistency in given advice.

Twenty Years of Unspecified Kidney Donation: Unspecified Donors Looking Back on Their Donation Experiences.

The Netherlands was the first European country to implement unspecified kidney donation in 2000. This qualitative study aimed to evaluate the experiences of unspecified kidney donors (UKDs) in our transplant institute to improve the care for this valuable group of donors. We conducted semi-structured interviews with 106 UKDs who donated between 2000-2016 (response rate 84%). Interviews were audio-recorded, transcribed verbatim and independently coded by 2 researchers in NVivo using thematic analysis. The following 14 themes reflecting donor experiences were found: Satisfaction with donation; Support from social network; Interpersonal stress; Complaints about hospital care; Uncertainty about donor approval; Life on hold between approval and actual donation; Donation requires perseverance and commitment; Recovery took longer than expected; Normalization of the donation; Becoming an advocate for living kidney donation; Satisfaction with anonymity; Ongoing curiosity about outcome or recipient; Importance of anonymous communication; Anonymity is not watertight. The data reinforced that unspecified kidney donation is a positive experience for donors and that they were generally satisfied with the procedures. Most important complaints about the procedure concerned the length of the assessment procedure and the lack of acknowledgment for UKDs from both their recipients and health professionals. Suggestions are made to address the needs of UKDs.

Ipsilateral Aorto-Iliac Calcification is Not Directly Associated With eGFR After Kidney Transplantation: A Prospective Cohort Study Analyzed Using a Linear Mixed Model.

Aorto-iliac calcification (AIC) is a well-studied risk factor for post-transplant cardiovascular events and mortality. Its effect on graft function remains unknown. The primary aim of this prospective cohort study was to assess the association between AIC and estimated glomerular filtration rate (eGFR) in the first year post-transplant. Eligibility criteria were: ≥50 years of age or ≥30 years with at least one risk factor for vascular disease. A non-contrast-enhanced CT-scan was performed with quantification of AIC using the modified Agatston score. The association between AIC and eGFR was investigated with a linear mixed model adjusted for predefined variables. One-hundred-and-forty patients were included with a median of 31 (interquartile range 26-39) eGFR measurements per patient. No direct association between AIC and eGFR was found. We observed a significant interaction between follow-up time and ipsilateral AIC, indicating that patients with higher AIC scores had lower eGFR trajectory over time starting 100 days after transplant (p = 0.014). To conclude, severe AIC is not directly associated with lower post-transplant eGFR. The significant interaction indicates that patients with more severe AIC have a lower eGFR trajectory after 100 days in the first year post-transplant.

Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study.

Introduction: The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here, we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch patients with aHUS after 3 months of therapy. Methods: All pediatric and adult patients with aHUS in native kidneys and a first-time eculizumab treatment were evaluated. In addition, an extensive cost-consequence analysis was conducted. Results: A total of 21 patients were included in the study from January 2016 to October 2020. In 17 patients (81%), a complement genetic variant or antibodies against factor H were identified. All patients showed full recovery of hematological thrombotic microangiopathy (TMA) parameters after the start of eculizumab. A renal response was noted in 18 patients. After a median treatment duration of 13.6 weeks (range 2.1-43.9), eculizumab was withdrawn in all patients. During follow-up (80.7 weeks [0.0-236.9]), relapses occurred in 4 patients. Median time to first relapse was 19.5 (14.3-53.6) weeks. Eculizumab was reinitiated within 24 hours in all relapsing patients. At last follow-up, there were no chronic sequelae, i.e., no clinically relevant increase in serum creatinine (sCr), proteinuria, and/or hypertension in relapsing patients. The low sample size and event rate did not allow to determine predictors of relapse. However, relapses only occurred in patients with a likely pathogenic variant. The cost-effectiveness analysis revealed that the total medical expenses of our population were only 30% of the fictive expenses that would have been made when patients received eculizumab every fortnight. Conclusion: It is safe and cost-effective to discontinue eculizumab after 3 months of therapy in patients with aHUS in native kidneys. Larger data registries are needed to determine factors associated with suboptimal kidney function recovery during eculizumab treatment, factors to predict relapses, and long-term outcomes of eculizumab discontinuation.

Strategies to address perceived barriers to timely kidney transplantation in the Netherlands: A qualitative study from a stakeholders' perspective.

Objective: We present strategies to perceived barriers to access to kidney transplantation (KT) in the Netherlands. Methods: This qualitative study (N = 70) includes nephrologists, social workers, surgeons, nurses, patients, former living kidney donors, policy employees, and insurance representatives. Interviews were conducted both in focus groups and individually and coded with NVivo. Results: Participants proposed strategies within five domains. 1.Policy: Making KT guideline more visible. 2.Medical: Increase access and transparency to KT medical eligibility criteria (e.g., age, BMI) for patients and healthcare providers. 3.Psychological: Support patients who continue to use dialysis because of social interaction opportunities associated with dialysis settings to find such interaction elsewhere. Link kidney patients with fears for KT to experienced experts or trained professionals. 4.Social: Support patients with language barriers with interpreters and visual explanations. Support patients using social media, e.g. Facebook, to identify potential donors. Better expectation management to reduce reports of inadequate aftercare for living donors. 5.Economical: Solving negative economic incentives for KT by changing incentives. Conclusion: Stakeholders see strategies for barriers in the entire care pathway. Innovation: This large qualitative study gives an important overview which strategies stakeholders see improving access to KT. Some strategies offer opportunities to solve barriers in the short-term.

Donor characteristics and their impact on kidney transplantation outcomes: Results from two nationwide instrumental variable analyses based on outcomes of donor kidney pairs accepted for transplantation.

Background: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals. Methods: This analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors. Findings: Incidences of congruent EGL (Netherlands: 1·2%, UK: 0·7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10-years Hazard Ratio for graft loss: 1·18 [1·03-1·35] p<0·018); and 5 years eGFR (48·6 [48·3-49·0] vs. 46·0 [44·5-47·6] ml/min in the symmetrical outcome group, p<0·001). Interpretation: Our results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes. Funding: None.

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes.

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96-0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy.

Impact of measured versus estimated glomerular filtration rate-based screening on living kidney donor characteristics: A study of multiple cohorts.

BACKGROUND: Most transplant centers in the Netherlands use estimated glomerular filtration rate (eGFR) for evaluation of potential living kidney donors. Whereas eGFR often underestimates GFR, especially in healthy donors, measured GFR (mGFR) allows more precise kidney function assessment, and therefore holds potential to increase the living donor pool. We hypothesized that mGFR-based donor screening leads to acceptance of donors with lower pre-donation eGFR than eGFR-based screening. METHODS: In this longitudinal cohort study, we compared eGFR (CKD-EPI) before donation in one center using mGFR-based screening (mGFR-cohort, n = 250) with two centers using eGFR-based screening (eGFR-cohort1, n = 466 and eGFR-cohort2, n = 160). We also compared differences in eGFR at five years after donation. RESULTS: Donor age was similar among the cohorts (mean±standard deviation (SD) mGFR-cohort 53±10 years, eGFR-cohort1 52±13 years, P = 0.16 vs. mGFR-cohort, and eGFR-cohort2 53±9 years, P = 0.61 vs. mGFR-cohort). Estimated GFR underestimated mGFR by 10±12 mL/min/1.73m2 (mean±SD), with more underestimation in younger donors. In the overall cohorts, mean±SD pre-donation eGFR was lower in the mGFR-cohort (91±13 mL/min/1.73m2) than in eGFR-cohort1 (93±15 mL/min/1.73m2, P<0.05) and eGFR-cohort2 (94±12 mL/min/1.73m2, P<0.05). However, these differences disappeared when focusing on more recent years, which can be explained by acceptance of more older donors with lower pre-donation eGFR over time in both eGFR-cohorts. Five years post-donation, mean±SD eGFR was similar among the centers (mGFR-cohort 62±12 mL/min/1.73m2, eGFR-cohort1 61±14 mL/min/1.73m2, eGFR-cohort2 62±11 mL/min/1.73m2, P = 0.76 and 0.95 vs. mGFR-cohort respectively). In the mGFR-cohort, 38 (22%) donors were excluded from donation due to insufficient mGFR with mean±SD mGFR of 71±9 mL/min/1.73m2. CONCLUSIONS: Despite the known underestimation of mGFR by eGFR, we did not show that the routine use of mGFR in donor screening leads to inclusion of donors with a lower pre-donation eGFR. Therefore eGFR-based screening will be sufficient for the majority of the donors. Future studies should investigate whether there is a group (e.g. young donors with insufficient eGFR) that might benefit from confirmatory mGFR testing.

A Novel High-throughput Droplet Digital PCR-based Indel Quantification Method for the Detection of Circulating Donor-derived Cell-free DNA After Kidney Transplantation.

BACKGROUND: Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as a marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR indel method that allowed for the absolute quantification of ddcfDNA. METHODS: In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pretransplantation; at 3, 7, and 180 d after transplantation; and at time of for-cause biopsies obtained within the first 180 d after transplantation. RESULTS: Median (interquartile range) ddcfDNA concentration was significantly higher on day 3 (58.3 [17.7-258.3] copies/mL) and day 7 (25.0 [10.4-70.8] copies/mL) than on day 180 after transplantation (4.2 [0.0-8.3] copies/mL; P < 0.001 and P < 0.001, respectively). At time of biopsy-proven AR (BPAR), between day 11 and day 180 after transplantation, ddcfDNA concentration was significantly higher (50.0 [25.0-108.3] copies/mL) than those when biopsies showed non-AR (0.0 [0.0-15.6] copies/mL; P < 0.05). ddcfDNA concentration within the first 10 d after transplantation showed no significant difference between recipients with BPAR and those with non-AR in their biopsy or between recipients with BPAR and ddcfDNA measured at day 3 and day 7. CONCLUSIONS: Unfortunately, ddcfDNA concentration is not a good biomarker to detect AR within the first 10 d after transplantation; however, BPAR occurring after 10 d after transplantation can be detected in kidney transplant recipients by ddcfDNA using a novel and unique high-throughput droplet digital PCR indel method.