Does pre‐emptive kidney transplantation with a deceased donor improve outcomes? Results from a French transplant network

Large analyses have demonstrated that pre‐emptive kidney transplantation (PKT) leads to significant improvements in patient and graft survival when compared with transplantation performed after a period of dialysis. We analysed 1585 patients who received a first renal transplantation from a deceased donor between 2000 and 2004 in four French transplantation centres. The objective was to compare the characteristics of the deceased donor transplantations with or without previous dialysis and to evaluate the impact of PKT and length of dialysis on patient and graft outcomes. Mean age of recipients was 48.1 ± 13.4 years, 62% were men, and 118 (7.4%) of them received a pre‐emptive transplantation. For the nonpre‐emptive patients, mean time on pretransplant dialysis was 3.4 ± 3.2 years. Pretransplant factors independently related to pre‐emptive transplantation were year of transplantation, centre and recipients characteristics: gender, diabetes history, blood group and donor age. Patients with pretransplant dialysis were three times more likely to have delayed graft function than pre‐emptive transplant patients, and were 10 times more likely to receive post‐transplant dialysis. Five‐year patient survival was 92.9%. Five‐year graft survival was 89.0%. Neither pre‐emptive transplantation nor time on dialysis was significantly associated with patient and/or graft survival.     

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor–recipient combination

The impact of donor quality on post–kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post‐KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5‐year post‐KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5‐year waitlist survival was 47.6%, and 5‐year post‐KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool ( www.transplantmodels.com/kdpi-epts ) can support individualized decision‐making on kidney offers in clinical practice.     

Why do some diabetic patients on the kidney transplant waiting list not receive a transplant?

The waiting list (WL) history of 405 diabetic patients placed on the kidney transplantation WL for the years 1993–2000 was examined. By 31 December 2000, 295 (73 %) patients had received a transplant. Of the remaining 110 patients 53 (13 %) were still on the WL; 27 of these were temporarily withdrawn, i.e. non-active, 46 others (11 %) had died and 11 (3 %) had been permanently removed. Patient follow-up continued until the end of 2002. Although the mean total time on the WL of the non-transplanted was twice that of the transplanted patients there were no significant differences in the mean active times on the WL. The mean cumulative withdrawal time of the transplanted and those on the active WL was less than 10 % of their total time on the list, but for the patients who had died or were withdrawn on 31 December 2000 it exceeded 50 %, usually because of diabetic complications. The 5-year survival of the transplanted patients was greatly superior to that of the non-transplanted, as expected. However, the better survival of the transplanted patients is not necessarily proof of a better treatment modality but rather a consequence of the exclusion from transplantation of patients suffering from diabetic complications. It is not justified to compare the survival of transplantable and non-transplantable WL patients.     

Should the family have a role in deceased organ donation decision-making? A systematic review of public knowledge and attitudes towards organ procurement policies in Europe

GoalTo assess public knowledge and attitudes towards the family’s role in deceased organ donation in Europe.MethodsA systematic search was conducted in CINHAL, MEDLINE, PAIS Index, Scopus, PsycINFO, and Web of Science on December 15th, 2017. Eligibility criteria were socio-empirical studies conducted in Europe from 2008 to 2017 addressing either knowledge or attitudes by the public towards the consent system, including the involvement of the family in the decision-making process, for post-mortem organ retrieval. Screening and data collection were performed by two or more independent reviewers for each record.ResultsOf the 1482 results, 467 studies were assessed in full-text form, and 33 were included in this synthesis. When the deceased has not expressed any preference, a majority of the public support the family's role as a surrogate decision-maker. When the deceased expressly consented, the respondents' answers depend on whether they see themselves as potential donors or as a deceased's next-of-kin. Answers also depend on the relationship between the deceased and the decision-maker(s) within the family, and on their ethnic or cultural background.ConclusionsPublic views on the authority of the family in organ donation decision-making requiere further research. A common conceptual framework and validated well-designed questionnaires are needed for future studies. The findings should be considered in the development of Government policy and guidance regarding the role of families in deceased organ donation.     

An international comparison of deceased donor kidney utilization: What can the United States and the United Kingdom learn from each other?

In transplant, meaningful international comparisons in organ utilization are needed. This collaborative study between the United Kingdom (UK) and the United States (US) aimed to develop a kidney utilization metric allowing for legitimate intercountry comparisons. Data from the UK and US transplant registries, including all deceased donor kidneys recovered from 2006 to 2017, were analyzed. To identify a potentially comparable kidney utilization rate (UR), several denominators were assessed. We discovered that the proportion of transplanted kidneys from elderly donors in the UK (10.7%) was 18 times greater than that in the US (0.6%). Conversely, en bloc pediatric kidney transplant was more common in the US. Donation after circulatory death utilization has risen in both countries but is twice as prevalent in the UK (39% of transplants) vs the US (20%). In addition, US and UK URs are not directly comparable due to fundamental system differences. However, using a suite of URs revealed practice areas likely to yield the most benefit if improved, such as efforts to increase kidney offer acceptance in the US and to reduce postacceptance discard in the UK. Methods used in this study, including novel intracountry risk‐adjusted UR trend logistic regression analyses, can be translated to other international transplant registries in pursuit of further global learning opportunities.     

Impact of donor cardiopulmonary resuscitation on the outcome of simultaneous pancreas–kidney transplantation—a retrospective study

Previous cardiac arrest in brain-dead donors has been discussed as a potential risk factor in pancreas transplantation (PT), leading to a higher rate of organ refusal. This study aimed to assess the impact of cardiopulmonary resuscitation (CPR) in brain-dead donors on pancreas transplant outcome. A total of 518 type 1 diabetics underwent primary simultaneous pancreas–kidney (SPK) transplantation at our center between 1994 and 2018. Patients were divided into groups, depending on whether their donor had been resuscitated or not. A total of 91 (17.6%) post-CPR donors had been accepted for transplantation (mean duration of cardiac arrest, 19.4 ± 15.6 min). Those donors were younger (P < 0.001), had lower pancreas donor risk index (PDRI, P = 0.003), and had higher serum creatinine levels (P = 0.021). With a median follow-up of 167 months (IQR 82–229), both groups demonstrated comparable short- and long-term patient and graft survival. The resuscitation time (<20 min vs. ≥20 min) also showed no impact, with similar survival rates for both groups. A multivariable Cox regression analysis suggested no statistically significant association between donor CPR and patient or graft survival. Our results indicate that post-CPR brain-dead donors are suitable for PT without increasing the risk of complications.     

Follow-up of kidney donors who developed uremia and went on the waiting list for a transplant: should they have allocation priority?

BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with chronic renal failure (CRF), and discussion about a regular follow-up program for donors, policies giving priority to kidney donors on the waiting list for a kidney, and a national record of donors. METHODS: We performed a Retrospective analysis of 470 records of our kidney donors from the kidney transplantation unit between 1977 and 1997. RESULTS: Five out of the 470 donors developed CRF (1.1%), with a calculated incidence of 610 per million people a year. CONCLUSION: The data showed that the risk of a donor developing CRF may be higher than in the in general population. These results showed the necessity of creating an effective follow-up program for donors and a national record.     

To screen or not to screen? The development of a prediction model for aorto-iliac stenosis in kidney transplant candidates

Screening for aorto-iliac stenosis is important in kidney transplant candidates as its presence affects pre-transplantation decisions regarding side of implantation and the need for an additional vascular procedure. Reliable imaging techniques to identify this condition require contrast fluid, which can be harmful in these patients. To guide patient selection for these imaging techniques, we aimed to develop a prediction model for the presence of aorto-iliac stenosis. Patients with contrast-enhanced imaging available in the pre-transplant screening between January 1st, 2000 and December 31st, 2018 were included. A prediction model was developed using multivariable logistic regression analysis and internally validated using bootstrap resampling. Model performance was assessed with the concordance index and calibration slope. Three hundred and seventy-three patients were included, 90 patients (24.1%) had imaging-proven aorto-iliac stenosis. Our final model included age, smoking, peripheral arterial disease, coronary artery disease, a previous transplant, intermittent claudication and the presence of a femoral artery murmur. The model yielded excellent discrimination (optimism-corrected concordance index: 0.83) and calibration (optimism-corrected calibration slope: 0.91). In conclusion, this prediction model can guide the development of standardized protocols to decide which patients should receive vascular screening to identify aorto-iliac stenosis. External validation is needed before this model can be implemented in patient care.     

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry – a retrospective study

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998–2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7–4.6) and 10.8% (95% CI: 10.1–11.5) versus 6.5% (95% CI: 5.7–7.4) and 12.2% (95% CI: 11.2–13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87–1.13) for patient survival and 1.03 (95% CI: 0.94–1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04–1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.     

To operate or not—the impact of a lecture on radical glioblastoma surgery and different treatment options on decision-making for oneself and patients

Background

Clinical decision-making involves a complex interaction between patients and caregivers. The medical knowledge and values of caregivers are essential for treatment recommendations. This study was undertaken to evaluate treatment recommendations by a group of Scandinavian neurosurgeons before and after an expert lecture on glioblastoma surgery.

Method

An interactive voting system was used to record responses to four questions regarding glioblastoma management before and after a 25-min lecture on the benefit of radical glioblastoma surgery.

Results

The majority of the audience aimed at radical surgery combined with radiotherapy before (76 %) and after (88 %) the lecture. The proportion who recommended immediate postoperative follow-up by MRI increased from 34 % to 75 %. Fourteen percent (before) and 45 % (after) recommended renewed surgery to remove small residuals in patients, while 52 % (before) and 60 % (after) would have wanted to be re-operated if they themselves had been patients.

Conclusion

The views on optimum management differed widely in a relatively homogeneous group of neurosurgeons. The lecture had a major impact on decision-making. A large proportion of the attendees recommended different management strategies for themselves and for their patients. The findings indicated the need to analyze the evaluation of medical knowledge, discuss the ethics of decision-making and encourage second opinions for serious neurosurgical decisions.     

Prospective multi-centric study to analyze pre-transplant compatibility algorithm for live-related donor kidney transplant in Indian setting: the “Delhi approach”!

BackgroundSince no single test is always accurate and sensitive, two or more tests are used to increase the precision of evaluation. Different algorithms have been proposed by centers in Leiden, Basel, Vienna and Minnesota, etc. With an intention to develop an optimal algorithm for India, we evaluated pre-transplant compatibility tests for live-donor kidney transplants. Three tests complement dependent cyto-toxicity cross-match (CDCXM), flow-cytometry cross-match (FCXM) and anti-HLA antibody screening (HAS) were performed and confirmed by the anti-HLA antibody identification (HAI) assay in a multi-centric trial (three transplant centers) in India.Materials and methodsAll prospective recipients (and their potential donors) underwent low-resolution HLA typing as well as CDCXM, FCXM and HAS assays. In addition, HAI {single antigen bead assay; (SAB)} was done for all recipients to identify possible anti-HLA antibodies. In a virtual cross-match (VXM), antibody specificity was mapped to donor HLA type to determine donor-specific antibodies (DSA). Only patients without DSA were cleared for the transplant. Alternatively, patients with DSA were offered an exchange in the kidney paired donation (KPD) program. The screening results (CDCXM, FCXM, and HAS) were analyzed, individually as well as in combination of screening assays (CDCXM+HAS, CDCXM+FCXM, and FCXM+HAS) and the results were compared with those from the HAI test.ResultsOut of 100 patients, 69 were males and 31 were females; 85 recipients (85%) underwent a kidney transplant. The sensitivity of CDCXM was only 12.1% and the specificity of CDCXM was 100%; whereas the sensitivity of FCXM was 84.8% and the specificity of FCXM was 89.6%. The sensitivity and specificity of class I HAS was 88.2% and 84.3%, respectively. The sensitivity and specificity class II HAS was 88.0% and 80.0%, respectively. However, when both class I/II HAS were tested together the sensitivity increased to 97.0% and the specificity to 82.1%. Similarly, the sensitivity of combined FCXM+HAS had the sensitivity of 100% and the specificity of 76.1%; CDCXM+FCXM had the sensitivity of 84.8% and the specificity of 89.6% and CDCXM+HAS assays reached 97% with the specificity of 82.1%.ConclusionsOur results showed that the algorithm of FCXM with HAS produced the best sensitivity of 100%. The specificity of 76.1% indicate that the combined FCXM+HAS assays may detect up to 24.9% false positive results. We suggest that these false-positives may be easily resolved by performing the virtual crossmatch based on HAI (SAB) results. In our reflex testing algorithmic approach only 49% patients needed HAI (SAB). Finally, our results suggested that the CDCXM assay may be discontinued in pre-transplant workup owing to its very low sensitivity (12.1%).     

Should the indications for laparascopic live donor nephrectomy of the right kidney be the same as for the open procedure? Anomalous left renal vasculature is not a contraindiction to laparoscopic left donor nephrectomy

BACKGROUND: The left kidney is preferred for live donation. In open live donor nephrectomy, the right kidney is selected if the left kidney has multiple renal arteries or anomalous venous drainage. With laparoscopic live donor nephrectomy (LLDN), there is reluctance to procure the right kidney because of the more difficult exposure and further shortening of the right renal vein (RRV) after a stapled transection. An experience with LLDN is reviewed to determine whether the right kidney should be procured laparoscopically. METHODS: From February 1995 to November 1999, 227 patients underwent live donor renal transplants with allografts procured by LLDN. The results of these transplants were analyzed. RESULTS: Of the 227 kidneys transplanted, 17 (7.5%) were right kidneys. In the early experience, three (37.5%) of the eight right renal allografts developed venous thrombosis, two of which had duplicated RRV. Based on these initially unacceptable results, donor evaluation and LLDN techniques were modified. Spiral computerized tomography (CT) replaced conventional angiography to define better the venous anatomy. LLDN was modified in one of three ways: (1) changing the stapler port placement such that the RRV was transected in a plane parallel to the inferior vena cava, (2) relocation of the incision for open division of RRV, or (3) lengthening of the donor RRV with a panel graft constructed of recipient greater saphenous vein. Finally, the recipient operation enjoined complete mobilization of the left iliac vein with transposition lateral to the iliac artery. With these modifications, there were no vascular complications with the subsequent nine right renal allografts (P<0.05). Of the left kidneys transplanted, 31 had multiple renal arteries, 14 had retroaortic or circumaortic veins, 4 had both multiple arteries and venous anomalies, and 1 had a duplicated IVC draining the left renal vein. There were no vascular complications with left renal allografts that had multiple arteries or venous anomalies. CONCLUSIONS: LLDN of the left kidney is technically easier. Left kidneys with multiple arteries or anomalous venous drainage are not problematic. The right kidney can be procured with LLDN; however, a rational approach to preoperative angiographic imaging, donor operation, and recipient operation is crucial.     

Managing highly sensitized renal transplant candidates in the era of kidney paired donation and the new kidney allocation system: Is there still a role for desensitization?

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting‐list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait‐listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.