Donor pretreatment with nebulized complement C3a receptor antagonist mitigates brain‐death induced immunological injury post–lung transplant

Donor brain death (BD) is an inherent part of lung transplantation (LTx) and a key contributor to ischemia‐reperfusion injury (IRI). Complement activation occurs as a consequence of BD in other solid organ Tx and exacerbates IRI, but the role of complement in LTx has not been investigated. Here, we investigate the utility of delivering nebulized C3a receptor antagonist (C3aRA) pretransplant to BD donor lungs in order to reduce post‐LTx IRI. BD was induced in Balb/c donors, and lungs nebulized with C3aRA or vehicle 30 minutes prior to lung procurement. Lungs were then cold stored for 18 hours before transplantation into C57Bl/6 recipients. Donor lungs from living donors (LD) were removed and similarly stored. At 6 hours and 5 days post‐LTx, recipients of BD donor lungs had exacerbated IRI and acute rejection (AR), respectively, compared to recipients receiving LD lungs, as determined by increased histopathological injury, immune cells, and cytokine levels. A single pretransplant nebulized dose of C3aRA to the donor significantly reduced IRI as compared to vehicle‐treated BD donors, and returned IRI and AR grades to that seen following LD LTx. These data demonstrate a role for complement inhibition in the amelioration of IRI post‐LTx in the context of donor BD.     

Early Lung Transplantation Success Utilizing Controlled Donation After Cardiac Death Donors

Donation-after cardiac death (DCD) donor organs have potential to significantly alleviate the shortage of transplantable lungs. However, only limited data so far describes DCD lung transplantation (LTx) techniques and results. This study aims to describe the Alfred Hospital's early and intermediate outcomes following DCD donor LTx. Following careful experimentation and consultation DCD guidelines were created to utilize Maastricht category III lung donors from either the ICU or operating room(OR), with a warm ischemic time(WIT) of <60 min. Between May 2006 and December 2007, 22 referred DCD donors led to 11 attempted retrievals after withdrawal, resulting in 8 actual bilateral LTx (2 donors did not arrest in prescribed period and 1 donor had nonacceptable lungs). ICU WIT = 38.4 min (range 20–54, OR WIT = 12.7 min (11–15), p < 0.05. Post-LTx, 1 pulmonary hypertensive patient required ECMO for PGD3. The mean group pO2/FiO2 ratio at 24 hours was 307.7 (240–507) with an ICU stay of 9.5 days (2–21) and ward stay of 21.5 days (11–76). All 8 survive at a mean of 311 days (10–573) with good performance status and lung function. In conclusion, the use of Maastricht category III lungs for human LTx is associated with acceptable early clinical outcomes.     

Long‐Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor‐Specific Immune Responses

Steady‐state alveolar macrophages (AMs) are long‐lived lung‐resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AMs of recipient origin seed the transplanted lungs. Origin of AMs was accessed using donor–recipient HLA mismatches. We demonstrate that 94–100% of AMs present in bronchoalveolar lavage (BAL) were donor derived and, importantly, AMs of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post‐LTx revealed that the majority of AMs (>87%) was donor derived. Elicitation of de novo donor‐specific antibody (DSA) is a major post‐LTx complication and a risk factor for development of chronic rejection. The donor AMs responded to anti‐HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AMs stimulated humoral and cellular immune responses to alloantigen and lung‐associated self‐antigens and led to bronchiolar obstruction. Therefore, donor‐derived AMs play an essential role in the DSA‐induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs.     

Donation After Circulatory Determination of Death Lung Transplantation for Pulmonary Arterial Hypertension: Passing the Toughest Test

Lung transplantation (LTx) is a therapeutic option for severe pulmonary arterial hypertension (PAH) patients failing optimal medical therapy. The use of donation after circulatory determination of death (DCDD) donor lungs for PAH LTx has rarely been reported, primarily reflecting concerns that DCDD lungs represent extended criteria donors, at risk of morbidity and mortality. A retrospective study of all Alfred Hospital DCDD and DNDD (donation after neurologic determination of death) PAH LTx was undertaken. Protocolized fluid/inotrope/ventilator and extracorporeal membrane oxygenation (ECMO) strategies were utilized. Since our first DCDD LTx in 2006, 512 LTx have been performed. Of 31 PAH recipients, 11 received DCDD lungs (11% of DCDD LTx) and 20 received DNDD lungs (5% of DNDD LTx) (p = 0.04). Only one PAH patient died on the LTx waiting list. Peri‐LTx ECMO was utilized in 3/11 (27%) DCDD and 6/20 (30%) DNDD PAH LTx (p = 0.68). Primary graft dysfunction, intensive care, and overall stay were the same in both groups. Survival at 1 and 8 years was 100% and 80% for DCDD versus 100% and 70% for DNDD LTx (p = 0.88), respectively. In conclusion, excellent results can be achieved for PAH LTx. DCDD donor lungs are not extended lungs per se having passed the toughest test.     

Donor history of asthma is not a contraindication to lung transplantation: 12-year single-center experience.

BACKGROUND: Donor asthma has been regarded as a contraindication to lung transplantation (LTx) because of concerns that pre-existing airway inflammation will predispose to early and late graft dysfunction. The aim of this study was to describe LTx outcomes in which lungs had been transplanted from donors with a history of asthma. METHODS: A retrospective chart review was undertaken of 743 consecutive donor lung referrals to the Alfred Hospital between 1990 and September 2002. Seventy-four were noted to have a history of asthma, including 18 in whom asthma was the cause of death. Twenty-seven patients became lung donors, of whom 16 were on asthma treatment (on-treatment group) and 11 were not (no-treatment group). RESULTS: From 27 lung donors, 35 LTx procedures were performed (16 double LTx [DLTx], 19 single LTx [SLTx]). Five recipients died at <30 days (including 3 of early graft failure in the no-treatment group), and 7 died at >30 days (only 1 due to BOS). The 30-day, 1-year and 5-year survival rates in the on- and no-treatment donor groups were 90% vs 76%, 74% vs 69% and 74% vs 60%, respectively, and were not significantly different from our overall LTx survival rates. There were no significant differences in percent predicted forced expiratory volume in 1 second, ICU stay or hospital stay overall, or when analyzed according to on treatment vs no treatment and SLTx vs DLTx. Only 2 procedures LTx were performed from fatal asthma donors, both of whom had subsequent graft dysfunction and died on Days 73 and 484, respectively. CONCLUSIONS: The use of lungs from carefully selected lung donors with a history of asthma may increase the donor pool with acceptable long-term outcomes. The use of fatal asthma donors remains problematic.     

A retrospective database analysis to evaluate the potential of ex vivo lung perfusion to recruit declined lung donors

Ex vivo lung perfusion (EVLP) is currently used for both standard and extended‐criteria donor (ECD) lungs. To enlarge the donor pool, we might have to extend the threshold for ECD donation. The purpose of this study was to estimate how many additional ECD lungs could be recruited by EVLP. We reviewed all multi‐organ donors (MODs) from our collaborative donor hospitals (January 2010–June 2015). All unused lung donors were categorized using registered donor data and evaluated by two independent investigators to identify which lungs could be transplanted after EVLP. 584 MODs were registered at our transplant center. 268 (45.9%) were declined as lung donor at the moment of registration, and 316 (54.1%) were considered as a donor for lung transplantation. In the latter, lungs from 220 (37.7%) donors were transplanted and 96 donors (16.4%) were not. We identified 78 of 364 declined donors (21.4%) whose lungs could potentially become transplantable after EVLP. With this retrospective database analysis of unused lung donors, we identified a large potential for EVLP to further increase the donor pool in transplant centers where the majority of donor lungs are already extended.     

A decade of extended‐criteria lung donors in a single center: was it justified?

Despite a worldwide need to expand the lung donor pool, approximately 75% of lung offers are not accepted for transplantation. We investigated the impact of liberalizing lung donor acceptance criteria during the last decade on the number of effective transplants and early and late outcomes in our center. All 514 consecutive lung transplants (LTx) performed between Jan 2000 and Oct 2011 were included. Donors were classified as matching standard criteria (SCD; n = 159) or extended criteria (ECD; n = 272) in case they fulfilled at least one of the following criteria: age >55 years, PaO₂/FiO₂ at PEEP 5 cmH₂O < 300 mmHg at time of offer, presence of abnormalities on chest X‐ray, smoking history, presence of aspiration, presence of chest trauma, or donation after circulatory death. Outcome parameters were primary graft dysfunction (PGD) grade at 0, 12, 24, and 48 h after LTx, time to extubation, stay in intensive care unit (ICU), early and late infection, acute rejection and bronchiolitis obliterans syndrome (BOS), and survival. Two hundred and seventy‐two recipients (63.1%) received ECD lungs. PGD grade at T0 was similar between groups, while at T12 (<0.01), T24 (<0.01), and T48 (<0.05), PGD3 was observed more often in ECDs. ICU stay (P < 0.05) was longer in ECDs compared with SCDs. Time to extubation, respiratory infections, acute rejection, lymphocytic bronchiolitis, BOS, and survival were not different between groups. Accepting ECDs contributed in increasing the number of lung transplants performed in our center. Although this lung donor strategy has an impact on early postoperative outcome, liberalizing criteria did not influence long‐term outcome after LTx.     

HLA‐G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06～UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04～UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.     

Effects of carbon monoxide on early dysfunction and microangiopathy following GalT‐KO porcine pulmonary xenotransplantation in cynomolgus monkeys

Background

Despite progress in the current genetic manipulation of donor pigs, most non‐human primates were lost within a day of receiving porcine lung transplants. We previously reported that carbon monoxide (CO) treatment improved pulmonary function in an allogeneic lung transplant (LTx) model using miniature swine. In this study, we evaluated whether the perioperative treatment with low‐dose inhalation of CO has beneficial effects on porcine lung xenografts in cynomolgus monkeys (cynos).

Methods

Eight cynos received orthotopic left LTx using either α‐1,3‐galactosyltransferase knockout (GalT‐KO; n = 2) or GalT‐KO with human decay accelerating factor (hDAF) (GalT‐KO/hDAF; n = 6) swine donors. These eight animals were divided into three groups. In Group 1 (n = 2), neither donor nor recipients received CO therapy. In Group 2 (n = 4), donors were treated with inhaled CO for 180‐minute. In Group 3 (n = 2), both donors and recipients were treated with CO (donor: 180‐minute; recipient: 360‐minute). Concentration of inhaled CO was adjusted based on measured levels of carboxyhemoglobin in the blood (15%‐20%).

Results

Two recipients survived for 3 days; 75 hours (no‐CO) and 80 hours (CO in both the donor and the recipient), respectively. Histology showed less inflammatory cell infiltrates, intravascular thrombi, and hemorrhage in the 80‐hour survivor with the CO treatment than the 75‐hours non‐CO treatment. Anti–non‐Gal cytotoxicity levels did not affect the early loss of the grafts. Although CO treatment did not prolong overall xeno lung graft survival, the recipient/donor CO treatment helped to maintain platelet counts and inhibit TNF‐α and IL‐6 secretion at 2 hours after revascularization of grafts. In addition, lung xenografts that were received recipient/donor CO therapy demonstrated fewer macrophage and neutrophil infiltrates. Infiltrating macrophages as well as alveolar epithelial cells in the CO‐treated graft expressed heme oxygenase‐1.

Conclusion

Although further investigation is required, CO treatment may provide a beneficial strategy for pulmonary xenografts.     

Lung transplantation from donors outside standard acceptability criteria – are they really marginal?

Lung transplantation (LTx) from “extended donor criteria” donors may reduce significantly organ shortage. However, its influence on results remains unclear. In this study, we evaluate retrospectively the results of LTx from donors outside standard criteria: PaO2/FiO2 ratio < 300 mmHg, age over 55 years, and history of smoking > 20 pack‐years. Two hundred and forty‐eight patients underwent first time LTx in our institution between January 2007 and January 2013. Seventy‐nine patients (Group I) received organs from “extended donor criteria” and 169 patients (Group II) from “standard donor criteria.” Recipients' and donors' demographics, perioperative variables, and outcome were compared. Donors from Group I were significantly older [median (interquartile range)]: 52.5 (44;58) vs. 42 (28.5;48.5) years (P < 0.001) with lower PaO2/FiO2 ratio: 366 ± 116.1 455 ± 80.5 mmHg (P < 0.001), higher incidence of smoking history: 57.7% vs. 41.8% (P = 0.013), and more extensive smoking history: 24(15;30) vs. 10(3.75;14) pack‐years (P < 0.001). Other parameters were comparable. Recipients' gender, diagnosis, percentage of patients operated on pump and receiving double LTx were also comparable. Recipients from Group I were significantly older: 50 (42;57) vs. 44 (29.5;53.5) years (P = 001). There were no differences observed in recipients' prevalence of primary graft dysfunction (PGD) grade 3 over first three postoperative days, duration of mechanical ventilation, intensive care and hospital length of stay, prevalence of rejection, and bronchiolitis obliterans syndrome (BOS). 90‐day, 1‐year, and 5‐year survival (Group I vs. II) were also similar: 88.6% vs. 91.7%, 83.2% vs. 84.6%, and 59% vs. 68.2% (log rank P = 0.367). Carefully selected donor lungs from outside the standard acceptability criteria may expand existing donor pool with no detrimental effect on LTx outcome.     

Acute toxicities after proton beam therapy following breast‐conserving surgery for breast cancer: Multi‐institutional prospective PCG registry analysis

We investigated adverse events (AEs) and clinical outcomes for proton beam therapy (PBT) after breast‐conserving surgery (BCS) for breast cancer. From 2012 to 2016, 82 patients received PBT in the prospective multi‐institutional Proton Collaborative Group registry. AEs were recorded prospectively at each institution. Median follow‐up was 8.1 months. Median dose was 50.4 Gy in 28 fractions. Most patients received a lumpectomy bed boost (90%) and regional nodal irradiation (RNI)(83%). Six patients (7.3%) experienced grade 3 AEs (5 with dermatitis, 5 with breast pain). Body mass index (BMI) was associated with grade 3 dermatitis (P = .015). Fifty‐eight patients (70.7%) experienced grade ≥2 dermatitis. PBT including RNI after BCS is well‐tolerated. Elevated BMI is associated with grade 3 dermatitis.     

Treatment with 3‐aminobenzamide during ex vivo lung perfusion of damaged rat lungs reduces graft injury and dysfunction after transplantation

Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3‐Aminobenzamide (3‐AB), an inhibitor of poly(ADP‐ribose) polymerase (PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3‐AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3‐AB: 1 hour WI + 3 hours EVLP + 3‐AB (1 mg^.mL^?1) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin‐6 and 10 (IL‐6, IL‐10) in BAL and plasma. 3‐AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs. 3‐AB also attenuated the IL‐6/IL‐10 ratio in BAL and plasma, supporting an improved balance between pro‐ and anti‐inflammatory mediators. Thus, 3‐AB reconditioning during EVLP of rat lung grafts damaged by WI markedly reduces inflammation, edema, and physiological deterioration after LTx, supporting the use of PARP inhibitors for the rehabilitation of damaged lungs during EVLP.     

Intensivist‐Led Management of Brain‐Dead Donors Is Associated with an Increase in Organ Recovery for Transplantation

The disparity between the number of patients in need of organ transplantation and the number of available organs is steadily rising. We hypothesized that intensivist‐led management of brain dead donors would increase the number of organs recovered for transplantation. We retrospectively analyzed data from all consented adult brain dead patients in the year before (n = 35) and after (n = 43) implementation of an intensivist‐led donor management program. Donor characteristics before and after implementation were similar. After implementation of the organ donor support team, the overall number of organs recovered for transplantation increased significantly (66 out of 210 potentially available organs vs. 113 out of 258 potentially available organs, p = 0.008). This was largely due to an increase in the number of lungs (8 out of 70 potentially available lungs vs. 21 out of 86 potentially available lungs; p = 0.039) and kidneys (31 out of 70 potentially available kidneys vs. 52 out of 86 potentially available kidneys; p = 0.044) recovered for transplantation. The number of hearts and livers recovered for transplantation did not change significantly. Institution of an intensivist‐led organ donor support team may be a new and viable strategy to increase the number of organs available for transplantations.     

Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20‐Year Follow‐up at a Single Center

The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty‐four grafts were from donors after cardiac death (DCD) and 16 grafts from heart‐beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first‐time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post‐LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow‐up biopsies were performed 18–20 years post‐LTx (n = 10) and 6 years post‐LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20‐year follow‐up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool.     

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.     

Strategies for Maximizing Heart and Lung Transplantation Opportunities in Japan

Introduction

Because the donor shortage is extremely severe in Japan because of a strict organ transplantation law, special strategies must be established to maximize heart transplantation (HTx) and lung transplantation (LTx) opportunities. The purpose of this study was to review our strategies to identify and manage heart and lung donors.

Method

Transplantation doctors themselves assessed their own donor heart and lung function before starting the procurement operation; skillful staff surgeons harvested the organs. Since November 2002, a special transplantation consultant doctor assessed donor organ function to identify useful organs and intensively cared for the donor to improve cardiac and lung function.

Results

Only 63 brain-dead donors have been available in Japan. However, 49 HTx (77.7%) and 39 LTx (19 bilateral and 20 single) were performed from 36 donors (57.1%). Thirty-six HTx donors were marginal, requring sustained high doses of inotropes (n = 26), low left ventricular ejection fraction (n = 5), cardiopulmonary resuscitation (n = 15), and age older than 55 years (n = 6). Twenty LTx donors had infected sputa or showed pneumonia using chest X-ray. None of 49 HTx recipients died of primary graft failure (PGF). Patient survival at 3 years after HTx was 98.0%. Although 5/39 LTx died early, including 2 of PGF, patient survival rate at 3 years was 66.9%.

Conclusion

Although the number of cases was still small, the availability of hearts and lungs has been high and the transplantation outcomes were acceptable. These strategies may be useful to maximize HTx/LTx opportunities.     

In situ lung perfusion is a valuable tool to assess lungs from donation after circulatory death donors category I–II

Donations after circulatory death (DCD) lung grafts are an alternative to extend the donor pool in lung transplantation. This study investigates the use of an in situ lung perfusion system (ISLP) in the donor to evaluate category I–II lungs. Pigs were sacrificed by ventricular fibrillation. All animals underwent 20 min of cardiopulmonary resuscitation and 5 min hands‐off period after which heparin was administered. In group [WI‐1], this was followed by 1 h of warm ischemia (WI) and 2 h of topical cooling (TC). In group [WI‐2], 2 h of WI was followed by 1 h of TC. In group [WI‐0], there was a minimal period of WI and no TC. In all three groups, the lungs were then evaluated during 60 min with ISLP. [WI‐0] lungs showed a significantly higher compliance and Δ PO₂/FiO₂ compared with [WI‐1] and [WI‐2]. PaCO₂ and lactate production were higher in [WI‐2] versus [WI‐0]. Wet/Dry weight ratio was significantly higher in [WI‐2] compared with [WI‐0] in two lung biopsy locations. A high W/D weight ratio was correlated with a lower compliance, higher lactate production, and a higher PaCO₂. ISLP is an effective way to assess the quality of lungs from category I–II DCD donors.     

Complications of Living Donor Hepatic Lobectomy—A Comprehensive Report

A wider application of living donor liver transplantation is limited by donor morbidity concerns. An observational cohort of 760 living donors accepted for surgery and enrolled in the Adult‐to‐Adult Living Donor Liver Transplantation cohort study provides a comprehensive assessment of incidence, severity and natural history of living liver donation (LLD) complications. Donor morbidity (assessed by 29 specific complications), predictors, time from donation to complications and time from complication onset to resolution were measured outcomes over a 12‐year period. Out of the 760 donor procedures, 20 were aborted and 740 were completed. Forty percent of donors had complications (557 complications among 296 donors), mostly Clavien grades 1 and 2. Most severe counted by complication category; grade 1 (minor, n = 232); grade 2 (possibly life‐threatening, n = 269); grade 3 (residual disability, n = 5) and grade 4 (leading to death, n = 3). Hernias (7%) and psychological complications (3%) occurred >1 year postdonation. Complications risk increased with transfusion requirement, intraoperative hypotension and predonation serum bilirubin, but did not decline with the increased center experience with LLD. The probability of complication resolution within 1 year was overall 95%, but only 75% for hernias and 42% for psychological complications. This report comprehensively quantifies LLD complication risk and should inform decision making by potential donors and their caregivers.     

Five‐year follow‐up after live donor nephrectomy – cross‐sectional and longitudinal analysis of a prospective cohort within the era of extended donor eligibility criteria

To establish the outcome of live kidney donors 5 years after donation, we investigated the risk for progressive renal function decline and quality of life (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine, hypertension, QoL and survival were assessed in a prospective cohort of 190 donors, who donated between 2008 and 2010. Data were available for >90%. The mean age predonation was 52.8 ± 11.5 years, 30 donors having pre‐existent hypertension. The mean follow‐up was 5.1 ± 0.9 years. Eight donors had died due to non‐donation‐related causes. After 5 years, the mean eGFR was 60.2 (95% CI 58.7–62.7) ml/min/1.73 m², with a median serum creatinine of 105.1 (95% CI 102.5–107.8) μmol/l. eGFR decreased to 33.6% and was longitudinally lower among men than women and declining with age (P < 0.001), without any association on QoL. Donors with pre‐existent and new‐onset hypertension demonstrated no progressive decline of renal function overtime compared to nonhypertensives. No donors were found with proteinuria, microalbuminuria or at risk for end‐stage renal disease. After an initial decline postdonation, renal function remained unchanged overtime. Men and ageing seem to affect renal function overtime, while decreased renal function did not affect QoL. These data support further stimulation of living kidney donation programmes as seen from the perspective of donor safety.