Survival Advantage Comparing Older Living Donor Versus Standard Criteria Donor Kidney Transplants.

The aim of this analysis was to explore mortality outcomes for kidney transplant candidates receiving older living donor kidneys (age ≥60 years) versus younger deceased donors or remaining on dialysis. From 2000 to 2019, all patients on dialysis listed for their first kidney-alone transplant were included in a retrospective cohort analysis of UK transplant registry data. The primary outcome was all-cause mortality, with survival analysis conducted by intention-to-treat principle. Time-to-death from listing was modelled using nonproportional hazard Cox regression models with transplantation handled as a time-dependent covariate. A total of 32,978 waitlisted kidney failure patients formed the primary study cohort, of whom 18,796 (58.5%) received a kidney transplant (1,557 older living donor kidneys and 18,062 standard criteria donor kidneys). Older living donor kidney transplantation constituted only 17.0% of all living donor kidney transplant activity (overall cohort; n = 9,140). Recipients of older living donor kidneys had reduced all-cause mortality compared to receiving SCD kidneys (HR 0.904, 95% CI 0.845-0.967, p = 0.003) and much lower all-cause mortality versus remaining on the waiting list (HR 0.160, 95% CI 0.149-0.172, p < 0.001). Older living kidney donors should be actively explored to expand the living donor kidney pool and are an excellent treatment option for waitlisted kidney transplant candidates.

All Expanded Criteria Donor Kidneys are Equal But are Some More Equal Than Others? A Population-Cohort Analysis of UK Transplant Registry Data.

Survival outcomes for kidney transplant candidates based on expanded criteria donor (ECD) kidney type is unknown. A retrospective cohort study was undertaken of prospectively collected registry data of all waitlisted kidney failure patients receiving dialysis in the United Kingdom. All patients listed for their first kidney-alone transplant between 2000-2019 were included. Treatment types included; living donor; standard criteria donor (SCD); ECD60 (deceased donor aged ≥60 years); ECD50-59 (deceased donor aged 50-59 years with two from the following three; hypertension; raised creatinine and/or death from stroke) or remains on dialysis. The primary outcome was all-cause mortality, with time-to-death from listing analyzed using time-dependent non-proportional Cox regression models. The study cohort comprised 47,917 waitlisted kidney failure patients, of whom 34,558 (72.1%) received kidney transplantation. ECD kidneys (n = 7,356) were stratified as ECD60 (n = 7,009) or ECD50-59 (n = 347). Compared to SCD, both ECD60 (Hazard Ratio 1.126, 95% CI 1.093-1.161) and ECD50-59 (Hazard Ratio 1.228, 95% CI 1.113-1.356) kidney recipients have higher all-cause mortality. However, compared to dialysis, both ECD60 (Hazard Ratio 0.194, 95% CI 0.187-0.201) and ECD50-59 (Hazard Ratio 0.218, 95% CI 0.197-0.241) kidney recipients have lower all-cause mortality. ECD kidneys, regardless of definition, provide equivalent and superior survival benefits in comparison to remaining waitlisted.

Machine perfusion organ preservation: Highlights from the American Transplant Congress 2022.

The American Transplant Congress 2022, which took place between June 4th and June 8th of 2022, was a hybrid meeting with in-person attendance in Boston-MA and a real-time virtual experience via an online platform. First, we identified abstracts discussing machine perfusion preservation for all organs, a hot topic and approach that may develop into the new gold standard of organ preservation in the near future. A total of 39 abstracts on organ machine preservation were presented at the meeting. Next, we selected abstracts which focus on advances including new approaches to organ preservation, promising biomarkers, ex-situ treatment including cellular therapies, and novel research areas. Here, we summarized the latest developments on machine perfusion preservation in both experimental and clinical studies.

Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study.

INTRODUCTION: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model. METHODS: Ten paired pig forelimbs were used for this study, grouped as either limb-only (LO, n = 5) perfusion, or limb-kidney (LK, n = 5) perfusion. Infrared thermal imaging was used to determine homogeneity of perfusion. Lactate, bicarbonate, base, pH, and electrolytes, along with an inflammatory profile generated via the quantification of cytokines and cell-free DNA in the perfusate were recorded. RESULTS: The addition of a kidney to a limb perfusion circuit resulted in the rapid stabilization of lactate, bicarbonate, base, and pH. Conversely, the LO circuit became progressively acidotic, correlating in a significant increase in pro-inflammatory cytokines. Global perfusion across the limb was more homogenous with LK compared to LO. CONCLUSION: The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis.

Macroscopic assessment of the quality of cold perfusion after deceased-donor kidney procurement: A United Kingdom population-based cohort study.

Concern regarding the quality of cold perfusion (QOP) during macroscopic assessment of procured kidneys is a common reason for discard. In the UK, QOP is routinely graded by both retrieving and implanting teams during back-bench surgery as: 1 (good), 2 (fair), 3 (poor) or 4 (patchy). We evaluated the association of this grading with organ utilization, graft outcomes, and agreement between teams. Data on all deceased-donor kidneys procured between January 2000 and December 2016 were analyzed for discard rates, while association with graft outcomes was studied in single adult transplants. Of 31,167 kidneys procured, 90.6%, 5.7%, 1.7%, and 2.1% were assigned grades 1, 2, 3, and 4, respectively, at retrieval. QOP was an independent risk factor of discard, with the highest rates observed in grade 3 kidneys (41.8%), compared to 6.5% in grade 1 (aOR 7.67, 95% CI 5.44-10.82, p < .001). Grading at retrieval was an independent predictor of delayed graft function (p = .019) and primary non-function (p = .001), but not long-term graft survival (p = .111). Implanting grade was an independent predictor of all three outcomes (p < .001, p < .001, and p = .002, respectively). Consistency of grading between teams was poor (Kappa = 0.179). QOP influences utilization and predicts outcomes, but a standardized and validated scoring system is required.

Outcomes in Third and Fourth Kidney Transplants Based on the Type of Donor.

BACKGROUND: An increasing number of patients are requiring multiple retransplants. We assessed outcomes of third and fourth kidney transplants, to aid decision making on the most suitable donor type. METHODS: Data were collected retrospectively for 2561 transplants, including 69 third and 8 fourth, performed from 2000 to 2017. Demographics and outcomes for the combined third/fourth group were compared to first and second transplants. Within the third/fourth kidney transplant group, comparisons were made between deceased donors (n = 39), live donor HLA-compatible (n = 23) and -incompatible (n = 13) transplants, as well as between standard (n = 25) and extended-criteria (n = 14) deceased donor transplants. RESULTS: Patient survival did not differ significantly by transplant number (P = 0.532), whereas death-censored graft survival declined progressively, from 89% at 5 years in first, 85% in second and 74% in the third/fourth transplant group (P < 0.001). Within the combined third/fourth transplant subgroup, 5-year graft survival was found to be 100% in recipients of HLA-compatible live donors, compared to 75% in deceased donors and 53% in HLA-incompatible live donors, although this difference did not reach statistical significance (P = 0.083). No significant difference in patient survival (P = 0.356) or complication rates (P = 0.757) were detected between these groups. For recipients of deceased donors in the third/fourth transplant group, there were no significant differences between standard versus extended-criteria donors for any of the outcomes considered. CONCLUSIONS: Despite variable functional outcomes, third and fourth kidney transplant recipients experience comparable patient survival rates to first and second transplants, regardless of the donor type. In selected patients, HLA-incompatible live donors and extended-criteria deceased donors should be considered.

Does bicarbonate prevent contrast-induced nephropathy in cardiovascular patients undergoing contrast imaging?

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether administering sodium bicarbonate (NaHCO3) prevents contrast-induced nephropathy (CIN) in cardiovascular patients undergoing contrast imaging. In total, 266 papers were found using the reported search, 16 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. CIN is thought to occur as a result of ischaemic or oxidative injury to the kidney. It is postulated that NaHCO3attenuates this renal damage by alkanizing renal tubular fluid thus reducing the generation of contrast-induced free radicals, which damage the kidney. Of the 16 trials, 15 recruited patients with various degrees of renal dysfunction at baseline. The benefit of using NaHCO3 was demonstrated at all stages of chronic kidney disease. Apart from four studies, 12 studies used low toxicity, low-osmolar contrast. Merten et al. published the first trial of NaHCO3 vs (saline) NaCl in preventing CIN, demonstrated a significantly lower rate in the NaHCO3 group and advocated its widespread use. Subsequent trials using the same regimen have collaborated these results. However, more recently, Gomes et al. concluded that NaHCO3 is not superior to saline-based hydration. Similarly, Brar et al. randomized 323 patients with moderate-to-severe renal insufficiency to receive either an NaHCO3 or an NaCl infusion and observed no difference in CIN rates. Two studies investigated the effects of rapid urine alkanization with bolus injections of NaHCO3 prior to contrast and found significant reductions in CIN rates compared with NaCl-treated groups. One study observed that NaCl is superior to NaHCO3, while all other studies showed a beneficial effect or no difference between NaCl- and NaHCO3-based hydration. The most recent meta-analysis by Jang et al. incorporated 3609 patients across 19 trials and concluded that NaHCO3-based hydration regimens are superior to NaCl-based ones. Based on this review, the authors recommend NaHCO3 alongside an NaCl hydration regimen. The exact regimen will depend on the context within which contrast is being administered and needs further evaluation.

What is the role of screening in the management of abdominal aortic aneurysms?

A best-evidence topic in vascular surgery was written according to a structured protocol. The question addressed was whether screening asymptomatic individuals for an abdominal aortic aneurysm (AAA) is feasible and improves disease-free survival. Seven studies presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and limitations of the studies are tabulated. In total, four randomized population-based studies have evaluated ultrasound screening for AAA: two British studies, Multicentre Aneurysm Screening Study (MASS) and the Chichester trial, and one each in Viborg County, Denmark and Western Australia. Participants were randomized to receive an invitation to screen or not. The MASS trial randomized 67 770 men, followed participants over 10 years and concluded that screening would almost half AAA-related deaths in men aged 65-74 years. The smaller Chichester trial included only 6040 men but demonstrated a 42% reduction in AAA-related mortality at 5 years, with ongoing benefit at 15 years (11% reduction). The Viborg County trial recruited 12 639 men aged 64-73 years, showed a 66% reduction in AAA-related mortality over 14 years. Finally, the Western Australia trial evaluated 41 000 men but included an older population of 65-83 years old. No benefit was seen in this age group but subgroup analysis of men aged 65-74 showed a significant mortality benefit. Only a small or insignificant benefit in all-cause mortality was seen in any of these studies. A recent meta-analysis of these trials has shown a significant benefit in AAA-related mortality in the long term and concluded that AAA screening is superior to other established screening programmes. The cost-effectiveness of screening was assessed in the MASS and Viborg County trials and was found to be substantially below the cost threshold set by the National Institute of Clinical Excellence for acceptance of interventions. Quality of life was assessed in the MASS and in a case-control study and showed no adverse effects that outweigh the benefits. We concluded that ultrasound screening for AAAs has met all the criteria to become a screening programme and would substantially reduce disease-related death with no adverse effect on quality of life.