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Severe acute respiratory syndrome coronavirus 2 is associated with high mortality among transplant recipients. Comparative data that define humoral responses to the Oxford-AstraZeneca (AZ) and BNT162b2 (Pfizer-BioNTech) vaccines are limited.We recruited 920 kidney transplant patients receiving at least 1 dose of severe acute respiratory syndrome coronavirus 2 vaccine, excluding patients with virus pre-exposure. Serological status was determined with the COVID-SeroKlir ELISA (Kantaro-EKF Diagnostics). Patients with a corrected antibody level of0.7 AU/mL were considered seronegative.Four hundred ninety-five AZ and 141 Pfizer patients had a sample analyzed after first dose and 593 after second dose (346 AZ versus 247 Pfizer). After first dose, 25.7% of patients seroconverted (26.6% AZ, 22.8% Pfizer). After second dose, 148 (42.8%) of AZ seroconverted compared with 130 (52.6%) of Pfizer (P = 0.02; hazard ratio, 1.48; 95% confidence interval, 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have significantly higher response than AZ patients (median 2.6 versus 1.78 AU/mL, P = 0.005).Patients on mycophenolate had a reduced seroconversion rate (42.2% versus 61.4%; P0.001; hazard ratio, 2.17) and reduced antibody levels (0.47 versus 1.22 AU/mL, P = 0.001), and this effect was dose dependent (P = 0.05). Prednisolone reduced the seroconversion from 58.2% to 43.6% (P = 0.03) among Pfizer but not AZ recipients. Regression analysis showed that antibody levels were reduced by older age (P = 0.002), mycophenolate (P0.001), AZ vaccine (versus Pfizer, P = 0.001), and male gender (P = 0.02). Sixteen of 17 serious postvaccine infections occurred to patients who did not seroconvert.Both seroconversion and antibody levels are lower in AZ compared with Pfizer vaccinated recipients following 2 vaccine doses. Mycophenolate was associated with lower antibody responses in a dose-dependent manner. Serious postvaccine infections occurred among seronegative recipients.

Contains fulltext : 229465.pdf (Publisher’s version ) (Closed access) BACKGROUND: Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS: This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO(2)), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS: Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m(2) (SD 19·3) in the HMPO(2) group versus 46·7 mL/min per 1·73m(2) (17·1) in HMP (mean difference 3·7 mL/min per 1·73m(2), 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO(2) group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO(2) (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). INTERPRETATION: HMPO(2) of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO(2) and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO(2) were suggested by analysis of secondary outcomes. FUNDING: European Commission 7th Framework Programme.

Background Postoperative infection after hand-assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. Methods Eligible donors were randomly and blindly allocated to preoperative single-dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days, including surgical site infection (SSI), urinary tract infection (UTI), and lower respiratory tract infection (LRTI). Findings In all, 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). Among them, 99% (291/293) completed follow-up. The total infection rate was 40.7% (59/145) in the placebo group and 23% (34 of 148) in the antibiotic group (P = 0.001). Superficial SSIs were 20.7% (30/145 patients) in the placebo group versus 10.1% (15/148 patients) in the antibiotic group (P = 0.012). LRTIs were 9% (13/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.046). UTIs were 4.1% (6/145) in the placebo group and 3.4% (5/148) in the antibiotic group (P = 0.72).Antibiotic prophylaxis conferred a 17.7% (95% confidence interval 7.2%-28.1%), absolute risk reduction in developing postoperative infection, with 6 donors requiring treatment to prevent 1 infection. Interpretation Single-dose preoperative antibiotic prophylaxis dramatically reduces post-HALDN infection rates, mainly impacting SSIs and LRTIs.

The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients. Methods Patients 60 years or older who received transplants from DCD donors 60 years or older, between February 2010 and January 2014, were identified from a prospectively maintained database. Results Over a 4-year period, 88 patients 60 years or older received DCD kidney transplants from donors 60 years or older. Of these 44 (55%) were 60 to 69 years old and 40 (45%) were 70 years or older. Median follow up was 63 months. Patient survival was 95% and 79% at 1 and 5 years, respectively, with a survival in those 70 years and older (69%) compared with those aged 60 to 69 (88%) years (P = .01). Censored for death graft survival was 94% and 80% at 1 and 5 years, respectively. Median estimated glomerular filtration rate at 12 months and 36 months was 36 mL/min (range, 11–70 mL/min) and 39.5 mL/min (range, 11–77 mL/min), respectively. Conclusions Older DCD kidneys, when transplanted into older recipients, result in good patient and graft survival and an acceptable graft function, especially considering their age. This represents a good use of this organ resource.

We aimed to analyse the efficacy of the Thymoglobulin dose used for induction in controlled DCD kidneys, and its initial impact on blood cell and CD3 count, as predictors of efficacy.140 DCD patients who received ATG induction, were analysed. Intended dose was 1.25 mg/kg/day over 5 days, rounded to nearest 25 mg and not exceeding 125 mg/dose. Outcomes included the total dose in relation with rejection, DGF, graft survival, eGFR. The cell count response to ATG was assessed as predictors of outcome.Graft survival, was 96.2%, 92.4%, 85% at 1, 3 and 5 years. Rejection was 7% at 1 year and associated with eGFR at 3 (p = 0.003) and 5 years. ATG dose was not predictive of rejection but was associated with the day5 leucocyte and lymphocyte count (p 0.001) and negatively with DGF (p = 0.05). In 31 patients day3 CD3 count was available and it was associated with rejection (p = 0.002), less DGF (p = 0.09), and 3 years eGFR (p = 0.01).Thymoglobulin provides excellent results in DCD kidneys that do not significantly differ with small dose variations. In higher doses it reduces DGF. Lymphocytes and CD3 count, may be useful surrogate markers of efficacy and outcome.

Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.

BackgroundSocioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion.MethodsThe Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes.ResultsPeritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the ‘Education’ domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced ‘2 or more peritonitis’ episodes ( p = 0.04) and were hospitalized for antibiotics ( p = 0.02).ConclusionThis study has shown that patients who live in more ‘educationally’ deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.

Background Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Methods Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Results Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5–79) and 42 (range, 15–85) mL/min compared with SKT of 35 (range, 10–65) and 32 (range, 6–65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% ( P = .52), and patient survival was 94% and 98%, respectively ( P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Conclusions Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission.

In a prospective case-control study we investigated the association of a common polymorphism of the interleukin 1 receptor antagonist gene (IL-1 RA) with the occurrence and the clinical characteristics of polycystic ovary syndrome (PCOS). Allele frequencies did not vary statistically significantly among women with PCOS and healthy controls or within the PCOS group with respect to their clinical characteristics.

The insulin-like growth factor binding protein (BP) secreted by bovine kidney (MDBK) cells has been purified by affinity chromatography on a rat IGF-2 Sepharose column. Purified BP migrated as a single band of Mr 40,000 upon SDS polyacrylamide gel electrophoresis. An N-terminal sequence of 53 residues was obtained which was very similar up to residue 21 to the corresponding rat BRL-3A BP sequence. In competitive binding experiments with bovine IGF-1 and IGF-2, and recombinant human IGF-1, BP had a similar affinity for these ligands when IGF-1 tracer was used, but a higher affinity for IGF-2 with IGF-2 as radioligand. The N-terminal destripeptide truncated form of bovine IGF-1, which has enhanced biological activity, was found to have a markedly reduced affinity for BP compared to intact IGF-1. The increased bioactivity of destripeptide IGF-1 can be explained by this reduced affinity for BP.

Pancreatitis following kidney transplantation was first described by Starzl in 1964 [19]. The incidence rate of the disease involving severe complications ranges from 1.2 to 6.8%. The number of risk factors, besides those of the normal population, is increased by a number of other factors, i.e. uremia, disorder of lipid metabolism, polycystic kidney, immunosuppressive drugs, cytomegalovirus infection, etc. The mortality of acute pancreatitis in a kidney transplant patient is, in spite of treatment with the most up-to-date methods, is much higher (53-60%) than that for a non-transplant patient. In the period between 27 June 1991 and 31 December 2000 the number of cadaver kidney transplants performed in the Transplantation Division of the 1st Department of Surgery of the Medical and Health-Science Centre of the University of Debrecen was 349. During this period 9 incidences of acute pancreatitis were found in 8 patients. The frequency of incidence was 2.56%. In the present communication we analyse the prognosis of 9 kidney transplant patients, with special respect to immunosuppression.One patient was administered Cyclosporin alone, four were given Cyclosporin and Steroids, a further one Cyclosporin, Steroids and Azathioprine, the remaining three were treated with Cyclosporin, steroids and Mycophenolate Mophetil. In six cases out of nine multiorgan insufficiency (kidney, lung, liver) was encountered on presentation, three cases were accompanied by peritonitis. In spite of early jejunal nutrition, intensive therapy, antibiotic treatment, CT monitoring, if needed, necrectomy and oncotomy, three of our patients died from multiorgan insufficiency induced by septico-toxic state (mortality 33.3%). Other six patients recovered.The mortality rate of acute pancreatitis is much higher in immunosuppressed patients. The role of the etiological factors is not unequivocal in the development of pancreatitis. Nevertheless, all possible risk factors have to be taken into consideration when starting the immunosuppressive treatment of transplant patients and during their follow-up. By optimally adjusting the immunosuppressants we can decrease the risk of pancreatitis, however, the prognosis of the diseases, in agreement with the data in the literature, cannot be considerably improved even with the most up-to-date methods.

The evidence to date suggests that vaping is not a safe alternative to smoking tobacco. This, coupled with the worrying trend of young nonsmokers being attracted to vaping, raises fears of yet another generation suffering from chronic lung disease and other acute and chronic health conditions. Finally, due to the insufficient regulations in several countries, up-to-date data on the prevalence of e-cigarette use and studies on the health's implications of their use are urgently needed to inform policy at a national and international level (ie, European Union). Pediatricians are typically on the front line for identifying emerging risks for children and adolescents ; therefore, they may effectively help increase awareness about the potential danger of vaping on health. Information on the use of vaping devices should be implemented worldwide and included in public health information and prevention programs.