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Background: Macrophages are involved in kidney transplants. The aim of the study was to investigate if changes exist in the levels of glomerular macrophage index (GMI) between two consecutive kidney transplant biopsies, and if so to determine their potential impact on graft survival. Methods: Two consecutive biopsies were performed on the same renal graft in 623 patients. GMI was categorized into three GMI classes: ≤1.8 Low, 1.9–4.5 Medium, and ≥4.6 High. This division yielded nine possible switches between the first and second biopsies (Low‐Low, Low‐Medium, etc.). Cox‐regressions were used and hazard ratios (HR) with 95% confidence interval (CI) are presented. Results: The worst graft survival was observed in the High‐High group, and the best graft survival was observed in the Low‐Low and High‐Low groups. Compared to the High‐High group, a reduction of risk was observed in nearly all other decreasing groups (reductions between 65% and 80% of graft loss). After adjustment for covariates, the risk for graft‐loss was lower in the Low‐Low (HR = 0.24, CI 0.13–0.46), Low‐Medium (HR = 0.25, CI 0.11–0.55), Medium‐Low (HR = 0.29, CI 0.11–0.77), and the High‐Low GMI (HR = 0.31, CI 0.10–0.98) groups compared to the High‐High group as the reference. Conclusions: GMI may change dynamically, and the latest finding is of most prognostic importance. GMI should be considered in all evaluations of biopsy findings since high or increasing GMI levels are associated with shorter graft survival. Future studies need to consider therapeutic strategies to lower or maintain a low GMI. A high GMI besides a vague histological finding should be considered as a warning sign requiring more frequent clinical follow up. [ABSTRACT FROM AUTHOR]

Background: Organ transplantation using grafts from elderly donors entails a higher risk for severe ischemia‐reperfusion injury (IRI). Advanced IRI after liver transplantation (LT) seems to be associated with the development of acute kidney injury (AKI). We studied if end‐ischemic hypothermic oxygenated machine perfusion (HOPE) of liver grafts, aimed at mitigating liver IRI, impacts on the frequency and severity of AKI after LT. Methods: LTs performed at our center between January 2017 and December 2022 using organs from deceased brain‐dead donors aged 70 or older were reviewed. From November 2020 on, HOPE was performed routinely in this donor category. The frequency and severity of AKI (KDIGO criteria) within 48 hours of graft reperfusion and the model of early allograft function (MEAF) were compared between HOPE‐LTs (n = 30) and control LTs (n = 71). Results: AKI developed in 23/30 (77%) HOPE‐LTs and in 40/71 (56%) control LTs (p = n.s.), with no difference in severity and timing between groups. Renal replacement therapy was required in 3/30 (10%) HOPE‐LTs and 6/71 (8%) control LTs. In addition, transaminase leak during the first week (marker of IRI) and MEAF were similar between groups. These findings persisted after propensity matching. Histology showed more hepatocyte vacuolization and higher Suzuki score in HOPE‐LTs. Although this analysis could have been underpowered, no trends supporting the benefit of HOPE on liver and renal injury after LT were ever identified. Conclusions: In conclusion, HOPE in this group of older donors does not seem to improve either graft IRI, or the incidence of early AKI after LT. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin A nephropathy (IgAN) and its systemic variant IgA vasculitis (IgAV) damage the glomeruli, resulting in proteinuria, hematuria and kidney impairment. Dendrin is a podocyte-specific protein suggested to be involved in the pathogenesis of IgAN. Upon cell injury, dendrin translocates from the slit diaphragm to the nucleus, where it is suggested to induce apoptosis and cytoskeletal changes, resulting in proteinuria and accelerated disease progression in mice. Here we investigated gene and protein expression of dendrin in relation to clinical and histopathological findings to further elucidate its role in IgAN/IgAV. Methods Glomerular gene expression was measured using microarray on 30 IgAN/IgAV patients, 5 patients with membranous nephropathy (MN) and 20 deceased kidney donors. Dendrin was spatially evaluated on kidney tissue sections by immunofluorescence (IF) staining (IgAN patients, n  = 4; nephrectomized kidneys, n  = 3) and semi-quantified by immunogold electron microscopy (IgAN/IgAV patients, n  = 21; MN, n  = 5; living kidney donors, n  = 6). Histopathological grading was performed according to the Oxford and Banff classifications. Clinical data were collected at the time of biopsy and follow-up. Results Dendrin mRNA levels were higher (P  = .01) in IgAN patients compared with MN patients and controls and most prominently in patients with preserved kidney function and fewer chronic histopathological changes. Whereas IF staining did not differ between groups, immunoelectron microscopy revealed that a higher relative nuclear dendrin concentration in IgAN patients was associated with a slower annual progression rate and milder histopathological changes. Conclusion Dendrin messenger RNA levels and relative nuclear protein concentrations are increased and associated with a more benign phenotype and progression in IgAN/IgAV patients. [ABSTRACT FROM AUTHOR]

Aim: To describe general observations of immunological reactions to foreign materials and to realize that CP titanium gives rise to a foreign body reaction with subsequent bone embedment when placed as oral implants. To analyse the possibility of titanium allergy. Materials and methods: The present paper is of a narrative review type. Hand and Medline searches were performed to evaluate marginal bone loss of oral implants and the potential of titanium allergy. Results: Immunological reactions to foreign substances include Type I hypersensitivity reactions such as allergy, Type II hypersensitivity reactions characterised by IgM or IgG antibodies that may react with blood group antigens at transfusion, and Type III hypersensitivity caused by antigen-antibody immune complexes exemplified by acute serum sickness. There is also Type IV hypersensitivity, or delayed hypersensitivity, which is typically found in drug and foreign body reactions. It proved very difficult to find a universally acceptable definition of reasons for marginal bone loss around oral implants, which lead to most varying figures of so-called peri-implantitis being 1% to 2% in some 10-year follow-up papers to between 28% and 56% of all placed implants in other papers. It was recognised that bone resorption to oral as well as orthopaedic implants may be due to immunological reactions. Today, osseointegration is seen as an immune-modulated inflammatory process where the immune system is locally either up- or downregulated. Titanium implant allergy is a rare condition, if it exists. The authors found only two papers presenting strong evidence of allergy to CP titanium, but with the lack of universally accepted and tested patch tests, the precise diagnosis is difficult. Conclusions: CP titanium acts as a foreign body when placed in live tissues. There may be immunological reasons behind marginal bone loss. Titanium allergy may exist in rare cases, but there is a lack of properly designed and analysed patch tests at present. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is frequent after liver transplantation (LT), with impact on graft function, morbidity and mortality. Although multifactorial, the pathophysiology of perioperative kidney injury remains unclear. Our aims were to analyze the frequency, evolution and risk factors for kidney impairment during the peri- and early post-operative period. In a prospective, single-center study of 27 adult patients undergoing first single-organ LT, we analyzed measured glomerular filtration rate (mGFR) pre-transplant, at post-operative day (POD) 10, and at 1, 3, 12 and 36 months. Kidney and liver graft biopsies were performed during LT. A median mGFR decline of 45% was detected from pre-transplant to POD 10, correlating strongly with the mGFR evolution from baseline to 12 months (rs = 0.80, p<.001) and baseline to 36 months (rs = 0.82, p<.001). AKI occurred in 59% of recipients within 48 h of LT, notably before the introduction of calcineurin inhibitors on POD 3. AKI was strongly associated with mGFR at 12 and 36 months. Kidney and liver graft biopsies showed only minor histological changes. Donor and recipient body mass index, recipient age, model of end-stage liver disease score, diagnosis of hepatitis C, donor cause of death, as well as bleeding, transfusions and duration of the anhepatic phase correlated with early kidney dysfunction. The greatest decline in mGFR was evident within 10 days and AKI within hours of LT, irrespective of baseline mGFR and before introduction of calcineurin inhibitors. Very early post-LT kidney injury has substantial consequences for long-term kidney function. [ABSTRACT FROM AUTHOR]

Introduction: The first live birth after uterus transplantation occurred in Sweden in 2014. Uterus transplantation has repeatedly, and at many centers worldwide, proven to be a feasible treatment for absolute uterine factor infertility. Hysterectomy in live donors and transplantation are well described in numerous reports. However, there are no reports of hysterectomy in the recipient after uterus transplantation, which will occur at either graft failure, after childbirth, or after numerous failed pregnancy attempts. We present the first report of hysterectomy in recipients after uterus transplantation with detailed analyses of findings in conjunction with graft failures. Material and Methods: An analysis of recipient hysterectomies (n = 10), performed in 2012–2020, was conducted. Data from the international uterus transplantation registry (ISUTx registry) were extracted, and medical records were systematically reviewed, to collect and compile characteristics of recipients and donors, as well as pre‐, per‐, and postoperative data, including clinical course of graft failures. Results: Hysterectomy in recipients was performed in conjunction with cesarean section (n = 3), 3–6 months after cesarean section (n = 3), or after failed pregnancy attempts (n = 1) or graft failure (n = 3). The durations of anesthesia (2 h 36 min to 7 h 35 min) and hysterectomy surgery (1 h 42 min to 5 h 52 min) ranged widely, with long perioperative interruptions for insertion of ureteral catheters in two cases. Adhesions to the uterus were abundant, the majority being mild. Three uteri that subsequently showed graft failure (hysterectomy at 1, 3, and 8 months post transplantation) showed histological signs of ischemia in biopsies taken 1‐week post‐transplant and early signs of central hypoperfusion by Doppler ultrasound. In these graft failure explants, there were no epithelial linings in the uterine cavity or in the cervix. The inner uterine wall was severely ischemic and/or necrotic, whereas outer parts were partly viable. There were signs of moderate atherosclerosis of uterine arteries but no rejection. Mild postoperative complications were frequent (6/10), with one supravaginal hematoma requiring surgical drainage. Conclusions: Hysterectomy after uterus transplantation is a complex and time‐consuming procedure, and perioperative ureteral catheters may be helpful. Histopathology of early cervical biopsies showing ischemic signs may indicate subsequent irreversible damage, leading to graft failure. [ABSTRACT FROM AUTHOR]

The acceptance of ABO-incompatible (ABOi) liver grafts will expand the donor pool for a patient in urgent need for a liver transplantation (LT). Here we report our results with emergency ABOi DD (deceased donor) LT using rituximab and antigen specific immunoadsorption. 2009 to 2019 we performed 20 ABOi DD LTs (adults n = 17, children n = 3) for patients in urgent need for a LT. Immunosuppression consisted of rituximab (n = 20) and basiliximab (n = 15) or anti-thymocyte globuline (n = 4), intravenous immunoglobulin (IVIG; n = 6), tacrolimus, prednisolone and mycophenolate mofetil. Fifteen patients were treated with IA (n = 14) or both IA and plasmapheresis (PP; n = 1) pre-transplant and 18 patients were treated with IA (n = 15) or both IA and PP (n = 3) post-transplant. The median pre-transplant MELD- score was 40 (range 18–40). Patient and graft survival and complications were compared to a 1:4 case matched control group of ABO-identical or compatible (ABOid/c) DDLT. The 1-, 3- and 5-year patient and graft survival rates were 85, 85 and 78% for the ABOi recipients and not significantly different compared to ABOid/c controls. Only one ABOi patient developed antibody-mediated rejection. Patient and graft survival after emergency ABOi DDLT using rituximab and immunoadorption was equal to ABOid/DDLT. ABOi DD LT was a successful approach to expand the donor pool for patients in urgent need for a liver graft. [ABSTRACT FROM AUTHOR]