Search Results (4)

Kidney transplantation is the best treatment for end-stage renal disease since it offers the greatest survival benefit compared to dialysis. The gap between the number of renal transplants performed and the number of patients awaiting renal transplants leads to a steadily increasing pressure on the scientific community. Kidney preimplantation biopsy is used as a component of the evaluation of organ quality before acceptance for transplantation. However, the reliability and predictive value of biopsy data are controversial. Most of the previously proposed predictive models were not associated with graft survival, but what has to be reaffirmed is that histologic examination of kidney tissue can provide an objective window on the state of the organ that cannot be deduced from clinical records and renal functional studies. The balance of evidence indicates that reliable decisions about donor suitability must be made based on the overall picture. This work discusses recent trends that can reduce diagnostic timing and variability among players in the decision-making process that lead to kidney transplants, from the pathologist’s perspective. Full article

Background: Kidney allografts with the presence of diffuse glomerular fibrin thrombi are typically rejected by most centers due to concern for poor allograft outcomes in the recipients. The aim of this study was to report our single center experience in the use of such deceased donor allografts. Methods: Retrospective single-center cohort study of kidney transplant recipients who received deceased donor allografts with moderate-to-severe diffuse glomerular fibrin microthrombi on the pre-implantation biopsy. Results: Three adult recipients received deceased donor kidney transplantation from donation after circulatory death donors. One patient was pre-emptive to dialysis at the time of transplant. The donors had moderate-to-severe diffuse glomerular fibrin thrombi on preimplantation biopsies with no evidence of cortical necrosis. Mean follow-up period was 196 days. None of the recipients developed delayed allograft function. The mean 3-month and 6-month creatinine were 1.6 and 1.5 mg/dL, respectively, with corresponding mean eGFRs (estimated glomerular filtration rates) of 45.7 and 47.3 mL/min/1.73m². Conclusions: After excluding significant cortical necrosis by experienced transplant renal pathologist, otherwise transplantable kidney allografts with diffuse fibrin thrombi may be successfully transplanted in renal transplant recipients with good renal outcomes. Full article

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A_2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A_2AR expression and PKA pathway were enhanced in DD kidneys. A_2AR gene expression correlated with TGF-β1 and other profibrotic markers, as well as CD163, C/EBPβ, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-β1 and A_2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A_2AR, which induces the M2 phenotype increasing CD163 and TGF-β1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A_2AR expression, which would activate the PKA–CREB axis, inducing the macrophage M2 phenotype, TGF-β1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A_2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and presents with genetic and clinical heterogeneity. ADPKD can also manifest extra-renally, and seminal cysts have been associated with male infertility in some cases. ADPKD-linked male infertility, along with female age, have been proposed as factors that may influence the clinical outcomes of preimplantation genetic testing (PGT) for monogenic disorders (PGT-M). Large PGT for aneuploidy assessment (PGT-A) studies link embryo aneuploidy to increasing female age; other studies suggest that embryo aneuploidy is also linked to severe male-factor infertility. We aimed to assess the number of aneuploid embryos and the number of cycles with transferable embryos in ADPKD patients after combined-PGT. The combined-PGT protocol, involving PGT-M by PCR and PGT-A by next-generation sequencing, was performed in single trophectoderm biopsies from 289 embryos in 83 PGT cycles. Transferable embryos were obtained in 69.9% of cycles. The number of aneuploid embryos and cycles with transferable embryos did not differ when the male or female had the ADPKD mutation. However, a significantly higher proportion of aneuploid embryos was found in the advanced maternal age (AMA) group, but not in the male factor (MF) group, when compared to non-AMA and non-MF groups, respectively. Additionally, no significant differences in the percentage of cycles with transferable embryos were found in any of the groups. Our results indicate that AMA couples among ADPKD patients have an increased risk of aneuploid embryos, but ADPKD-linked male infertility does not promote an increased aneuploidy rate. Full article