Malignant Tumors Identified in Adult Polycystic Kidney Disease Can Be Derived from Both Proximal Tubular and Distal Tubular Origins.

Unlabelled: Adult polycystic kidney disease (APKD) is a genetic disorder leading to premature renal dysfunction and failure. The prevalence of malignant renal tumors occurring in the APKD setting has been rarely reported.

Objective: To better characterize malignant renal tumors in nephrectomy specimens of APKD and apply modern pathologic evaluation.

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

Objective: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli.

Methods: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22).

Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

Background: Collapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear.

Methods And Results: Patient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection.

Clarithromycin-Associated Acute Liver Failure Leading to Fatal, Massive Upper Gastrointestinal Hemorrhage from Profound Coagulopathy: Case Report and Systematic Literature Review.

While erythromycin has caused numerous cases of acute liver failure (ALF), clarithromycin, a similar macrolide antibiotic, has caused only six reported cases of ALF. A new case of clarithromycin-associated ALF is reported with hepatic histopathology and exclusion of other etiologies by extensive workup, and the syndrome of clarithromycin-associated ALF is better characterized by systematic review. A 60-year-old nonalcoholic man, with normal baseline liver function tests, was admitted with diffuse abdominal pain and AST = 499 U/L and ALT = 539 U/L, six days after completing a 7-day course of clarithromycin 500 mg twice daily for suspected upper respiratory infection.

Defective CD8 Signaling Pathways Delay Rejection in Older Recipients.

CD8+ T cells play a cardinal feature in response to alloantigens and are able to generate effector/memory T cells independently from CD4+ T cells. To investigate the impact of aging on CD8 T cells, we used a fully mismatched mouse skin transplant model. Our findings showed a prolonged allograft survival in older recipients associated with a significant increase of CD4+ and CD8+ CD44high CD62Llow effector/memory T cells and a reduced systemic IFNγ production.

Animal models of chronic allograft injury: contributions and limitations to understanding the mechanism of long-term graft dysfunction.

Advances in immunosuppression have reduced the incidence of acute graft loss after transplantation, but long-term allograft survival is still hindered by the development of chronic allograft injury, a multifactorial process that involves both immunologic and nonimmunologic components. Because these components become defined in the clinical setting, development of animal models enables exploration into underlying mechanisms leading to long-term graft dysfunction. This review presents animal models that have enabled investigation into chronic allograft injury and discusses pivotal models currently being used.

Prolonged graft survival in older recipient mice is determined by impaired effector T-cell but intact regulatory T-cell responses.

Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4(+) T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4(+)CD44(high)CD62L(low)).

Impact of innate and adaptive immunity on rejection and tolerance.

Until recently, research on transplantation rejection and tolerance has been directed toward deciphering the mechanisms of the adaptive immune system. However, the emergence that the innate immune system, the body's first-line defense against pathogens, has a strong influence on adaptive immunity has galvanized interest in elucidating the interplay between these two arms of the immune system. The discovery of Toll-like receptors and the characterization of the cellular mediators involved in innate immunity have provided growing evidence that innate immunity affects the adaptive immune response.