Antibody Mediated Rejection in Kidney Transplant Recipients

Antibody mediated rejection (ABMR) presents a significant challenge for long term graft survival in kidney transplantation. New technologies, including genomic studies and assays to detect and define donor-specific antibodies, have provided important insights into the pathophysiology and diagnosis of ABMR. Unfortunately, this progress has not yet translated into better outcomes for patients, as in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. This chapter reviews the current understanding of ABMR, and details its diagnosis, and treatments, both those established in current routine clinical practice and those on the horizon

Primerjava incidence črevesnih tumorjev povzročenih z 1,2-dimetilhidrazinom med sevoma podgan Wistar in Fischer

Background. Many investigators have observed differences in the susceptibilityto induce intestinal tumors by 1,2-dimethylhydrazine (DMH) between various strains of rodents. The results are difficult to compare because of the different regimes used for induction. The purpose of our study was to evaluate the influence of strain on DMH-induced intestinal tumors between Wistar and Fischer rats. Materials and rreethods. We used 29 Fischer and 30 Wistar male rats that were injected subcutaneously DMH, weekly, at a dosage of 25 mg/kg-body weight for 20 weeks. After 25 weeks from the beginningof the experiment, the animals were sacrificed and autopsied. The complete length of colorectum and all macroscopic changes were examined histologically. Results. The induction of intestinal tumors was 97% in Fischerrats and 100% in Wistar rats. In Wistar rats 184 tumors were found: 133adenomas, 50 tubular adenocarcinomas and 1 signet-cell carcinoma. 77% of careinamas were found in colorectum and 23% in the small intestine. In Fiseherrats, 126 tumors were found: 94 adenomas, 26 tubular adenocarcinomas, 5signet-cell carcinomas and 1 mucinous carcinoma42% of carcinomas were foundin the colorectum and 58% in the small intestine. The strain difference in the incidence of all induced tumors was statistically significant (P=0.001). The differences in the occurrence of the malignant and benign tumors was also significant (P<0.001P=0.011). Extra intestinal tumors were not found. Conclusions. Wistar rats showed greater percentage of colorectal tumors, and also the distribution of tumors in colorectum resembled more the distribution found in human pathology. That is why we reeommend Wistar rat rather than Fischer rat for the research work on the colorectal tumors.Izhodišče. Pri eksperimentalni indukciji intestinalnih tumorjev z 1,2-dimetilhidrazinom (DMH) so raziskovalci opazovali različno občutljivost posameznih sevov podgan. Rezultate je težko primerjati zaradi uporabe različnih režimov indukcije. Naš namen je bil oceniti vpliv sevov Wistar in Fischer podgan na indukcijo intestinalnih tumorjev z DMH. Materiali in metode.Uporabili smo 29 samcev seva Fischer in 30 samcev seva Wistar. Crevesnetumorje smo inducirali s podkožno aplikacijo DMH v dozi 25 mg/kg, enkrat tedensko, 20 tednov zapored. Po 25 tednih smo živali žrtvovali in jih obducirali. Histološko smo ovrednotili vse makroskopske najdbe ter celotno dolžino debelega črevesa. Rezultati. Indukcija črevesnih tumorjev je uspela pri 97% živali seva Fischer in 100% seva Wistar. Pri sevu Wistar smo našli 184tumorjev, od tega 133 adenomov, 50 tubulnih adenokarcinomov in 1 pečatnocelični karcinom77% karcinomov smo našli v kolorektumu, 23% pa v tankem črevesu. Pri sevu Fischer smo našli 126 tumorjev, od tega 94 adenomov, 26 tubulnih adenokarcinomov, 5 pečatnoceličnih karcinomov in 1 mucinozni karcinom. V tankem črevesu smo našli 58% karcinomov, 42% pa v kolorektumu. Zunajčrevesnih tumorjev nismo našli pri nobenem sevu. Razlika med sevoma v pojavnosti vseh črevesnih tumorjev je bila statistično značilna (P=0,001). Značilni sta bili tudi razliki v pojavnosti malignih (P<0,001) in benignih (P=0,011) tumorjev. Zaključki. Pri živalih seva Wistar smo ugotovili statistično značilno večjo pojavnost tumorjev debelega črevesa. Tudi razporeditev tumorjev v debelem črevesu pri sevu Wistar je bila bolj podobna razporeditvi pri človeku. Zato se nam zdi sev Wistar primernejši kot sev Fischer za eksperimentalni model za študije tumorjev debelega črevesa

Viral Infections after Kidney Transplantation: CMV and BK

Opportunistic infections commonly occur during the first 6 months after kidney transplant, including cytomegalovirus (CMV) and polyomaviruses. Viral pathogens such as CMV and polyomaviruses, JC or BK virus (BKV), are able to replicate in the kidney and/or cause systemic disease, and symptomatic infection with these agents can be associated with significant morbidity and mortality in immunocompromised host. While BK virus usually replicates in kidney transplant causing BK virus nephropathy (BKN) with characteristic decoy cells in the urine, CMV infection more often leads to systemic infection involving the gastrointestinal tract (GIT), lungs, or liver and can only sporadically be detected in renal transplant. In both cases, the disease is most often due to reactivation of a latent virus. Prevention and early treatment of posttransplant infection are therefore crucial with kidney transplant recipients. Since BKV viruria and viremia can be seen without renal injury and viral nephropathy, a diagnosis of BKN must be confirmed by renal biopsy. To date, preemptive treatment is the best strategy for CMV infection, while no available standard therapy, except for reduction of immunosuppression, is available for BKV infection

Pathophysiological Changes and Systemic Inflammation in Brain Dead Organ Donors: Effect on Graft Quality

Transplantation is the definitive treatment of end-stage organ disease. As the shortage of suitable organs poses its main limitation, the active management of potential organ donors becomes increasingly more important. The majority of solid organs are still obtained from donors after confirmed brain death. Brain death is the complete and irreversible cessation of all brain functions, and triggers a variety of severe pathophysiological changes in cardiovascular, hormonal and metabolic status that can result in organ damage. Moreover, brain death is associated with massive inflammatory response with a cytokine storm and complement activation that increases graft immunogenicity and adversely affects graft survival. Organs from brain-dead donors are more prone to graft dysfunction and rejection when compared to organs obtained from living donors. Brain death is thus believed to be an important risk factor influencing the quality of organs before procurement

The role of IgA in the pathogenesis of IgA nephropathy

Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans, predominantly present in the mucosal areas where its main functions are the neutralization of toxins, prevention of microbial invasion across the mucosal epithelial barrier, and simultaneous maintenance of a physiologically indispensable symbiotic relationship with commensal bacteria. The process of IgA biosynthesis, interaction with receptors, and clearance can be disrupted in certain pathologies, like IgA nephropathy, which is the most common form of glomerulonephritis worldwide. This review summarizes the latest findings in the complex characteristics of the molecular structure and biological functions of IgA antibodies, offering an in-depth overview of recent advances in the understanding of biochemical, immunologic, and genetic factors important in the pathogenesis of IgA nephropathy

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned

The Role of IgA in the Pathogenesis of IgA Nephropathy

Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans, predominantly present in the mucosal areas where its main functions are the neutralization of toxins, prevention of microbial invasion across the mucosal epithelial barrier, and simultaneous maintenance of a physiologically indispensable symbiotic relationship with commensal bacteria. The process of IgA biosynthesis, interaction with receptors, and clearance can be disrupted in certain pathologies, like IgA nephropathy, which is the most common form of glomerulonephritis worldwide. This review summarizes the latest findings in the complex characteristics of the molecular structure and biological functions of IgA antibodies, offering an in-depth overview of recent advances in the understanding of biochemical, immunologic, and genetic factors important in the pathogenesis of IgA nephropathy

The role of immune-related miRNAs in the pathology of kidney transplantation

MicroRNAs (miRNAs) are members of the non-coding regulatory RNA family that play pivotal roles in physiological and pathological conditions, including immune response. They are particularly interesting as promising therapeutic targets, prognostic and diagnostic markers due to their easy detection in body fluids and stability. There is accumulating evidence that different miRNAs provide disease-specific signatures in liquid samples of distinct kidney injuries. Using experimental models and human samples, there have been numerous suggestions that immune-related miRNAs are also important contributors to the development of different kidney diseases as well as important markers for monitoring response after kidney transplantation. However, there are limited data for understanding their function in the molecular pathways of allograft pathologies. In our review, we focused on microRNAs that are related to different aspects of immune response after kidney transplantation