Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles.

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI

Cytomegalovirus seroprevalence among solid organ donors in hungary: correlations with age, gender, and blood group

BACKGROUND: Cytomegalovirus (CMV) is endemic throughout the world, affecting most of the population, but the seroprevalence of CMV is known to vary among countries. CMV causes a mild infection in persons with intact immunity; however, CMV infection in organ transplantation is associated with significant morbidity and mortality. The present retrospective study was designed to evaluate the age-, gender-, and blood group-adjusted CMV seroprevalence among solid organ donors, representing fairly the overall Hungarian population (according to Hungarian Central Statistic Institute). This information is important for calculating risk-factors for CMV-seronegative recipients. No nationwide estimates of CMV seroprevalence in Hungary (as a representative of Eastern Middle Europe) have been published yet. METHODS: We investigated 2070 organ donors for CMV seroprevalence by measuring the CMV-specific immunoglobulin G. The donors were divided into 3 age groups (2-20, 21-50, and 51-70 years old). A study was also conducted on a fourth group consisting of 200 residents from an old age home. CMV seroprevalence differences were searched according to age-, gender- and blood-group distribution. RESULTS: The CMV seroprevalence of organ donors is 85% and of all investigated persons is 86%. The age-specific prevalence increases, starting from 72% in the first group to 99% in the fourth group. Seroprevalence of females was found to be significantly higher than of males (P = .0001). CONCLUSION: We have shown that the overall CMV seroprevalence in the Hungarian population is moderately high at 86%. The opportunity for CMV-seronegative recipients to get a graft from a seronegative donor is statistically only 2%. The seroprevalence of the youngest age group is 72% and so it can be concluded that the Hungarian population acquires the infection mainly in childhood or in the early adulthood. Female gender is a risk factor for CMV infection. This fact must be taken into consideration during the planning of patients' follow-up, prophylaxis, and therapy

Antioxidant and antiapoptotic activities of deprenyl and estradiol co-administration in aged rat kidney

Aging is a progressive degeneration process in living organisms. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has antioxidant, antiapoptotic and neuroprotective effects. Estradiol is also a neuroprotective and antioxidant hormone. The objective of this study was to determine whether the antioxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat kidney. Wistar Albino female rats were divided into six groups as follows; young (3 months old) control, aged (24 months old) control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and sham. All rats except for the sham group were injected for 21 days. Determination of oxidative stress parameter was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining and caspase-3 immunohistochemistry were performed. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation relative to aged control and sham-injected rats. The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. Deprenyl and estradiol replacement attenuated age-related changes in renal morphology. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat kidney by decreasing oxidative stress