At the moment it is unknown to what extent the impaired function of T lymphocytes in ESRD patients depends on uremia, and to what extent on hemodialysis (HD) procedure. Therefore, the purpose of the study was to evaluate percentages of T lymphocyte subpopulations ex vivo, plasma concentrations of IL12p70, TNF, IL-10, IL-6, IL-1β, IL-8 cytokines and selected proliferation parameters of in vitro activated T lymphocytes in HD patients before and after single HD procedure using flow cytometry. We demonstrated that the percentage of CD8+ cells ex vivo was decreased while the CD4+/CD8+ ratio was increased after HD procedure. Also, there was significant decrease in the percentage of CD8+HLA-DR+, CD8+CD69+ and CD8+CD95+ cells after HD. At the same time, an increase in the percentage of CD4+CD95+ cells was observed after HD. From all analyzed cytokines, only the concentration of IL-8 was significantly decreased after HD procedure. A single HD session enhanced proliferation capacity of CD4+ cells but not CD8+ cells in vitro by increasing number of cell divisions and percentage of dividing cells. Our results show that a single hemodialysis can have immunomodulatory effect on HD patients and may contribute to the state of immune deficiency observed in patients with ESRD.

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Background/Aims: This retrospective study analysed hypertension management and adherence to blood pressure (BP) targets among renal transplant recipients (RTRs) under specialized care in the Outpatient Transplantation Unit in the Department of Nephrology, Transplantology and Internal Medicine at Gdansk University Hospital. Methods: Medical records of 101, 316, 639 and 818 RTRs diagnosed with hypertension, who received outpatient care in 2001, 2006, 2011 and 2014, respectively were analysed in four independent cross-sectional surveys. All RTRs received antihypertensive regimens. Results: The overall most commonly used antihypertensive agents were beta-blockers (BB) (range 66.3-82.5%) followed by calcium channel blockers (CCB) (range 52.8-64.2%). Whilst a significant, upward tendency of BB usage (p<0.01) was observed, CCB usage (p<0.001) displayed a downward tendency as a first line therapy in the subsequent years. The average number of antihypertensive agents used per patient increased significantly from 2.24±1.03 in 2001 to 2.55±1.25 in 2014 (p<0.05). The most frequently used combination of hypotensive therapy consisted of two or three antihypertensive drugs depending on the survey. The most common two drug combination consisted of BB and CCB followed by BB accompanied by angiotensin converting enzyme inhibitors. A significant, upward tendency in the use of four (p<0.001) and five (p<0.05) antihypertensive drugs simultaneously, was observed in subsequent years. The target values of BP i.e. <140/90 mmHg were accomplished in 47, 58, 60 and 46% of RTRs in subsequent years. In a secondary - stratified analysis of data from 2014, younger patients (p<0.05), patients with better graft function (p<0.001), patients treated with a higher number of antihypertensive agents (p<0.001) and those not treated with BB (p<0.01) were shown to reach the BP target of below 140/90 mmHg more often. Conclusion: The study showed intensification of hypertension treatment in RTRs in subsequent years with BB assuming a dominant role.

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IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. We performed a genome-wide association study involving 10,146 kidney biopsy-diagnosed IgAN cases and 28,751 matched controls across 17 international cohorts. We defined 30 independent genome-wide significant risk loci jointly explaining 11% of disease risk. A total of 16 loci were novel, including TNFSF4, REL, CD28, CXCL8/PF4V1, LY86, LYN, ANXA3, TNFSF8/15, REEP3, ZMIZ1, RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The SNP-based heritability of IgAN was estimated at 23%. We observed a positive genetic correlation between IgAN and total serum IgA levels, allergy, tonsillectomy, and several infections, and a negative correlation with inflammatory bowel disease. All significant non-HLA loci shared with serum IgA levels had a concordant effect on the risk of IgAN. Moreover, IgAN loci were globally enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. The explained heritability was enriched in the regulatory elements of cells from the immune and hematopoietic systems and intestinal mucosa, providing support for the pathogenic role of extra-renal tissues. The polygenic risk of IgAN was associated with early disease onset, increased lifetime risk of kidney failure, as well as hematuria and several other traits in a phenome-wide association study of 590,515 individuals. In the comprehensive functional annotation analysis of candidate causal genes across genome-wide significant loci, we observed the convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.