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.
•Losartan shows marginal influence on graft function and minimal adverse effects in kidney transplant recipients.•There are no significant short-term effects of renin-angiotensin-aldosterone system ...blockade on kidney allograft fibrosis biomarkers.•It may have a positive effect on cardiovascular risk in kidney transplant recipients.
There is a controversy over the renoprotective and cardioprotective effects of renin-angiotensin-aldosterone system blockade in kidney transplant recipients (KTRs). The aim of the study was to evaluate the short-term effects of losartan on allograft injury, cardiovascular risk biomarkers and safety of the treatment in KTRs.
An interim analysis of a prospective, open, multicenter, controlled clinical trial CELART (Cardiovascular Effects of Losartan After Renal Transplantation) was performed. KTRs were allocated to losartan (L) 50 to 100 mg or standard hypotensive treatment (ST) group to reach target blood pressure (BP) <140/90 mm Hg. The short-term effects of the therapy were evaluated after 6 months: estimated glomerular filtration rate (eGFR), albuminuria, the intrarenal fibrosis biomarkers: urine excretion of transforming growth factor β-1 (TGFβ-1) and procollagen type III amino terminal propeptide (PIIINP), cardiac biomarker: serum concentration of N-terminal-pro-B-type natriuretic peptide (NT-proBNP), 24-hour ambulatory BP measurement, and hemoglobin and potassium concentrations.
At baseline the groups did not differ with respect to age, primary nephropathy, comorbidity, immunosuppressive therapy, albuminuria, and graft function. A total of 61 (L group) and 73 (ST group) patients reached the target BP and completed protocol at 6 months. After 6 months of therapy there were no significant differences in changes of eGFR, albuminuria, hemoglobin and potassium concentrations, urine excretion of PIIINP, and TGFβ-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP.
Losartan shows minimal adverse effects and no influence on graft function and biomarkers of graft fibrosis. It may have a positive effect on cardiovascular risk in KTRs. Further interim analyses of the CELART study will be conducted.
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.
•The desensitization protocol (IVIG + rituximab) allows highly immunized patients to undergo organ transplantation.•In short-term analysis, no acute rejection was observed and graft function was ...satisfactory.•Desensitization was associated with an increased risk of infection, especially fungal pneumonia.
The increasing number of highly immunized patients waiting for kidney transplantation is a significant problem in Europe as the proportion of such patients has doubled in the last decade. Transplantation in this group is enabled by desensitization methods, i.e., intravenous pharmacotherapy with human immunoglobulin (IVIG), anti-CD20 monoclonal antibody (rituximab), and plasma exchange. The objective was to evaluate the efficacy and safety of this protocol.
The inclusion criteria: presence of established anti-HLA antibodies with complement-binding capacity, i.e., anti-HLAC1q+ (>MFI 15,000 for the most common antigens), no renal transplantation within 1 year after activation on the waiting list. Thirteen patients were selected for the procedure. IVIG was administered twice (2 g/kg-maximum 140 g/dose). Between IVIG doses, patients received rituximab (375 mg/m2). Anti-HLA was tested after 1 and 2 months after completion of the procedure.
All patients have completed the protocol. No significant changes after desensitization in the amount/profile of alloantibodies were observed. However, with negative vCM for HLA-A/B/DR (no DSA against the reported donor) and negative CM-CDC, according to the allocation system, patients were given priority on the recipient list. Seven out of 13 patients received a transplant within 12 months after treatment (mean 11.5 weeks). Renal graft function was good (mean creatinine level after 1 month: 1.5 mg/dL). No incidents of acute rejection were reported. The most common complications were infections (especially pneumonia).
The desensitization protocol (IVIG + rituximab) allows highly immunized patients to undergo organ transplantation. In short-term analysis, no acute rejection was observed, graft function was satisfactory. Desensitization was associated with an increased risk of infection.