Desensitization of Highly Immunized Kidney Transplant Recipients Awaiting Transplantation-Polish Single-Center Experience.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Short-term Effects of Losartan on Cardiovascular Risk and Allograft Injury Biomarkers in Kidney Transplant Recipients.

BACKGROUND: 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. METHODS: 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 ß-1 (TGFß-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. RESULTS: 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 TGFß-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP. CONCLUSIONS: 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.

The influence of a single hemodialysis procedure on human T lymphocytes.

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-1ß, 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.

Dietary supplement use among patients with chronic kidney disease.

BACKGROUND: Dietary supplements (DS) are available over the counter, but patients with impaired renal function are specifically at risk for toxicity when consuming certain DS. The aim of this study was to evaluate the prevalence and characteristics of DS use in patients with chronic kidney disease (CKD). MATERIAL AND METHODS: A cross-sectional, controlled DS use survey (22 questions) was conducted among 180 CKD patients (stage 1-5, dialysis, kidney transplant), with 60 patients without CKD serving as controls. RESULTS: DS use did not differ significantly between subjects with and without CKD, unless the CKD patients were on dialysis. In the CKD group, 20% admitted to use DS regularly and 22% did not take the mat all. In the controls, DS consumption was 17% and 13%, respectively (NS). The DS use was higher among women ascompared to men (89% vs. 70%; p < 0.005), and people living in cities versus those living in the country side (81% vs. 63%; p < 0.05). DS most commonly used were: vitamins, minerals, and herbs. Major indications for DS use included: musculoskeletal issues, general health improvement and prevention of urinary tract infections. Subgroup analyses revealed that dialysis patients were characterized by a significantly higher DS use in comparison to CKD stage 1-5 subjects and renal transplant recipients. The decision to introduce DS was made by the physician in 54% of cases; by a pharmacist in 9% of cases, and by the patients themselves in 37%. Only 21% of patients with CKD, and 27% of subjects without CKD, declared knowledge of any possible side-effects associated with DS (NS). CONCLUSIONS: The use of DS among patients with CKD is similar to patients without CKD, with the exception of those on dialysis. Vitamins and minerals were the most commonly reported DS consumed. The knowledge on potential side-effectof DS was limited to approximately one-fourth of those surveyed.

Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional Analyses.

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.

[Health awareness and cooperation with the patient in the therapeutic process in a population of patients with chronic kidney disease in the center of Gdansk].

Chronic kidney disease (CKD) is considered as a disease of civilization of the XXI century. The increase of patients with CKD is associated with a higher incidence of hypertension, diabetes and aging. Hypertension occurs in 60-90% of patients with CKD. It is worth to underline that the nephroprotective therapy can delay or even stop the progression of CKD to end-stage renal disease. The therapy nephroprotective should be understood as both pharmacological and nonpharmacological treatment. The aim of this study was to evaluate the health awareness of patients with CKD, as well as the degree of patient compliance especially in terms of pharmacological and non-pharmacological treatment. Material and Methods: A crosssectional survey was offered for 1300 patients with CKD who are are under the care of the Department of Nephrology, Transplantology and Internal Medicine, University Hospital in Gdansk. 972 patients (M/F) (74.8%) responded positively to participate in the study Results: It was shown that 91.2% of the patients measured blood pressure at home. 41.2% measured blood pressure everyday and 54.2% of patients used at least one non-pharmacological treatment for hypertension. 71.7% of patients declared that buy all drugs prescribed by the doctor. 53.4% of patients used the possibility of substitution drugs prescribed by a doctor for cheaper preparations recommended by the pharmacist. 85.7% of patients taking medicines according to doctor's advice (frequency, dose). Conclusions: The results of the study indicate that the education of patients, the therapeutic process and their health awareness are good, especially among patients treated with peritoneal dialysis. It should be continued as educational program because these activities may contribute to improving the prognosis and quality of life. A patients after kidney transplantation are particularly vulnerable to the effects of failure to comply with recommendations.