Anaemia treatment in chronically dialysed children: a multicentre nationwide observational study.

OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard therapy in children with anaemia in chronic kidney disease. The aim of this study was to describe the efficacy and details of ESA treatment in a population of dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective observational design and was performed in 12 dialysis centres. The study group comprised 117 dialysed children with a mean age at enrolment of 165.33 (97.18-196.45) months. RESULTS: Dialysed children were treated mostly with epoietin beta and darbepoietin. The mean dose of ESA was 99 (68-147) U/kg/week with a significant difference between patients on peritoneal dialysis [83 (54-115)] and haemodialysis [134 (103-186)] (p < 0.0001). The mean haemoglobin of all the time-point tests during 6 months was 10.91 ± 1.18 g/dl. The efficacy of anaemia treatment was unsatisfactory in 52% of subjects. In multivariate analysis, initial haemoglobin level <10 g/l, any infection, younger age at first dialysis, malnutrition and inadequate ESA dosage remained significant predictors of anaemia. CONCLUSIONS: The study revealed that anaemia treatment in Polish children is unsatisfactory. Late commencement of the treatment, inadequate dosing, malnutrition and infections could constitute risk factors for therapy failure.

[Influence of vitamin E and N-acetylcysteine on intracellular oxidative stress in T lymphocytes in children treated with dialysis]. / Wplyw witaminy E oraz N-acetylocysteiny na wewnatrzkomórkowy stres oksydacyjny limfocytów T u dzieci leczonych dializami.

UNLABELLED: End-stage renal disease (ESRD) patients are subjected to enhanced oxidative stress. Excess of reactive oxygen species (ROS) may lead to the functional disabilities of lymphocytes. The aim of the study was to investigate the effect of vitamin E and N-acetylcysteine (NAC) on antioxidant status and intracellular oxidative stress in T-cells in children treated with dialysis. MATERIAL AND METHODS: 18 children treated with dialysis (hemodialysis n = 5 and peritoneal dialysis n = 13) were enrolled into the study. The age range was 2-20 ys. with a mean of 10.94 +/-5.86 ys. Vitamin E and NAC were given for six months orally. Throughout the study total antioxidant status (TAS), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, and intracellular oxidative stress in T lymphocytes was measured. RESULTS: In children treated with dialysis, TAS was significantly reduced compared to the controls (p = 0.012). We found no differences in GPx and SOD activities between patient and control groups. Mean fluorescence intensity (MFI), which reflected intracellular oxidative stress, was significantly increased in: CD3+, CD3+CD4- and CD8+CD28-. After six months of antioxidant treatment, a significant reduction in MFI was noted in most T-cell subsets (p < 0.001). MFI in T-helper cells remained unchanged. Although there was a trend toward rise in TAS and GPx activity, only significant differences in SOD activity were found (p = 0.022). CONCLUSIONS: In children with ESRD treated with dialysis reduced TAS coexists with enhanced intracellular oxidative stress in T lymphocytes. The combined treatment with vitamin E and NAC lead to the reduction in oxidative stress within T-cells that might be of therapeutic value in dialyzed patients.

[Yersiniosis as a cause of acute tubulointerstitial nephritis and acute renal failure--case report]. / Jersinioza jako rzadka przyczyna ostrego sródmiazszowego zapalenia nerek i niewydolnosci nerek--opis przypadku.

Tubulointerstitial nephritis (TN) is a heterogenous disease, where disturbances of the interstitial tissue and renal tubules are found. Different immunological and nonimmunological mechanisms initiated by infectious and non-infectious factors may lead to TN. A case of 13-years-old girl with primary diagnosis of acute pyelonephritis is presented. The abdominal pain, headache, pain in lumbar region and intermittent fever with loss of appetite were observed in this girl a few weeks before admission. Microcytic anemia, proteinuria and glucosuria, azotemia and elevated markers of inflammatory response were found. In ultrasound examination heterogenous cortex echogenicity of both kidneys and disturbances in parenchymal blood flow were observed. In renal scintigraphy the discriminated catch index was found. Kidney biopsy revealed the edema of the interstitial space with mononuclear and lymphocyte infiltration. The diagnosis of TN was established upon the history, clinical examination, results of laboratory tests, kidney imaging and biopsy. After steroid and doxycycline treatment an improvement and normalization of the results of laboratory tests were observed. It seems to be justified to consider Yersinia infection as a cause of acute tubulointerstitial nephritis.

Abnormal cytokine synthesis as a consequence of increased intracellular oxidative stress in children treated with dialysis.

BACKGROUND/AIM: End-stage renal disease (ESRD) induces a clinical state of immunodeficiency with a higher incidence of infections and higher mortality due to infectious complications compared with the normal population. The definite mechanism responsible for the host defense alterations is not well understood. The aim of the study was to investigate intracellularly the relationship between cytokine synthesis and oxidative stress in peripheral blood lymphocytes in children with ESRD. METHODS: Twenty-one children (age 11.7 +/- 5.8 years) with ESRD treated with hemodialysis (HD; n = 10) and peritoneal dialysis (PD; n = 11) were studied. Nine healthy children of comparable age formed the control group. To determine intracellular oxidative stress we used dihydrorhodamine-123 (DHR), which after oxidation to rhodamine-123 (RHO) emitted a bright fluorescent signal. Intracellular oxidation of DHR in T lymphocytes reflected intracellular oxidative stress. The intracellular synthesis of cytokines (IL-2, IFN-gamma, IL-4, IL-6) was also measured. Both parameters were detected at a single-cell level by flow cytometry. Lymphocyte subsets were evaluated using the monoclonal antibodies conjugated with fluorochromes. RESULTS: We found that in T lymphocytes the mean fluorescence intensity (MFI), which reflected intracellular oxidative stress, was increased in ESRD patients compared to the controls (CD3+: 34.77 +/- 11.55 vs. 22.55 +/- 4.97, p < 0.01; CD3+CD8+: 34.31 +/- 12.17 vs. 20.77 +/- 4.89, p < 0.01; CD3+CD4+: 36.06 +/- 6.98 vs. 24.44 +/- 7.68, p < 0.001). HD patients showed slightly higher MFI compared to PD patients in CD3+ cells (39.32 +/- 11.70 vs. 30.63 +/- 10.20, NS), in CD3+CD8+ cells (37.90 +/- 14.32 vs. 31.06 +/- 9.34, NS) and in CD3+CD4+ cells (40.10 +/- 2.28 vs. 29.33 +/- 7.06, p < 0.001). The intracellular synthesis of IL-2 was higher in ESRD patients compared to the controls, both in CD3+ cells (31.34 +/- 9.80 vs. 20.49 +/- 15.26%, p < 0.05) and in CD3+CD4+ cells (36.10 +/- 8.69 vs. 24.03 +/- 16.95%, p < 0.05). The intracellular synthesis of IFN-gamma, IL-4 and IL-6 was significantly lower in the ESRD group compared to the controls. Interestingly, in patients treated with HD, negative correlations between the degree of intracellular oxidative stress and intracellular cytokine synthesis in CD3+ lymphocytes were found. CONCLUSION: Our results show that patients with ESRD, especially those treated with HD, present increased oxidative stress in T lymphocytes, which may lead to decreased cytokine synthesis and abnormal immune response.

[Intracellular synthesis of cytokines as the index of function of peripheral blood lymphocytes and monocytes in children with first relapse of nephrotic syndrome]. / Wewnatrzkomórkowa synteza cytokin jako wykladnik funkcji limfocytów i monocytów u dzieci z I rzutem zespolu nerczycowego.

BACKGROUND: Nephrotic Syndrome (NS) is a disease in which immune system function disorders play an important role. The aim of the study was an assessment of intracellular expression of cytokines in primary NS including assessment of intracellular expression of monokines (TNF-alpha, IL-8) in non-specific LPS stimulation system and intracellular expression of lymphokines (IL-2, INF-gamma, IL-4, IL-6) in experimental system with application of stimulation with ionomycin and PMA. METHODS: The study included 47 children with NS aged 2-16 years. After activation of whole blood cells in the presence of brefeldin A the cells were labelled with monoclonal antibodies against surface antigens. In the second phase the cells underwent permeabilisation and were labelled with monoclonal antibodies against individual cytokines. RESULTS: The studies performed demonstrated in children with NS relapse an increase of intracellular synthesis of cytokines characteristic of Th1 system (IL-2) and a decrease of synthesis of cytokines characteristic of Th2 system (IL-4, IL-6). In these patients an increase was also found of intracellular synthesis of proinflammatory monokines (TNF-alpha and IL-8). The studies performed, confirmed the earlier observations concerning abnormal cellular response in NS and demonstrated that differences in serum concentrations of individual cytokines may result from disturbances in their intracellular synthesis.