Oxidative stress markers in young hemodialysis patients - a pilot study.

AIMS: Studies in young hemodialysis patients without significant comorbidities might increase the understanding of incipient vascular pathology in uremia. We investigated whether a specific pattern of oxidative stress markers with potential prognostic significance could be identified in this population. MATERIAL AND METHODS: We performed a cross-sectional matched case control study of 25 young hemodialysis patients (age 18 - 40 years) without known comorbidity factors. Patients were matched pairwise to healthy controls, and markers of oxidative stress were analyzed for associations with surrogate parameters of vascular structure and function. RESULTS: Oxidized low-density lipoproteins (OxLDL) were similar in patients and controls whereas conjugated dienes were increased in the very low-density lipoproteins (VLDL) fraction (20 +/- 6 vs. 12 +/- 5 micromol/l, p < 0.0001), but not in the low-density lipoproteins (LDL) fraction (16 +/- 6 vs. 18 +/- 6 micromol/l). Superoxide dismutase (SOD) activity was diminished in patients (1,117 +/- 151 vs. 1,299 +/- 88 U/g Hb, p < 0.0001), but there was no difference in glutathione peroxidase (GPx) activity. Oxidative stress expressed as the ratio of oxidized and reduced glutathione (GSSG/GSH) was increased in patients (0.25 +/- 0.18 vs. 0.13 +/- 0.04, p = 0.0048). Intima-media thickness (IMT) of the common carotid artery (0.70 +/- 0.12 vs. 0.62 +/- 0.08 mm, p = 0.0007) was significantly increased, and postischemic peak flow (PIPF) by venous occlusion plethysmography was severely diminished in patients (632 +/- 319 vs. 1,057 +/- 543% of basal flow, p < 0.0001). None of the markers of oxidative stress was independently associated with IMT or PIPF or a significant discriminator between patients and controls by multivariate regression. CONCLUSIONS: In this pilot study of exclusively young patients on hemodialysis, oxidative stress markers were of limited clinical value in identifying young patients at risk for vascular complications.

Thoracic versus whole body bioimpedance measurements: the relation to hydration status and hypertension in peritoneal dialysis patients.

The whole body bioimpedance technique is a highly promising non-invasive, reproducible, fast and inexpensive bed-side method for monitoring hydration status. Using segmental bioimpedance measurements, it is possible to obtain information about the fluid change in each body segment (Song, Lee, Kim and Kim 1999 Perit. Dial. Int. 19 386-90). In this pilot study we have measured 25 male patients (30-65 yr, BMI 20-32 kg m(-2)) undergoing continuous ambulatory peritoneal dialysis (CAPD). Tetrapolar impedance measurements were obtained using the right-side technique (whole body), and a segmental impedance method focused in the thorax region. Blood pressure (BP) measurements were taken manually with a sphygmomanometer. Patients were classified as either stable (group 0) or unstable (group 1) using clinical parameters of overall cardiovascular risk. The Mahalanobis distance (dM2) was calculated for the mean blood pressure (BP(mean)), and the impedance parameter R normalized by body height H for the right-side (R(RS)/H) and the thorax segment (R(TH)/H). Differences between groups were significant (p < 0.0001) for R(TH)/H and for BP(mean), and less significant (p = 0.016) for R(RS)/H. Group 1 patients showed a small dM2 as compared with a reference patient (a critical patient with acute lung edema) with high BP(mean) and low values of R(TH)/H and R(RS)/H. Moreover, Group 0 patients showed a larger dM2 with respect to the reference patient, with lower BP(mean) and higher values of R(TH)/H and R(RS)/H. All patients classified as unstable by clinical assessment were correctly classified using R(TH)/H in conjunction with BP(mean) using dM2. Segmental-monofrequency non-invasive bioimpedance of the thoracic region could provide a simple, objective non-invasive method of support for facilitating the clinical assessment of CAPD patients.

[Kidney transplantation in childhood and adolescence]. / Nierentransplantation im Kindes- und Jugendalter.

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.

The lignan (+)-episesamin interferes with TNF-α-induced activation of VSMC via diminished activation of NF-ĸB, ERK1/2 and AKT and decreased activity of gelatinases.

AIM: Activation of vascular smooth muscle cells (VSMC), a key event in the pathogenesis of atherosclerosis, is triggered by inflammatory stimuli such as tumour necrosis factor-alpha (TNF-α) causing a mitogenic VSMC response. The polyphenol (+)-episesamin (ES) was shown to counteract TNF-α-induced effects, for example in macrophages. Aiming for novel therapeutic options, we here investigated whether ES protects VSMC from TNF-α-induced growth and migration, which both contribute to the onset and progression of atherosclerosis. METHODS: Human and murine VSMC were treated with combinations of ES and TNF-α. Expressions of mRNA were analyzed by RT-PCR. Enzymatic activities and proliferation were determined by specific substrate assays. Cell signalling was analyzed by Western blot and reporter gene assays. Migration was assessed by wound healing assays. RESULTS: ES at 1-10 µm reduced basal and TNF-α-induced VSMC proliferation and migration due to impaired activation of extracellular signal-regulated kinases (ERK)1/2, Akt (protein kinase B), nuclear factor-kappa B (NF-ĸB) and vascular cell adhesion molecule (VCAM)-1. This was accompanied by reduced expression and secretion of matrix metalloproteinases (MMP)-2/-9, which are known to promote VSMC migration. Specific inhibitors of Akt, NF-ĸB and MMP-2/-9 reduced TNF-α-induced VSMC proliferation, confirming ES-specific effects. Besides, ES reduced TNF-α- and H2O2 -induced oxidative stress and in parallel induces anti-inflammatory haem oxygenase (HO)-1 expression. CONCLUSION: ES interferes with inflammation-associated VSMC activation and subsequent decreased proliferation and migration due to anti-oxidative properties and impaired activation of NF-ĸB, known contributors to atherogenesis. These results suggest ES as a complemental treatment of VSMC specific vascular diseases such as atherosclerosis.

Long-term treatment with growth hormone has no persisting effect on lipoprotein(a) in patients with Turner's syndrome.

Treatment with recombinant human GH (rhGH), alone or in combination with the anabolic steroid oxandrolone (OX), has been recommended for girls with Turner's syndrome to improve final height. Several cardiovascular risk factors have been described in patients with Turner's syndrome, but the effect of therapy with rhGH and OX on lipoprotein(a) [Lp(a)] has not been investigated. Lp(a) serum levels and apolipoprotein(a) phenotypes were determined in 46 girls with Turners syndrome (aged 6-15 yr) during treatment with different combinations of rhGH and OX for 24-36 months (median, 27 months). Lp(a) serum levels showed little variation during 30 months of treatment in all treatment groups. Lp(a) levels showed no significant change in 25 patients receiving only rhGH and in 21 patients receiving rhGH and OX in combination. Treatment effects were independent of apolipoprotein(a) phenotypes and were not influenced by pubertal status. These data indicate that long term administration of rhGH has no significant impact on serum Lp(a) levels in girls with Turner's syndrome.

Lipid levels in monocytes of patients with moderate hyperlipoproteinemia.

Recent studies suggest that circulating blood monocytes may serve as a lipid clearance system in early atherosclerotic lesions. To evaluate the influence of moderate hyperlipoproteinemia on monocyte lipid concentrations, we measured fasting serum and monocyte lipid levels in 7 healthy individuals, in 7 patients with primary hypercholesterolemia and in 17 patients with secondary dyslipidemia due to chronic renal failure; 10 of these patients were treated by hemodialysis (HD) and 7 patients by continuous ambulatory peritoneal dialysis (CAPD). The hypercholesterolemic patients had elevated serum levels of total cholesterol, LDL-cholesterol and apolipoprotein (apo) B, but normal plasma triglycerides. Patients on dialysis had elevated serum levels of triglycerides, serum cholesterol (CAPD only) and VLDL- and LDL-cholesterol (CAPD only) and apo B (CAPD only), whereas HDL-cholesterol and apo A-I levels (HD only) were decreased. In monocytes, we measured the content of free cholesterol (FC), cholesteryl esters (CE) and triglycerides (TG). The normal mean intracellular concentrations of FC, CE and TG were 48.3, 1.7 and 2.4 micrograms/mg cell protein, respectively. All monocyte lipid levels were similar in patients and controls, with the exception of a decreased content of FC (30.8 micrograms/mg) in monocytes of HD patients. We conclude that moderate increases in serum lipoprotein lipid levels are not associated with lipid accumulation in monocytes.

A 12-year-old boy with fatal hemolytic-uremic-syndrome, excessive neutrophilia and elevated endogenous granulocyte-colony-stimulating-factor serum concentrations.

We report the case of a 12-year-old boy with fatal enteropathic hemolytic-uremic syndrome who developed excessive neutrophilia in the course of his disease, his leukocyte count exceeding 200,000/mm3. Neutrophilia, as it was observed in this case, is an extreme manifestation of a phenomenon, that is commonly observed in hemolytic-uremic syndrome [Salzmann et al. 1991]. Neutrophilia is suspected to be correlated with a bad prognosis [Walters et al. 1989], but further explanation of this phenomenon is needed. Other underlying diseases related with neutrophilia, especially hematologic malignancies, could be ruled out by far. We examined endogenous G-CSF serum concentrations of the HUS patient from day 6 to 13 in the course of the disease. The assayed concentrations were found to be elevated in the first two samples taken (peak level 340 pg/ml). In the samples taken after plasmapheresis had started, G-CSF concentrations were not found to be elevated. The peak of neutrophilia was reached short before death on day 13 of the disease. We also measured the serum G-CSF concentrations of 28 children aged 3 months to 12 years, who were treated with various infectious and noninfectious diseases in our hospital. In none of the examined samples was there a G-CSF serum concentration exceeding 50 pg/ml. The reported case shows evidence that the commonly observed coincidence of leukocytosis and HUS may reflect the role of G-CSF (and other cytokines) in the inflammatory process underlying the HUS.

Renal tubular dysgenesis: a report of two cases.

Renal tubular dysgenesis, a congenital disorder of renal tubular development, was diagnosed in two newborns with oligohydramnios and Potter phenotype. Renal tubular dysgenesis (RTD) is a recently recognized congenital disorder of renal tubular development associated with oligohydramnios, Potter phenotype, and neonatal respiratory and renal failure. We report two newborn siblings with typical clinical and anatomic features of RTD. The diagnosis was proven by autopsy in one child. The pediatrician should consider the diagnosis of RTD in a child with congenital anuria and structurally normal kidneys on ultrasound, especially if a maternal history of late trimester oligohydramnios is present.

Undertreatment of cardiac risk factors in adolescents with renal failure.

Cardiovascular disease (CVD) is the most common cause of death in adults with end-stage renal disease and after renal transplantation, and the relative excess of mortality is greatest in the young. The most likely explanation is the dramatic accumulation of both classical and uremic risk factors leading to atherosclerosis, uremic vasculopathy, and uremic cardiomyopathy. Prospective studies have established the significance of classical and uremic risk factors for the occurrence of CVD in the normal population and in the population with chronic renal disease alike. However, whether and to what degree modification of risk factors by therapeutic intervention can lower morbidity and mortality rates is as yet unknown.

Treatment of relapsing peritonitis in pediatric patients on peritoneal dialysis.

Relapsing peritonitis is often due to bacterial colonization of the Tenckhoff catheter and may require removal of the catheter in patients on peritoneal dialysis. The efficacy of a Tenckhoff catheter decontamination procedure was examined in 9 pediatric patients aged 1.5-18 years and compared to the outcome of a historical control group. After repeated dialysate cultures had become negative and cell count was normalized (< 100/ul), intraluminal urokinase (5000 IU/ml) and intraluminal high concentrated antibiotics (vancomycin, fosfomycin, cefotaxim) were instilled sequentially for 3 h and 1 h respectively. This procedure was performed once daily for three days. In addition, the connector was exchanged on the last day. This regimen prevented relapsing peritonitis in all study patients, whereas in the control group in 75.8% of events further relapses occurred, necessitating removal of the Tenckhoff catheter in 7/19 (36.8%) episodes. No side effects of intraluminal urokinase were recorded in any of the patients. We conclude that intraluminal urokinase and intraluminal high concentrated antibiotics combined with connector device exchange are highly effective for prevention of further relapses of peritonitis and reduce the need for Tenckhoff catheter exchange.

[Personality and rehabilitation in young adults with renal replacement therapy]. / Persönlichkeitsstruktur und Rehabilitation bei jungen Erwachsenen mit Nierenersatztherapie.

To evaluate the personality structure of young adults treated with renal replacement therapy (RRT) since childhood, we studied 36 patients who had commenced RRT before age 18. At the time of investigation 17 patients were dialyzed and 13 had a functioning renal transplant. Of the dialysis patients, 7 had been transplanted previously. These patients were compared to 26 young adults (minimum age 16) with diabetes mellitus type I (DM) of comparable duration. We used the FP1 test (half-form R; 138 items) by J. Fahrenberg to evaluate personality structure in patients and controls. The results show in general very little difference compared to published normal values and only slight differences between the groups studied. However, there was a trend for RRT patients to feel more aggressive and inhibited than patients with DM. Transplanted patients tended to feel more worried about health problems, while hemodialysis patients felt more self-assured than DM patients. Although it is difficult to assess the psychological burdens of chronic illness and the influence of continuing psychosocial support, it seems remarkable that a better than expected psychiatric adjustment has also been reported in other studies of patients with RRT. In conclusion, adult patients with RRT since childhood have a favorable personality profile as measured by self-evaluation with the FP1-R test, inspite of the well-known multiple medical and social handicaps of this patient population.

Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies.

BACKGROUND: A catheter lock solution containing 1.35% taurolidine and 4% citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds. AIM: To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter (CVC) lock solutions in paediatric patients with haematological malignancies. METHODS: Seventy-one patients aged 1.4-18 years were randomized to two treatment groups using either heparin (N = 36) or taurolidine citrate (N = 35). Infectious complications and clinical side-effects were prospectively monitored and microbial colonization of catheters was assessed at the time of removal. FINDINGS: There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group (0.3 vs 1.3 infections per 1000 catheter-days; P = 0.03). Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups. Microbial colonization was found in 25.4% catheters. The time of no-lock use, but not the type of lock solution or time of observation, was a significant predictor of catheter colonization (P = 0.004). Colonization was not observed in CVCs used immediately with taurolidine citrate lock. Seven patients in the taurolidine citrate group (20%) experienced side-effects (nausea, vomiting, abnormal taste sensations). CONCLUSION: The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients. Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion, but not after a period of no-lock catheter use.

Uremia-related vascular calcification: more than apatite deposition.

In the present study, we characterized and compared the mineral phase deposited in the aortic wall of two different frequently used chronic renal failure rat models of vascular calcification. Vascular calcification was induced in rats by either a 4-week adenine treatment followed by a 10-week high-phosphate diet or 5/6 nephrectomy followed by 6 weeks of 0.25 microg/kg/day calcitriol treatment and a high-phosphate diet. Multi-element mapping for calcium and phosphate together with mineral identification was performed on several regions of aortic sections by means of synchrotron X-ray-mu-fluorescence and diffraction. Bulk calcium and magnesium content of the aorta was assessed using flame atomic absorption spectrometry. Based on the diffraction data the Von Kossa-positive precipitate in the aortic regions (N=38) could be classified into three groups: (1) amorphous precipitate (absence of any diffraction peak pattern, N=12); (2) apatite (N=16); (3) a combination of apatite and magnesium-containing whitlockite (N=10). The occurrence of these precipitates differed significantly between the two models. Furthermore, the combination of apatite and whitlockite was exclusively found in the calcitriol-treated animals. These data indicate that in adenine/phosphate-induced uremia-related vascular calcification, apatite is the main component of the mineral phase. The presence of magnesium-containing whitlockite found in addition to apatite in the vitamin D-treated rats, has to be seen in view of the well-known vitamin D-stimulated gastrointestinal absorption of magnesium.

Severe parvovirus B19 encephalitis after renal transplantation.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Severe atherosclerosis of the aorta and development of peripheral T-cell lymphoma in an adolescent with angiolymphoid hyperplasia with eosinophilia.

We report an adolescent girl with a history of angiolymphoid hyperplasia with eosinophilia (ALHE) diagnosed at the age of 10 years. The patient also suffered from chronic persistent multiresistant herpes simplex virus infection. Atherosclerotic occlusive disease of the abdominal aorta and its major branches was observed at the age of 17 years, necessitating vascular surgical intervention 1 year later because of disease progression. Histological examination of the aorta disclosed widespread atherosclerosis and high levels of gene expression of both T-helper cell type (Th) 1- and Th2-derived cytokines. This suggests that a highly stimulated systemic immune response including increased production of both Th1- and Th2-derived cytokines such as interferon-gamma and interleukin-4 may result in severe atherosclerotic lesions at a very young age. In addition, the patient developed a peripheral T-cell lymphoma at the age of 18 years. Neither systemic atherosclerosis nor T-cell lymphoma has been reported in association with ALHE. It is suggested that a highly stimulated dysfunctional immune response may play a key role in persistent inflammatory disease and premature development of atherosclerosis as well as malignant transformation of T cells.

Disturbances of lipid metabolism in children with chronic renal failure.

This review discusses the pathogenesis, clinical significance and current therapy of hyperlipoproteinaemia (HLP) in children with chronic renal failure. Uraemic dyslipidaemia, characterized by hypertriglyceridaemia and low high-density lipoprotein-cholesterol levels, is present in the majority patients with chronic renal failure. In addition, serum levels of total cholesterol, very low-density lipoprotein-cholesterol, low-density lipoportein-cholesterol and apolipoprotein B are frequently elevated. The pathophysiological mechanisms causing these disturbances are complex and mainly involve a diminished catabolism of triglyceride-rich lipoproteins. For unknown reasons and independent of other lipoproteins, serum levels of the highly atherogenic and thrombogenic lipoprotein(a) are also often elevated. HLP is an important factor in cardiovascular morbidity and mortality. In addition, dyslipidaemia may enhance progression of renal disease in patients with residual renal function. Therefore, treatment of HLP seems indicated in overtly hyperlipidaemic patients, but until there is more experience with lipid-lowering drugs in children, no safe recommendations for pharmacological treatment of HLP can be given. Dietary modifications can be recommended only to a limited extent.