Although clearance of beta(2)-microglobulin is greater with hemodiafiltration than with high-flux hemodialysis, beta(2)-microglobulin concentrations after long-term hemodiafiltration are only slightly less than those obtained with high-flux hemodialysis. Resistance to beta(2)-microglobulin transfer between body compartments could explain this observation. beta(2)-Microglobulin kinetics were determined in patients receiving on-line post-dilution hemodiafiltration for 4 h with 18 l of filtration. Plasma beta(2)-microglobulin concentrations were measured during and for 2 h following hemodiafiltration and immediately before the next treatment. The filter clearance of beta(2)-microglobulin was determined from arterial and venous concentrations. The beta(2)-microglobulin generation rate was calculated from the change in the plasma concentration between treatments. The intercompartmental clearance was obtained by fitting the observed concentrations to a two-compartment, variable volume model. The plasma clearance of beta(2)-microglobulin by the filter was 73 +/- 2 ml/min. Plasma beta(2)-microglobulin concentrations decreased by 68 +/- 2% from pre- to post-treatment (27.1 +/- 2.2-8.5 +/- 0.7 mg/l), but rebounded by 32+/-3% over the next 90 min. The generation rate of beta(2)-microglobulin was 0.136 +/- 0.008 mg/min. The model fit yielded an intercompartmental clearance of 82 +/- 7 ml/min and a volume of distribution of 10.2 +/- 0.6 l, corresponding to 14.3 +/- 0.7% of body weight. Hemodiafiltration provides a beta(2)-microglobulin clearance of similar magnitude to the intercompartmental clearance within the body. As a result, intercompartmental mass transfer limits beta(2)-microglobulin removal by hemodiafiltration. This finding suggests that alternative strategies, such as increased treatment times or frequency of treatment, are needed to further reduce plasma beta(2)-microglobulin concentrations.

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Restless legs syndrome (RLS) is a common cause of sleep disturbance and is frequently experienced by hemodialysis patients. Factors triggering the disease in uremia have not yet been identified. To our knowledge, the course of RLS symptoms after kidney transplantation has not been investigated systematically. We investigated the clinical long-term course of RLS in hemodialysis patients who underwent kidney transplantation. Patients were given a standardized questionnaire three times: at baseline, and twice after their kidney transplants. The severity of RLS was rated by the patients (0 =no symptoms, 10 = very severe symptoms). The description of the final outcome was based on the last follow-up visit. Eleven of 64 hemodialysis patients with RLS received a transplant (5 men, 6 women; severity of RLS at baseline, 7.8 +/- 0.7 [mean +/- SEM]). In all patients, RLS symptoms disappeared within 1 to 21 days after transplantation. At follow-up visits, 4 patients whose transplanted kidneys still functioned well were still free of RLS symptoms up to the longest follow-up period of 9 years. In 3 other patients, RLS symptoms gradually reappeared (severity, 1 +/- 0). In 3 of 11 patients, the transplant failed and RLS symptoms reoccurred within 10 days to 2 months (severity, 7.3 +/- 2.6). RLS symptoms reoccurred in 1 patient with failure of the transplant but disappeared again after a second, successful transplant. Kidney transplantation has a strong and positive influence on RLS symptoms in hemodialysis patients. Hemodialysis patients can expect a substantial improvement of RLS symptoms after a successful kidney transplant.

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.

BackgroundRestless legs syndrome (RLS) is a sleep related movement disorder that occurs both in an idiopathic form and in symptomatic varieties. RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet. Therefore, a case–control association study of these variants in ESRD patients was performed.MethodsThe study genotyped 10 iRLS associated variants at four loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, and PTPRD, in two independent case–control samples from Germany and Greece using multiplex PCR and MALDI-TOF (matrix assisted laser desorption/ionisation time-of-flight) mass spectrometry. Statistical analysis was performed as logistic regression with age and gender as covariates. For the combined analysis a Cochran–Mantel–Haenszel test was applied.ResultsThe study included 200 RLS-positive and 443 RLS-negative ESRD patients in the German sample, and 141 and 393 patients, respectively, in the Greek sample. In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (Pnom≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (Pnom≤0.08, ORs 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (Pcorrected=0.0013, OR 1.47).ConclusionsThis is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD.

The inadequate response of immune cells to circulating apoptotic products, such as nucleosomal DNA fragments, is assumed to be a potent stimulus for the production of autoantibodies during the pathogenesis and progression of systemic lupus erythematosus (SLE). Here, we analyzed the levels of circulating nucleosomes, caspases, and C-reactive protein in sera of 244 individuals with various autoimmune diseases (155 with autoimmune hepatic disorders, 25 with ANCA-associated vasculitis, and 64 with various connective tissue diseases), and 32 healthy controls. Nucleosomes and caspase activities were significantly elevated in sera of patients with hepatic autoimmune diseases, connective tissue diseases, and particularly in ANCA-associated vasculitis when compared with healthy individuals. Nucleosomes showed a correlation with caspases, and caspases with C-reactive protein, but nucleosomes did not correlate with C-reactive protein. Serum levels of the apoptotic products, nucleosomes, and caspases are increased in various autoimmune diseases but may not be solely responsible for antinucleosome antibody production in SLE patients. It remains to be clarified whether qualitative changes in nucleosomes are linked with pathogenesis and disease progression in SLE.

MR perfusion parameters can be used to assess effect of RAS on parenchymal perfusion. Perfusion measurements reflect renal function as measured with serum creatinine levels.

Renal artery stenosis (RAS) is the leading cause of secondary hypertension. Magnetic resonance (MR) imaging and in particular MR angiography have evolved into important diagnostic tools for the detection and grading of RAS due to the lack of ionizing radiation and nephrotoxic contrast agent. This review describes state-of-the-art MR angiographic techniques and introduces the reader to current concepts of RAS grading with MR angiography. We compare MR angiography with conventional angiography and intravascular ultrasound as a standard of reference. The technical basis of functional imaging techniques such as arterial spin labeling perfusion measurements, contrast-enhanced perfusion measurements, and MR flow measurements are explained. Their value for the grading and detection of RAS and for the differentiation of renovascular from renal parenchymal disease is discussed. An overview about imaging during and after interventional therapy of RAS and an introduction to the current understanding of prediction of successful interventional therapy finishes this review.