Many plasmapheresis patients (24% in our center) also require hemodialysis. We report here on techniques for performing both processes simultaneously in a single extracorporeal circuit containing both a hemodialyzer and a hollow fiber membrane plasma filter. The combination proved technically straightforward and maintained the known solute removal efficacy of both constituent processes.

Kidney biopsies in 2 females with nephrotic syndrome were suggestive of membranous nephropathy at routine light microscopy and immunohistochemistry. Electron microscopy on re-embedded paraffin tissue, however, revealed that the light microscopic pattern was due to a fibrillary glomerulonephritis with a dominant membranous manifestation. These findings suggest that (a) fibrillary glomerulonephritis may be mis-/under-diagnosed at light microscopy; and (b) in reality, a subset of therapy refractory membranous nephropathies might represent fibrillary glomerulopathies. Therefore, electron microscopy is mandatory in any case of membranous nephropathy with therapy refractory nephrotic syndrome or an unusual immunohistological staining pattern, e.g. with mesangial immunoreactivity.

Introduction: An association between idiopathic Restless legs syndrome (iRLS) and intronic and intergenic variants in MEIS1 (Chromosome 2), BTBD9 (Chromosome 9) and MAP2K5/LBXCOR1 (Chromosome 15) was recently shown. RLS is a common complaint of patients with end-stage renal disease (ESRD), but the etiology of uraemic RLS (uRLS) is still unknown. Our aim was to investigate whether these genetic variants play also a role in this entity.

A 27-year-old woman suddenly developed persistent rotatory dizziness with unsteadiness on standing and walking, associated with symptoms relating to the autonomic nervous system, all signs and symptoms disappearing without treatment in 3 days. Ten days before this episode she had noticed progressive bilateral impairment of hearing accompanied by tinnitus. Caloric and audiometric tests confirmed bilateral impairment of the audiovestibular organ. A week later she also developed bilateral iritis and papillitis. The constellation of ocular and audiovestibular signs suggested Cogan's syndrome. Under high-dosage glucocorticoid treatment (initially 1,000 mg/d prednisolone intravenously for 3 days, then 100 mg/d orally in decreasing doses down to 10 mg daily) the ocular signs improved, but the bilateral hearing impairment persisted. A recurrence occurred after 5 months, while on a prednisolone dosage of 10 mg daily, together for the first time with arthralgias, suggesting systemic involvement. Although the symptoms quickly subsided when dosage was increased to 100 mg daily, repeated attempts at dose reduction brought about renewed exacerbation at 70 mg daily. As the necessary high steroid dosage led to severe side effects, an immunosuppressive drug was added (100 mg cyclophosphamide and 20 mg prednisolone, both daily; later 5 mg methotrexate weekly and 4 mg prednisolone every other day). The symptoms had not recurred when re-examined 7 months later.

Introduction: Restless legs syndrome (RLS) is a common complaint of patients with end-stage renal disease (ESRD). There is also evidence of a high prevalence of unrecognized cognitive impairment and increased levels in depression and anxiety in the dialysis population. The purpose of the current study was to examine differences in mood and cognitive performance between ESRD- patients with and without RLS.

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.

PURPOSE:To prospectively assess feasibility of renal magnetic resonance (MR) perfusion measurement method based on turbo fast low-angle shot sequences for grading effect of renal artery stenosis (RAS) on parenchymal perfusion. MATERIALS AND METHODS:Institutional review board approved this study, and patients gave written consent. Seventy-three patients (34 male, 39 female; age range, 17-84 years) who were clinically suspected of having RAS underwent contrast material-enhanced (gadodiamide) saturation-recovery turbo fast low-angle shot imaging for measurement of renal perfusion and high-spatial-resolution MR angiography for RAS detection and grading. Degree of stenosis was evaluated as high grade (>/=75% stenosis), low to intermediate grade (>0% to <75% stenosis), or absent. High temporal resolution of the turbo fast low-angle shot sequence allowed acquisition of an exact first-pass tracing of the contrast agent bolus from which a signal intensity (SI)-time curve was derived. On the basis of this curve, mean transit time (MTT) of the contrast agent bolus, maximal upslope (MUS) of the curve, maximum SI, and time to SI peak (TTP) were calculated with a gamma variate fit. Wilcoxon rank sum test, Pearson product moment correlation, and paired t test were used for statistical analysis. RESULTS:Twenty-four renal arteries had high-grade RAS, 12 renal arteries had low- to intermediate-grade RAS, and 104 renal arteries had no RAS. Significant differences between patients without stenoses or with low- to intermediate-grade stenoses and patients with high-grade stenoses were found for MTT, MUS, and TTP (P < .001). Perfusion parameters were correlated with patients' serum creatinine levels, and significant correlations were found for MTT (r = 0.41), MUS (r = 0.48), and TTP (r = 0.4), with P < .001. CONCLUSION: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.

AIM:In patients with end-stage renal disease (ESRD) cardiovascular morbidity and mortality are increased. Apart from traditional and uremia-specific factors oxidative stress has been implicated as a main risk factor. This study investigated the influence of two different high-flux hemodialysis membranes on parameters of oxidative stress during a dialysis session.PATIENTS AND METHODS:14 stable ESRD patients were enrolled in the study and randomly assigned to high-flux hemodialysis using either a polyamide membrane (Polyflux 14; PA group) or a new polysulfone membrane (Diacap Polysulfone HI PS 15; PS group). All patients received 6 treatments with the same membrane. During the 5th treatment parameters of dialysis efficiency, biocompatibility (cell counts, complement C3a, thrombin-antithrombin complex) and oxidative stress (lipid peroxides, total antioxidative capacity) were measured.RESULTS:Parameters of dialysis efficiency and biocompatibility were similar in both treatment groups. At the beginning of the dialysis session both groups showed a low to moderate level of oxidative stress and a reduced total antioxidative capacity as compared to healthy controls. Both parameters deteriorated significantly during the extracorporeal procedure with a similar magnitude in both membrane groups. No correlation between oxidative or antioxidative capacity and parameters of biocompatibility or dialysis efficiency could be found.CONCLUSIONS:Dialysis with synthetic high-flux membranes induces a temporary deterioration of oxidative stress parameters in ESRD patients despite good dialysis efficiency and biocompatibility.

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.

Die Kombination aus morphologischer und funktioneller Magnetresonanztomographie (MRT) ermöglicht einen umfassenden Untersuchungsalgorithmus für die Detektion und Charakterisierung fokaler und diffuser Veränderungen des Nierenparenchyms. Umschriebene Raumforderungen der Niere können mit hoher Genauigkeit differenziert werden. Der Einsatz neuer MRT-Techniken wie die kontrastmittelverstärkte zeitaufgelöste Perfusionsmessung der Nieren eröffnet die Beurteilung von diffusen vaskulären oder entzündlichen Erkrankungen, z.B. chronischen ischämischen Veränderungen bei Transplantatnieren, intrarenalen segmentalen Nierenarterienstenosen oder diffusen Entzündungsprozessen wie der Malakoplakie. Zukünftige Entwicklungen unter Einsatz neuer Kontrastmitteln lassen eine frühe bildgebende Darstellung von Glomerulonephritiden erwarten. Mit der zeitaufgelösten kontrastmittelverstärkten MR-Urographie können Abflusshindernisse bezüglich ihrer urodynamischen Relevanz erfasst werden. Verschiedene Formen von retroperitonealen Entzündungsprozessen wie dem perirenalen M. Ormond lassen sich darstellen. Kongenitale Fehlbildungen der Nieren und Harnwege können durch den Einsatz von MR-Angiographie und MR-Urographie erkannt und differenziert werden. Bei der Erkennung maligner Erkrankungen der Ureteren ist derzeit die Mehrschicht-Computertomographie (MS-CT) die bevorzugte Untersuchungsmethode, da auf multiplanar rekonstruierten Schichten auch kleine Transitionalzellkarzinome erkannt werden können. Die MS-CT spielt auch bei der Stein-Diagnostik eine entscheidende Rolle.

We present the case of a 75-year-old female with weight loss, anemia, systemic signs of inflammation, mild renal insufficiency, microscopic hematuria, mixed glomerular and tubular proteinuria, and high titers of PR3-ANCA. Renal biopsy demonstrated interstitial nephritis with some sclerosed but otherwise normal glomeruli. Extensive work-up showed no signs of granulomatous inflammation or other vasculitic organ involvement. We presumed this to be a rare renal manifestation of ANCA-associated disease with the presence of sclerosed glomeruli suggesting a previous history of glomerular involvement. In view of the absence of active vasculitic or granulomatous disease, treatment was limited to low-dose corticosteroids with good response.

A268 Aim: Growing organ-shortage in renal transplantation forces potential donors as well as involved physicians (i.e. surgeons, urologists, nephrologists) to promote living kidney donation, even in donors with minor or major health problems. This may imply a conflict to the Hippocratic oath: “Primum nil nocere”. To reconsider our rules and recommendations we analysed 10 years of donor selection. Patients & methods: From October 1994 – March 2004 233 kidney donors underwent preoperative check-up. All eligible candidates (compatible with respect to ABO and X-match) stated no evident health problems or complaints. Special emphasis was given to cardio-vascular risks, all pts above age > 60yrs or overt risk profile for cardio-vascular diseases underwent extended cardiological examination including myocardial scintigraphy, CT-screening for coronary calcification and - if necessary - coronary angiography. 41 pts (17.5 %) were not accepted for donor-nephrectomy. The following reasons led to rejection of the potential donor: Coronary heart disease (CHD) 10 (4.3%); metabolic syndrome 7 (3%); microalbuminuria 5 (2.2%), limited renal function (MAG-3/Inulin-clearance) 5 (2.2%), conditions each with 2 pts (0.9%): obesity, MGUS, abnormal renal vessels, sarcoidosis, hypertension (not controlled). 1 pt. (0.4%) was excluded due to constant erythrocyturia reflecting glomerular damage. In 3 pts. /1.3%) nephrectomy was not completed facing intraoperative complications (cardiac arrest [vaso-vagal], bronchial spasm and detection of a small renal carcinoma. Conclusion: Exclusion from donor nephrectomy caused deep disappointment to donors as well as recipients. Attempts to perform kidney donation at other institutions were undertaken and were sometimes successful. Weighting the patients (donor) autonomy with high priority in the decisions process in future it may be feasible to accept donors with informed consent about evident health problems. For example: stable CHD, mikroalbuminuria without diabetes or hypertension, slightly diminished renal function. Doing so, the society should be aware that a further step on “the slippery slope” in the field of transplantation is made.

Acute and chronic rejection after kidney transplantation has long been exclusively attributed to cellular and vascular mechanisms. Modern immunosuppressive therapy, therefore, addresses the cellular immune system. Rising experiences in kidney transplantation in the last few decades have revealed that some types of rejection are refractory to the conventional immunosuppressive treatment. Humoral rejection. which has previously been reported as a crucial factor in hyperacute rejection, is now suspected to play also an important role in acute and chronic rejection. Acute humoral rejection (AHR) is characterized by immunohistochemical detection of C4d deposits in peritubular capillaries. As shown for other antibody-mediated diseases, such as some autoimmune diseases, plasmapheresis has been suggested to be an efficient therapeutic approach in AHR. We present four patients with C4d-positive AHR in the early phase after kidney transplantation. In three of the four patients, humoral graft rejection was successfully treated by plasmapheresis. Graft function was significantly improved with a stable long-term outcome. One patient lost the graft. Although the number of patients with C4d-positive AHR treated by plasmapheresis is limited, plasma exchange appears to be an efficient and powerful therapeutic approach to control humoral rejection.

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.

Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins from whole blood and is therefore an easy and rapid procedure. The majority of patients reaches >60% acute low-density lipoprotein cholesterol (LDL-C) reduction using either the DALI 750 or 1000 configuration. However, in patients with extremely high LDL-C levels or very large blood volumes, these configurations may lead to suboptimal results. The current study was performed to test the safety and efficacy of DALI 1250. In a severely obese patient (185 cm, 133 kg, blood volume 7.2 L, LDL-C 239 mg/dl), 11 L of blood (1.53-fold patient blood volume) was processed at a flow rate of 80 ml/min in 2.5 h; a combined heparin-plus-citrate anticoagulation regimen was used. Commercially available DALI 1250 and DALI hardware and disposables were manufactured by Fresenius HemoCare Adsorber Technology, St. Wendel, Germany. Twenty weekly sessions were performed. Clinically and technically, the apheresis sessions were completely uneventful. As compared to DALI 1000 (n = 4 sessions), the reduction rates by DALI 1250 (n = 20) improved for LDL-C (from 52% to 66%), lipoprotein (a) (Lp[a]) (53% vs. 66%), and fibrinogen (11% vs. 16%). There was a slight increase in high-density lipoprotein cholesterol (HDL-C) loss (20% vs. 24%). Moreover, the absolute amount of LDL-C removed per session increased from 5.06 g to 5.94 g. Laboratory safety parameters remained within the normal range, the anticoagulation was well controlled, and the pressure gradients over the adsorber remained constant. In this case report, DALI 1250 was perfectly safe and significantly increased the efficacy of LDL-C and Lp(a) elimination compared to standard DALI. Thus, this high-efficiency version of DALI may be used in patients with extremely high LDL-C levels and/or large blood volumes.

Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 +/- 0.04 to 1.06 +/- 0.3 mPa (-10%) while EA improved from 22.8 +/- 4.4 to 13.3 +/- 4.5 (arbitrary units) (-42%). LDL-cholesterol, Lp(a), and very-low-density lipoprotein (VLDL)-cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.

The potential to treat life-threatening conditions with therapeutic plasma exchange (TPE) is limited to a few situations. In severe pulmonary hemorrhage as a complication of several immune disorders (e.g., antiglomerular basement membrane antibody disease, Wegener's granulomatosus, lupus erythematosus), TPE should only be considered after conventional measures (mostly pulses of methylprednisolone) have been applied. Idiopathic familial and nonfamilial thrombotic thrombocytopenic purpura as well as the subset of the hemolytic uremic syndrome not associated with diarrhea are clear indications for TPE using fresh frozen plasma as replacement fluid. Patients with myasthenic crisis will also benefit from TPE and will improve within 1 day. Acute pancreatitis as a complication of the chylomicronemia syndrome has a poor prognosis and should be treated with TPE without any delay. In the case of drug overdose or intoxication, the efficiency of TPE to remove the offending drug is usually overestimated. In this situation, TPE is useful only when the plasma protein binding of the substance is high (>80%) and the volume of distribution is low (<0.2 L/kg body weight). TPE is not without risks and hazards (e.g., vascular access, bleeding, allergy), which should also be considered when discussing this extracorporeal therapy in otherwise refractory clinical conditions.

Systemic lupus erythematosus is a chronic autoimmune disease which commonly involves the kidneys. Despite great improvement in survival over the past years due to immunosuppressive therapy, renal failure remains an important cause of morbidity and mortality. In view of the pathogenesis of lupus nephritis, the use of less toxic and more specific ways of treatment such as the extracorporeal removal of pathogenetically relevant autoantibodies seems rational. On the basis of currently available studies, plasma exchange used alone or as an adjunct to conventional immunosuppressive therapy offers no clear benefit over standard immunosuppression in patients with active lupus nephritis and therefore cannot be recommended. However, although not proven, plasmapheresis might be beneficial in patients with acute life-threatening disease, for which high-dose immunosuppressive therapy may not be possible, or as an adjunct procedure for patients not responding to conventional therapy. Rather than the unselective removal of plasma, adsorption procedures allow the selective or specific removal of immunoglobulins, which seems to be a more reasonable approach in lupus nephritis. The results of the first clinical trials using different adsorption columns seem promising, but their use cannot be recommended until well-designed, case-controlled studies have been performed to prove their usefulness and cost effectiveness in lupus nephritis. So far, clear-cut recommendations regarding type of adsorption column, intensity and duration of treatment, and accompanying immunosuppressive treatment cannot be given.

Background and aim of study. in routine DALI apheresis - the first technique for direct adsorption of lipoproteins from whole blood - heparin plus citrate (ACD-A) is used as anticoagulation regimen. However, recently several publications have warned of heparin-induced thrombocytopenia as a rare but potentially life-threatening complication of heparin administration (HIT type 2). The aim of the present study was therefore to test the efficacy and biocompatibility of DALI using a heparin-free anticoagulation regimen consisting exclusively of citrate.Methods. Four symptomatic hypercholesterolemic patients on regular DALI apheresis were switched to the heparin-free protocol for two sessions each. Two of the patients were on oral anticoagulation using phenprocoumon. in the weekly sessions, 1.3 patient blood volumes were processed at a blood flow rate of 60 ml/min using ACD-A at a ratio of 1:20 (v/v) during adsorber priming and the session.Results. Clinically, all sessions were essentially uneventful. Uncorrected lipoprotein reductions amounted to 65% for LDL-C, 62% for Lp(a), 53% for VLDL-C, 24% for HDL-C, 17% for triglycerides and 19% for fibrinogen. Cell counts remained virtually constant. No signs of hemolysis or clotting could be detected Thromboplastin time (Quick) was slightly prolonged and partial thromboplastin time (PTT) moderately elevated in all patients. In constrast, whole blood coagulation time acc. to Lee-White and activated clotting times were increased only in orally anticoagulated patients. Biocompatibility in terms of complement, leukocyte and thrombocyte activation was excellent. Bradykinin activation was moderate peaking at 3038 pg/ml in the efferent line. Systemic thrombin-antithrombin complex (TAT) reflected perfect anticoagulation in orally anticoagulated patients and adequate anticoagulation in the patients without phenprocoumon.Conclusion. in this pilot study, heparin-free DALI apheresis was safe and effective and may thus be performed in LDL-apheresis dependent patients who suffer from heparin intolerance.

BACKGROUND AND OBJECTIVE:Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are primary necrotizing ANCA associated systemic vasculitides with preferential involvement of small and medium-sized vessels. It was the aim of this study to evaluate retrospectively data regarding diagnostic and clinical features collected over a long period on patients with WG and MPA at one medical centre. Additionally, the question was addressed whether both diseases are being more frequently diagnosed since the introduction of serological tests for ANCA.PATIENTS AND METHODS:The files of all patients with WG (n = 48) and MPA (n = 6) seen between 1976 and 1997 by our nephrology team were evaluated with respect to clinical presentation (signs and symptoms, outcome, complications) and relevant laboratory data (e.g. blood count, ESR, renal function, CRP, ANCA).RESULTS:Five of 48 patients with WG (24 males, 24 females, 22-67 and 18-77 years) had been diagnosed with the disease in the first 10 years before and 43 after ANCA serology became available. All MPA cases (6 males) had been diagnosed after 1992 and showed renal involvement. The pattern of organ involvement in this cohort with WG was the same as that recorded in the literature. Laboratory tests revealed raised ESR in 85%, anemia in 79%, ANCAs in 91% and increased CRP in 73%. A localized form of WG had been present in 15% of patients, the generalized in 85%. Treatment of the generalized form largely followed the Fauci scheme, achieving remission in 97%. After one year of immunosuppressive treatment 93% of patients with WG were still alive, 74% after 5 years.CONCLUSION:This is the first report in Central Europe to have analysed data on patients with WG and MPA, followed up for 20 years at one centre. There were no significant differences in the pattern of organ involvement, results of treatment and prognosis from previously published multicenter studies. Our data demonstrate that the diagnosis of WG has been more frequently made since the introduction of immunological tests for ANCA.