The KTx360°-study: a multicenter, multisectoral, multimodal, telemedicine-based follow-up care model to improve care and reduce health-care costs after kidney transplantation in children and adults.

BACKGROUND: Follow-up care after kidney transplantation is performed in transplant centers as well as in local nephrologist's practices in Germany. However, organized integrated care of these different sectors of the German health care system is missing. This organizational deficit as well as non-adherence of kidney recipients and longterm cardiovascular complications are major reasons for an impaired patient and graft survival. METHODS: The KTx360° study is supported by a grant from the Federal Joint Committee of the Federal Republic of Germany. The study will include 448 (39 children) incident patients of all ages with KTx after study start in May 2017 and 963 (83 children) prevalent patients with KTx between 2010 and 2016. The collaboration between transplant centers and nephrologists in private local practices will be supported by internet-based case-files and scheduled virtual visits (patient consultation via video conferencing). At specified points of the care process patients will receive cardiovascular and adherence assessments and respective interventions. Care will be coordinated by an additional case management. The goals of the study will be evaluated by an independent institute using claims data from the statutory health insurances and data collected from patients and their caregivers during study participation. To model longitudinal changes after transplantation and differences in changes and levels of immunosuppresive therapy after transplantation between study participants and historical data as well as data from control patients who do not participate in KTx360°, adjusted regression analyses, such as mixed models with repeated measures, will be used. Relevant confounders will be controlled in all analyses. DISCUSSION: The study aims to prolong patient and graft survival, to reduce avoidable hospitalizations, co-morbidities and health care costs, and to enhance quality of life of patients after kidney transplantation. TRIAL REGISTRATION: ISRCTN29416382 (retrospectively registered on 05.05.2017).

[Symptom experience of patients after allogenic renal transplantation]. / Das Symptomerleben von Patienten nach allogener Nierentransplantation.

BACKGROUND: Quality of life and medication adherence of patients after renal transplantation (RTx) is most affected by problems associated with immunosuppressive symptoms. However, these problems are often underestimated in frequency and level of distress by professionals involved in transplantation. The aim of this study was to determine symptom occurrence and distress associated with current immunosuppressive medication following RTx. METHOD: A cross-sectional study was conducted to assess symptom experience using the Modified Transplant Symptom Occurrence and Symptom Distress Scale-Revised 59 with bivariate subgroup analysis. RESULTS: 605 renal transplant recipients completed the survey. The most common symptoms were dry skin, erectile problems, bruises, muscle weakness and tiredness. The erectile problems, menstrual problems, sores or warts around genitals, feelings of anxiety and joint pain appeared to be the most distressing symptoms. A significantly higher level of symptom prevalence and distress was associated with a number of sociodemographic, disease-related and drug-related factors. CONCLUSION: The study results increase awareness for a careful symptom assessment and provide the basis for strategies to control symptoms. That should lead to improved quality of life and medication adherence with long patient and graft survival.

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus.

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for approximately 5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. CONCLUSIONS: Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.

Treatment of PTLD with rituximab and CHOP reduces the risk of renal graft impairment after reduction of immunosuppression.

We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (+/- rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of >1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup. Patients treated with IR+chemotherapy +/- rituximab had a noninferior graft function compared with untreated controls suggesting that the negative impact of IR on the renal graft function can be fully compensated by the immunosuppressive effect of CHOP. The immunosuppressive effect of single agent rituximab may partially compensate the negative impact of IR on the graft function. Thus, it is possible to reduce immunosuppression when using chemotherapy to treat PTLD.

[Renal cell carcinoma: unusual late metastases 14 and 23 years after kidney transplantation]. / Nierenzellkarzinom: Ungewöhnliche Spätmetastasierung 14 und 23 Jahre nach allogener Nierentransplantation.

HISTORY AND FINDINGS: An asymptomatic 70-year-old man was found to have a tumor in the region of the left adrenal gland, having undergone cadaveric kidney transplantation 23 years ago. Two years before this a right nephrectomy had been performed for a renal cell carcinoma. There was no left kidney because of agenesis. 14 years after the kidney transplantation a metastasis of the renal cell carcinoma was identified in the thyroid gland. After its resection no further metastases had been discovered. INVESTIGATIONS: Laboratory tests were unremarkable. But a tumor was detected in the left adrenal gland by computed tomography. DIAGNOSIS, TREATMENT AND COURSE: The left adrenal gland was successfully resected. Its histology confirmed a second metastasis of the renal cell carcinoma 23 years after renal transplantation, but no other metastases were found. CONCLUSIONS: Kidney transplantation can be successfully performed even in patients with pre-existing carcinoma. A late metastasis of a renal carcinoma may occur. Close long-term follow-up of the patients is therefore essential.

Geographical prevalence, risk factors and impact of hepatitis B and C after renal transplantation.

BACKGROUND: Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations. OBJECTIVE: To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients. METHODS: From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence of > or = 5% HBV or > or = 10% HCV. RESULTS: The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD. CONCLUSIONS: Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Relationship of hepatitis B or C virus prevalences, risk factors, and outcomes in renal transplant recipients: analysis of German data.

BACKGROUND: Chronic liver disease resulting from hepatitis B (HBV) and hepatitis C (HCV) virus infections is still a major concern in kidney recipients. Our aim was to evaluate the prevalences, risk factors, and impact of HBV and HCV infections in adult renal transplant recipients in Germany. MATERIALS AND METHODS: Data were collected on 1633 kidney recipients transplanted between 1989 and 2002 at the 21 German renal transplant centers participating in MOST, the prospective Multinational Observational Study in Transplantation. Subgroup analyses compared HBV- and HCV-positive patients vs those with HBV/HCV-negative serology at the time of transplantation. RESULTS: The prevalences of 4.4% (n = 72) for HBV and 5.8% (n = 94) for HCV showed a marked decline over the last 15 years. Retransplantations were significantly more common among HBV+ (29%) and HCV+ (36%) than HBV-/HCV- patients (12%). HCV+ patients experienced significantly longer dialysis times and received significantly more pretransplantation blood transfusions. Between all groups, no significant differences were observed in acute rejection rate at 12 months or in renal graft function up to 5 years posttransplantation (mean glomerular filtration rate: HBV+, 57.3 mL/min; HCV+, 58.5 mL/min; HBV-/HCV-, 59 mL/min). No progressive elevations in liver enzymes and bilirubin were noted during the 5-year observation period. CONCLUSIONS: HBV and HCV infections currently have a low prevalence among German kidney graft recipients. Long dialysis times, blood transfusions, and retransplantations were identified as risk factors for hepatitis infections. At 5 years posttransplantation, kidney and liver functions did not differ significantly between HBV+ and HCV+ vs HBV-/HCV- renal transplant recipients.

Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial.

Oral ganciclovir prophylaxis and intravenous preemptive therapy are competitive approaches to prevent cytomegalovirus (CMV) disease after renal transplantation. This trial compared efficacy, safety and long-term graft outcome in 148 renal graft recipients randomized to ganciclovir prophylaxis (N = 74) or preemptive therapy (N = 74). Hierarchical testing revealed (i) patients with CMV infection had more severe periods of impaired graft function (creatinine clearance(max-min) 25.0 +/- 14.2 mL/min vs. 18.1 +/- 12.5 mL/min for patients without CMV infection; p = 0.02),(ii) prophylaxis reduced CMV infection by 65% (13 vs. 33 patients; p < 0.0001) but (iii) creatinine clearance at 12 months was comparable for both regimes (54.0 +/- 24.9 vs. 53.1 +/- 23.7 mL/min; p = 0.92). No major safety issues were observed, and patient survival at 12 months was similar in both groups (5 deaths [6.8%] vs. 4 [5.4%], p = 1.0000). Prophylaxis significantly increased long-term graft survival 4 years posttransplant (92.2% vs. 78.3%; p = 0.0425) with a number needed to treat of 7.19. Patients with donor +/recipient + CMV serostatus had the lowest rate of graft loss following prophylaxis (0.0% vs. 26.8%; p = 0.0035). In conclusion, it appears that routine oral prophylaxis may improve long-term graft survival for most renal transplant patients. Preemptive therapy can be considered in low risk patients in combination with adequate CMV monitoring.

Prospective age-matching in elderly kidney transplant recipients--a 5-year analysis of the Eurotransplant Senior Program.

Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors.

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.

INTRODUCTION: Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. METHODS: The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). RESULTS: In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. CONCLUSIONS: Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.

Cyclosporine-based immunosuppressive strategies for kidney recipients: interim analysis of German data from the Multinational Observational Study (MOST).

INTRODUCTION: We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome. METHODS: As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002. RESULTS: Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.8 months posttransplant) and 821 patients on maintenance therapy (median 71 months posttransplant). Triple regimens with CsA + mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2 receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%), while mono and dual regimen use de novo is declining (de novo 4%, maintenance 20%). Among 689 patients transplanted between 1987 and 2002 with outcome data, the mean incidence of acute rejection during the first posttransplant year was 21.6%. Rejection rates on initial therapy with CsA + MMF + Ste +/- antibodies (n = 517) averaged 17.8%. CONCLUSIONS: Between 1987 and 2002, CsA-based immunosuppression combined with MMF and Ste became the most commonly used strategy for both initial and maintenance therapy after kidney transplantation in Germany, yielding the low acute rejection rates particularly when combined with IL-2Ra.

Delayed graft function: risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study.

BACKGROUND: Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. RESULTS: Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. CONCLUSIONS: Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease.

Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to end stage liver disease in about 20-30% of these patients. Apart from the virus itself, host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation. The first group was typed serologically and compared with 331 blood and liver donors. The second group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease.

Native pyeloureterostomy after kidney transplantation: experience in 48 cases.

Necrosis and stenosis of the ureter are severe complications after kidney transplantation and occur with mean incidence of 2,9-13,4 %. Several surgical techniques like simple nephrostomy or complex urinary tract reconstruction have been applied for repair. In this study, our experience with native pyeloureterostomy (NPUS) using the native ureter is presented. Between March 1978 and June 1996, 2,592 kidney transplantations were performed in our institution. In 48 patients (1,9%), secondary urinary tract reconstruction by NPUS was necessary. These patients were evaluated retrospectively by review of the case notes. At the time of operation the mean age was 45 +/- 14 years. Indications for NPUS were distal ureteral stenosis (n = 29), necrosis (n = 17), bleeding (n = 1) or iatrogenic lesion of the ureter (n = 1). The mean time period between transplantation and urinary tract reconstruction was 20 +/- 23 days (range: 1-90 days) for necrosis and 404 +/- 637 days (range: 14-2,385 days) for stenosis. A pyeloureterostomy was technically feasible in all patients using the recipient's ipsilateral ureter. In 40 out of 48 patients the graft developed a normal function postoperatively (follow up: 39 +/- 48 months). A graft nephrectomy was necessary only in one patient, because of complete pyelonnecrosis 6 days after NPUS. Two grafts were lost due to acute rejection. Data of five patients were not available > 15 years after successful reconstruction. We can conclude that NPUS is a safe and simple rescue technique for the treatment of distal ureteral complications after kidney transplantation. Therefore, this technique should be the therapy of choice when secondary reconstruction by re-ureteroneocystostomy is not possible.

Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

BACKGROUND: In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. METHODS: Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. RESULTS: Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming units/ml). CONCLUSIONS: Extended high-flux dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent dialysis (high urea clearance, low treatment costs). High efficiency, simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended time periods (18 h) as well as for shorter intermittent renal replacement therapy in critically ill patients.

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes. The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.