CMV late phase-induced mTOR activation is essential for efficient virus replication in polarized human macrophages.

Human cytomegalovirus (CMV) remains one of the most important pathogens following solid-organ transplantation. Mounting evidence indicates that mammalian target of rapamycin (mTOR) inhibitors may decrease the incidence of CMV infection in solid-organ recipients. Here we aimed at elucidating the molecular mechanisms of this effect by employing a human CMV (HCMV) infection model in human macrophages, since myeloid cells are the principal in vivo targets of HCMV. We demonstrate a highly divergent host cell permissiveness for HCMV with optimal infection susceptibility in M2 but not M1 polarized macrophages. Employing an ultrahigh purified HCMV stock we observed rapamycin-independent viral entry and induction of IFN-ß transcripts, but no proinflammatory cytokines or mitogen-activated protein kinases and mTOR activation early after infection. However, in the late infection phase, sustained mTOR activation was observed in HCMV-infected cells and was required for efficient viral protein synthesis including the viral late phase proteins pUL-44 and pp65. Accordingly, rapamycin strongly suppressed CMV replication 3 and 5 days postinfection in macrophages. In conclusion, these data indicate that mTOR is essential for virus replication during late phases of the viral cycle in myeloid cells and might explain the potent anti-CMV effects of mTOR inhibitors after organ transplantation.

Kidney biopsy in patients with diabetes mellitus.

BACKGROUND: The clinical consequences of the results obtained by kidney biopsy in patients with diabetes mellitus Type 1 or Type 2 have been controversial. Our study was conducted to assess clinical symptoms and histological diagnoses in patients with diabetes mellitus Type 1 and Type 2 undergoing kidney biopsy. DESIGN, SETTING AND PATIENTS: Observational study. The study included data from 567 consecutive renal biopsies of patients with diabetes mellitus Type 1 or 2 and chronic kidney disease (CKD) examined by standard histopathological procedures. The main outcome measures were incidence of diabetic nephropathy (DN) and glomerulonephritis (GN), predictors for the presence of both DN or GN. RESULTS: Approximately 70% of patients with diabetes mellitus Type 1 or 2 and evidence for CKD had DN. Glomerular diseases present in approximately 30% of patients with diabetes were predominantly immune complex GN and secondary focal glomerulosclerosis, followed by IgA-GN, which was associated with microhematuria (p = 0.01) and hypertension (p = 0.04). Only a minority had membranous GN, which was associated with nephrotic syndrome (p = 0.004). Progressive CKD predicted the presence of GN in diabetes mellitus Type 2 (r = -0.98; p = 0.02). CONCLUSION: GN is not uncommon in patients with diabetes and evidence for CKD. Kidney biopsy should therefore be considered in patients with diabetes and progressive CKD.

[Urinary tract infections]. / Harnwegsinfektionen.

Urinary tract infections occur very frequently in the community and in hospitalized patients and are mainly caused by Escherichia (E.) coli. Depending on virulence determinants of uropathogenic microorganisms and host-specific defense mechanisms, urinary tract infections can manifest as cystitis, pyelonephritis (bacterial interstitial nephritis), bacteremia or urosepsis. Uncomplicated urinary tract infections in otherwise healthy women should be treated for 3-7 days depending on the antibiotic therapy chosen, even if spontaneous remission rates of up to 40% have been reported. Antibiotics of the first choice for empirical treatment of uncomplicated urinary tract infection are fluoroquinolones, pivmecillinam and fosfomycin. A huge problem is the increasing antimicrobial resistance of uropathogenic microorganisms. Complicated urinary tract infections associated with anatomical and/or functional abnormalities of the urinary tract and/or comorbidities such as diabetes or immunosuppressive therapy, need longer antibiotic treatment (e.g. 10-14 days) as well as interdisciplinary diagnostic procedures. Treatment of community acquired urosepsis includes cephalosporins of the third generation, piperacillin/tazobactam or ciprofloxacin. For nosocomial urosepsis the combination with an aminoglycoside or a carbapenem is recommended.

Postprandial blood glucose level in maintenance hemodialysis patients predicts post-transplant-diabetes-mellitus.

Post-transplant-diabetes-mellitus (PTDM) is a frequent complication after kidney transplantation. One-hundred-and-seven patients with kidney transplantation were screened for the occurrence of PTDM. Of these, full data sets from 49 subjects were available with documented glucose concentrations during maintenance hemodialysis (MHD) and regular clinical follow-up of 7-34 months. For assessment of glucose metabolism the response to a standard meal during MHD was used in normoglycemic patients based on fasting blood glucose. Abnormal postprandial blood glucose concentration was defined as >140 mg/dl 2 h after food intake.Twelve end stage renal disease patients had abnormal postprandial blood glucose on MHD. All 12 subjects but also four MHD patients with normal postprandial and fasting blood glucose values developed PTDM. Multivariate Cox-regression analysis revealed that abnormal postprandial blood glucose is a strong predictor for PTDM (Hazard ratio: 42.3 (IQR: 7.9-227.2); p<0.001). Fasting blood glucose (94 vs. 100 mg/dl) was not different between MHD patients who did (n=16) or did not (n=33) develop PTDM.This study suggests that measurement of postprandial blood glucose during MHD identifies patients who develop PTDM after kidney transplantation. It should be used for screening of patients at risk.

The multifunctional role of mTOR in innate immunity: implications for transplant immunity.

The mammalian target of rapamycin (mTOR) is an evolutionary conserved serine-threonine kinase that senses various environmental stimuli in most cells primarily to control cell growth. Restriction of cellular proliferation by mTOR inhibition led to the use of mTOR inhibitors as immunosuppressants in allogeneic transplantation as well as novel anticancer agents. However, distinct inflammatory side effects such as fever, pneumonitis, glomerulonephritis or anemia of chronic disease have been observed under this treatment regime. Apart from the mere cell-cycle regulatory effect of mTOR in dividing cells, recent data revealed a master regulatory role of mTOR in the innate immune system. Hence, inhibition of mTOR promotes proinflammatory cytokines such as IL-12 and IL-1beta, inhibits the anti-inflammatory cytokine IL-10 and boosts MHC antigen presentation via autophagy in monocytes/macrophages and dendritic cells. Moreover, mTOR regulates type I interferon production and the expression of chemokine receptors and costimulatory molecules. These results place mTOR in a complex immunoregulatory context by controlling innate and adaptive immune responses. In this review, we discuss the clinical consequences of mTOR-inhibitor therapy and aim to integrate this recent data into our current view of the molecular mechanisms of clinically employed mTOR inhibitors and discuss their relevance with special emphasis to transplantation.

Late onset Pneumocystis pneumonia in renal transplantation after long-term immunosuppression with belatacept.

Interference with T-cell function increases the risk of infections, especially during the early post-transplant period. Belatacept, a costimulation blocker, is currently being tested in phase III clinical trials. Here we report a renal transplant recipient who received belatacept and developed severe Pneumocystis jirovecii pneumonia (PCP) with fatal superinfections 4 years post transplant. Cytomegalovirus infection preceded PCP, which typically occurs in overimmunosuppressed patients, but has not yet been reported under T-cell costimulation blockade in transplant patients. This case illustrates the possibility of excessive immunosuppression even with a lymphocyte-specific regimen.

Immunoadsorption in SLE: three different high affinity columns are adequately effective in removing autoantibodies and controlling disease activity.

INTRODUCTION: Pathogenic autoantibodies (Abs) are a hallmark of SLE and their rapid removal is beneficial in active SLE. Immunoadsorption (IAS) is effective in removing serum levels of all classes of immunoglobulin (Ig), immune complexes (IC) and anti-dsDNA Abs and appears superior to plasmapheresis with respect to side effects. IAS can be performed with different columns, which use different ligands to bind their target. In particular, high affinity columns are in the focus of interest. Their ligands are either sheep IgG directed against human Ig (Ig-column, Ig-Therasorb®), or staphylococcal Protein A (ProtA-column, Immunosorba®), or the synthetic peptide Gam146 (GAM-column, Globaffin®). In our experience Ig-columns have been effective in treating active renal SLE. However, no analysis has so far been published on which column type should be preferred in treating SLE patients. PATIENTS AND METHODS: Among our SLE patients maintained on prolonged IAS therapy, we identified those with stable renal SLE and low to moderate disease activity who were successfully treated by using Ig-columns. Six of these patients were switched to ProtA-columns, keeping the rest of the protocol and the medication constant. In addition, two patients were switched from Ig- to GAM-columns. RESULTS: All types of columns significantly lowered the serum levels of IgG, IgM, and anti-dsDNA Abs. Disease activity was constantly low before and after the switch, as were parameters of renal function. In addition, patients with highly active disease were effectively treated when ProtA- (n=6) or GAM-columns (n=1) were used as first-line extracorporeal treatment. CONCLUSION: Our data demonstrate that all columns are adequately effective in controlling key parameters of SLE. Thus, it is not the type of the ligand, but only the outcome, i.e. the successful removal of Ig, IC, and (auto-) Abs that is required for controlling SLE activity.

Current concepts of molecular defence mechanisms operative during urinary tract infection.

Mucosal tissues such as the gastrointestinal tract are typically exposed to a tremendous number of microorganisms and many of them are potentially dangerous to the host. In contrast, the urogenital tract is rather infrequently colonized with bacterial organisms and also devoid of physical barriers as a multi-layered mucus or ciliated epithelia, thereby necessitating separate host defence mechanisms. Recurrent urinary tract infection (UTI) represents the successful case of microbial host evasion and poses a major medical and economic health problem. During recent years considerable advances have been made in our understanding of the mechanisms underlying the immune homeostasis of the urogenital tract. Hence, the system of pathogen-recognition receptors including the Toll-like receptors (TLRs) is able to sense danger signalling and thus activate the host immune system of the genitourinary tract. Additionally, various soluble antimicrobial molecules including iron-sequestering proteins, defensins, cathelicidin and Tamm-Horsfall protein (THP), as well as their role for the prevention of UTI by modulating innate and adaptive immunity, have been more clearly defined. Furthermore, signalling mediators like cyclic adenosine monophosphate (cAMP) or the circulatory hormone vasopressin were shown to be involved in the defence of uropathogenic microbes and maintenance of mucosal integrity. Beyond this, specific receptors e.g. CD46 or beta1/beta 3-integrins, have been elucidated that are hijacked by uropathogenic E. coli to enable invasion and survival within the urogenital system paving the way for chronic forms of urinary tract infection. Collectively, the majority of these findings offer novel avenues for basic and translational research implying effective therapies against the diverse forms of acute and chronic UTI.

Urinary tract infection in renal transplant recipients.

Urinary tract infection (UTI) is common in renal transplant recipients. Frequency of UTIs depend on many factors such as age, female gender, kidney function, co-morbidity, type and amount of immunosuppression, urological instrumentation and/or the follow-up period (short term or long term) after kidney transplantation. UTI may worsen graft and patient survival. A significant proportion of renal transplant recipients with UTIs may develop acute pyelonephritis (APN), which is an independent risk factor for deterioration of graft function. Renal transplant recipients with UTIs are often clinically asymptomatic as a consequence of immunosuppression. UTI, however, may progress to APN (particularly in the early post-transplant period), bacteraemia and the full blown picture of urosepsis. Strategies for long term prophylaxis and antimicrobial treatment of UTI in renal transplant recipients are discussed.

Posttransplant HLA alloreactivity in stable kidney transplant recipients-incidences and impact on long-term allograft outcomes.

Humoral alloreactivity is well established to predict adverse allograft outcomes. However, in some recipients, alloantibodies may also occur in the absence of graft dysfunction. We evaluated if and how often complement- and noncomplement-fixing alloantibodies are detectable in stable recipients and whether, in this context, they affect long-term outcomes. Sera obtained from 164 kidney transplant recipients at 2, 6 and 12 months were evaluated by FlowPRA screening and single-antigen testing for detection of IgG- or C4d-fixing HLA panel reactivity and donor-specific antibodies (DSA). Applying stringent criteria, we selected 34 patients with an uneventful 1-year course (no graft dysfunction or rejection) and excellent graft function at 12 months [estimated glomerular filtration rate (eGFR) >or=60 mL/min and proteinuria

Postprandial intradialytic dysglycaemia and diabetes in maintenance haemodialysis patients.

BACKGROUND: Although the risk of developing dysglycaemia has been investigated in different communities this incidence is poorly studied in patients on maintenance haemodialysis (MHD). MATERIALS AND METHODS: In a multicentre observational cohort study the occurrence of dysglycaemia was assessed in 239 primary normoglycaemic end stage renal disease (ERSD) patients on MHD. Dysglycaemia (fasting blood glucose > 110 mg dL(-1), > 140 mg dL(-1) 2 h after food intake) or diabetes (fasting blood glucose > 126 mg dL(-1) or > 200 mg dL(-1) at any time) were defined according to WHO criteria and cases were compared with age matched controls within the cohort. RESULTS: Dysglycaemia was found in 82 primary normoglycaemic ESRD patients (34%) within 31 months after initiation of MHD. In 31 of these patients type 2 diabetes was diagnosed. When compared with matched control MHD patients differences in body mass index (BMI), HbA1c and postprandial blood glucose were detectable (P < 0.05). Increments in 0.1% of HbA1c were related with 11% higher odds for dysglycaemia (P = 0.002). In a subgroup of 36 primary normoglycaemic MHD patients who developed dysglycaemia event-free survival was 64%, 53%, 31%, 17% and 11% after 1, 2, 3, 4 and 5 years of haemodialysis treatment. CONCLUSION: Onset of dysglycaemia or diabetes is frequent in ESRD patients after onset of chronic haemodialysis. Routine measurement of blood glucose before and after haemodialysis should be implemented as a standard of care during MHD.

Cartilage biomarkers in hemodialysis patients and the effect of beta2-microglobulin on articular chondrocytes.

OBJECTIVE: Dialysis-related amyloidosis (DRA) is a severe complication of maintenance hemodialysis (HD). Given the predominant deposition of beta(2)-microglobulin (beta2m) fibrils on articular cartilage in early DRA, we investigated the significance of beta2m and its relationship to distinct cartilage biomarkers in early DRA diagnosis in HD patients. Furthermore, we assessed the effects of beta2m on articular chondrocytes in vitro. METHODS: Serum samples from 133 patients were collected before and after HD. Type II collagen cleavage product (C2C), procollagen II c-propeptide (CPII), aggrecan chondroitin sulfate 846 epitope (CS-486) and cartilage oligomeric matrix protein (COMP) levels were determined by enzyme-linked immunosorbent assay. Primary bovine articular chondrocytes were cultured as monolayers and incubated with beta2m at 1.5mg/l and 20mg/l. Cartilage glucosaminoglycan synthesis was measured by [(35)S]sulfate incorporation. mRNA expression of interleukin (IL)-1beta, matrix metalloproteinases (MMPs)-3 and -9 was measured by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Incubation with beta2m at 20mg/l significantly decreased matrix biosynthesis. PCR analysis revealed an increase of IL-1beta, as well as MMPs-3 and -9 on the mRNA level. C2C/CPII, CS-486 and COMP levels were increased only in a subset of patients without a significant correlation with beta2m concentrations. A subgroup analysis elucidated an increase in type II collagen degradation during the first years of HD, as shown by the elevation of C2C/CPII ratio. CONCLUSION: beta2m exerted anti-anabolic effects on articular chondrocytes in vitro and might be involved in cartilage degradation in HD patients. beta2m serum levels, however, did not reflect cartilage degradation in DRA. The assessment of C2C/CPII, CS-486 or COMP concentrations apparently has minor relevance in DRA diagnosis in HD patients. However, the increased type II collagen breakdown within 5 years after HD onset possibly mirrors the early stages of DRA. Thus, the C2C/CPII ratio could be employed in longitudinal studies, since it may reflect a risk for DRA related arthropathy development in a subset of patients.

Detecting prostate cancer by intracellular macrophage prostate-specific antigen (PSA): a more specific and sensitive marker than conventional serum total PSA.

BACKGROUND: Serum prostate-specific antigen (PSA) is a standard method and a widely used marker for prostate cancer, but it has a poor specificity for early detection. Herein we demonstrate that intracellular macrophage PSA (imPSA) enables screening and differentiation between benign and malignant prostate disease. MATERIALS AND METHODS: The efficacy of intracellular macrophage PSA in circulating and tissue macrophages was therefore investigated in a double-centre study of 38 prostate cancer patients and 36 healthy controls by fluorescent-activated cell sorting analysis and immunohistology. RESULTS: Both methods uncovered the existence of PSA-positive macrophages specific for patients with prostate cancer. In addition, we demonstrate the superiority of our new test over standard serum total PSA in a blinded double-centre trial. ImPSA had a marked higher sensitivity and specificity than serum total PSA (imPSA: sensitivity 92%, specificity 92%, positive predictive value 92%; serum total PSA: sensitivity 79.5%, specificity 87.5%, positive predictive value 26.8%). CONCLUSION: In this study, we demonstrate that imPSA is a new prostate cancer screening method that is highly sensitive and more specific than standard PSA testing.

In vitro detection of C4d-fixing HLA alloantibodies: associations with capillary C4d deposition in kidney allografts.

Capillary C4d deposition is a valuable marker of antibody-mediated rejection (AMR). In this analysis, flow cytometric detection of alloantibody-triggered C4d deposition to HLA antigen-coated microparticles ([C4d]FlowPRA) was evaluated for its value as a marker for C4d deposition in renal allografts. For comparative analysis, 105 first renal biopsies performed for graft dysfunction and an equal number of concurrent sera were subjected to immunohistochemistry and [C4d] plus standard [IgG]FlowPRA, respectively. C4d deposition/fixation was detected in 17 biopsies and, applying [C4d]FlowPRA HLA class I and II screening, also in a small number of corresponding sera (N = 20). IgG reactivity detected by standard [IgG]FlowPRA was more frequent (49% of sera). Comparing [C4d]FlowPRA screening with capillary C4d staining, we found a high level of specificity (0.92 [95% confidence interval: 0.86-0.98]), which far exceeded that calculated for [IgG]FlowPRA (0.60 [0.50-0.70]). [IgG]FlowPRA screening, however, turned out to be superior in terms of sensitivity (0.94 [0.83-1.05] vs. 0.76 [0.56-0.97] calculated for C4d-fixing panel reactivity). Remarkably, posttransplant single antigen testing for identification of complement-fixing donor-specific alloreactivities failed to improve the predictive value of FlowPRA-based serology. In conclusion, our results suggest that detection of complement-fixing HLA panel reactivity could provide a specific tool for monitoring of C4d-positive AMR.

Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multicenter trials.

AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa in a large cohort of dialysis patients. METHODS: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10 and 13 g/dl and efficacy was evaluated during a 4-week evaluation period. RESULTS: In the 1,101 patients assigned to Q2W darbepoetin alfa (i.v., n = 196, s.c., n = 905), mean (SD) Hb levels were 11.53 (0.77) g/dl at baseline and 11.35 (1.04) g/dl at evaluation (mean change in Hb -0.27 g/dl, 95% confidence interval 0.34, -0.20). Hb levels were maintained between 10 and 13 g/dl during evaluation in 85% of patients. Darbepoetin alfa doses were similar at baseline and evaluation, and the i.v. and s.c. routes were associated with similar efficacy and dose requirements. Darbepoetin alfa was well-tolerated. CONCLUSIONS: Q2W darbepoetin alfa is effective in maintaining Hb levels in dialysis patients switched from weekly rHuEPO, regardless of the route of administration and with no notable increase in the weekly equivalent dose.

The role of peritoneal dialysis in the management of treatment-resistant congestive heart failure: A European perspective.

Patients with congestive heart failure (CHF) resistant to conventional treatment have a poor prognosis. Extracorporeal ultrafiltration (UF) appears to be the therapy of choice for short-term management of such patients with severe fluid overload, whereas peritoneal dialysis (PD) may be the therapy of choice for the long-term treatment. Fluid removal results in reduction of plasma volume, improvement of hyponatremia, reduction in pulmonary capillary wedge pressure, improvement of New York Heart Association functional heart failure class, improvement of functional rehabilitation and quality of life, reduction of hospitalizations and readmissions, as well as improvement in diuretic responsiveness. Whether extracorporeal UF and/or PD modifies the survival rate of patients with refractory CHF needs to be determined in prospective randomized controlled trials.

The role of tidal peritoneal dialysis in modern practice: A European perspective.

Tidal peritoneal dialysis (TPD) has been introduced to optimize adequacy of peritoneal dialysis (PD). Early studies reported similar or even better small solute clearances with TPD than those achieved with continuous ambulatory peritoneal dialysis or continuous cyclic peritoneal dialysis. However, in many studies treatment volumes were much higher during TPD compared with other PD modalities. Based on current evidence, TPD provides no advantage of increased small solute clearances, middle molecule clearances, or peritoneal ultrafiltration as compared to non-tidal automated peritoneal dialysis (APD) when dialysate flow is kept constant. However, TPD reduces drainage pain and nightly alarms during cycler treatment. Tidal volume should be kept as high as possible in these patients, especially in those with low average peritoneal transport rates. Based on theoretical considerations and little evidence, TPD could provide better clearances than conventional APD when a very high dialysate flow (>or=5 l/h) is used. Such dialysate flow rates are not routinely prescribed in home APD patients. However, they may be interesting for in-center PD patients. One randomized crossover trial reported higher small solute clearances with TPD compared to non-tidal APD in patients with acute renal failure. TPD is also the preferred treatment modality in patients with ascites as it allows a controlled outflow of fluid from the peritoneal cavity. Newer treatment modalities, for example, continuous flow PD, may be interesting alternatives in an effort to increase efficacy of PD in the future. However, because such treatment regimens are expensive and elaborate they have not been established for routine use until now.

Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia.

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3-5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212 pg/ml (36-577) vs 42 pg/ml (17-150); P < 0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862 pg/ml (431-2423) vs 141 pg/ml (102-471); P < 0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml appears to be a clinically meaningful threshold for thyroidectomy.

Adequacy of automated peritoneal dialysis with and without manual daytime exchange: A randomized controlled trial.

Until now, it remains unclear whether the addition of manual daytime exchanges or increasing the nightly dialysate flow is the best strategy to optimize automated peritoneal dialysis (APD) treatment. In this open-label randomized controlled crossover trial, 18 patients with high-average (HA) or low-average (LA) peritoneal transport rates sequentially underwent two different APD regimens for 7 days each, with an intermittent washout period of 7 days. 'Manual exchange' treatment was a conventional APD with low nightly dialysate flow and one manual daytime exchange. 'High-flow' treatment was defined by cycler therapy with high dialysate flow but without manual daytime exchange. Creatinine clearances (8.56+/-1.22 vs 7.87+/-1.04 l/treatment, P = 0.011) and urea nitrogen clearances (12.83+/-1.98 vs 11.68+/-1.06 l/treatment, P = 0.014) were significantly increased during 'high-flow' treatment compared to 'manual exchange' treatment. Sodium removal was significantly lower and glucose absorption was higher with the 'high-flow' regimen. Phosphate clearances, beta2-microglobulin clearances, ultrafiltration, and peritoneal protein loss were not different between the two treatment modalities. Subgroup analysis dependent on peritoneal transport types showed that the effect on clearances was most marked and significant in HA transporters, whereas sodium removal was lowest in LA transporters. We conclude that small solute clearances can be significantly improved and middle molecule clearances maintained in APD patients by increasing the nightly dialysate flow instead of adding a manual daytime exchange. However, the possible benefit of better clearances with higher nightly treatment volumes has to be weighed against increased costs and the possible negative impact of impaired sodium removal, especially in LA transporters.

ESPEN Guidelines on Enteral Nutrition: Adult renal failure.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in nephrology patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They were discussed and accepted in a consensus conference. Because of the nutritional impact of renal diseases, EN is widely used in nephrology practice. Patients with acute renal failure (ARF) and critical illness are characterized by a highly catabolic state and need depurative techniques inducing massive nutrient loss. EN by TF is the preferred route for nutritional support in these patients. EN by means of ONS is the preferred way of refeeding for depleted conservatively treated chronic renal failure patients and dialysis patients. Undernutrition is an independent factor of survival in dialysis patients. ONS was shown to improve nutritional status in this setting. An increase in survival has been recently reported when nutritional status was improved by ONS.