Biocompatible hemodialysis membranes for acute renal failure.

BACKGROUND: Acute renal failure (ARF) is associated with substantial morbidity and mortality. Some studies have reported a survival advantage among patients dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM). These findings were not consistently observed in subsequent studies. OBJECTIVES: To ascertain whether the use of BCM confers an advantage in either survival or recovery of renal function over the use of BICM in adult patients with ARF requiring intermittent hemodialysis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE (from 1966), EMBASE (from 1980), the Mexican Index of Latin American Biomedical Journals IMBIOMED (from 1990), the Latin American and Caribbean Health Sciences Literature Database LILACS (from 1982), and reference lists of articles. Search date: January 2007 SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing the use of a BCM with a BICM in patients > 18 years of age with ARF requiring intermittent hemodialysis. DATA COLLECTION AND ANALYSIS: Two authors extracted the data independently. Cellulose-derived dialysis membranes were classified as BICM, and synthetic dialyzers were considered as BCM. The main outcomes were all-cause mortality and recovery of renal function by type of dialyzer. We further explored these outcomes according to the flux properties (high-flux or low-flux) of each of these dialyzers. A meta-analysis was conducted by combining data using a random-effects model. MAIN RESULTS: Ten studies were included in the primary analysis of mortality, with a total of 1100 patients. None of the pooled risk ratios (RRs) reached statistical significance. The pooled RR for mortality was 0.93 (95% confidence interval (CI) 0.81 to 1.07). The overall RR for recovery of renal function, which was inclusive of 1038 patients from nine studies, was 1.09 (95% CI 0.90 to 1.31). The pooled RR for mortality by dialyzer flux property was 1.05 (95% CI 0.81 to 1.37). The pooled RR for recovery of renal function by flux property was 1.30 (95% CI 0.83 to 2.02). A meta-analysis of mortality among kidney transplant recipients was not possible, however the analysis of recovery of renal function in this patient population revealed an RR of 1.05 (95% CI 0.87 to 1.26). Results of sensitivity analyses did not differ significantly from the primary analyses. AUTHORS' CONCLUSIONS: There is no demonstrable clinical advantage to the use of BCM versus BICM in patients with ARF who require intermittent hemodialysis.

Recovery of acute renal failure following bilateral renal artery angioplasty and stenting.

Atherosclerotic renovascular disease commonly coexists with chronic kidney disease, and its optimal management remains unsettled. In this case report, we describe a 75-year-old woman with chronic kidney disease and critical atherosclerotic bilateral renal artery stenosis, who presented with a hypertensive emergency and developed acute renal failure following antihypertensive treatment. Bilateral percutaneous transluminal renal angioplasties (PTRA) with stent placement were performed and resulted in immediate recovery of renal function. The existing literature on this impressive response to PTRA is reviewed and discussed.

Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

CREB transcription factor modulates Bcl2 transcription in response to C5a in HL-60-derived neutrophils.

BACKGROUND: Complement fragment C5a and neutrophils have been implicated in the pathogenesis of renal disease and C5a has also been shown to delay apoptosis of human neutrophils via a transcription-independent pathway. However, transcription-dependent pathways have not been well described. The present study examined whether activation of HL-60-derived neutrophils by C5a modulates the transcription of two members of the Bcl2 family, Bax (pro-apoptotic) and Bcl2 (anti-apoptotic) molecules, and whether the cAMP-response element-binding protein (CREB) transcription factor mediates these effects through the phosphatidylinositol 3-kinase (PI3K)/Akt and extra-cellular signal-regulated kinase (ERK) signalling pathways. MATERIALS AND METHODS: The human promyelocytic leukaemia HL-60 cell line was differentiated into neutrophils using 1.25% DMSO. Differentiated cells were incubated with recombinant human C5a for 30-120 min with, or without, pretreatment with wortmannin or PD98059. The cells were lysed and quantified for gene-specific Bax and Bcl2 mRNA. In separate experiments, cells were incubated with C5a for 5-30 min with, or without, pretreatment with wortmannin, PD98059, or alkaline phosphatase. Cells were then lysed and immunoblotted using antihuman phospho-CREB (Ser133) antibody. Apoptosis was assessed by measuring active caspase-3 in differentiated HL-60 cells. RESULTS: C5a inhibited caspase-3 activation in HL-60-derived neutrophils (P=0.003). C5a significantly increased the expression of Bcl2 mRNA (P=0.028), which was time-dependent, peaking at 30 min, and was abrogated in the presence of either wortmannin or PD98059 (both P=0.028). The C5a had no impact on Bax mRNA expression. The Bax : Bcl2 mRNA ratio markedly decreased at 30 min (P=0.028). Time-dependent effect of C5a on CREB phosphorylation was demonstrable and rapid, peaking at 5 min, and was abrogated by either wortmannin or PD98059 (both P=0.028). Phosphorylation of CREB, but not of Akt and ERK, was inhibited by alkaline phosphatase (P=0.028). The effect of C5a on Bcl2 mRNA expression was abrogated by alkaline phosphatase (P=0.028). The Bax : Bcl2 mRNA ratio markedly increased in the presence of alkaline phosphatase (P=0.046). CONCLUSIONS: This study demonstrates that C5a induces Bcl2 mRNA transcription in HL-60-derived neutrophils, which is mediated in part by CREB through the convergence of the PI3K/Akt and ERK-signalling pathways.

Biocompatible hemodialysis membranes for acute renal failure.

BACKGROUND: Acute renal failure (ARF) is associated with substantial morbidity and mortality. Some trials have reported a survival advantage among patients dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM). These findings were not consistently observed in subsequent studies. OBJECTIVES: To ascertain whether the use of BCM confers an advantage in either survival or recovery of renal function over the use of BICM in adult patients with ARF requiring intermittent hemodialysis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library - Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004), the Mexican Index of Latin American Biomedical Journals IMBIOMED (1990 to January 2004), the Latin American and Caribbean Health Sciences Literature Database LILACS (1982 to January 2004), and reference lists of articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing the use of a BCM with a BICM in patients > 18 years of age with ARF requiring intermittent hemodialysis. DATA COLLECTION AND ANALYSIS: Two authors extracted the data independently. Cellulose-derived dialysis membranes were classified as BICM, and synthetic dialyzers were considered as BCM. The main outcomes were all-cause mortality and recovery of renal function by type of dialyzer. We further explored these outcomes according to the flux properties (high-flux or low-flux) of each of these dialyzers. A meta-analysis was conducted by combining data using a random-effects model. MAIN RESULTS: Nine studies were included in the primary analysis of mortality, with a total of 1062 patients. None of the pooled RR's reached statistical significance. The pooled relative risk (RR) for mortality was 0.93 (95% confidence interval (CI) = 0.81 to 1.07). The overall RR for recovery of renal function, inclusive of 1038 patients from nine studies was 1.09 (95% CI 0.90 to 1.31). The pooled RR for mortality by dialyzer flux property was 1.03 (95% CI 0.82 to 1.30). The RR for recovery of renal function by flux property was 0.85 (95% CI 0.55 to 1.31). A meta-analysis of mortality of kidney transplant recipients was not possible, but the analysis of recovery of renal function in this patient population was 1.09 (95% CI 0.91to 1.31). Results of sensitivity analyses did not differ significantly from the primary analyses. AUTHORS' CONCLUSIONS: There is no demonstrable clinical advantage to the use of BCM versus BICM in patients with ARF who require intermittent hemodialysis.

Ribavirin monotherapy for hepatitis C virus-associated membranous nephropathy.

Glomerular diseases associated with hepatitis C virus (HCV) infection are increasingly being recognized. Antiviral therapy with interferon-alpha (IFN-alpha) and ribavirin eradicate viral activity in a significant proportion of patients with chronic active hepatitis, often with amelioration of extrahepatic manifestations, including glomerular pathology. Unfortunately, adverse effects often preclude the use of IFN-alpha. We describe a patient with refractory nephrotic syndrome secondary to HCV-associated membranous nephropathy who sustained a complete remission following the initiation of ribavirin monotherapy. The existing literature on the association between these two disorders and therapy with ribavirin is reviewed.

Anti-oxidants reverse uraemia-induced down-regulation of mitochondrial membrane potential and interleukin-10 production.

BACKGROUND: The anti-inflammatory cytokine, interleukin-10 (IL-10), has potent immunomodulatory effects. We hypothesized that previously reported defective synthesis of IL-10 by immunocompetent cells exposed to a uraemic milieu may be due to impaired mitochondrial membrane potential (MMP). MATERIALS AND METHODS: The human promonocytic THP-1 cell line was differentiated to monocytes and incubated with pooled control or uraemic plasma with and without catalase or N-acetyl L-cysteine (NAC). Basal hydrogen peroxide (H(2)O(2)) production was measured by flow cytometry. To measure MMP, cells were stained with rhodamine 123 (Rh123) and the uptake of Rh123 assessed by flow cytometry. To assess the relative contribution of the NADPH oxidase and mitochondrial electron transport chain (ELT) to endotoxin (ET)-stimulated IL-10 production among monocytic cells, cells were incubated with and without a selective NADPH oxidase inhibitor, apocynin and mitochondrial ELT inhibitors, diphenyliodinium and rotenone, washed and ET-stimulated IL-10 production was measured. In other experiments, cells were incubated with pooled control or uraemic plasma in the presence or absence of antioxidants followed by overnight incubation with ET. IL-10 production by monocytes in the cell supernatant was then quantified. RESULTS: Basal H(2)O(2) production was significantly higher among differentiated THP-1 cells exposed to uraemic plasma compared with normal plasma (180.57 +/- 10.24 vs. 41.57 +/- 8.98 MCI; P = 0.02). Uraemic plasma also down regulated MMP (4.60 +/- 1.28 vs. 8.00 +/- 1.59 MCI with normal plasma; P = 0.03). Both diphenyliodinium and rotenone, selective inhibitors of the mitochondrial ELT, inhibited ET-stimulated IL-10 production. In contrast, apocynin, a selective NADPH oxidase inhibitor, did not inhibit ET-stimulated IL-10 production. Further, ET-stimulated IL-10 production by cells incubated with uraemic plasma was significantly lower when compared to cells exposed to normal plasma. Pre-incubation with catalase and NAC restored uraemia-induced down regulation of MMP. In addition, ET-stimulated IL-10 production by cells incubated with uraemic plasma was also restored by both catalase and NAC. CONCLUSIONS: Our observations suggest that ET-stimulated IL-10 synthesis by monocytic cells is mitochondrial ELT-dependent and NADPH oxidase-independent. Monocytic cells exposed to a uraemic environment exhibit higher basal ROS production, lower MMP, and impaired ET-stimulated IL-10 synthesis. Anti-oxidants restore MMP and up-regulate ET-stimulated IL-10 synthesis.

C5a delays apoptosis of human neutrophils via an extracellular signal-regulated kinase and Bad-mediated signalling pathway.

AIMS: We recently demonstrated that complement fragment C5a delays apoptosis of human neutrophils via induction of the phosphatidylinositol-3 kinase (PI 3-K) pathway. In the present study, we examined whether C5a modulates neutrophil survival through the extracellular signal-regulated kinase (ERK) and Bad-mediated signalling pathway. METHODS: Human neutrophils were isolated by percoll gradient and preincubated for 1 h with or without PD98059 (20 microM), a specific ERK inhibitor, followed by incubation with C5a (1 microg mL(-1)) for 24 h. Apoptosis was quantified by flow cytometry, using propidium iodide nuclear staining. Extracellular signal-regulated kinase downstream signalling events were evaluated by measuring the expression of cytosolic total and phosphorylated p44/p42 proteins, and Bad phosphorylation using immunoblot analyses. These time-dependent analyses were performed over a brief exposure to C5a (0-30 min). Modulation of cytosolic caspase-9 and caspase-3 activity was measured by Western blot analyses. RESULTS: C5a inhibited neutrophil apoptosis (P=0.04), which was abrogated in the presence of PD98059 (P=0.04). Time-dependent effect of C5a on p44/p42 phosphorylation was rapid, peaked at 5 min, and was abrogated by the ERK inhibitor (P=0.04). In addition, brief stimulation of neutrophils with C5a induced phosphorylation of Bad, which was inhibited by the ERK inhibitor (P=0.03). Further, C5a suppressed the proteolytic cleavage of caspase-9 and caspase-3, which was reversed by ERK inhibition. Finally, blockade of both the ERK (with PD98059) and PI 3-K (with wortmannin) pathways did not induce additive inhibition of neutrophil apoptosis by C5a. CONCLUSION: This study demonstrates that in addition to the PI 3-K pathway, C5a also inhibits neutrophil apoptosis via an ERK-signalling pathway, resulting in phosphorylation of Bad and blockade of proteolytic cleavage of caspases. The activation of this additional survival-signalling pathway may be another important cellular mechanism that enhances neutrophil survival in inflammatory states.

Crescentic fibrillary glomerulonephritis associated with hepatitis C viral infection.

Fibrillary glomerulonephritis (FGN) is a pathological diagnosis that is rarely associated with systemic disorders. In this case report, we describe a woman who presented with FGN of the crescentic type in association with hepatitis C viral infection. The existing literature on the association between these 2 disorders is reviewed, and postulated therapy is presented.

Quantification of Bax and Bcl2 in polymorphonuclear leukocytes from haemodialysis patients: relation to hydrogen peroxide.

BACKGROUND: Bax and Bcl2 are two apoptosis-related molecules that play an important role in determining cell fate following oxidative injury. In the present study, we explored the relation of hydrogen peroxide (H2O2) generation by polymorphonuclear cells (PMNs) to the cytosolic expression of Bax and Bcl2 proteins and apoptosis in haemodialysis (HD) patients. METHODS: Cytosolic generation of H2O2 by PMNs from control subjects and HD patients was measured by flow cytometry using the dichlorofluorescin diacetate assay. Bax and Bcl2 expression was detected by flow cytometry using FITC-conjugated antibodies. Apoptosis was quantified by flow cytometry using propidium iodide nuclear staining. To examine the effect of H2O2 on Bcl2 and Bax expression, PMNs from control subjects were briefly exposed to H2O2 (0.1-100 microM) for 10 min and then washed and cultured for 6 h, with or without catalase, a H2O2 detoxifying molecule. Bcl2 and Bax expression was determined by Western blot analysis. RESULTS: Basal H2O2 generation by resting PMNs was significantly higher in HD patients compared with control subjects (211 +/- 115 vs. 23 +/- 5 MFI; P=0.002). However, PMNs from HD patients did not undergo accelerated programmed cell death compared with control subjects (58 +/- 7% vs. 46 +/- 5; P=0.14). Polymorphonuclear cells cytosolic Bcl2 was undetected in control subjects but detected in 25% of HD patients, and Bax was more frequently detected in PMNs from HD patients (75% vs. 67%; P=0.04). In the HD patients with detectable cytosolic Bax and Bcl2 proteins, the Bax to Bcl2 ratio inversely correlated with H2O2 levels (P<0.0001). Finally, brief exposure of PMNs to 0.1-100 microM of H2O2 resulted in a marked increase in Bcl2 expression (P=0.001), which was prevented by catalase (P=0.05). There was no apparent effect on Bax expression. CONCLUSIONS: This study demonstrates that in HD patients, high-resting cytosolic H2O2 production by PMNs is not associated with accelerated in vitro apoptosis, and that the Bax/Bcl2 system may counter-balance the deleterious effects of reactive oxygen species in human PMNs.

Sleep quality and clinical correlates in patients on maintenance dialysis.

BACKGROUND: Sleep quality is a subject of increasing interest to clinicians caring for dialysis patients. Self-assessed sleep disturbances have been associated with quality of life outcomes. The goal of this study was to identify clinical and laboratory parameters that are independently associated with overall sleep quality among prevalent dialysis patients. METHODS: The Epworth Sleepiness Scale (ESS) and the Sleep Problems Index (SPI), a questionnaire derived from the Medical Outcomes Study, were administered to 71 dialysis patients and 68 subjects without known kidney disease (control group). The ESS and the SPI sleep item responses between the 2 groups were compared. The sleep items from the SPI were also aggregated into a sleep quality score. Multivariate linear regression analyses of sleep quality scores were used to identify clinical factors that were independently associated with poor sleep. RESULTS: The ESS score was not significantly different between the 2 groups. However, the responses to the SPI sleep items demonstrated significantly impaired subjective sleep quality in dialysis patients compared with control subjects. In addition, overall sleep quality, as measured by the aggregated sleep score, was lower in dialysis patients compared with the control group (41 vs. 47, p < 0.001). In multivariate analyses, factors that were independently associated with poor sleep quality in dialysis patients were male gender (p = 0.006), history of coronary artery disease (p = 0.003), and high phosphate level (p = 0.05). CONCLUSION: This study demonstrates that global sleep quality of dialysis patients is substantially impaired. Poor sleep quality was associated with male gender, coronary artery disease and high serum phosphate level, a modifiable factor. Future studies are needed to examine the relationship of serum phosphate level to sleep quality in dialysis patients.

Impact of iron dextran on polymorphonuclear cell function among hemodialysis patients.

BACKGROUND: Polymorphonuclear cell (PMN) dysfunction and the increased use of parenteral iron may be important contributory factors to bacterial infections among patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). We compared the in vitro impact of a commonly used parenteral iron preparation, iron dextran, on PMN function and viability between a group of HD patients with normal iron indices and healthy subjects. METHODS: Eleven patients with ESRD on HD and 10 healthy subjects were studied. PMN harvested from heparinized blood were incubated with iron dextran (0 - 20 mM) in culture medium (RPMI) for 24 hours at 37 degrees C with 5% CO2 following which function and viability were assessed by flow cytometry using appropriate fluorescent labels. RESULTS: Unstimulated, S. aureus and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated hydrogen peroxide (H2O2) production was significantly higher in PMN unexposed to iron dextran from HD patients compared to those from healthy subjects. Iron dextran had no impact on unstimulated PMN H2O2 production in either group. In the healthy group, the only significant change occurred with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) stimulation, where cells exposed to 0.2 and 2.0 mM iron dextran produced less H2O2 relative to PMN unexposed to iron dextran (p < 0.05). In the HD group, all concentrations of iron dextran significantly attenuated H2O2 production stimulated by S. aureus, fMLP and PMA compared to PMN unexposed to iron dextran. Although PMN phagocytosis decreased with exposure to increasing concentration of iron dextran in both healthy subjects and HD patients, these changes did not achieve statistical significance. No significant changes in PMN viability or apoptosis were seen in either group after exposure to iron dextran. CONCLUSIONS: These results indicate that iron dextran, a standard parenteral iron preparation, attenuates PMN function in HD patients with normal iron indices at clinically relevant concentrations. Further studies are required to evaluate and compare the impact of newer preparations of parenteral iron, such as iron sucrose and ferric gluconate, on PMN function.

Effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure: a meta-analysis.

BACKGROUND: The effect of biocompatibility of hemodialysis membranes on mortality in acute renal failure (ARF) has been a subject of intense debate, with some, but not all studies reporting a lower risk of death among patients with ARF dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes (BICM). OBJECTIVES: We performed a meta-analysis of group data extracted from previously published studies of controlled clinical trials to assess the impact of BCM on the mortality among patients with ARF who required intermittent hemodialysis (IHD). METHODS: BCM and BICM were defined as synthetic and cellulose-derived membranes (cuprophan and cellulose acetate), respectively. All controlled clinical trials comparing the effect of BCM to BICM on clinical outcomes in the setting of ARF were included. Original articles as well as abstracts were included. Data in Tables, Figures, and text were independently extracted by 2 of the authors. Risk ratios (RR) for mortality were combined using the random-effects model. RESULTS: Seven studies with a total of 722 patients met the inclusion criteria. One hundred seventy-two (45%) of 384 patients died in the BCM group, compared with 156 (46%) of 338 patients in the BICM group. The RRs for mortality ranged from 0.56-1.28. Overall, the pooled RR for mortality was 0.92 (95% CI = 0.76-1.13) in favor of the BCM group. However, the test for heterogeneity in RR among studies was significant (chi2 = 8.6, p < 0.05). One study accounted for this significance, and once removed from the model, the RR for mortality was 0.94 (95% CI = 0.79-1.12), and the test for heterogeneity among studies lost its significance. Subgroup analyses comparing BCM to cuprophan membranes revealed that the RR for mortality was 0.82 (95% CI = 0.62 - 1.08) in favor of the BCM group, whereas in the subgroup of studies comparing BCM to cellulose acetate, the RR for mortality was 1.11 (95% CI = 0.87-1.44) in favor of the BCM group. CONCLUSION: This metaanalysis demonstrates that the use of BCM does not significantly affect mortality among patients with ARF who require IHD. However, subgroup analyses suggest that cellulose acetate membranes may offer a survival advantage when compared with synthetic membranes, which, in turn, may be more beneficial than cuprophan membranes. Available evidence does not permit a recommendation for or against the use of BCM in ARF. Large trials and pooled analyses of individual patient-level data will be required to assess sources of variability among studies and non-fatal outcomes of ARF.

Pulmonary infectious mortality among patients with end-stage renal disease.

BACKGROUND: Infection is the second-leading cause of death among patients with end-stage renal disease (ESRD). This is due in part to advanced age, comorbid conditions, and immune dysfunction observed in uremic states. Although one may hypothesize that pulmonary infectious mortality is higher among patients with ESRD compared with the general population (GP), no such data are currently available. METHODS: We compared annual pulmonary infectious mortality rates among patients with ESRD to those in the GP. The data were abstracted from the United States Renal Data System and the National Center for Health Statistics, respectively, and were stratified by age, gender, race, and presence or absence of diabetes mellitus (DM). In the GP, primary and multiple cause-of-death analyses were performed to account for potential limitations of the data sources. RESULTS: Overall, pulmonary infectious mortality rate was 14-fold to 16-fold higher in dialysis patients and approximately twofold higher in renal transplant recipients compared with the GP. After stratification for age, differences between groups decreased but retained their magnitude. CONCLUSION: Patients with ESRD treated with dialysis have higher pulmonary infectious mortality rates compared with the GP, even after stratification for age, race, and DM. Consequently, this patient population must be considered at high risk for the development of lethal pulmonary infections.

Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation.

The use of herbal medicine has become increasingly popular in the United States. Hypericum perforatum (St. John's wort) is an herbal extract that is used widely as a folk remedy for depression. In this case report, we describe a kidney transplant recipient who developed marked reduction of cyclosporine therapeutic activity after the self-initiation of St. John's wort. Postulated mechanisms for the ability of this herbal extract to interact with pharmaceutical medications are presented, and the existing literature is reviewed.

Hemodialysis in acute renal failure: does the membrane matter?

Patients who develop hospital-acquired acute renal failure (ARF) that require dialytic support have high mortality rates. The potential impact of dialyzer membrane biocompatibility on clinical outcomes in ARF has been a subject of ongoing controversy. This article summarizes the clinical trials published to date that have examined the effect of dialyzer membrane biocompatibility on clinical outcomes of patients with ARF who require intermittent hemodialysis. A redirection of research endeavors in the field of dialysis in ARF is also argued.

Mechanisms of neutrophil apoptosis in uremia and relevance of the Fas (APO-1, CD95)/Fas ligand system.

The regulation of neutrophil apoptosis in chronic renal failure (CRF) has not been clearly defined. The Fas/FasL system is an important apoptotic regulatory pathway in a wide variety of cells. Fas is a widely expressed cell surface protein that transduces an apoptotic signal after interaction with its natural ligand FasL. In contrast to the extensive tissue distribution of Fas, constitutive expression of FasL is relatively limited. We examined Fas and FasL expression by neutrophils in healthy subjects, patients with CRF, and patients on hemodialysis (HD) and peritoneal dialysis (PD). Fas expression was significantly higher among patients with CRF compared with control subjects, HD patients, and PD patients. FasL expression was significantly higher among patients with CRF compared with control subjects. At 24 h, neutrophil apoptosis was higher among patients with CRF compared with control subjects. Furthermore, high-neutrophil Fas expression was paralleled by a higher sensitivity to Fas-mediated apoptosis. There was a strong correlation between Fas-stimulated apoptosis and creatinine clearance as well as Fas expression. Finally, we found that uremic serum increased the expression of neutrophil-associated Fas and FasL proteins, when compared with normal serum. Further studies are under way to examine the regulation of this pathway in the uremic environment.

Apoptosis of leukocytes: basic concepts and implications in uremia.

Circulating blood leukocytes have short life expectancies and end their lives by committing programmed cell death or apoptosis. Apoptosis is an active form of cell death that is initiated by a number of stimuli and is intricately regulated. Apoptosis in both excessive and reduced amounts has pathological implications. Evidence suggests that apoptosis may play a role in the pathophysiology of immune dysfunction in uremia. Indeed, accelerated programmed cell death has been observed in lymphocytes, monocytes, and polymorphonuclear leukocytes among patients with chronic renal failure. This may be due in part to the retention of uremic toxins. The aim of this article is to review the evidence for accelerated leukocyte apoptosis, key regulatory apoptotic pathways, and the possible role of this highly organized process in the pathogenesis of immune dysfunction in uremia.

Pyrogenic reactions following gentamicin therapy: an alternative explanation.

A hypothesis is proposed, arguing that gentamicin administration in a single daily dose results in higher peak tissue concentration, marked bacteriolysis with endotoxin (ET) release and consequent ET-mediated febrile host responses, which resemble Jarisch-Herxheimer reactions.