Background/Aims

With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers’ recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT.

Methods

In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h.

Results

Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters.

Conclusions

CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance.

Patients with chronic kidney disease (CKD) must manage numerous medical treatments and lifestyle changes that strain their treatment adherence. An important strategy to improve adherence is to activate the patients’ motivation to manage their CKD. This article describes an approach for enhancing patients’ motivation for change, called motivational interviewing (MI), a treatment that is increasingly being used in health care settings to counsel patients with chronic diseases. Its basic principles, techniques, empirical support, published applications for improving CKD patients’ self-management, and how to learn MI are presented. Research is needed to determine the efficacy and mechanisms of MI for CKD treatment as well as the development of innovative ways to deliver it to patients and train busy health care practitioners in the approach.

Wearable blood processing devices offer an attractive solution to problems inherent in clinic-based, intermittent end-stage renal disease therapies. What is involved in transitioning even a part of the current clinic-based population to ambulatory therapy has not been clearly enumerated. This paper addresses what a first-generation wearable device might accomplish, how issues of safety will need to be addressed, and what will make the device attractive to, and manageable by, the patient. Medical, technological, and economic issues are identified.

Background

End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important. Aims: Theaim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials.

Methods

In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients’ self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden.

Conclusions

Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.

Acute lung injury (ALI) and acute kidney injury (AKI) are complications often encountered in the setting of critical illness. Both forms of end-organ injury commonly occur in similar settings of systemic inflammatory response syndrome, shock, and evolving multiple organ dysfunction. Recent elucidation of the pathobiology of critical illness has led to a more basic mechanistic understanding of the complex interplay between injured organs in patients with multiple organ dysfunction syndrome; this has been aptly called ‘the slippery slope of critical illness’ [Kidney Int Suppl 1998;66:S25–S33]. Distant organ effects of apparently isolated injuries to the lungs, gut, and kidneys have all been discovered in recent years. In this article, we will review the harmful bidirectional interaction between ALI and AKI, which appears to be a common clinical syndrome with routine clinical implications. We will review the current understanding of lung-kidney interactions from both perspectives, including the renal effects of ALI and mechanical ventilation, and the pulmonary sequelae of AKI. In this review of the emerging evidence of deleterious bidirectional organ cross talk between lung and kidney, we will focus on the role of ventilator-induced kidney injury in the pathogenesis of AKI in patients with ALI.

Endothelial progenitor cells are cells derived from the bone marrow that circulate in the bloodstream and can exhibit phenotypic characteristics of endothelial cells. They are thought to be involved in postnatal vasculogenesis and to potentially help repair injured endothelium. Circulating endothelial cells are mature endothelial cells in the circulation, and endothelial vesicles or microparticles are thought to be derived from the membranes of endothelial cells as a result of injury or activation. Recent research has focused on using these markers of endothelial injury and repair to assess the state of endothelial health. These efforts have been hampered by lack of uniformity in methodology and terminology. Recent developments in flow cytometry techniques have allowed better characterization and definition of these cells. We review the common techniques used to identify and isolate these cells, clinical studies in patients with chronic kidney disease (CKD) where they serve as markers of endothelial health and predictors of outcome, and possible mechanisms of progenitor cell dysfunction in CKD.

Background/Aims

Etanercept is a tumor necrosis factor-α antagonist used in inflammation-mediated conditions. Continuous venovenous hemofiltration (CVVH) has also been used in patients with inflammatory conditions. This study evaluated etanercept clearance using an in vitro CVVH model.

Methods

Etanercept clearance was assessed in vitro in bovine blood at 1–3 mg/l final serum concentration, and urea control at 750 mg/l. CVVH was performed using polyacrylonitrile, polysulfone, and polymethylmethacrylate filters at 3 l/h ultrafiltrate and 200 ml/min blood flow rates. Transmembrane clearance was estimated using sieving coefficient calculations, and adsorptive removal rate was approximated using a mass balance calculation.

Results

Urea sieving coefficient remained constant (1.04 ± 0.01). Ultrafiltrate etanercept concentrations were undetectable (sieving coefficient < 0.02) and transmembrane and adsorptive clearances were negligible.

Conclusion

Etanercept is not cleared appreciably by transmembrane or adsorptive mechanisms in CVVH using polyacrylonitrile, polysulfone, or polymethylmethacrylate hemofilters.

Despite advances in renal replacement therapy, the mortality of acute kidney injury (AKI) has remained high, especially when associated with distant organ dysfunction such as acute lung injury (ALI). Mortality rates for combined AKI/ALI reach 80% in critically ill patients. While the clinical presentation of AKI-associated ALI is characterized by increased pulmonary edema, a defining feature of the syndrome, the AKI-induced lung effects extend beyond simple volume overload. Furthermore, ALI and associated mechanical ventilation frequently lead to a decline in renal hemodynamics, structure and function. New experimental data have emerged in recent years focusing on the interactive effects of kidney and lung dysfunction, and these studies have highlighted the pathophysiological importance of proinflammatory and proapoptotic pathways as well as the complex nature of interorgan crosstalk. This review will examine our current understanding of the deleterious kidney-lung crosstalk in the critically ill.

This study used multi-frequency bioimpedance spectroscopy (BIS) of the arm and whole body to estimate muscle mass (MM) and subcutaneous adipose tissue (SAT) in 31 hemodialysis (HD) patients comparing these results with magnetic resonance imaging (MRI) and body potassium (40K) as gold standards. Total body and arm MM (MMMRI) and SAT (SATMRI) were measured by MRI. All measurements were made before dialysis treatment. Regression models with the arm (aBIS) and whole body (wBIS) resistances were established. Correlations between gold standards and the BIS model were high for the arm SAT (r2 = 0.93, standard error of estimate (SEE) = 3.6 kg), and whole body SAT (r2 = 0.92, SEE = 3.5 kg), and for arm MM (r2 = 0.84, SEE = 2.28 kg) and whole body MM (r2 = 0.86, SEE = 2.28 kg). Total body MM and SAT can be accurately predicted by arm BIS models with advantages of convenience and portability, and it should be useful to assess nutritional status in HD patients.

The pathogenesis of cardiac failure involves activation of the neurohumoral axis including stimulation of the sympathetic nervous system, the renin-angiotensin-aldosterone, and nonosmotic vasopressin systems. While these responses are critical in maintaining arterial pressure, they are associated with renal vasoconstriction, as well as sodium and water retention. In advanced circumstances, renal dysfunction and hyponatremia occur with cardiac failure. Even a modest rise in serum creatinine related to diminished renal function in heart failure patients is associated with increased risk for cardiovascular morbidity and mortality. Similarly, increased thirst and the nonosmotic stimulation of vasopressin in advanced cardiac failure leads to hyponatremia, which is also a major risk factor for mortality. Currently, V2 vasopressin receptor antagonists have been shown to correct hyponatremia in cardiac failure. One such agent, conivaptan, also is a V1 receptor antagonist which could theoretically benefit heart failure patients by decreasing cardiac afterload and remodeling. The effect of V2 receptor antagonists to correct hyponatremia in heart failure patients appears to be quite safe. However, to date no effect on mortality has been demonstrated.

The pathogenesis of cardiac failure involves activation of the neurohumoral axis including stimulation of the sympathetic nervous system, the renin-angiotensin-aldosterone, and nonosmotic vasopressin systems. While these responses are critical in maintaining arterial pressure, they are associated with renal vasoconstriction, as well as sodium and water retention. In advanced circumstances, renal dysfunction and hyponatremia occur with cardiac failure. Even a modest rise in serum creatinine related to diminished renal function in heart failure patients is associated with increased risk for cardiovascular morbidity and mortality. Similarly, increased thirst and the nonosmotic stimulation of vasopressin in advanced cardiac failure leads to hyponatremia, which is also a major risk factor for mortality. Currently, V2 vasopressin receptor antagonists have been shown to correct hyponatremia in cardiac failure. One such agent, conivaptan, also is a V1 receptor antagonist which could theoretically benefit heart failure patients by decreasing cardiac afterload and remodeling. The effect of V2 receptor antagonists to correct hyponatremia in heart failure patients appears to be quite safe. However, to date no effect on mortality has been demonstrated.

Introduction

Achieving normohydration remains a non-trivial issue in haemodialysis therapy. Preventing the deleterious effects of fluid overload and dehydration is difficult to achieve. Objective and clinically applicable methods for the determination of a target representing normohydration are needed.

Methods

Whole-body bioimpedance spectroscopy (50 frequencies, 5–1,000 kHz) in combination with a physiologic tissue model can provide an objective target for normohydration based on the concept of excess extracellular volume. We review the efficacy of this approach in a number of recent clinical applications. The accuracy to determine fluid volumes (e.g. extracellular water), body composition (e.g. fat mass) and fluid overload was evaluated in more than 1,000 healthy individuals and patients against available gold standard reference methods (e.g. bromide, deuterium, dual-energy X-ray absorptiometry, air displacement plethysmography, clinical assessment).

Results

The comparison with gold standard methods showed excellent accordance [e.g. R2 (total body water) = 0.88; median ± SD (total body water) = −0.17 ± 2.7 litres]. Agreement with high-quality clinical assessment of fluid status was demonstrated in several hundred patients (median ± SD = −0.23 ± 1.5 litres). The association between ultrafiltration volume and change in fluid overload was reflected well by the method (median ± SD = 0.015 ± 0.8 litres). The predictive value of fluid overload on mortality underlines forcefully the clinical relevance of the normohydration target, being secondary only to the presence of diabetes. The objective normohydration target could be achieved in prevalent haemodialysis patients leading to an improvement in hypertension and reduction of adverse events.

Conclusion

Whole-body bioimpedance spectroscopy in combination with a physiologic tissue model provides for the first time an objective and relevant target for clinical dry weight assessment.

Background/Aims

Cytokine overproduction has been noted during the aggravation of clinical conditions. Countermeasures to control hypercytokinemia are therefore important in critical care. We investigated the clinical efficacy of hemoadsorption therapy using a new cytokine-adsorbing device in critically ill patients with persistent or severe hypercytokinemia.

Methods

Direct hemoperfusion using the CYT-860, a cytokine-adsorber column (CYT-860-DHP), was performed in critically ill patients with hypercytokinemia. To evaluate the efficacy of CYT-860-DHP, changes in pathological and clinical parameters were examined.

Results

Seven patients with hypercytokinemia and a SOFA score of ≥5 underwent CYT-860-DHP treatment. Four patients survived 28 days after CYT-860-DHP treatment. Significant decreases in blood levels of cytokines were observed. PaO2/FIO2 improved significantly.

Conclusion

The possibility that CYT-860-DHP treatment can reduce blood cytokine levels and thereby improve the general condition of patients was suggested. These findings warrant the initiation of a prospective randomized trial to evaluate the clinical efficacy of CYT-860-DHP treatment.