Andrew Davenport

Icodextrin Improves the Fluid Status of Peritoneal Dialysis Patients: Results of a Double-Blind Randomized Controlled Trial

Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the studys inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.

Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure

ObjectiveTo determine whether continuous modes of renal replacement therapy result in improved cardiovascular stability compared with standard daily intermittent treatment in critically ill patients. DesignProspective, randomized controlled trial. SettingIntensive care unit in a quaternary referral center for liver failure/transplantation. PatientsThirty-two consecutive, critically ill, mechanically ventilated patients with combined acute hepatic and renal failure. InterventionsPatients were randomized to treatment with either intermittent machine hemofiltration or continuous modes of renal replacement therapy; continuous arteriovenous hemofiltration (CAVH) or arteriovenous hemofiltration with dialysis (CAVHD), provided intracranial pressure was controlled. Measurements and Main ResultsCardiac output, tissue oxygen delivery (&U1E0A;o2), and uptake were assessed during 32 treatments with intermittent machine hemofiltration (4 hrs) and during the first 5 hrs of 25 continuous treatments (CAVH and CAVHD). During the first hour of treatment, there was a reduction in cardiac index of 15 ± 2% during intermittent machine hemofiltration compared with no significant change during the continuous modes of treatment (CAVH/CAVHD) (3±3%;p < .05). This reduction in cardiac output during intermittent machine hemofiltration was associated with a maximum reduction in mean arterial pressure from 82 ± 2 to 66 ± 2 mm Hg (p < .001), a reduction in pulmonary artery occlusion pressure of 27 ± 4%, tissue &U1E0A;o2 of 15 ± 3%, and tissue oxygen uptake of 12 ± 5%, with no significant change in systemic vascular resistance and an increase in pulmonary vascular resistance of 50 ± 12%. In addition, there was a maximum increase in intracranial pressure of 45 ± 5% during the first hour of intermittent machine hemofiltration. There were no significant changes during the same time period during the continuous modes of renal replacement therapy. ConclusionsIn critically ill patients, in whom &U1E0A;o2 is impaired, the use of continuous forms of renal replacement therapy is preferred for its improved cardiovascular tolerance compared with daily intermittent machine treatments. (Crit Care Med 1993; 21:328–338)

Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis

Objectives To propose an improvement on the current classification of renal dysfunction in cirrhosis. Clinicians caring for patients with cirrhosis recognize that the development of renal dysfunction is associated with significant morbidity and mortality. While most cases of renal dysfunction in cirrhosis are functional in nature, developed as a result of changes in haemodynamics, cardiac function, and renal auto-regulation, there is an increasing number of patients with cirrhosis and structural changes in their kidney as a cause of renal dysfunction. Therefore, there is a need for a newer classification to include both functional and structural renal diseases. Design A working party consisting of specialists from multiple disciplines conducted literature search and developed summary statements, incorporating the renal dysfunction classification used in nephrology. These were discussed and revised to produce this proposal. Setting Multi-disciplinary international meeting. Patients None. Interventions Literature search using keywords of cirrhosis, renal dysfunction, acute kidney injury (AKI), chronic kidney injury (CKD), and hepatorenal syndrome. Results Acute kidney injury will include all causes of acute deterioration of renal function as indicated by an increase in serum creatinine of >50% from baseline, or a rise in serum creatinine of ≥26.4µmol/L (≥0.3mg/dL) in <48hours. Chronic renal disease will be defined as an estimated glomerular filtration rate (GFR) of <60ml/min calculated using the Modification of Diet in Renal Disease 6 (MDRD6) formula, recognising that the MDRD6 formula is not perfect for the cirrhotic patients and this may change as improved means of estimating GFR becomes available. Acute on chronic kidney disease will be defined as AKI superimposed on existing chronic renal disease using the above definitions for AKI and CKD. Conclusions Accepting this new classification will allow studies into the epidemiology, incidence, prevalence, natural history and the development of new treatments for these subtypes of renal dysfunction in cirrhosis.

Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial

Summary Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Interpretation Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. Funding National Institute of Allergy and Infectious Diseases, Grant R01AI051355 and Wellcome Trust, Grant 078332. Sponsor: University College London (UCL).

Intradialytic complications during hemodialysis

With the advent of developments and advances in hemodialysis machine technology, dialysate water purification, and dialyzers, the clinical spectrum of intradialytic complications has changed over the decades. In the pioneering days of hemodialysis, patients could develop allergic reactions to dialyzer membranes, sterilizing and reprocessing agents, coupled with machines that could not accurately control ultrafiltration rates, and chemically and bacterially contaminated dialysate. Whereas today, although cardiovascular problems remain the most common intradialytic complication, these are mainly due to the time restraints of trying to cope with excessive dialytic weight gains and achieve target dry weight on a thrice weekly schedule, coupled with an aging elderly dialysis population with increasing co‐morbidity.

Cognitive impairment and 7-year mortality in dialysis patients.

BACKGROUND Although dementia has predicted mortality in large dialysis cohorts, little is known about the relationship between less pronounced cognitive deficits and mortality in patients with end-stage renal disease. This study assessed whether cognitive impairment without dementia was an independent predictor of 7-year survival in dialysis patients after controlling for other risk factors. STUDY DESIGN Prospective single-cohort study. SETTING & PARTICIPANTS 145 prevalent dialysis patients from 2 units in London, UK, were followed up for 64.3 ± 27.4 months and censored at the time of change to a different treatment. PREDICTORS Cognitive impairment, defined as performance 1 standard deviation less than normative values on 2 or more cognitive tests within a neurocognitive battery assessing attention/concentration, memory, and psychomotor function domains. Depression, quality-of-life, and clinical measures also were obtained. OUTCOMES & MEASUREMENTS All-cause mortality was the primary outcome. Cox proportional hazard models were used to assess the contribution of demographics and clinical and psychological measures and cognitive impairment to mortality. RESULTS 98 (67.6%) patients were cognitively impaired at baseline. At follow-up, 56 (38.6%) patients had died, 29 of cardiac causes. Unadjusted Kaplan-Meier analysis showed higher mortality in cognitively impaired patients, in whom 7-year survival was 49% versus 83.2% in those with no cognitive impairment (P < 0.001). Mortality risk associated with cognitive impairment remained significant in adjusted analysis controlling for sociodemographic, clinical, and psychological factors (adjusted HR, 2.53; 95% CI, 1.03-6.22; P = 0.04). LIMITATIONS Small sample size and number of events. CONCLUSIONS Cognitive impairment is an independent predictor of mortality in dialysis patients. Although the implications of early recognition and treatment of cognitive impairment for clinical outcomes are unclear, these results suggest that patient management protocols should attempt to ensure prevention of cognitive decline in addition to managing coexisting medical conditions.

Epidemiology of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference

Sean M. Bagshaw, Dinna N. Cruz, Nadia Aspromonte, Luciano Daliento, Federico Ronco, Geoff Sheinfeld, Stefan D. Anker, Inder Anand, Rinaldo Bellomo, Tomas Berl, Ilona Bobek, Andrew Davenport, Mikko Haapio, Hans Hillege, Andrew House, Nevin Katz, Alan Maisel, Sunil Mankad, Peter McCullough, Alexandre Mebazaa, Alberto Palazzuoli, Piotr Ponikowski, Andrew Shaw, Sachin Soni, Giorgio Vescovo, Nereo Zamperetti, Pierluigi Zanco, Claudio Ronco and for the Acute Dialysis Quality Initiative (ADQI) Consensus Group

The role of bioimpedance and biomarkers in helping to aid clinical decision-making of volume assessments in dialysis patients

Bioimpedance analysis (BIA) derives two main pieces of information--total tissue fluid content, which when referring to the whole patient is equivalent to the total body water (TBW), and cell mass, which in the limbs mainly reflects muscle. The relationship between these measures, expressed in different ways, is abnormal in dialysis patients due to muscle wasting combined with tissue overhydration. In both dialysis modalities this is associated with aging, comorbidity, and inflammation, and there is a conflict between achieving euvolemia to improve blood pressure control and prevent left ventricular hypertrophy on one hand, but risking episodes of hypovolemia and loss of residual renal function on the other. In peritoneal dialysis, the situation is exacerbated by hypoalbuminemia, whereas in hemodialysis BIA is unable to distinguish between the plasma volume and tissue edema components of interdialytic weight gain. In longitudinal studies BIA can identify changes in hydration following a defined intervention, and spontaneous loss in TBW consequent on muscle wasting not appreciated clinically, resulting in a failure to sufficiently reduce the dry weight. Cardiac biomarkers provide additional information but it is not clear whether this reflects fluid status or underlying structural organ damage. Intervention studies are now needed that show how this information is best used to improve patient outcomes, including meaningful end points such as hospitalization and survival.

Comparison of Multifrequency Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry Assessments in Outpatient Hemodialysis Patients

BACKGROUND Malnutrition is common in hemodialysis patients and closely related to increased morbidity and mortality. As such, simple, reliable, and easily available methods of determining nutritional status and recognition of short-term changes in body composition are desirable for routine clinical practice. STUDY DESIGN Diagnostic test study. SETTING & PARTICIPANTS 53 stable adult hemodialysis patients attending for thrice-weekly outpatient hemodialysis in a university tertiary hospital dialysis center. INDEX TEST Comparison of dual-energy x-ray absorptiometry (DEXA) and multifrequency bioelectrical impedance analysis (BIA) using a tetrapolar 8-point tactile electrode system as 2 index tests of body composition. REFERENCE TEST None. RESULTS Assessment of whole-body composition showed that lean body mass measured using the 2 techniques correlated highly, with good method agreement shown using a Bland-Altman plot (r = 0.92; P < 0.001; bias, +1 g [95% CI, -1,173 to 1,175]), as did fat mass (r = 0.93; P < 0.001; bias, -157 g [95% CI, -1,251 to 937]). Similarly, segmental analysis of lean body mass showed strong correlations between lean body mass of the trunk and right and left legs with small bias (r = 0.85, 0.89, and 0.86, respectively; P < 0.001; Bland-Altman bias, -859, +364, and +552 g, respectively), but weaker correlations for lean body mass for the right and left arm (r = 0.69 and 0.75, respectively; P < 0.001; Bland-Altman bias, -240 and +12 g, respectively). Bone mineral content derived using multifrequency BIA overestimated that measured using DEXA (r = 0.77; P < 0.001; bias, +530 g [95% CI, 422-638]). LIMITATIONS Retrospective study in a healthy ambulant outpatient cohort. CONCLUSIONS Compared with DEXA, multifrequency BIA appears to be a robust tool for measuring and monitoring total-body fat and lean body mass in hemodialysis patients; however, there is less agreement in bone mineral content assessment between the 2 methods.

Online haemodiafiltration: definition, dose quantification and safety revisited

The general objective assigned to the EUropean DIALlysis (EUDIAL) Working Group by the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on haemodiafiltration (HDF) therapies. Several reports suggest that those therapies potentially improve the outcomes for end-stage renal disease patients. Europe is the leader in the field, having introduced the concept of ultra-purity for water and dialysis fluids and with notified bodies of the European Community having certified water treatment systems and online HDF machines. The prevalence of online HDF-treated patients is steadily increasing in Europe, averaging 15%. A EUDIAL consensus conference was held in Paris on 13 October 2011 to revisit terminology, safety and efficacy of online HDF. This is the first report of the expert group arising from that conference.