Graham Woodrow

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.

The clinical and biochemical features of acute renal failure due to rhabdomyolysis.

Rhabdomyolysis caused 28 out of 903 (3.1%) of cases of severe acute renal failure (ARF) treated at Leeds General Infirmary over a 14-year period (1980-1993). The commonest cause of rhabdomyolysis was muscle compression, usually due to drug- or alcohol-induced coma. Other causes included fits, infection, acute limb ischemia, trauma, and heat stroke. Prognosis was relatively good, with a 78.6% survival rate and recovery of renal function to normal in all survivors who were followed up. The creatinine/urea ratio was higher in ARF due to rhabdomyolysis than in an unselected group of patients with other causes of ARF but not when the comparison was with sex- and age-matched controls with ARF. This suggests that this previously described feature of rhabdomyolysis simply reflects the increased muscle mass of a younger group of patients, rather than a specific effect of muscle damage. Clinical features of muscle damage were often absent and so the possibility of rhabdomyolysis should be considered in appropriate settings if the diagnosis is to be made early enough to administer treatment that may prevent ARF and the consequences of the compartment syndrome.

Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange

BACKGROUND Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumour necrosis factor-alpha, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. METHODS 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at -1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status. RESULTS In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated; the only predictor of between-patient variability on multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily ultrafiltration, urine volume, fluid or inflammatory status. CONCLUSIONS This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.

Summary of the 5th Edition of the Renal Association Clinical Practice Guidelines (2009-2012)

Robert Mactier, Simon Davies, Chris Dudley, Paul Harden, Colin Jones, Suren Kanagasundaram, Andrew Lewington, Donald Richardson, Maarten Taal, Peter Andrews Richard Baker, Cormac Breen, Neill Duncan, Ken Farrington, Richard Fluck, Colin Geddes, David Goldsmith, Nic Hoenich, Stephen Holt, Alan Jardine, Sarah Jenkins, Mick Kumwenda, Elizabeth Lindley, Mark MacGregor, Ashraf Mikhail, Edward Sharples, Badi Shrestha, Rajesh Shrivastava, Simon Steddon, Graham Warwick, Martin Wilkie, Graham Woodrow, Mark Wright

Low thrombogenicity of polyethylene glycol–grafted cellulose membranes does not influence heparin requirements in hemodialysis

Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.

Segmental bioelectrical impedance in patients with chronic renal failure.

We studied changes in hydration by whole body and segmental (arm, leg and trunk)bioelectrical impedance analysis (BIN in patients with chronic renal failure (CRF) undergoing haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Mean (SD) fluid removal by haemodialysis of 1.38 (0.81) kg was overestimated by whole body BIA at 1.83 (1.13) I, P < 0.005. Peritoneal fluid drained from the CAPD patients of 1.88 (0.36) kg was underestimated by whole body BIA at 0.59 (0.35) I, P < 0.0001. Resistance and reactance significantly increased for the whole body and all segments (except trunk reactance) after haemodialysis. Drainage of CAPD fluid resulted in smaller increases in trunk resistance and whole body resistance. The increase in trunk resistance was less in CAPD than haemodialysis patients, even though the volume of fluid drained from the peritoneum in CAPD patients exceeded that removed from the whole body during haemodialysis. We conclude that whole body BIA does not estimate changes in body fluid with sufficient accuracy to be of use in clinical practice. Segmental impedance may be a potentially useful method for investigation of regional changes in body fluid, though is insensitive to changes within the peritoneal cavity.

Effect of peritoneal fluid on whole body and segmental multiple frequency bioelectrical impedance in patients on peritoneal dialysis.

Objective: We investigated the ability of whole body and segmental multiple frequency bioelectrical impedance (MFBIA) to detect peritoneal fluid in peritoneal dialysis patients.Design: Prospective study.Setting: Teaching hospital renal unit.Subjects: Patients on regular peritoneal dialysis.Interventions: Whole body and segmental MFBIA measurements before and after drainage of peritoneal fluid.Results: Changes estimated by MFBIA in total body water (−0.4 (0.8) litres) and extracellular water (−0.3 (0.3) litres) were much lower than the actual changes (2.0 (0.4) litres), P<0.0001. Derived resistances Recf and Ricf increased significantly for the trunk but not for total body measurements and changes did not correlate with volumes of fluid drained.Conclusions: MFBIA is limited in its ability to detect intraperitoneal fluid, using both whole body and segmental techniques.European Journal of Clinical Nutrition (2000) 54, 450–451

Renal Association Clinical Practice Guideline on Peritoneal Dialysis

Peritoneal dialysis (PD) is long established as a major option for renal replacement therapy in patients with end-stage renal disease. It is an important part of an integrated service for renal replacement therapy that is frequently selected by patients as their preferred initial mode of therapy and is a therapeutic option for patients wishing or needing to swap from HD and after renal transplant failure. This guideline is an update of the PD module published on-line on the Renal Association website, www.renal.org in 2007. The English language literature was searched to identify relevant articles on PD published between 2006 and 2010 including: . Medline search using ‘peritoneal dialysis’ combined with relevant terms . Cochrane Database of Systematic Reviews . Review of other national/international PD clinical guidelines . Identification of further articles quoted in identified papers

Renal Association Clinical Practice Guideline on peritoneal dialysis in adults and children

These guidelines cover all aspects of the care of patients who are treated with peritoneal dialysis. This includes equipment and resources, preparation for peritoneal dialysis, and adequacy of dialysis (both in terms of removing waste products and fluid), preventing and treating infections. There is also a section on diagnosis and treatment of encapsulating peritoneal sclerosis, a rare but serious complication of peritoneal dialysis where fibrotic (scar) tissue forms around the intestine. The guidelines include recommendations for infants and children, for whom peritoneal dialysis is recommended over haemodialysis.Immediately after the introduction there is a statement of all the recommendations. These recommendations are written in a language that we think should be understandable by many patients, relatives, carers and other interested people. Consequently we have not reworded or restated them in this lay summary. They are graded 1 or 2 depending on the strength of the recommendation by the authors, and A-D depending on the quality of the evidence that the recommendation is based on.

Changes in Body Composition in the Two Years after Initiation of Haemodialysis: A Retrospective Cohort Study

Malnutrition is common in haemodialysis (HD) and is linked to poor outcomes. This study aimed to describe changes in body composition after the initiation of HD and investigate whether any routinely collected parameters were associated with these changes. The study cohort came from the HD population of a single centre between 2009 and 2014. Body composition measurements were obtained from a database of bioimpedance results using the Body Composition Monitor (BCM), while demographics and laboratory values came from the renal unit database. Primary outcomes were changes in normohydration weight, lean tissue mass and adipose tissue mass over the two years after HD initiation. A total of 299 patients were included in the primary analyses, showing an increase in adipose tissue, loss of lean tissue and no significant change in normohydration weight. None of the routinely collected parameters were associated with the lean tissue changes. Loss of lean tissue over the first year of dialysis was associated with increased mortality. The results showing loss of lean tissue that is not limited to those traditionally assumed to be at high risk supports interventions to maintain or improve lean tissue as soon as possible after the initiation of HD. It highlights the importance of monitoring nutrition and the potential for routine use of bioimpedance.