Ole Simonsen

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.

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

BACKGROUNDnRandomized 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.nnnMETHODSn50 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnThis 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.

The effects of low-sodium peritoneal dialysis fluids on blood pressure, thirst and volume status

Background. Poor ultrafiltration is associated with worse outcomes in peritoneal dialysis (PD) patients. This might in part reflect problems associated with salt and water excess. Increasing the diffusive component of peritoneal sodium removal using low-sodium PD fluids might have beneficial effects on blood pressure (BP), thirst and fluid status that could translate into clinical benefits. Methods. Using a multicentre, prospective, baseline controlled (1 month), non-randomized intervention (2 months) design, two novel solutions designed from predictions using the three-pore model were investigated. In group A ([Na+] = 115 mmol/l), the glucose (G) was increased to 2.0% to compensate for reduced osmolality whereas in group B ([Na+] = 102 mmol/l), it was unchanged (2.5%). Both solutions were substituted for one 3- to 5-h exchange per day and no change was made to the rest of the dialysis regime. Results. Ten patients in group A and 15 in group B completed the study. Both solutions resulted in significant increases (30–50 mmol/dwell) in diffusive sodium removal during the test exchanges, P < 0.001. Ultrafiltration was maintained in group A but reduced in group B. Ambulatory nocturnal mean BP fell in group A [93.1 ± 10.6 mmHg (±SD) versus 85.1 ± 10.2 mmHg, P < 0.05], but was stable in group B (95.4 ± 9.4 versus 95.1.1 ± 10.7 mmHg, NS). Thirst reduced independent of appetite and mood in both groups by 2 months, more markedly in group A. Indices of fluid status, including TBW by bioimpedance and D dilution also improved in group A, P < 0.05, whereas weight increased in group B. Conclusions. Increasing the diffusive component of sodium removal whilst maintaining ultrafiltration is associated with improvements in BP, thirst and fluid status. The lack of effect seen with uncompensated low-sodium dialysate suggests that these benefits cannot be achieved by manipulation of dialysate sodium removal alone. These observations provide valuable information of the design of future randomized studies to establish the clinical role for low-sodium dialysis fluids.

Successful thrombolysis of neonatal bilateral renal vein thrombosis originating in the IVC

We describe a case of inferior vena cava thrombosis (IVC) leading to bilateral renal vein thrombosis and renal failure in a neonate, which was successfully treated by thrombolysis. A male neonate, born at term by vaginal delivery (Apgar score 9–10–10) and weighing 4210 g at birth after a normal pregnancy, presented at 9 days of age due to failure to thrive and gross haematuria. At admission the child weighed 4200 g and appeared to be dehydrated. He was anuric with a serum creatinine of 222 μmol/L (reference 14–37 μmol/L), severe metabolic acidosis and respiratory difficulties. He had a palpable abdominal mass on the left side of the abdomen. Ultrasound examination showed enlarged hyperechogenic kidneys, especially on the left side. The renal veins and IVC could not be visualised. Magnetic resonance (MR) angiography revealed thrombosis of the IVC from the bifurcation up to the hepatic veins (Fig. 1a, b) and extending into both renal veins. There was no evidence of adrenal haemorrhage. Treatment with warfarin (Waran; Nycomed, Zurich, Switzerland) was initiated (Fig. 1c), and systemic lowmolecular weight heparin (LMWH) (dalteparin sodium, Fragmin; Pfizer, New York, NY). The dose was adjusted by following levels of anti-Factor Xa geared at 0.5–1.0 kIE/L. Because the ultrasound did not show any change in the size of the thrombus, warfarin was discontinued, and local fibrinolysis was initiated [1, 2]. An angio-catheter was inserted into the occluding thrombus in the IVC, and continuous infusion of recombinant tissue plasminogen activator (rt-PA) (Actilyse; Boehringer, Ingelheim, Germany) was administered at 0.1 mg/kg/hour. The rt-PA treatment was monitored by an analysis of plasma fibrinogen levels. Systemic LMWH was continued in order to prevent thromboembolism, and fresh frozen plasma was infused daily. Cranial ultrasound was performed daily due to the risk of intracranial haemorrhage. Three days after the patient had been admitted, systemic LMWH was switched to unfractionated heparin (LEO Pharma, Ballerup, Denmark) infusion because the level of anti-FXa was too low. The dose of unfractionated heparin was monitored by activated clotting time targeted at 180–200 s. Local rt-PA treatment was discontinued due to excessive bleeding from the peritoneal dialysis catheter insertion site. Pediatr Nephrol (2009) 24:2069–2071 DOI 10.1007/s00467-009-1172-3

Small Distal Muscles and Balance Predict Survival in End-Stage Renal Disease.

Background/Aims: Survival for patients on renal replacement therapy (RRT) has been shown to correlate to the level of physical activity and exercise capacity. We examined whether composite measures of functional status at the start of RRT predict survival. Methods: In this retrospective study, the same physiotherapist, using a standardized battery of tests for functional status, tested 134 patients at the start of RRT. Results: At the end of the observation period, 112 patients (84%) were still alive. Age (p < 0.0001), co-morbidity (p = 0.028), hand grip strength (right: p = 0.0065; left: p = 0.0039), standing heel rise (right: p = 0.011; left: p = 0.004) and functional reach (p = 0.015) were significant predictors of survival. After adjustment for sex, age and co-morbidity, hand grip strength left (p = 0.023) was a significant predictor of survival. Conclusion: Hand grip strength, standing heel rise and functional reach at the start of RRT seem to affect survival. A 50% reduction in hand grip strength left was associated with an almost 3-fold increase in mortality. Deterioration of function in small distal muscles and balance may be early signs of uraemic myopathy. A relatively simple and clinically feasible battery of tests can help detect patients at risk.

Excellent long time survival for Swedish patients starting home-hemodialysis with and without subsequent renal transplantations.

Survival for patients on dialysis is poor. Earlier reports have indicated that home‐hemodialysis is associated with improved survival but most of the studies are old and report only short‐time survival. The characteristics of patient populations are often incompletely described. In this study, we report long‐term survival for patients starting home‐hemodialysis as first treatment and estimate the impact on survival of age, comorbidity, decade of start of home‐hemodialysis, sex, primary renal disease and subsequent renal transplantation. One hundred twenty‐eight patients starting home‐hemodialysis as first renal replacement therapy 1971–1998 in Lund were included. Data were collected from patient files, the Swedish Renal Registry and Swedish census. Survival analysis was made as intention‐to‐treat analysis (including survival after transplantation) and on‐dialysis‐treatment analysis with patients censored at the day of transplantation. Ten‐, twenty‐ and thirty‐year survival were 68%, 36% and 18%. Survival was significantly affected by comorbidity, age and what decade the patients started home‐hemodialysis. For patients younger than 60 years and with no comorbidities, the corresponding figures were 75%, 47% and 23% and a subsequent renal transplantation did not significantly influence survival. Long‐term survival for patients starting home‐hemodialysis is good, and improves decade by decade. Survival is significantly affected by patient age and comorbidity, but the contribution of subsequent renal transplantation was not significant for younger patients without comorbidities.