Regional citrate anticoagulation is safe in intermittent high-flux haemodialysis treatment of children and adolescents with an increased risk of bleeding.

BACKGROUND: Regional citrate anticoagulation (RCA) is strongly recommended for adults with an increased risk of bleeding complications. The objective of this retrospective analysis was to evaluate an RCA protocol concerning feasibility and safety in intermittent high-flux haemodialysis (iHD) treatment in children and adolescents. METHODS: Eighteen children and adolescents aged 5-17 years (median 15 years) underwent 74 iHD treatment sessions with RCA. Twelve of 18 patients presented with overt local or diffuse haemorrhage before beginning the HD sessions, and six had an increased risk of haemorrhagic complications. Forty children on acute haemodialysis with general heparin anticoagulation, matched for bleeding risk, age and body surface area, served as a control group. Citrate 3% solution was begun with 3.3% blood flow rate, and calcium gluconate 10% substitution was started with 0.4% of blood flow rate. Citrate flow was adapted to achieve a post-filter ionized calcium of ≤0.30 mmol/L; calcium substitution was adapted to maintain the patients' serum calcium levels within the physiological range. Calcium-free dialysis fluid was used. The blood flow rate ranged from 3 to 5 mL per minute and kilogram body weight. RESULTS: Regional anticoagulation was successfully achieved within the extracorporeal blood circuit, while the coagulation of all 18 patients remained within physiological parameters. No adverse effects of RCA were observed. In all 18 children, neither new haemorrhage nor worsening of the bleeding situation occurred, and in 10/12 patients, bleeding stopped during dialysis with RCA. In contrast, one-third of the control group developed new haemorrhagic complications or presented with worsening of pre-existing bleeding during haemodialysis (P = 0.006). CONCLUSION: RCA is feasible, safe and effective in paediatric intermittent haemodialysis treatment.

Continuous venovenous haemodialysis (CVVHD) and continuous peritoneal dialysis (CPD) in the acute management of 21 children with inborn errors of metabolism.

BACKGROUND: Newborns with inborn errors of metabolism often present with hyperammonaemic coma, requiring prompt diagnosis and specific medical therapy, nutritional support and efficient toxin removal. Little information regarding the efficacy and safety of continuous venovenous haemodialysis (CVVHD) as an option for extracorporal ammonia detoxification in children is available. METHODS: Twenty-one patients with hyperammonaemia [19 neonates (mean age 4.1 +/- 2.4 days) and two children 1 and 7 years of age, respectively] were admitted to our hospital for dialysis between 1996 and 2008. Seventeen children (15 neonates), received CVVHD. Four neonates received continuous peritoneal dialysis (CPD). All started medical treatment with sodium benzoate, l-arginine hydrochloride and carnitine as well as protein-restricted parenteral diets with high caloric intake before dialysis. RESULTS: Plasma ammonia levels (range 464-7267 microg/dl before dialysis and 27-3317 microg/dl after dialysis) were significantly reduced by 50% within 4.7 +/- 2.5 h with CVVHD compared with 13.5 +/- 6.2 h with CPD (P < 0.0001). Plasma ammonia levels <200 microg/dl critical range were achieved within 22.4 +/- 18.1 h in CVVHD patients compared with 35.0 +/- 24.1 h with CPD. Depending on the weight and blood pressure stability of the patients, mean blood flow velocities of 9.8 +/- 3.4 ml/kg/min and mean dialysate flow rates of 3925 +/- 2398 ml/min/1.73 m(2) were employed. Blood and dialysate flows significantly correlated with ammonia clearance and decay of ammonia in vivo. Because of the severe underlying disease, 18% of CVVHD patients died compared with 50% undergoing CPD. In total, 82% of CVVHD patients survived the first 6 months after dialysis. Among these, 43% were without sequelae, 43% developed moderate mental retardation, and two (14%) developed severe mental retardation. CONCLUSION: CVVHD effectively and quickly eliminates plasma ammonia. To optimize long-term mental outcome, rapid identification and appropriate treatment of the underlying disease as well as starting dialysis early are of enormous therapeutic value.

A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD.

BACKGROUND: A multicenter, randomized, open-label, crossover study was performed to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder, with calcium acetate in pediatric patients with chronic kidney disease (CKD). METHODS: Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly assigned to the following treatment scheme: 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were measured every 2 weeks, and phosphate binder dosages were adjusted, if needed. Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period. The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment. RESULTS: Forty-four patients were screened. Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for the crossover analysis. There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups. Total cholesterol (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate treatment, whereas metabolic acidosis was more frequent with sevelamer treatment (P < 0.005). CONCLUSION: Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer.

Reduced systemic advanced glycation end products in children receiving peritoneal dialysis with low glucose degradation product content.

BACKGROUND: Glucose degradation products (GDP) in peritoneal dialysis (PD) solutions are toxic to the peritoneal membrane and promote the formation of advanced glycation end products (AGE), which contribute to accelerated atherosclerosis and amyloidosis. Double chamber PD solutions have a markedly reduced GDP content. METHODS: We analysed GDP and AGE kinetics in 21 children (7 months to 18 years) on automated PD in a prospective multicentre trial with randomized administration of single chamber, high-GDP and double-chamber, low-GDP dialysis solution for 12 weeks each. Total AGE fluorescence, carboxymethyllysine (CML, ELISA) and 3-deoxyglucosone (3-DG, HPLC) were measured in plasma and PD effluent during a 4 h peritoneal equilibration test. Plasma AGE profiles were assessed by size selective gel permeation chromatography and compared with 23 healthy controls. RESULTS: Initial effluent 3-DG concentrations were 140+/-55 and 25+/-4 micromol/l with high- and low-GDP PD fluid, respectively and declined to 53+/-32 and 7+/-2 micromol/l within 4 h dwell time (P<0.001). The ex vivo AGE generating capacity was three times higher with the high-GDP solution and decreased significantly with dwell time. Plasma AGE levels were 1.8-7.4-fold above those of healthy controls; the elevation was most marked for the small molecular fraction (<2 kDa). Plasma AGE and CML levels were significantly higher after 12 weeks exposure to high-GDP solution (20991+/-4145 AU and 1505+/-617 ng/ml) than following treatment with low-GDP fluid (17518+/-4676 AU and 1151+/-438 ng/ml; both P<0.05). Four hour AGE clearance was higher with low-GDP solution (0.74+/-0.3 vs 0.44+/-0.15 ml/min*1.73 m2, P<0.01). CONCLUSION: GDP are rapidly absorbed from the peritoneal cavity. Administration of PD solutions with low-GDP content reduces plasma AGE levels and may thus improve the cardiovascular risk profile of dialysed children.

Antiviral treatment of chronic hepatitis B with lamivudine in pediatric renal transplantation.

Renal transplantation in patients with chronic hepatitis B virus (HBV) infection is known to be associated with an increased risk for exacerbation of liver dysfunction. Lamivudine has been proven to be a potent inhibitor of hepatitis B virus replication in adults after kidney transplantation. Little is known about its efficacy and safety in pediatric renal transplant recipients. Three cases serve for the discussion to demonstrate the complexity of the clinical course and effective treatment of chronic hepatitis B in pediatric patients awaiting renal transplantation. Two patients on dialysis with a high HBV replication rate were treated with lamivudine before transplantation. After the viral load had decreased below the detection limit, they underwent transplantation successfully. Despite intensified immunosuppression to treat a rejection episode in one and a relapse of the nephrotic syndrome in the other patient, the viral load remained <2.5 pg/mL. Both patients developed a mutation in the YMDD motif of the HBV genome associated with an increase in the HBV replication rate >10,000 pg/mL without deterioration of the liver function. In a third patient with a chronic HBV infection with a low replication rate, lamivudine was started about nine months after kidney transplantation due to an increasing viral load after treatment of an acute rejection episode. Six months later, the HBV DNA was no longer detectable. The patient had no signs of liver dysfunction. Lamivudine in the treatment of chronic HBV infection in pediatric renal recipients seems to be safe and effective in preventing acute liver deterioration. Three clinical cases are discussed with regard to current options in monitoring and antiviral treatment of chronic HBV in pediatric renal transplant recipients.

Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis.

Acid-base balance and peritoneal membrane longevity are of utmost relevance for pediatric patients undergoing peritoneal dialysis (PD). PD fluids with neutral pH and reduced glucose degradation product contents are considered more biocompatible, because they preserve peritoneal cell functions in vitro. To investigate the clinical effects of a novel PD fluid buffered with 34 mM pure bicarbonate at neutral pH, a randomized, prospective, crossover comparison with conventional, acidic, 35 mM lactate PD fluid was performed for two consecutive 12-wk periods with 28 children (age, 6 mo to 15 yr) undergoing automated PD (APD). Blood bicarbonate levels and arterial pH were significantly higher after 3 mo of bicarbonate PD (24.6 +/- 2.3 mM and 7.43 +/- 0.06, respectively), compared with lactate PD (22.8 +/- 3.9 mM and 7.38 +/- 0.05, respectively; P < 0.05). This effect was reversible among patients who returned from bicarbonate to lactate fluid. Low initial pH and young patient age independently predicted increased blood pH during bicarbonate APD. Peritoneal equilibration tests revealed subtle changes in solute transport, with a less steep creatinine equilibration curve during bicarbonate dialysis, suggesting reduced peritoneal vasodilation. The peritoneal release of carcinogen antigen-125 increased twofold during bicarbonate APD (29 +/- 15 versus 15 +/- 8 U/ml per 4 h, P < 0.01), which is consistent with recovery of the mesothelial cell layer. This effect was fully reversed when the patients returned to lactate fluid. Effluent carcinogen antigen-125 levels were inversely correlated with peritoneal glucose exposure during lactate but not bicarbonate APD, indicating improved in vivo mesothelial cell tolerance of high-dose glucose with the neutral-pH PD fluid with reduced glucose degradation product content. Among children undergoing APD, neutral-pH, bicarbonate-buffered PD fluid provides more effective correction of metabolic acidosis and better preservation of peritoneal cell mass than do conventional, acidic, lactate-based fluids.