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.

Ghrelin and other appetite-regulating hormones in paediatric patients with chronic renal failure during dialysis and following kidney transplantation.

BACKGROUND: Patients with renal insufficiency often suffer from cachexia and growth retardation due to low appetite and increased resting metabolic rate. The neuroendocrine hormone ghrelin, a growth hormone secretagogue, enhances food intake, but its role in the development of a cachectic state in renal insufficiency is unclear. Objective. The aim of our study was to investigate the plasma concentration of total ghrelin and other hormones involved in appetite regulation in children with preterminal chronic renal failure (CRF, n = 24), children undergoing dialysis (n = 19), children after renal transplantation (RTx, n = 59) and healthy controls (n = 10). RESULTS: Total ghrelin was significantly elevated in CRF patients (1370 +/- 182 pg/ml; mean +/- SEM) when compared to control subjects (682 +/- 106 pg/ml; P = 0.016) or patients following RTx (859 +/- 51 pg/ml; P = 0.002). Furthermore, a negative correlation between glomerular filtration rate and total ghrelin was observed in CRF and transplant recipients (r = 0.36, P = 0.0006). BMI SDS (standard deviation score) is lower in CRF patients compared to the other groups (P < 0.0001). Leptin, adiponectin, blood glucose, insulin, IGF-I, IGFBP-3 and growth hormone concentrations did not differ among groups. CONCLUSIONS: We observed elevated ghrelin levels in uraemic patients despite poor appetite, but the underlying reasons remain unclear. Normal ghrelin levels can be re-achieved following RTx.

Ischemia-induced association of the stress protein alpha B-crystallin with I-band portion of cardiac titin.

During ischemia the cardiac stress protein, alpha B-crystallin, was shown by immunoelectron microscopy to translocate to the N(2)-line area of myofibrillar I-bands of rat cardiomyocytes where alpha B-crystallin resisted extraction with 1 m NaSCN and 2 m urea as did titin. Actin became completely extracted under these conditions, indicating association of alpha B-crystallin with titin the only remaining non-actin cytoskeletal component of I-bands outside Z-disks. Titin, extracted from ischemic pig myocardium, was shown to copurify with alpha B-crystallin. Further evidence for binding of alpha B-crystallin to titin was obtained by dot-blot assays in which biotinylated alpha B-crystallin was demonstrated to bind to the titin-enriched fraction immobilized on nitrocellulose. Binding of alpha B-crystallin to titin during cardiac ischemia could serve to stabilize titin against denaturation and might provide an endogenous mechanism to delay ischemic damage of this important elastic component of myofibrils.