Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis

Fifty peritoneal biopsies (PB) from 35 patients with end-stage renal disease, treated by continuous ambulatory peritoneal dialysis (CAPD) and aged 2 months to 18 years, were examined by light microscopy (n=50) and/or scanning electron microscopy. PB were performed during surgical procedures immediately before the start of, during, or after the cessation of CAPD treatment. PB from 15 children without renal disease undergoing laparatomy were examined similarly. Before the start of CAPD, a scarcity and shortening of the mesothelial microvilli was observed by scanning electron microscopy. During and after CAPD, variable alterations of mesothelium, interstitium and capillaries were found. The mesothelial layer was absent in all 5 PB obtained during episodes of active peritonitis. In patients treated by CAPD for longer than 6 months, mesothelial denudation was observed more frequently (6/11) than in children treated for shorter periods (1/7) (P<0.08). Fibrosis of the peritoneal membrane was present in about 50% of patients during or after the cessation of CAPD without impairment of peritoneal function. No correlation was found between the presence of fibrosis and the frequency of peritonitis or the duration of CAPD treatment.     

Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins in Chronic Renal Failure: Evidence for Reduced Secretion of IGFs

To test the hypothesis that growth hormone (GH) insensitivity is responsible, amongst other mechanisms, for impaired growth in uraemic children, insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein-1 (1GFBP-1), IGFBP-2 and IGFBP-3 were measured by radioimmunoassay in normal control children, in patients with end-stage renal failure (n = 51) and in patients with preterminal chronic renal failure (n = 11) and the production rate of IGF was calculated. A unique pattern of normal IGF-I and IGF-II levels and markedly increased levels of all three IGFBPs was present in uraemia. Measurement of free IGF-II binding capacity, and affinity cross-linking experiments showed that the excess immuno-reactive IGFBP was able to bind IGFs. To explain the excess of unoccupied IGF binding sites in uraemia, a mathematical model was developed which describes the production of IGFs and their interaction with IGFBP. Calculations of IGF secretion rates suggested that production of IGF is two orders of magnitude lower in uraemic children than in control children, despite normal GH secretion. It is concluded that in uraemia there is a relative GH insensitivity with respect to IGF production.     

Anthranilic Acid–uraemic Toxin Damaged Red Cell’s Membrane

Normocytic normochromic anaemia is a common syndrome present in patients with chronic renal insufficiency (CRI). Simultaneously in these patients the increase in L-tryptophan (TRP) degradation via kynurenine pathway is observed. On the basis of these observations we tried to examine whether one of the TRP metabolites, anthranilic acid (AA), shows interaction with membranes of erythrocytes and because of that it may contribute to anaemia development. In patients with CRI we have observed changes characteristic for normocytic normochromic anaemia, such as the decrease in erythrocyte count, haemoglobin concentration, haematocrit and the decrease in erythrocyte osmotic resistance as well as the increase in AA concentration in plasma in comparison to healthy subjects. We have also noticed the existence of a positive correlation between anthranilic acid concentration and creatinine and urea concentrations and also negative relationships between anthranilic acid concentration and haematological parameters. Moreover, incubation of healthy erythrocytes with 10 and 100 μM AA caused haemolysis curve movement to the right, which shows decrease in osmotic resistance. In conclusion, the increase in plasma AA concentration might be one of many factors, which damage erythrocyte membrane, and thereby contributes to anaemia development in patients with CRI.     

Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases

Summary Tranexamic acid is a potent antifibrinolytic drug frequently used in the treatment of haematuria and a number of other haemorrhagic conditions. Since it is eliminated mainly in the urine, the drug accumulates in patients with uraemia. The excretion of tranexamic acid in patients with renal failure has been investigated and dosage recommendations are given for tranexamic acid therapy in cases of renal failure.     

Hypocalcaemic Effect of WR-2721, S-2 (3-Aminopropylamino) Ethyl-phosphorothioic Acid in an Anuric Haemodialysis Patient

The radio- and chemoprotective agent, S-2 (3-aminopropylamino)ethyl-phosphorothioic acid (WR 2721) has been reported to lowerhypercalcaemia in patients with cancer, probably by increasedrenal calcium excretion and decreased parathyroid hormone (PTH)secretion and bone calcium resorption. The present study reportsthe first clinical use of WR-2721 in an anuric haemodialysispatient with severe secondary hyperparathyroidism. The drugwas administered intravenously at different doses, i.e. 150,300, and 500 mg/m². The infusion was followed by a strikingdecrease of plasma immunoreactive (i) PTH within 30 min. Thenadir of the iPTH decrease was reached at 60 min and was followedby a steady return to previous values. Serum ionised calciumdecreased more progressively from 1.55 mmol/l initially to 1.30mmol/l at 4 h after the 300-mg dose, remained at that levelat 24 h, but rose again to pre-infusion values after 48 h. Theextent and duration of the decrease in plasma iPTH and ionisedcalcium were dose-dependent. The circulating iPTH at 24 h wasinversely related to the corresponding plasma ionised calciumconcentration and had risen above preinfusion values at thattime. Plasma concentrations of three other hormones, i.e. renin,insulin, and prolactin, were not affected by the administrationof WR-2721. In conclusion, WR-2721 can induce a decrease in serum ionisedcalcium in the absence of any excretory kidney function. Therapid effect of the drug on circulating iPTH supports the notionof an interference with PTH secretion or catabolism.     

Safety and efficacy of calcium carbonate in children with chronic renal failure

The safety and clinical efficacy of calcium carbonate therapy in children with chronic renal failure were assessed in 68 patients (average age 8.38 years) during a mean follow-up period of 19.9 months (range 1.2-49.4). Forty-seven episodes of hypercalcaemia occurred in 29 children (3.5 episodes per 100 patient-months). There were no significant differences in mean GFR or biochemical parameters between these patients at the start of calcium carbonate therapy and the group of children who never experienced hypercalcaemia. Good control of secondary hyperparathyroidism and a significant reduction in serum aluminum were achieved. Two of 23 hypercalcaemic patients showed nephrocalcinosis on ultrasonography. 99Tc pyrophosphate scanning failed to detect any other ectopic calcification. The incidence of hypercalcaemia increased significantly when the GFR was less than 15 ml/min per 1.73 m2 and was most frequent in children receiving dialysis (48 episodes per 100 patient-months). The decrease in GFR during therapy was significantly more in the hypercalcaemic group compared to the normocalcaemic group (P less than 0.01), despite no irreversible acute effects of hypercalcaemia being observed on the rate of decline of GFR. We believe that the reduced renal homeostatic reserve is a major factor predisposing to hypercalcaemia. Consequently calcium carbonate is safe to use in children with severe chronic renal failure with close biochemical monitoring; the benefits over aluminium phosphate binders far outweigh the risks of hypercalcaemia and ectopic calcification.     

The immune status of uraemic children/adolescents with chronic renal failure and renal replacement therapy

In adults with chronic renal failure (CRF) and/or renal replacement therapy (RRT) various immunological abnormalities have been described, but few data are available for the paediatric age group. We performed basic in vitro immunological studies in 26 patients 10 months–19 years of age with advanced renal failure, 11 with CRF (creatinine clearance 16.8±5.2 ml/min per 1.73 m²), 15 on RRT with haemodialysis (HD;n=9) and continuous ambulatory peritoneal dialysis (CAPD;n=6) as well as in 16 healthy controls. None had clinical evidence of deranged immune function. No significant differences were found in the percentages of B- and T-cells, T-cell subsets CD3, CD4, CD8 and mitogenic responses to phytohaemagglutinin and concanavalin A (Con A) between RRT patients (HD=CAPD) and control children. Most parameters in CRF patients were also normal, although they had a low percentage of B-cells (12.1±4.1; RRT: 19.7±6.5; controls: 18.5±7.1;P<0.01), relatively low levels of serum immunoglobulin G (948.4±209.4 mg/dl; HD: 1374.7±235.2 mg/dl;P<0.01; CAPD: 966.3±430.2 mg/dl, NS) and a high normal response to Con A (34.3±13.6 cpm ×10^–3; RRT: 34.5±11.3 cpm ×10^–3; controls: 23.4±9.9 cpm ×10^–3,P<0.01). All these values were, however, well within the normal accepted range. These data indicate that children/adolescents with CRF and/or RRT have no significant basic in vitro immunological defects. This study did not test the functional immune status of the young uraemic patients.     

Kinetics of erythropoiesis in dialysis patients receiving recombinant erythropoietin treatment

In eleven patients with uraemia on intermittent haemodialysis treatment, recombinant human erythropoietin (rHuEpo) was used at a dosage schedule of 100 IU/kg bodyweight thrice weekly. Erythrokinetic studies (blood volume, RBC survival and iron kinetics) were performed in nine cases before and after 6 months of treatment. The remaining two patients had only RBC and plasma volume determinations before and after treatment. Although total blood volume remained unchanged, RBC volume was increased in all cases. Red cell loss was not modified, and quantitative improvement of RBC production was noted in all cases. No qualitative defect of erythroid maturation or release was observed in the treated patients. In conclusion, rHuEpo treatment improves the anaemia of haemodialysis patients by normalising circulating RBC volume only through an increase in red cell production.     

Albumin catabolism measurement by a double tracer technique in uraemic patients during a single dialytic treatment

Abstract. In order to explain the pathogenesis of protein depletion in chronic uraemia, 13 measurements of albumin catabolism were performed in uraemic patients undergoing haemo-or peritoneal dialysis treatment, during either the early phase or steady uraemic state. Catabolism was determined during a single haemo-or peritoneal dialysis by a double tracer technique (Human Serum Albumin and sodium iodide labelled with two different isotopes of iodine). The output from both albumin and iodine systems was measured in the dialysis solution flowing out from the peritoneum or artificial kidney. The radioactive iodide arising in dialysate from albumin breakdown was concentrated by the use of an anion exchange resin. Catabolic rate was three times the normal in 3 patients showing clinical features of hypercatabolism (true rapid loss of body weight) in the early phase of uraemia, or during relapse of it; albumin turnover rate returned to normal in 2 of these patients, when measured during clinical steady state conditions. This behaviour suggests highly increased catabolism, not counterbalanced by a correspondingly increased synthesis, as the cause of albumin depletion in chronic uraemia.     

血液透析治疗12例尿毒症合并脑出血的疗效分析

目的：分析短时、高频血液透析在无抗凝或小剂量低分子肝素抗凝时治疗尿毒症合并脑出血的疗效。方法：回顾性分析本院2007年8月～2011年3月收治的尿毒症合并脑出血患者12例,在入院后常规内科治疗的基础上加无肝素或小剂量低分子肝素抗凝,短时、高频血液透析治疗,即住院第1周每日透析1次,每次2～2.5h。结果：所有患者均顺利渡过脑出血急性期,挽救了患者的生命,为患者后期康复、功能锻炼创造时机。结论：短时、高频血液透析在无抗凝或小剂量低分子肝素抗凝时治疗尿毒症合并脑出血是安全、有效的,值得临床推广应用。