Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease.

The present single-center cohort study was based on a clinical intensive care unit database containing data on 1128 consecutive children undergoing their first operation for congenital heart disease between 1993 and 2002 at Aarhus University Hospital, Skejby, Denmark. A total of 130 (11.5%) children developed postoperative acute renal failure (ARF) managed with peritoneal dialysis (PD). Logistic regression analysis was used to examine risk factors for complications related to PD and to compare mortality between ARF and non-ARF patients controlling for potential confounding factors. A total of 43 complications related to PD were registered in 27 (20.8%) patients. Major complications were seen in eight (6.2%) patients, and only two (1.5%) patients were switched to hemodialysis after peritonitis and hemicolectomy due to bowel perforation. The main risk factors for complications to PD were duration of PD, high RACHS-1 score (Risk Adjusted Classification for Congenital Heart Surgery), and hyperkalemia at initiation of PD. Overall, in-hospital mortality was 6.8% (76/1128). Mortality of ARF patients was 20.0% compared to 5.0% among non-ARF patients (adjusted odds ratio=1.91, 95% confidence interval=1.10-3.36). After stratification, ARF was strongly associated with increased mortality in the subgroups of patients with the lowest overall risk of dying (age> or =1 year, body weight> or =5 kg, RACHS-1 score <3, and no preoperative cyanosis). For patients at high risk of dying (age <1 year, body weight <5 kg, RACHS-1 score> or =3, cardiopulmonary bypass time> or =60 min, and preoperative cyanosis), the association between ARF and mortality was substantially weaker. In conclusion, postoperative ARF was associated with increased mortality in children operated for congenital heart disease. Major complications to PD were few, and our data strongly support that PD is a simple, safe, feasible, and robust dialysis modality for the management of ARF in children.

Evidence that treatment of ESRD patients with recombinant human erythropoietin induces immunosuppression without affecting the distribution of peripheral blood mononuclear cell subpopulations.

Fifteen patients with end-stage renal disease (ESRD) were blood sampled before and 1-, 2-, 3-, and 6 months after institution of recombinant human erythropoietin (r-HuEPO) therapy. Subpopulations of immunocompetent peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry using monoclonal antibodies against various T-lymphocyte antigens, B-lymphocytes, natural killer (NK)-cells, monocytes, and macrophages, and finally bone marrow progenitor cells. Functional properties of peripheral T-lymphocytes were analyzed by proliferation assays with mitogens, alloantigens and microbiological antigens. All patients but 3 responded with sufficient correction of the anaemia. The absolute number of leucocytes and lymphocytes remained unchanged during the study. Likewise, a remarkable intraindividual months to month constancy in the relative distribution of all PBMC subsets analyzed was recorded during the observation period, although some interindividual variability was observed. In contrast, the T-lymphocyte responsiveness decreased significantly except for 2 out of 11. We conclude, that treatment of renal anemia with r-HuEPO seems to induce immunosuppression in ESRD patients without affecting the distribution of various PBMC subsets.

Comparison of the pharmacokinetics of tacrolimus and cyclosporine at equivalent molecular doses.

Even though calcineurin inhibitors, namely Tacrolimus (FK) and Cyclosporine (CsA) share similar physicochemical properties and a common mechanism of action, their pharmacokinetics (pk) are different and unpredictable. Both drugs are metabolized by cytochrome P450-3A4 isoforms in the liver and in the mucosa of the upper gastrointestinal tract. FK in clinical practice is given in doses up to 50-fold lower than those of CsA due to its greater potency. It is often assumed that the diverse dosing contributes to the observed pharmacokinetic differences between the two drugs. The objective of the present study was to compare single-dose pk profiles of the two drugs, following oral and intravenous administration, on the basis of equivalent molecular dosing, thus ruling out the quantitative factor. Five healthy volunteers and 14 dialysis patients (7 hemodialysis, 7 peritoneal dialysis) were included in the study. Comparing the pharmacokinetic parameters obtained from the drugs, it appeared that cyclosporine has an greater primary volume of distribution and clearance rate compared to tacrolimus. No other statistically significant differences were observed regarding bioavailability, absorption rate, or elimination rate. The only significant correlation between the pk values of the drugs was in primary volume of distribution. We conclude that even at equivalent molecular doses the pk of each drug remains unique and unpredictable. Furthermore our data fail to reveal significant correlations between the bioavailability, clearance, absorption, and elimination rates of the two drugs.

[Repeated episodes of massive fetomaternal hemorrhage in the same woman]. / Gentagne tilfaelde af massiv føtomaternel blødning hos samme kvinde.

A case of recurrent fetomaternal haemorrhage is described. The Kleihauer test is recommended in the monitoring of patients at risk.

[Massive feto-maternal hemorrhage. Diagnosis, quantitation, etiology and (para-clinical findings)]. / Massiv føto-maternel blødning. Diagnostik, kvantitering, aetiologi og (para-)kliniske fund.

Massive feto-maternal haemorrhage occurs with a frequency of approximately 1 out of 1,000 deliveries and involves a considerable risk for intrauterine/perinatal morbidity and mortality. Three cases of massive feto-maternal haemorrhage are described. Methods of diagnosis and quantitation are reviewed. The etiological conditions are briefly mentioned and clinical and paraclinical aspects in the fetus/infant and also the mother are reviewed. Investigation for feto-maternal haemorrhage should be undertaken in all cases of unexplained stillbirth and perinatal death and in all cases with hypovolaemic shock or non-haemolytic anaemia in neonates. In addition, investigation should be undertaken in selected cases with deterioration of fetal condition after eg trauma to the uterus, external version and amniocentesis, particularly in cases with massive vaginal haemorrhage and/or aspiration of haemorrhagic amniotic fluid. In these latter cases, it may also be of value to carry out Kleihauer's test on aspirate from the vagina and/or amniotic fluid with the object of determining whether the haemorrhage is of fetal or maternal origin.

Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children.

BACKGROUND: Limited data exist on the risk factors for acute renal failure (ARF) following cardiac surgery in children with congenital heart disease. This cohort study was conducted to examine this subject, as well as changes in the incidence of ARF from 1993 to 2002, the in-hospital mortality and the time spent in the intensive care unit (ICU). METHODS: One thousand, one hundred and twenty-eight children, operated on for congenital heart disease between 1993 and 2002, were identified from our prospectively collected ICU database to obtain data on potential risk factors. RESULTS: A total of 130 children (11.5%) developed ARF after surgery. A young age [> or =1.0 vs. <0.1 year; odds ratio (OR), 0.23; 95% confidence interval (CI), 0.12-0.46], high Risk Adjusted Classification of Congenital Heart Surgery (RACHS-1) score (OR, 2.72; 95% CI, 1.66-4.45) and cardiopulmonary bypass (CPB) (<90 min vs. none; OR, 2.68; 95% CI, 1.03-6.96; > or =90 min vs. none; OR, 12.94; 95% CI, 5.46-30.67) were independent risk factors for ARF. The risk of ARF decreased during the study period. Children with ARF spent a significantly longer time in the ICU (2-7 days vs. <2 days, P = 0.002; > or =7 days vs. <2 days, P < 0.001) compared with non-ARF patients, and showed increased in-hospital mortality (20% vs. 5%, P < 0.001). CONCLUSION: A young age, high RACHS-1 score and CPB were independent risk factors for ARF after surgical procedures for congenital heart disease in children. The risk of ARF decreased during the study period. Children with severe ARF spent a longer time in the ICU, and the mortality in ARF patients was higher than that in non-ARF patients.

Triiodothyronine stimulates growth of peripheral blood mononuclear cells in serum-free cultures in uremic patients.

The effect of triiodothyronine (T3) on the responses to mitogens and on the production of prostaglandin E2 and interleukin 2 were studied in serum-free cultures of peripheral blood mononuclear cells (PBMC) in 20 patients undergoing hemodialysis and in 30 control subjects. T3 increased the growth of PMBC induced by phytohemagglutinin and pokeweed mitogen in both groups. PBMC reached growth maximum at 0.5 nM T3 when stimulated by phytohemagglutinin in both groups. At higher concentrations of T3 the effect declined in the control group, but the response of uremic PBMC was constant. The response to T3 of pokeweed mitogen stimulated PBMC was lower in the uremic patients. The production of prostaglandin E2 by PBMC was higher in the uremic patients than in the controls. T3 had no effect on prostaglandin E2 production. Indomethacin alone and in combination with T3 had a stimulatory effect on cell growth in the patient group. T3 had no effect on the release of interleukin 2 by PBMC. An additive effect of interleukin 2 and T3 was observed in cultures stimulated by suboptimal concentrations of the mitogens. In conclusion, the impaired growth of PBMC in serum-free cultures from uremic patients was enhanced, however, not normalized, by external addition of T3, inhibition of prostaglandin E2 synthesis, and addition of interleukin 2.

Application of an enzyme-linked immunoassay for the measurement of pregnancy zone protein (PZP) in cell culture supernatants and sera.

A simple and sensitive enzyme-linked immunosorbent assay (ELISA) measuring specifically the pregnancy zone protein (PZP) was constructed. The assay range was 2.0-500 micrograms/l. The intra-assay coefficient of variation (CV%) was 5.9% at the level of 100 micrograms/l and 3.5% at 10 micrograms/l. The imprecision between runs was 4.5% at 100 micrograms/l and 7.6% at 10 micrograms/l. Recovery of the native PZP standard added to serum-free cell culture medium was 98.1 +/- 3.7% (mean +/- SD), and recovery from serum of women in late pregnancy was 96.0 +/- 9.3%. Recovery from PZP-chymotrypsin (PZP-CT) complexes added to serum-free medium was 141 +/- 4.3%. There was no detectable cross-reactivity between the anti-human PZP antibody and human alpha 2-macroglobulin (alpha 2-M). The dose-response of two PZP standards and the PZP serum concentrations of 100 blood donors were determined. Furthermore, the serum level of PZP from 11 patients suffering from IgA myeloma was quantitated and found within the normal range when compared to serum levels of healthy blood donors of the same age and sex. Finally, supernatants from serum-free cultures of different human peripheral blood mononuclear cell (PBM) subpopulations were assayed. Neither of them were found to exhibit any detectable increase in PZP concentration during culture, but cultures of monocytes were found to produce alpha 2-M.