Liver cell transplantation in severe infantile oxalosis--a potential bridging procedure to orthotopic liver transplantation?

BACKGROUND: The infantile form of primary hyperoxaluria type I (PHI) is the most devastating PH subtype leading to early end-stage renal failure and severe systemic oxalosis. Combined or sequential liver-kidney transplantation (LKTx) is the only curative option but it involves substantial risks, especially in critically ill infants. The procedure also requires resources that are simply not available to many children suffering from PHI worldwide. Less invasive and less complex therapeutic interventions allowing a better timing are clearly needed. Liver cell transplantation (LCT) may expand the narrow spectrum of auxiliary measures to buy time until LKTx for infants can be performed more safely. METHODS: We performed LCT (male neonate donor) in a 15-month-old female in reduced general condition suffering from systemic oxalosis. Renal replacement therapy, initiated at the age of 3 months, was complicated by continuous haemodialysis access problems. Living donor liver transplantation was not available for this patient. Plasma oxalate (Pox) was used as the primary outcome measure. RESULTS: Pox decreased from 104.3±8.4 prior to 70.0±15.0 µmol/L from Day 14 to Day 56 after LCT. A significant persistent Pox reduction (P<0.001) comparing mean levels prior to (103.8 µmol/L) and after Day 14 of LCT until LKTx (77.3 µmol/L) was seen, although a secondary increase and wider range of Pox was also observed. In parallel, the patient's clinical situation markedly improved and the girl received a cadaveric LKTx 12 months after LCT. However, biopsy specimens taken from the explanted liver did not show male donor cells by amelogenin polymerase chain reaction. CONCLUSIONS: With due caution, our pilot data indicate that LCT in infantile oxalosis warrants further investigation. Improvement of protocol and methodology is clearly needed in order to develop a procedure that could assist in the cure of PHI.

Respiratory and general outcome in neonates with renal oligohydramnios--a single-centre experience.

BACKGROUND: Renal oligohydramnion (ROH) is predominantly caused by congenital abnormalities of the kidney and urogenital tract (CAKUT). Although the number of neonates born with chronic renal failure is small, they provide many challenges, and among the most problematic are respiratory management and long-term treatment of chronic renal failure. We studied the value of prenatal and perinatal variables to predict survival and the general long-term outcome of our ROH population. Method. A single-centre retrospective chart review was conducted in 36 neonates with ROH treated between 1996 and 2007. Respiratory data sets including minimum inspiratory oxygen concentration (FiO(2), 1d), best oxygenation index (BOI, 1d) and minimum arterial partial carbon dioxide (pCO(2), 1d) at the first day of life were available in 23 children requiring intubation. RESULTS: ROH causes were obstructive uropathy (n = 19), polycystic kidney disease [autosomal recessive polycystic kidney disease (ARPKD) n = 5 and autosomal dominant polycystic kidney disease n = 1], renal agenesis/dysplasia (n = 10) and bilateral renal vein thrombosis (n = 1). Survival until discharge was 64% (23/36), and overall survival was 58% (21/36). Seven patients died within 48 h from respiratory failure. Non-survivors had a higher minimum FiO(2) and pCO(2) (1d) compared to survivors (P < 0.001). Mean BOI (1d) was 6.2 in survivors versus 43.9 in the non-surviving group (P < 0.001). Logistic regression showed that BOI (28 gestational weeks) retained significance in predicting survival until discharge. CONCLUSIONS: The attitude toward initiating dialysis in neonates is changing and long-term outcome in the absence of severe comorbidity is promising. Prenatal prediction concerning respiratory and renal outcome in fetuses with ROH is difficult. Our data suggest that BOI (1d) and onset of ROH may be reliable predictors of respiratory prognosis in children born with ROH.

NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced fibrosis in patients with NAFLD.

AIMS: To develop, validate and compare a non-invasive fibrosis scoring system for non-alcoholic fatty liver disease (NAFLD) derived from routinely obtained clinical and biochemical parameters. METHODS: 267 consecutive patients with biopsy proven fatty liver or non-alcoholic steatohepatitis were randomly assigned to the estimation (2/3) or validation (1/3) group to develop a model for the prediction of advanced fibrosis. Univariate statistics were performed to compare patients with and without advanced fibrosis, and following a multivariate logistic regression analysis a new scoring system was constructed. This non-invasive Koeln-Essen-index (NIKEI) was validated and compared to the FIB-4 index by calculating the area under the receiver operating characteristic curve (AUC). We evaluated a stepwise combination of both scoring systems for the precise prediction of advanced fibrosis. To set in contrast, we additionally tested the diagnostic accuracy of the AST/ALT ratio, BARD score and the NAFLD fibrosis score in our cohort. RESULTS: Age, AST, AST/ALT ratio, and total bilirubin were identified as significant predictors of advanced fibrosis and used to construct the NIKEI with an AUC of 0.968 [0.937; 0.998] compared to 0.929 [0.869; 0.989] for the FIB-4 index. The absence of advanced fibrosis could be confirmed with excellent accuracy (99-100%). The positive predictive value of the FIB-4 index was higher (100% vs. 60%), however, the false negative rate was also high (33%). With a stepwise combination of both indices 82%-84% of biopsies would have been avoidable without a single misclassification. The AUROC for AST/ALT ratio, the NAFLD fibrosis score, and the BARD score were 0.81 (95% CI, 0.72-0.90), 0.96 (95% CI 0.92-0.99), and 0.67 (95% CI 0.55-0.78), respectively. CONCLUSION: The NIKEI can reliably exclude advanced fibrosis in subjects with NAFLD. In combination with the FIB-4 index misclassification with inadequate clinical management can be avoided while the need for liver biopsies can be reduced.

Efficacy and safety of moxifloxacin as antibacterial prophylaxis for patients receiving autologous haematopoietic stem cell transplantation: a randomised trial.

Patients receiving high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) are at high risk of infections, especially bacteraemia. A prospective, double-blind, randomised, placebo-controlled, single-centre, pilot study was performed on oral moxifloxacin 400mg versus placebo for preventing bacteraemia in PBSCT recipients. Patients received moxifloxacin or placebo for the duration of neutropenia or until emergence of fever or other infections necessitating intravenous antibiotic treatment. Of 68 patients included in the trial, 2 were excluded from the trial before taking their first dose. The remaining 66 patients were eligible for evaluation in the intention-to-treat analysis set. Neutropenia with an absolute neutrophil count of <500cells/µL developed in 30 moxifloxacin-treated patients (88.2%) and 21 patients in the placebo group (65.6%) (P<0.03). Nine patients (26.5%) and eight patients (25.0%), respectively, were prematurely discontinued from study treatment. Breakthrough bacteraemia occurred in 3 moxifloxacin-treated patients (8.8%) and 9 patients in the placebo group (28.1%) (P=0.042). The time period until fever was 9.5 days [95% confidence interval (CI) 8.06-10.94 days) and 7.69 days (95% CI 6.51-8.85 days), respectively (P=0.0499). There was no difference in adverse events or toxicities between the groups. Moxifloxacin prevented bacteraemia and shortened febrile episodes in patients receiving autologous PBSCT. No significant increase of adverse events in the moxifloxacin arm was observed, possibly due to the rather small sample size.