Genotype correlates with the natural history of severe bile salt export pump deficiency Highlights NAPPED is the largest global database of genotyped patients with BSEP deficiency. The genotype of patients with BSEP deficiency predicts survival with native liver. Genotype predicts long-term benefit of interruption of enterohepatic circulation. Serum bile acids can be a surrogate marker for long-term outcome. Treatment of patients with BSEP deficiency should be based on genotype.

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication); FIC1-A (n=67; no PPTM), FIC1-B (n=29; one PPTM) or FIC1-C (n=34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs <194 µmol/L: 49% versus sBAs ≥194 µmol/L: 15%; P=0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P=0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P=0.06) and post-SBD sBA concentrations <65μmol/L (P=0.05) tended to be associated with improved NLS. Conclusion:Less than half of FIC1 deficiency patients reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

BACKGROUND The pediatric peritoneal dialysis (PD) program in Cipto Mangunkusumo Hospital, Indonesia was started in 2014. However, there has been no published data on the patients’ outcome. This study was aimed to report the characteristics and outcomes of a continuous ambulatory peritoneal dialysis (CAPD) program for children. METHODS This retrospective study was conducted in Cipto Mangunkusumo Hospital as a national referral hospital. Data were collected from medical records of patients aged ≤18 years with end-stage renal disease who underwent CAPD in 2014–2019. The baseline characteristics, PD-related infection rate, as well as patient and technique survivals were analyzed. RESULTS Out of 60 patients who underwent CAPD, 36 (60%) were boys on the age range of 4 months–18 years. The mean follow-up duration was 12 (95% confidence interval [CI] = 9.4–15.3) months. The number of PD related infections increased along with the growing number of patients on CAPD. The peritonitis rate was 0.42 episodes per year at risk, and the most common etiology was alpha-hemolytic Streptococcus (5/24, [20.8%]). The 1- and 3-year technique survival rates were 60.3% (95% CI = 44.5–72.9) and 43.9% (95% CI = 23.2–62.9). The 1- and 3-year patient survival rates were 69.6% (95% CI = 52.5–81.5) and 58% (95% CI = 31.2–77.5). CONCLUSIONS In this unit, CAPD could be performed in children as young as 4 months of age. The peritonitis rate was relatively low which was likely caused by skin-derived microorganisms. Both technique survival and patient survival were also relatively low.

Iron deficiency anemia is common in children with end-stage renal disease (ESRD) on long-term hemodialysis receiving erythropoiesis-stimulating agents. One approach to maintain the iron profile and hemoglobin levels is maintenance therapy with regular low doses of intravenous (IV) iron after initial iron repletion therapy; however, evidence for the benefits of this approach is lacking. This study evaluated the effect of IV iron maintenance therapy on anemia in children on regular hemodialysis. This retrospective cohort study included 41 pediatric ESRD patients with normal hemoglobin and iron status who underwent regular hemodialysis at the Pediatric Dialysis Unit of Cipto Mangunkusumo Hospital, Indonesia, between January 2015 and April 2019. Among these, 21 received IV iron maintenance therapy with two doses of 2 mg/kg of IV iron sucrose every 2 weeks (the treatment group) and 20 did not (the comparison group). Changes in hemoglobin and transferrin saturation were assessed after 6 weeks of observation and compared between the two groups. There was a significant reduction in the mean hemoglobin level compared with the baseline level in the comparison group (21 g/L; 95% CI, 9.3–33 g/L; p=0.001) but not in the treatment group (0.7 g/L; 95% CI, −6.6–8 g/L; p=0.84). The risk of anemia was lower in the treatment group (relative risk = 0.42; 95% CI, 0.22–0.79; p=0.003). Although majority of the patients had high baseline ferritin level, this study indicates that in our setting, ferritin may not be a reliable parameter to review the iron status, as it can be affected by chronic inflammation. Hence, the decision to start IV iron maintenance therapy in patients with hyperferritinemia should consider the patient’s clinical condition and morbidity. To conclude, the coadministration of IV iron maintenance therapy is beneficial for maintaining hemoglobin levels and preventing anemia in children with ESRD who are undergoing regular hemodialysis, have achieved the target hemoglobin levels, and have normal iron status.