Differential response to renal replacement therapy in neonatal‐onset inborn errors of metabolism

Porta, Francesco; Peruzzi, Licia; Bonaudo, R; Pieretti, Silvia; Busso, Marta; Cocchi, Enrico; Conio, Alessandra; Pagliardini, Veronica; Spada, Marco

doi:10.1111/nep.13409

Cited by 10 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Due to limitations in access to diagnostic equipment and laboratories in local hospitals, pre‐diagnoses of IMDs may occur late. Diagnostic tests and treatments should be carried out at the same time 16 . Such disorders usually require urgent detoxification treatment, and our hospital serves as a reference center given the availability of hemodialysis and advanced treatment options.…”

Section: Discussionmentioning

confidence: 99%

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for

Eminoğlu

Yekedüz

Doğulu

et al. 2022

Pediatrics International

View full text Add to dashboard Cite

Background We aimed to assess symptoms, laboratory findings, and radiological abnormalities in patients diagnosed with inherited metabolic disorders (IMDs) in the neonatal intensive care unit. Methods A total of 6,150 newborns treated in a third‐level neonatal intensive care unit between 2012 and 2020 in Turkey were screened, of which 195 consulted with a suspicion of metabolic disease based on their clinical, laboratory, or radiological findings were included in the present study. Results The prevalence of IMDs in the patients was 1:94.6. Those consulted in the department of pediatric metabolism were divided into two groups, with the 65 diagnosed with IMDs assigned as Group I, and the 130 patients who were not diagnosed with IMDs as Group II. The most common IMDs were organic acidemias (29.23%) and urea cycle disorders (UCDs) (26.15%). The rates of consanguinity marriage (75.3% vs 37.6%, P < 0.001), siblings diagnosed with an IMD (27.6% vs 3.8%, P < 0.001), and sibling death (56.9% vs 14.6%, P < 0.001) were higher in Group I than in Group II. Hyperammonemia (61.5% vs 18.4%, P < 0.001) was the most common laboratory finding in Group I, and anemia (Group I 60.0% vs 43.0% P = 0.033), metabolic acidosis (53.8% vs 36.9%, P = 0.028) and respiratory alkalosis (16.9% vs 1.5%, P < 0.001) were all higher in Group I. Conclusions This retrospective study found that the results of clinical findings and basic laboratory tests could be strong indicators of IMDs, although extensive newborn screening tests and advanced biochemical and genetic tests should be carried out for the diagnosis of IMDs in newborns.

show abstract

Section: Discussionmentioning

confidence: 99%

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for

Eminoğlu

Yekedüz

Doğulu

et al. 2022

Pediatrics International

View full text Add to dashboard Cite

show abstract

“…Accordingly, the elimination of toxic metabolites to avoid neurological complications should be considered a medical emergency. CKRT is an effective treatment for acute crises in some IEM [ 13 , 14 ]. In the present study, CKRT was shown to quickly reduce toxic metabolites (ammonia, leucine) in patients diagnosed with IEM.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of continuous venovenous hemodiafiltration in the acute treatment of inherited metabolic disorders

et al. 2021

View full text Add to dashboard Cite

Background Continuous kidney replacement therapies (CKRT) have been reported to be an effective approach to removing toxic metabolites in inborn errors of metabolism (IEM). The present study evaluates efficiency and complications of CKRT in children with IEM. Methods Patients diagnosed with IEM who underwent CKRT in pediatric and neonatal intensive care units were analyzed. CKRT were initiated in patients with persistently high blood ammonia levels (≥ 500 μmol/L), blood ammonia levels > 250 μmol/L in the presence of moderate encephalopathy, high blood leucine levels (≥ 1500 μmol/L), and blood leucine levels < 1500 μmol/L in the presence of deteriorating neurological status or persistent metabolic acidosis. Results Of 22 patients enrolled, nine (40.9%) Maple syrup urine disease (MSUD), eight (36.4%) urea cycle disorders (UCD), and five (22.7%) organic acidemias (OA). Median age was 72.3 [9.9–1040.8] days. In total, 28 dialysis sessions were analyzed [16 (57.1%) continuous venovenous hemodialysis, and 12 (42.9%) continuous venovenous hemodiafiltration]. A significant decrease was noted in leucine levels (from 1608.4 ± 885.3 to 314.6 ± 109.9 µmol/L) of patients with MSUD, while ammonia levels were significantly decreased in patients with UCD and OA (from 1279.9 ± 612.1 to 85.1 ± 21.6 µmol/L). The most frequent complications of CKRT were thrombocytopenia (60.7%), hypotension (53.6%), and hypocalcemia (42.9%). Median age of patients with hypotension treated with vasoactive medications was significantly lower than median age of those with normal blood pressure. Conclusion CKRT is a reliable approach for effective and rapid removal of toxic metabolites in children with IEM, and CKRT modalities can be safely used and are well-tolerated in infants.

show abstract

“…Neonatal-onset UCDs or OAs are life-threatening disorders leading to hyperammonemic coma and requiring early specific emergency treatments [17,18]. Patients surviving the neonatal period experience recurrent metabolic decompensations later in life (generally triggered by undercurrent catabolic stressors) and poor prognosis in spite of appropriate long-term conventional management [1].…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

Spada

Porta

Righi

et al. 2019

Stem Cell Rev and Rep

Self Cite

View full text Add to dashboard Cite

Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders.

show abstract

Differential response to renal replacement therapy in neonatal‐onset inborn errors of metabolism

Cited by 10 publications

References 18 publications

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for

Characteristics of continuous venovenous hemodiafiltration in the acute treatment of inherited metabolic disorders

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

Contact Info

Product

Resources

About