Explore the vast range of titles available.

Primary hyperoxaluria type 1 is caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. This trial tested whether an oligonucleotide drug can reduce the production of hepatic oxalate.

BackgroundPrimary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018–004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here.MethodsOf the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7–20.5) months).ResultsLumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)).ConclusionsLumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1.A higher resolution version of the Graphical abstract is available as Supplementary information

Purpose To assess a possible association between marked proteinuria and the risk of preeclampsia with severe features, as defined by the American College of Obstetricians and Gynecologists. Methods This retrospective study included data recorded at a tertiary university-affiliated hospital between 2017 and 2022. Women at or beyond 24 weeks of gestation with proteinuria (protein levels > 300 mg in a 24 h urine collection) and normal blood pressure during the initial 48 h of admission were included. Obstetrical and neonatal outcomes were compared between women with mild proteinuria (300–1000 mg/24 h) and marked proteinuria (≥ 1000 mg/24 h). Results Among the women with marked proteinuria (n = 48) compared to those with mild proteinuria (n = 108), the incidences were higher of preeclampsia (50.0% vs. 22.2%, p = 0.001) and of preeclampsia with severe features (18.8% vs. 2.8%, p < 0.001). In multivariate analysis that adjusted for maternal age, primiparity, multiple pregnancy, uric acid level > 6 mg/dL and aspirin treatment, marked proteinuria was a risk factor for preeclampsia with severe features (adjusted odds ratio [aOR] = 10.2, confidence interval [CI] 95% 1.9–54.0, p = 0.007) and for small-for-gestational-age infants (aOR = 2.4, 95% CI 1.02–5.6, p = 0.001). Among women with marked compared to mild proteinuria, rates were also higher of labor induction (58.3% vs. 25.9%, p < 0.001), indicated preterm delivery (41.7% vs. 25.0%, p = 0.04) and admission to the neonatal intensive care unit (44.1% vs. 25.8%, p = 0.017). Conclusions Women with marked compared to mild isolated proteinuria showed higher risk of developing preeclampsia with severe features and of delivering small-for-gestational-age neonates.

BackgroundPrimary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the liver defect of oxalate metabolism, which leads to kidney failure and systemic manifestations. Until recently, liver transplantation was the only definitive treatment. The timing of liver transplantation can be early, while kidney function is still normal (pre-emptive liver transplantation—PLT), or when the patient reaches stage 5 chronic kidney disease (CKD) and needs combined liver-kidney transplantation. We aimed to determine the long-term kidney outcomes of PLT in PH1 patients.MethodsA retrospective single-center study of PH1 patients who were followed in our center between 1997 and 2017. We compared the kidney outcomes of patients who underwent PLT to those who presented with preserved kidney function and did not undergo PLT.ResultsOut of 36 PH1 patients, 18 patients were eligible for PLT (eGFR > 40 mL/min/1.73 m2 at the time of diagnosis). Seven patients underwent PLT (PLT group), while 11 continued conservative treatments (PLTn group). In the PLT group, the median eGFR at the time of PLT and at the end of the follow-up period (14–20 years) was 72 (range 50–89) and 104 (range 86–108) mL/min/1.73 m2, respectively, and no patient died or reached stage 5 CKD. In the PLTn group, eight patients (72.7%) reached stage 5 CKD (median time to kidney replacement therapy was 11 years), and two patients died from disease complications (18.2%).ConclusionsPre-emptive liver transplantation preserved kidney function in patients with PH1 in our cohort. Early intervention can prevent kidney failure and systemic oxalosis in PH1.