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Nephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11-28% of NL and/or NC, suggesting additional NL/NC-associated genetic loci await discovery. Therefore, we employed genomic approaches to discover novel genetic forms of NL/NC.Exome sequencing and directed sequencing of the OXGR1 locus were performed in a worldwide NL/NC cohort. Putatively deleterious rare OXGR1 variants were functionally characterized.Exome sequencing revealed a heterozygous OXGR1 missense variant (c.371TG, p.L124R) co-segregating with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multi-generational family with five affected individuals. OXGR1 encodes 2-oxoglutarate (α-ketoglutarate) receptor 1 in the distal nephron. In response to its ligand α-ketoglutarate (AKG), OXGR1 stimulates the chloride-bicarbonate exchanger Pendrin, which also regulates transepithelial calcium transport in cortical connecting tubules. Strong amino acid conservation in orthologues and paralogues, severe in silico prediction scores, and extreme rarity in exome population databases suggested the variant was deleterious. Interrogation of the OXGR1 locus in 1107 additional NL/NC families identified five additional deleterious dominant variants in five families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in NL/NC subjects relative to ExAC controls (ΧRare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease.

Despite increasing knowledge about the optimal treatment for patients with severe COVID-19, data from different cohorts suggested that survival of patients treated with ECMO seemed to decline over the course of the pandemic.In this non-interventional retrospective single-center registry study we analyzed all consecutive patients tested positive for SARS-CoV-2 infection and supported with VV ECMO in our center during the first three waves of the pandemic. From March 2020 through June 2021, 59 patients have been included.Overall 90-day survival was 32%. Besides changes in drug treatment for COVID-19 and a lower PaOVV ECMO has shown to be a feasible and safe support option for patients with severe respiratory failure due to COVID-19. The results from this single-center study confirm findings from other cohorts showing declining survival rates of patients treated with VV ECMO during the COVID-19 pandemic, however, the specific reasons for this finding remain unclear.