Primary hypomagnesaemia is composed of a heterogeneous group of disorders characterized by renal or intestinal Mg(2+) wasting, often associated with disturbances in Ca(2+) excretion. We identified a putative dominant-negative mutation in the gene encoding the Na(+), K(+)-ATPase gamma-subunit (FXYD2), leading to defective routing of the protein in a family with dominant renal hypomagnesaemia.
Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a 'polar track' demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its b-branched methyl group. Two critical central phenylalanines that directly coordinate F-through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F-through its partially positive g-methylene in mimicry of phenylalanine's quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F-anion.
Background
Acute kidney injury (AKI) incidence is increasing, however AKI is often missed at the emergency department (ED). AKI diagnosis depends on changes in kidney function by comparing a serum creatinine (SCr) measurement to a baseline value. However, it remains unclear to what extent different baseline values may affect AKI diagnosis at ED.
Methods
Routine care data from ED visits between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. We evaluated baseline definitions with criteria from the RIFLE, AKIN and KDIGO guidelines. We evaluated four baseline SCr definitions (lowest, most recent, mean, median), as well as five different time windows (up to 365 days prior to ED visit) to select a baseline and compared this to the first measured SCr at ED. As an outcome, we assessed AKI prevalence at ED.
Results
We included 47,373 ED visits with both SCr-ED and SCr-BL available. Of these, 46,100 visits had a SCr-BL from the − 365/− 7 days time window. Apart from the lowest value, AKI prevalence remained similar for the other definitions when varying the time window. The lowest value with the − 365/− 7 time window resulted in the highest prevalence (21.4%). Importantly, applying the guidelines with all criteria resulted in major differences in prevalence ranging from 5.9 to 24.0%.
Conclusions
AKI prevalence varies with the use of different baseline definitions in ED patients. Clinicians, as well as researchers and developers of automatic diagnostic tools should take these considerations into account when aiming to diagnose AKI in clinical and research settings.
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