Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI.

summary Fatty acid composition was determined in cells of strains CBhS and CBp7 of Rhizobium leguminosarum bv. viciae grown at four temperatures (10, 15, 22 and 30°C), and in bacteroids and nodules formed with faba bean (Vicia faba L.) grown at two day/night temperature regimes (22/15 and 15/10°C). Growth temperature markedly affected the fatty acid composition of free‐living bacteria in both strains studied, and both showed similar variations at each temperature. The proportion of unsaturated fatty acids increased significantly with lowering of temperature. The major fatty acid found in bacteria and bacteroids was cis‐vaccenic (C18: 1Δ11), which comprised up to c. 78 (bacteria) and 56% (bacteroids) of total fatty acids. The presence of polyunsaturated fatty acids (linoleic (C18:Δ,9,12) and linolenic (C18:3Δ9,12,15) acids) was noted only in bacteroids, indicating changes following the differentiation of bacteria into bacteroids in the nodules. The fatty acid composition of nodules was similar to that of bacteroids, although major differences were found in their proportions. The different day/night temperature regimes had contrasting effects in bacteroids and in nodules. In bacteroids of both strains, the proportions of stearic (C18:0) and linoleic (C18:Δ9,12) acids decreased at the lower temperature regime. In nodules, the proportion of stearic (C18:0) acid decreased, while that of linolenic (C18:3Δ9,12,15) acid increased at the lower temperature regime. However, those of cis‐vaccenic (C18:1Δ11), linoleic (C18:Δ9,12,15) and palmitic (C16:0) acids increased or decreased depending on the rhizobial strain. The proportion of unsaturated fatty acids increased with the lowering of temperatures in bacteroids of both strains, and varied in whole nodules depending on the strain. Strain CBp7 showed a greater symbiotic efficiency (dry matter yield) than strain CBh5 under both temperature regimes, but no relationship was found with the proportion of unsaturated fatty acids of bacteria, bacteroids or nodules.

The method for midazolam using DBS was validated and showed an excellent performance. Excellent correlations were observed when the same collection procedures were used.