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Conclusions: Using the new ELISA that targets the biologically active site of renalase, we show that loss of GFR is associated with decreasing total renalase levels, a finding opposite from previous studies using commercially available ELISA assays. By contrast, % free renalase increases with loss of GFR. Both % free renalase and free renalase independently predicted mortality. Future studies should focus on understanding the factors that regulate the balance between total and free renalase and how changes in renalase levels affect survival.

AimTh1 cells have potent pro‐inflammatory properties and have been shown to play an important role in the development and progression of acute renal injury to chronic renal disease. The aim of this study is to test the hypothesis that chronic renal damage in mice with renal artery stenosis (RAS) would be ameliorated in mice with homozygous deletion of the Th1 transcription factor T‐bet.MethodsC57BL6/J (WT) and C57BL6/J mice with homozygous deletion of T‐bet (KO) were obtained from Jackson Laboratory. Renal artery stenosis surgery (RAS) was performed by placement of a polytetrafluoroethylene cuff on the right renal artery of KO (KO RAS group, n=5) and WT mice (WT RAS group, n=6). Sham (SH) surgery was performed with manipulation of the right renal artery without cuff placement in KO (KO SH group, n=4) and WT mice (WT SH group, n=5). Renal blood perfusion and oxygenation (R2*) were measured using 16.4T MRI. Blood pressure measurements were done using tail‐cuff method. Kidneys were harvested at 28 days after RAS for assessment of histology.ResultsBaseline intra‐renal perfusion in both KO RAS and WT RAS mice was reduced to a similar extent following cuff placement. In KO RAS group, baseline intra‐renal perfusion (795 ± 57 ml/100g/min) was reduced to 234 ± 22 ml/100g/min (p<0.0001 vs baseline, mean reduction 71%) and in WT RAS group, baseline intra‐renal perfusion (836 ± 87 ml/100g/min) was reduced to 220 ± 21 ml/100g/min (p=0.002 vs baseline, mean reduction 74%). Both KO RAS and WT RAS mice developed hypertension, which persisted throughout the 4 week study. WT RAS group showed significant elevation in cortical R2*, a measure of hypoxia, following RAS compared to their baseline (p=0.002). KO RAS mice showed slightly higher R2* value, which was not significantly different from their baseline values. The weight of the stenotic kidney of the KO RAS group (105 ± 11.6 mg) was significantly lower than the KO SH mice (178 ± 14.1 mg, p=0.0021) but significantly higher than the WT RAS group (51.7 ± 7.9 mg, p=0.0010). On histologic and immune‐histochemical analysis, we observed that the stenotic kidney of the KO RAS group had significantly lower (%) cortical tubular atrophy (15% ± 6.7, p<0.0001) compared to WT RAS mice (81.7% ± 7). KO RAS group had significantly lower macrophage (MQ) (p=0.0016) and T cell influx (p=0.0052) compared to the WT RAS, as assessed by the % of cortical surface areas staining positive for F4/80 (MQ) and CD3 (T cell). When compared to their respective shams, KO RAS showed no significant differences in the % cortical tubular atrophy, MQ and CD3+ T cell influx.ConclusionWe conclude that deficiency of Th1 transcription factor T‐bet, protects against chronic renal injury as evidenced by the less cortical atrophy in KO RAS compared to WT RAS group, despite a similar elevation in blood pressure and reduction in perfusion. This model may provide a novel therapeutic target to prevent renal disease progression in patients with renovascular hypertension.Support or Funding InformationNational Institutes of Health Grant AI 100911This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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