What the authors of this paper did was ask what would happen if KIM1 was overexpressed in the kidney. To do this, they created a conditional knock-in of KIM1 leading to constitutive expression in the tubules. The mice were normal at birth but by 2 weeks were already smaller than their littermates with about half as many glomeruli. The glomeruli looked normal histologically at that point. The mice subsequently developed severe tubular inflammation and fibrosis. This was accompanied by proteinuria, hypertension and anemia. All of this appeared to be driven by the tubulointerstitial inflammation and there was no evidence of a primary glomerular disease. So, mice with uninhibited KIM1 expression rapidly developed ESRD in the absence of any other insults.
By obstructing a single kidney in the mouse, you can induce inflammation and fibrosis. The authors next used this model in wild-type mice and in mice with a KIM1 mutant that lead to decreased activity. The mice with the KIM1 mutant were protected from renal fibrosis.
I love this paper. I am a fan of biomarkers at the best of times but this is really exciting. This suggests that KIM1, rather than being a marker of damage, is in fact a mediator of renal damage and could potentially be a target for future therapies to prevent damage, for ex
ample after AKI.
Honorable mention goes to the paper in CJASN that finally put the dagger in the heart of urinary eosinophils that I had previously blogged about. Good riddance.
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Check out the coverage of top nephrology stories from around the blogosphere including eAJKD, Precious Bodily Fluids, Nephron Power, Whiz Bang and a few others coming soon.