Animal experimental studies in different acute kidney disease (AKI) models suggest that AKI is a status of transient renal Klotho deficiency. Lack of Klotho can stem from a variety of causes, including ischemia-reperfusion injury, ureteric obstruction, lipopolysaccharide, hypovolemia, and nephrotoxins.
Klotho down-regulation may be a general phenomenon of kidney damage, regardless of etiology. Based on current clinical observations and benchwork from our lab and others, we propose that Klotho repletion is a good strategy for protecting the kidney under various circumstances:
- When given before exposure to renal insults, Klotho may protect the kidney from AKI.
- When given after the onset of AKI, Klotho may suppress renal fibrosis and retard the progression of chronic kidney disease (CKD).
On the other hand, we revealed Klotho-deficient mice have poorer renal function and worse kidney histology compared to wild-type mice after CKD induction, suggesting that Klotho deficiency is not a mere biomarker for CKD but is actually pathogenic for CKD progression.
Currently there are limited studies examining Klotho effect on CKD development. We used one transgenic Klotho overexpressor to test it and obtained very encouraging results.
We are now testing the effectiveness of Klotho protein by intraperitoneal administration via osmotic minipumps.
Klotho may be a unique protein that not only serves as a potentially useful biomarker for kidney disease, but also functions as a renoprotective protein to protect the kidney against acute damage, promote renal tissue regeneration, and prevent or retard progression to CKD, through many yet-to-be identified mechanisms.