scholarly journals Insulin resistance as a novel therapeutic target in patients with chronic kidney disease treated with dialysis

2010 ◽  
Vol 120 (1-2) ◽  
pp. 54-58
Author(s):  
Piotr Wesołowski ◽  
Marek Saracyn ◽  
Zbigniew Nowak ◽  
Zofia Wańkowicz
Keyword(s):  
Insulin Resistance ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Target ◽  
Novel Therapeutic

Failure to sense energy depletion may be a novel therapeutic target in chronic kidney disease

2019 ◽  
Vol 95 (1) ◽  
pp. 123-137 ◽  
Author(s):  
Hiroaki Kikuchi ◽  
Emi Sasaki ◽  
Naohiro Nomura ◽  
Takayasu Mori ◽  
Yoji Andrew Minamishima ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Target ◽  
Energy Depletion ◽  
Novel Therapeutic

scholarly journals Proteolytic Cleavage by Matriptase Exacerbating Kidney Injury: a Novel Therapeutic Target

2019 ◽  
Author(s):  
Shota Ozawa ◽  
Masaya Matsubayashi ◽  
Hitoki Nanaura ◽  
Motoko Yanagita ◽  
Kiyoshi Mori ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Fate ◽  
Therapeutic Target ◽  
Therapeutic Strategy ◽  
Progressive Disease ◽  
Kidney Injury ◽  
Podocyte Injury ◽  
Kidney Glomerulus ◽  
Novel Therapeutic

AbstractChronic kidney disease (CKD) is a progressive disease, and podocyte injury is a potential mechanism. We found that Matriptase was activated at podocytes in CKD patients and mice while a Matriptase inhibitor slowed the progression of mouse kidney disease. The mechanism could be accounted for by an imbalance favoring Matriptase over its cognate inhibitor, hepatocyte growth factor activator inhibitor type 1 (HAI-1), as conditional depletion of HAI-1 in podocytes accelerates podocyte injury. Intriguingly, the N-terminal of Podocin (Podocin-N), as a consequence of Matriptase cleavage of Podocin, translocates to nucleoli. These results suggest that aberrant activation of Matriptase would cause podocyte injury, and a targeting Matriptase could be a novel therapeutic strategy for CKD patients.Significant statementChronic kidney disease (CKD) is a progressive disease. If podocytes, which are specialized cells of the kidney glomerulus that wrap around capillaries, are injured, kidney injury is exacerbated. Thus, a therapeutic strategy to addressing CKD would be to block podocyte injury. The present study provides evidence that Matriptase cleaves Podocin, a component of podocyte slit membrane, and the N-terminal of podocin translocates to nucleoli, causing kidney injury. Our findings show that the N-terminal of Podocin plays an efficient role for cell fate in podocytes. In addition, the inhibition of Matriptase would be a potential therapeutic target for CKD.

scholarly journals ATP-citrate lyase as a therapeutic target in chronic kidney disease: a Mendelian Randomization analysis

2021 ◽  
Author(s):  
Pedrum Mohammadi-Shemirani ◽  
Michael Chong ◽  
Nicolas Perrot ◽  
Marie Pigeyre ◽  
Gregory R. Steinberg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Whole Blood ◽  
Therapeutic Target ◽  
Mendelian Randomization ◽  
Atp Citrate Lyase ◽  
Mendelian Randomization Analysis ◽  
Citrate Lyase ◽  
Ckd Stage ◽  
Randomization Analysis

Background: ATP-citrate lyase (ACLY) inhibition is a promising therapeutic target for dyslipidemia, atherosclerotic cardiovascular disease, non-alcoholic steatohepatitis, and metabolic syndrome. Genetic analysis of its role in chronic kidney disease (CKD) has not been performed. Methods: We constructed a genetic instrument by selecting variants associated with ACLY expression level in the expression quantitative trait loci genetics consortium (eQTLGen) that includes blood samples from 31,684 participants. In a two-sample Mendelian randomization analysis, we then evaluated the effect of genetically predicted ACLY expression on risk of CKD, estimated glomerular filtration rate (eGFR), and microalbuminuria using the CKD Genetics consortium (CKDGen), United Kingdom biobank, and the Finnish Genetics consortium (FinnGen) totaling 66,396 CKD cases and 958,517 controls. Results: ACLY is constitutively expressed in all cell types including in whole blood. The genetic instrument included 13 variants and explained 1.5% of variation in whole blood ACLY gene expression. A 34% reduction in genetically predicted ACLY expression was associated with a 0.04 mmol/L reduced low-density lipoprotein cholesterol (P = 3.4 x 10-4) and a 9% reduced risk of CKD (stage 3,4,5, dialysis or eGFR below 60 ml/min/1.73m2) (OR = 0.91, 95% C.I. 0.85-0.98, P = 0.008), but no association was observed with eGFR nor microalbuminuria. Conclusion: Mendelian Randomization analysis provides cautious optimism regarding the possibility of ACLY as a therapeutic target for CKD.

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