Background/aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD.
Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague-Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age.
Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP.
Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD.
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Am J Physiol Renal Physiol
November 2024
Mayo Translational PKD Center, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States.
Abnormalities in distinct metabolic pathways have been associated with the pathogenesis and progression of many forms of kidney disease. Metabolomics analyses can be used to determine organ-specific metabolic fingerprints and, ideally, should represent the metabolic state of the organ at the exact moment the sample is harvested. However, conventional harvesting methods depend on posteuthanasia tissue harvest, which results in ischemia conditions and metabolome changes that could potentially introduce artifacts into the final studies.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
June 2024
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents.
View Article and Find Full Text PDFPhysiol Rep
September 2023
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Metformin (MET) has the potential to activate p-AMPK and block mTORC1-induced proliferation of tubular cells in PKD kidneys. The aim of this study was to determine the effects of MET on cyst growth, kidney function, AMPK and mTOR signaling, and lactate levels in male PCK rats, a Pkhd1 gene mutation model of human autosomal recessive polycystic kidney disease (ARPKD). MET 300 mg/kg/day IP from days 28 to 84 of age resulted in a mean serum metformin level that was 10 times the upper limit of therapeutic, no effect on cyst indices, nephrotoxicity, and increased serum lactate.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
April 2023
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States.
Congenital hepatic fibrosis / Autosomal recessive polycystic kidney disease (CHF/ARPKD) is an inherited neonatal disease induced by mutations in the gene and characterized by cysts, and robust pericystic fibrosis in liver and kidney. The PCK rat is an excellent animal model which carries a mutation and exhibits similar pathophysiology. We performed RNA-Seq analysis on liver samples from PCK rats over a time course of postnatal day (PND) 15, 20, 30, and 90 using age-matched Sprague-Dawley (SD) rats as controls to characterize molecular mechanisms of CHF/ARPKD pathogenesis.
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