Growth and development alter susceptibility to acute renal injury

• Published in: Kidney international Vol. 74; no. 5; pp. 674 - 678
• Main Authors: Zager, Richard A., Johnson, Ali C.M., Naito, Masayo, Lund, Steve R., Kim, Nayeon, Bomsztyk, Karol
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2008; Nature Publishing; Elsevier Limited
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - genetics; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; acute renal failure; Age Factors; Animals; Biological and medical sciences; Body Weight; Cholesterol - blood; Cholesterol - metabolism; Endotoxemia - complications; endotoxin; Glycerol - toxicity; Hydroxymethylglutaryl CoA Reductases - genetics; Injuries of the urinary system. Foreign bodies. Diseases due to physical agents; Kidney - drug effects; Kidney - growth & development; Kidney - metabolism; Kidney - pathology; Male; maleate; Maleates - toxicity; Medical sciences; Mice; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Organ Size; Receptors, LDL - genetics; Renal failure; rhabdomyolysis; RNA Polymerase II - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sterol Regulatory Element Binding Proteins - metabolism; Traumas. Diseases due to physical agents; rhabdomyolysis; acute renal failure; maleate; endotoxin; Kidney disease; Nephrology; Urinary system disease; Growth; Acute; Rhabdomyolysis; Kidney traumatism; Endotoxin; Urology; Acute renal failure; Toxin; Striated muscle disease; Development
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2008.251

Many of the studies of acute renal injury have been conducted in young mice usually during their rapid growth phase; yet, the impact of age or growth stage on the degree of injury is unknown. To address this issue, we studied three forms of injury (endotoxemic-, glycerol-, and maleate-induced) in mice ranging in age from adolescence (3 weeks) to maturity (16 weeks). The severity of injury within each model significantly correlated with weight and age. We also noticed a progressive age-dependent reduction in renal cholesterol content, a potential injury modifier. As the animals grew and aged they also exhibited stepwise decrements in the mRNAs of HMG CoA reductase and the low density lipoprotein receptor, two key cholesterol homeostatic genes. This was paralleled by decreased amounts of RNA polymerase II and the transcription factor SREBP1/2 at the reductase and lipoprotein receptor gene loci as measured by chromatin immunoprecipitation. Our study shows that the early phase of mouse growth can profoundly alter renal susceptibility to diverse forms of experimental acute renal injury.