Risk Factors For Renal Senescence And Aging EGFR Decline

Background and Objective:Kidney disease is encountered commonly and frequently in the elderly,which endangers the health of the elderly.The pathological basis of multiple renal diseases in the elderly is renal senescence.Previous research revealed that a young blood environment decreases aging of senile kidneys.The selected internal environmental factor--stem cell factor(SCF)is closely related to the development of renal interstitial fibrosis in the elderly through the SCF/c-kit pathway.The progress of renal interstitial fibrosis will lead to the decrease of glomerular filtration rate(GFR),which is an important clinical manifestation of renal aging.However,the aging decline of GFR is affected by many factors.Our previous study also showed that 43%of the 245 healthy subjects had an average annual decrease rate of eGFR less than 1%or greater than 0 during the five-year follow-up.The CKD-EPI formula combined with serum creatinine and serum Cystatin C index,CKD-EPI(CysC-SC)equation,has better accuracy for the elderly population whose mGFR is more than 60 ml/min/1.73 m2.Previous studies have confirmed that calorie and nutrient intake,inflammatory status and sex hormones may be involved in kidney aging.but do they affect the aging change of eGFR?It's not clear.This study is based on the previous work,wild C57BL/6 mice and SCF ligand(C-Kit-/-)mutant mice(Wps/Wps strain mice)are used to establish a natural aging animal model,to verify the role of SCF/c-Kit pathway in the natural aging of kidney and explore its mechanism preliminarily;A cross-sectional study was conducted to verify the age-related changes of eGFR in healthy people,and to further clarify the relationship between inflammation,nutritional intake and sex hormones and eGFR in healthy people.The purpose of this study is to provide basic research evidence for in-depth analysis of renal aging mechanism,and provide clues and references for clinical prevention and treatment of aging eGFR decline and delaying renal agingMaterials and methods:In the first part of the study,wild C57BL/6 mice and Wps/Wps strain mice were selected as the research objects.8 mice in each group were bred for 22 months to construct the natural aging animal model.Blood and kidney tissue samples were collected to detect renal function and pathology,as well as the expression of senility(pl6),inflammation(IL-1?,IL-6 and pNF-KB),fibrosis(TGF-?1,a-SMA and Co ?)in renal tissue using Western Blotting.In the second part of the study,a multi-center,cross-sectional large sample epidemiological survey was performed.The calorie and nutrient intake were calculated by retrospective dietary investigation.eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)formula,and the change of inflammatory cytokine,sex hormone and biochemical indexes were also detected.The correlation between eGFR and those indexes in overall population,adult group and elderly group was analyzed.Results:The first part of the research results show that:?There was no significant difference in serum creatinine and BUN levels between wild mice and Wps/Wps mice(P>0.05).?Compared with wild mice,the expression of p16 protein was significantly decreased in Wps/Wps mice(P<0.05).Renal interstitial fibrosis was significantly alleviated,and the expressions of TGF-1,a-SMA and Co ? protein were significantly reduced(P<0.05);The expressions of IL-1?,IL-6 and pNF-KB were significantly downregulated(P<0.05).These results suggest that blockade of SCF/c-Kit pathway can alleviate renal inflammation,renal interstitial fibrosis and renal aging.The second part of the research results show that:? Both male and female,eGFR decreased with aging(P<0.01),but no significant difference was found between male and female(P>0.05).? A significant positive correlation was found between eGFR with testosterone,estradiol and progesterone in adult women(P<0.01).? The independent influencing factors of eGFR in overall population were Body Mass Index(BMI),mean arterial pressure,serum albumin,serum transferrin,interleukin-6(IL-6),estradiol,progesterone,fiber intake,thiamine and niacin intake;in adult group were mean arterial pressure,serum albumin,high sensitivity C reactive protein(hsCRP),estradiol and magnesium intake;and in elderly group was only IL-6.Conclusion:Blockade of SCF/c-Kit pathway can alleviate renal inflammation,renal interstitial fibrosis and renal aging.eGFR decreased with aging,inflammatory status is an important influencing factor of eGFR in healthy population,especially in the elderly.And there is a significant correlation between eGFR and sex hormones in adult women.