{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Greenberg JH"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","NIH","NIDDK","National Institute of Child Health and Human Development"],"pagination":["2664-2677"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8722795"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(10)"],"pubmed_abstract":["

Background

Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.

Methods

We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.

Results

Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.

Conclusions

After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children."],"journal":["Journal of the American Society of Nephrology : JASN"],"pubmed_title":["Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children."],"pmcid":["PMC8722795"],"funding_grant_id":["R01DKD072381","K23 DK118198","L40 DK110937","U01 DK102730","P30DK079310-07","U01 DK103225","K08DK110536","K24DK090203","R01HL085757","U01 DK082185","U01DK082185","K08 DK110536","U24 DK066116","UL1 TR001863","U01-DK-66174","U01DK-082194","R37 DK039773","U01 DK066116","R37DK039773","U01-DK-66143","R01 HL085757","U01 DK066174","U01DK66174","K24 DK078737","R01 DK072381","K24 DK090203","U01 DK082194","U01 DK085660","U01 DK085689","U01 DK066143","P30 DK079310","K24DK078737","U01-DK-66116","U01 DK106982","K23DK118198-01A1"],"pubmed_authors":["Waikar SS","Warady B","Coca S","Abraham A","Sarnak M","Ganz P","Kimmel PL","Rebholz C","Shou H","Rhee E","Dubin R","Deo R","Ramachandran VS","Kusek JW","Bonventre J","Xie D","Feldman HI","Ix JH","Parikh C","Rovin B","Schelling JR","Ix J","Furth S","CKD Biomarker consortium","Shlipak MG","Vasan RS","CKD Biomarkers Consortium","Grams M","Sabbisetti VS","Whitehead K","Schelling J","Ballard S","Warady BA","Greenberg JH","Jogalekar MP","Denburg M","Parikh CR","Waikar S","Coresh J","Hostetter T","Gutierrez OM","Bonventre JV","Sabbisetti V","Abraham AG","Collins H","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children.","description":"

Background

Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.

Methods

We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.

Results

Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.

Conclusions

After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Oct","modification":"2026-05-31T02:12:01.896Z","creation":"2025-02-19T01:21:21.402Z"},"accession":"S-EPMC8722795","cross_references":{"pubmed":["34544821"],"doi":["10.1681/ASN.2021010094","10.1681/asn.2021010094"]}}