TY - JOUR
T1 - Urine biomarkers of kidney tubule health, injury, and inflammation are associated with progression of CKD in children
AU - Greenberg, Jason H.
AU - Abraham, Alison G.
AU - Xu, Yunwen
AU - Schelling, Jeffrey R.
AU - Feldman, Harold I.
AU - Sabbisetti, Venkata S.
AU - Ix, Joachim H.
AU - Jogalekar, Manasi P.
AU - Coca, Steven
AU - Waikar, Sushrut S.
AU - Shlipak, Michael G.
AU - Warady, Bradley A.
AU - Vasan, Ramachandran S.
AU - Kimmel, Paul L.
AU - Bonventre, Joseph V.
AU - Denburg, Michelle
AU - Parikh, Chirag R.
AU - Furth, Susan
N1 - Publisher Copyright:
© 2021 by the American Society of Nephrology.
PY - 2021/10
Y1 - 2021/10
N2 - 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 a-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 a-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 a-1 microglobulin concentrations were each associated with CKD progression in children.
AB - 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 a-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 a-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 a-1 microglobulin concentrations were each associated with CKD progression in children.
UR - http://www.scopus.com/inward/record.url?scp=85116515937&partnerID=8YFLogxK
U2 - 10.1681/ASN.2021010094
DO - 10.1681/ASN.2021010094
M3 - Article
C2 - 34544821
AN - SCOPUS:85116515937
SN - 1046-6673
VL - 32
SP - 2664
EP - 2677
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
IS - 10
ER -