Susan L Furth1, Chris Pierce2, Wun Fung Hui3, Colin A White4, Craig S Wong5, Franz Schaefer6, Elke Wühl6, Alison G Abraham2, Bradley A Warady7. 1. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: furths@email.chop.edu. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 3. Department of Pediatrics, Queen Elizabeth Hospital, Hong Kong. 4. Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 5. Division of Pediatric Nephrology, University of New Mexico Children's Hospital, Albuquerque, NM. 6. Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Im Neuenheimer Feld 430, Heidelberg, Germany. 7. Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, MO.
Abstract
RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. OUTCOME: A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. ANALYTICAL APPROACH: Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. RESULTS: Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. LIMITATIONS: Observational study, used cross-validation rather than external validation. CONCLUSIONS: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.
RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. OUTCOME: A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. ANALYTICAL APPROACH: Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. RESULTS: Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. LIMITATIONS: Observational study, used cross-validation rather than external validation. CONCLUSIONS: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.
Authors: Bradley A Warady; Alison G Abraham; George J Schwartz; Craig S Wong; Alvaro Muñoz; Aisha Betoko; Mark Mitsnefes; Frederick Kaskel; Larry A Greenbaum; Robert H Mak; Joseph Flynn; Marva M Moxey-Mims; Susan Furth Journal: Am J Kidney Dis Date: 2015-03-19 Impact factor: 8.860
Authors: Susan L Furth; Alison G Abraham; Judith Jerry-Fluker; George J Schwartz; Mark Benfield; Frederick Kaskel; Craig Wong; Robert H Mak; Marva Moxey-Mims; Bradley A Warady Journal: Clin J Am Soc Nephrol Date: 2011-08-12 Impact factor: 8.237
Authors: Dana Y Fuhrman; Michael F Schneider; Katherine M Dell; Tom D Blydt-Hansen; Robert Mak; Jeffrey M Saland; Susan L Furth; Bradley A Warady; Marva M Moxey-Mims; George J Schwartz Journal: Clin J Am Soc Nephrol Date: 2017-05-25 Impact factor: 8.237
Authors: Craig S Wong; Christopher B Pierce; Stephen R Cole; Bradley A Warady; Robert H K Mak; Nadine M Benador; Fredrick Kaskel; Susan L Furth; George J Schwartz Journal: Clin J Am Soc Nephrol Date: 2009-03-18 Impact factor: 8.237
Authors: Elke Wühl; Antonella Trivelli; Stefano Picca; Mieczyslaw Litwin; Amira Peco-Antic; Aleksandra Zurowska; Sara Testa; Augustina Jankauskiene; Sevinc Emre; Alberto Caldas-Afonso; Ali Anarat; Patrick Niaudet; Sevgi Mir; Aysin Bakkaloglu; Barbara Enke; Giovanni Montini; Ann-Margret Wingen; Peter Sallay; Nikola Jeck; Ulla Berg; Salim Caliskan; Simone Wygoda; Katharina Hohbach-Hohenfellner; Jiri Dusek; Tomasz Urasinski; Klaus Arbeiter; Thomas Neuhaus; Jutta Gellermann; Dorota Drozdz; Michel Fischbach; Kristina Möller; Marianne Wigger; Licia Peruzzi; Otto Mehls; Franz Schaefer Journal: N Engl J Med Date: 2009-10-22 Impact factor: 91.245
Authors: Susan L Furth; Stephen R Cole; Marva Moxey-Mims; Frederick Kaskel; Robert Mak; George Schwartz; Craig Wong; Alvaro Muñoz; Bradley A Warady Journal: Clin J Am Soc Nephrol Date: 2006-07-19 Impact factor: 8.237
Authors: George J Schwartz; Michael F Schneider; Paula S Maier; Marva Moxey-Mims; Vikas R Dharnidharka; Bradley A Warady; Susan L Furth; Alvaro Muñoz Journal: Kidney Int Date: 2012-08 Impact factor: 10.612
Authors: Daryl J McLeod; Christina B Ching; Yuri V Sebastião; Jason H Greenberg; Susan L Furth; Kirk M McHugh; Brian Becknell Journal: Pediatr Nephrol Date: 2018-10-13 Impact factor: 3.714
Authors: Erica Winnicki; Kirsten L Johansen; Michael D Cabana; Bradley A Warady; Charles E McCulloch; Barbara Grimes; Elaine Ku Journal: J Am Soc Nephrol Date: 2019-07-18 Impact factor: 10.121
Authors: Derek K Ng; Matthew B Matheson; Bradley A Warady; Susan R Mendley; Susan L Furth; Alvaro Muñoz Journal: Am J Epidemiol Date: 2019-12-31 Impact factor: 4.897
Authors: Denver D Brown; Jennifer Roem; Derek K Ng; Kimberly J Reidy; Juhi Kumar; Matthew K Abramowitz; Robert H Mak; Susan L Furth; George J Schwartz; Bradley A Warady; Frederick J Kaskel; Michal L Melamed Journal: Clin J Am Soc Nephrol Date: 2020-05-28 Impact factor: 8.237
Authors: Michael F Schneider; Alvaro Muñoz; Elaine Ku; Bradley A Warady; Susan L Furth; George J Schwartz Journal: Am J Kidney Dis Date: 2020-09-06 Impact factor: 8.860
Authors: Yuri V Sebastião; Jennifer N Cooper; Brian Becknell; Christina B Ching; Daryl J McLeod Journal: Pediatr Nephrol Date: 2020-06-25 Impact factor: 3.714
Authors: Derek K Ng; Yunwen Xu; Julien Hogan; Jeffrey M Saland; Larry A Greenbaum; Susan L Furth; Bradley A Warady; Craig S Wong Journal: Pediatr Nephrol Date: 2020-05-03 Impact factor: 3.714
Authors: Meredith A Atkinson; Derek K Ng; Bradley A Warady; Susan L Furth; Joseph T Flynn Journal: Pediatr Nephrol Date: 2020-02-03 Impact factor: 3.714