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Estimation of Albumin-Creatinine Ratio From Protein-Creatinine Ratio in Urine of Children and Adolescents With CKD

2020; Elsevier BV; Volume: 77; Issue: 5 Linguagem: Inglês

10.1053/j.ajkd.2020.07.015

1523-6838

Michael F. Schneider, Álvaro Muñoz, Elaine Ku, Bradley A. Warady, Susan L. Furth, George J. Schwartz,

Healthcare cost, quality, practices

Albuminuria and proteinuria are key prognostic indicators of disease progression in chronic kidney disease (CKD).1Fuhrman D.Y. Schneider M.F. Dell K.M. et al.Albuminuria, proteinuria, and renal disease progression in children with CKD.Clin J Am Soc Nephol. 2017; 12: 912-920Crossref PubMed Scopus (34) Google Scholar, 2Lambers Heerspink H.J. Gansevoort R.T. Brenner B.M. et al.Comparison of different measures of urinary protein excretion for prediction of renal events.J Am Soc Nephrol. 2010; 21: 1355-1360Crossref PubMed Scopus (119) Google Scholar, 3Furth S.L. Pierce C. Hui W.F. et al.Estimating time to ESRD in children with CKD.Am J Kidney Dis. 2018; 71: 783-792Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Models to predict time to kidney failure invariably use either albuminuria (urinary albumin-creatinine ratio [UACR]) or proteinuria (urinary protein-creatinine ratio [UPCR]).4Grams M.E. Li L. Greene T.H. et al.Estimating time to ESRD using kidney failure risk equations: results from the African American Study of Kidney Disease and Hypertension (AASK).Am J Kidney Dis. 2015; 65: 394-402Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar,5Tangri N. Stevens L.A. Griffith J. et al.A predictive model for progression of chronic kidney disease to kidney failure.JAMA. 2011; 305: 1553-1559Crossref PubMed Scopus (616) Google Scholar UACR is recommended as the preferred metric for several reasons.6Kidney Disease: Improving Global Outcomes (KDIGO)2012 Clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl. 2013; 3: 1-150Abstract Full Text Full Text PDF Scopus (1297) Google Scholar A recent method from Weaver et al7Weaver R.G. James M.T. Ravani P. et al.Estimating urine albumin-to-creatinine ratio from protein-to-creatinine ratio: development of equations using same-day measurements [erratum in J Am Soc Nephrol. 2020;31(5):1140].J Am Soc Nephrol. 2020; 31: 591-601Crossref PubMed Scopus (14) Google Scholar to estimate UACR from measured UPCR is a substantial improvement over previous equations,5Tangri N. Stevens L.A. Griffith J. et al.A predictive model for progression of chronic kidney disease to kidney failure.JAMA. 2011; 305: 1553-1559Crossref PubMed Scopus (616) Google Scholar which assumed a constant relationship over the full range of proteinuria. The relationship between UPCR and UACR in children and adolescents may differ by CKD cause (ie, glomerular disease vs congenital anomalies of the kidney and urinary tract) and that found in adults. Therefore, we examined separately the relationship between proteinuria and albuminuria in participants from the CKD in Children (CKiD) study, 228 with glomerular CKD and 523 with nonglomerular CKD. CKiD is a multicenter prospective cohort study of children with CKD across North America.8Furth S.L. Cole S.R. Moxey-Mims M. et al.Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study.Clin J Am Soc Nephrol. 2006; 1: 1006-1015Crossref PubMed Scopus (284) Google Scholar Beginning in January 2005, study participants have been seen at annual follow-up visits. Beginning in June 2008, urine albumin measurement was added to the panel of tests at each visit. Our study population consisted of the 751 participants enrolled before 2017 who had UACR measured. Urinary albumin was measured using an immunoturbidimetric assay (Roche Diagnostics) and then divided by urinary creatinine to obtain UACR. Total urinary protein content was determined by a turbidimetric method using benzethonium chloride (Roche Diagnostics) and was divided by urinary creatinine to obtain UPCR. Because albumin is a subset of protein, and to use an unbounded dependent variable with the ultimate aim of estimating UACR from UPCR (both in mg/g), we first modeled logalbuminprotein−albumin as a function of log-transformed UPCR (ie, logalbuminprotein−albumin =μlogUPCR + error, where error ∼ Normal(0, σ2)) for each of the 2 groups of children. Based on the nonparametric splines fit to the scatter plot, we allowed for possible nonlinearity of the relationship between the 2 variables using restricted linear splines (Item S1). The proportion of the protein made up of albumin was estimated by simply rearranging these equations, giving albuminprotein=[1+exp(−μ(log(UPCR)))]−1. Multiplying the estimated albuminprotein by UPCR yielded the desired estimate of UACR. Participant characteristics by glomerular vs nonglomerular CKD are shown in Table S1. UPCR and UACR among those with glomerular CKD were higher than those of children with nonglomerular CKD (UPCR, 595 vs 258 mg/g; UACR, 397 vs 68 mg/g). Figure 1 shows the relationship between UPCR and albuminprotein for children with glomerular (left panel) and nonglomerular (right panel) CKD. When age and sex were allowed to modify the intercept in both equations shown in Fig 1, only age for children younger than 15 years significantly modified the intercept in the nonglomerular group. Thus, our final equations to estimate albuminprotein for children were as follows. For children with glomerular CKD the estimated ratio is 0.724 if UPCR ≥ 1,000 mg/g, and if UPCR < 1,000 mg/g, the estimated ratio is:=1/[1+0.382(UPCR1,000)-0.579] For children with nonglomerular CKD, the equations to estimate the ratio differ between 3 different UPCR ranges. If UPCR ≥ 1,000 mg/g:=1/[1+0.642×0.906(Age-15)ifAge<15] If 100 ≤ UPCR < 1,000 mg/g:=1/[1+0.642(UPCR1,000)-0.720×0.906(Age-15)ifAge<15] If UPCR < 100 mg/g:=1/[1+3.369×0.906(Age-15)ifAge<15] To estimate UACR, we simply multiply estimated albuminprotein by UPCR because protein cancels out in the numerator and denominator. In this population of children and adolescents with CKD, we found the relationship between UPCR and albuminprotein is different by CKD diagnosis. Testing the accuracy of our formula using a different set of UACR measurements from subsequent visits on the same individuals, there was a negligible difference in medians (glomerular, 38 mg/g; nonglomerular, −15 mg/g). Furthermore, because CKD in most adults is glomerular, we compared our formula from children with glomerular CKD to the formula obtained using quantile regression on a sample of more than 47,000 adults by Weaver et al.7Weaver R.G. James M.T. Ravani P. et al.Estimating urine albumin-to-creatinine ratio from protein-to-creatinine ratio: development of equations using same-day measurements [erratum in J Am Soc Nephrol. 2020;31(5):1140].J Am Soc Nephrol. 2020; 31: 591-601Crossref PubMed Scopus (14) Google Scholar Figure 2 shows estimated UACR using both formulas for a range of UPCR up to 4,000 mg/g, although for the median (and third quartile), our proposed estimates are systematically higher (eg, median estimated UACR of 1,450 vs 1,416 mg/g given UPCR = 2,000 mg/g, using our formula vs that of Weaver et al, respectively), the estimates are close to each other. Although a similarity in estimates does not constitute external validation, it is comforting that 2 formulas developed in very different populations provide similar estimates. Research idea and study design: MFS, AM, EK, GJS; data analysis/interpretation: MFS, AM, EK, BAW, SLF, GJS; supervision or mentorship: AM, GJS. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. Data reported here were collected by the CKiD Study (https://statepi.jhsph.edu/ckid) with clinical coordinating centers (Principal Investigators) at Children's Mercy Hospital and the University of Missouri - Kansas City (BAW) and Children's Hospital of Philadelphia (SF), Central Biochemistry Laboratory (GJS) at the University of Rochester Medical Center, and data coordinating center (AM and Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. CKiD is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases , with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development , and the National Heart, Lung, and Blood Institute ( U01-DK-66143 , U01-DK-66174 , U24-DK-082194 , U24-DK-66116 ). The CKiD funders did not have any role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. EK is a consultant for Tricida and Reata. GJS is a consultant for Tricida. The remaining authors declare that they have no relevant financial interests. Received January 30, 2020. Evaluated by 3 external peer reviewers and a statistician, with direct editorial input from an International Editor, who served as Acting Editor-in-Chief. Accepted in revised form July 6, 2020. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies. Download .pdf (.12 MB) Help with pdf files Supplementary File (PDF)Figure S1, Table S1.