Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKD

Abstract

Background and objectives: The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes.

Design, setting, participants, & measurements: Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression (n=647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m²). Parametric time-to-event analysis (n=751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR.

Results: The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m² lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. Individuals with ACR<30 mg/g, but a UP/C≥0.2 mg/mg, had a mean eGFR that was 9.3 ml/min per 1.73 m² lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. When categories of ACR and Unon-alb/cr were created on the basis of clinically meaningful cutoff values of UP/C with the same sample sizes for comparison, the relative times (RTs) to the composite end-point were almost identical when comparing the middle (RT=0.31 for UP/C [0.2-2.0 mg/mg], RT=0.38 for ACR [56-1333 mg/g], RT=0.31 for Unon-alb/cr [118-715 mg/g]) and the highest (RT=0.08 for UP/C [>2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (<30, 30-300, >300 mg/g).

Conclusions: In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar.

Keywords: Cross-Sectional Studies; Disease Progression; Follow-Up Studies; Humans; Linear Models; Renal Insufficiency, Chronic; Renal Replacement Therapy; Sample Size; albuminuria; creatinine; diabetes mellitus; glomerular filtration rate; kidney; pediatrics; progression of chronic renal failure; proteinuria; renal function decline.

Figure 1.

Collinearity between the three methods to quantify proteinuria at the index study visit, n=751. The dashed line shown in each of the panels in Figure 1 is the line on which all of the data would fall if there were perfect agreement between the two variables.

Figure 2.

Similar prognostic ability for each of the three methods to quantify proteinuria for characterizing a >50% decline in GFR or need for RRT based on clinically meaningful cutoffs of UP/C (Kaplan–Meier, dashed lines and Generalized Gamma, solid lines). Left panel: UP/C categorized as <0.2, 0.2–2.0, and >2.0; middle panel: ACR categorized as <56, 56 to <1333, and >1333; right panel: Unon-alb/cr categorized as <118, 118 to <715, and >715. n=751. ACR, urine albumin-to-creatinine ratio; Unon-alb/cr, urine nonalbumin-to-creatinine ratio; UP/C, urine protein-to-creatinine ratio.

Figure 3.

Similar prognostic ability for each of the three methods to quantify proteinuria for characterizing a >50% decline in GFR or need for RRT based on clinically meaningful cutoffs of ACR (Kaplan–Meier, dashed lines and Generalized Gamma, solid lines). Left panel: UP/C categorized as <0.139, 0.139–0.630, and >0.630; middle panel: ACR categorized as <30, 30–300, and >300; right panel: Unon-alb/cr categorized as <86, 86–273, and >273. n=751. ACR, urine albumin-to-creatinine ratio; Unon-alb/cr, urine nonalbumin-to-creatinine ratio; UP/C, urine protein-to-creatinine ratio.