Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA Nephropathy

Abstract

Background and objectives: Proteinuria is an independent predictor for IgA nephropathy (IgAN) progression. Urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and 24-hour urine protein excretion (UPE) are widely used for proteinuria evaluation in clinical practice. Here, we evaluated the association of these measurements with clinical and histologic findings of IgAN and explored which was the best predictor of IgAN prognosis.

Design, setting, participants, & measurements: Patients with IgAN were followed up for ≥12 months, were diagnosed between 2003 and 2012, and had urine samples available (438 patients). Spot urine ACR, protein-to-creatinine ratio, and 24-hour UPE at the time of renal biopsy were measured on a Hitachi Automatic Biochemical Analyzer 7180 (Hitachi, Yokohama, Japan).

Results: In our patients, ACR, protein-to-creatinine ratio, and 24-hour UPE were highly correlated (correlation coefficients: 0.71-0.87). They showed good relationships with acknowledged markers reflecting IgAN severity, including eGFR, hypertension, and the biopsy parameter (Oxford severity of tubular atrophy/interstitial fibrosis parameter). However, only ACR presented with positive association with the Oxford segmental glomerulosclerosis/adhesion parameter and extracapillary proliferation lesions. The follow-up time was 37.0 (22.0-58.0) months, with the last follow-up on April 18, 2014. In total, 124 patients reached the composite end point (30% eGFR decline, ESRD, or death). In univariate survival analysis, ACR consistently had better performance than protein-to-creatinine ratio and 24-hour UPE as represented by higher area under the curve using time-dependent survival analysis. When adjusted for well known risk factors for IgAN progression, ACR was most significantly associated with the composite end point (hazard ratio, 1.56 per 1-SD change of standard normalized square root-transformed ACR; 95% confidence interval, 1.29 to 1.89; P<0.001). Compared with protein-to-creatinine ratio and 24-hour UPE, addition of ACR to traditional risk factors resulted in more improvement in the predictive ability of IgAN progression (c statistic: ACR=0.70; protein-to-creatinine ratio =0.68; 24-hour UPE =0.69; Akaike information criterion: ACR=1217.85; protein-to-creatinine ratio =1229.28; 24-hour UPE =1234.96; P<0.001).

Conclusions: In IgAN, ACR, protein-to-creatinine ratio, and 24-hour UPE had comparable association with severe clinical and histologic findings. Compared with protein-to-creatinine ratio and 24-hour UPE, ACR showed slightly better performance in predicting IgAN progression.

Keywords: Follow-Up Studies; Glomerulonephritis, IGA; Humans; IgA nephropathy; Kidney Failure, Chronic; Prognosis; Urinalysis; albuminuria; creatinine; proteinuria.

Figure 1.

Correlation among albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and 24-hour urine protein excretion (UPE). Scatter plots show correlations (A) between ACR and PCR, (B) between ACR and 24-hour UPE, and (C) between PCR and 24-hour UPE.

Figure 2.

Time–dependent receiver operating characteristics (ROC) curves with composite outcome as the status variable. The areas under the receiver operating characteristics curve (AUCs) were compared among albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and 24-hour urine protein excretion (UPE) at (A) 60 and (B) 96 months and (C) against each time during follow-up. Using composite end point as a status variable, ACR showed consistently higher AUCs at each survival time during follow-up compared with PCR and 24-hour UPE.

Figure 3.

Kaplan–Meier renal survival curves of patients with IgA nephropathy according to albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and 24-hour urine protein excretion (UPE) levels. The patients were divided into four equal groups according to the quartiles of ACR, PCR, and 24-hour UPE distribution. Patients with IgA nephropathy in the first quartile group had the highest proteinuria, whereas those in the fourth quartile group had the lowest proteinuria. Kaplan–Meier survival analyses were performed to compare patients with the composite outcome in each group with different (A) ACR, (B) PCR, or (C) 24-hour UPE values.