Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients

Background: Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is believed to be predominantly an interstitial process, albuminuria in this case might reflect tubular damage. Accordingly, we investigated the value of albuminuria, proteinuria, and tubular damage markers (KIM-1 [kidney injury molecule 1], NAG [N-acetyl-beta-D-glucosaminidase], NGAL [neutrophil gelatinase-associated lipocalin], and H-FABP [heart fatty acid binding protein]) in predicting graft outcome in kidney transplant recipients. Study Design: Prospective observational cohort study. Setting & Participants: 606 patients visiting our outpatient kidney transplant clinic in 2001-2003 were included and used in the analysis for death-censored graft failure. Median follow-up was 4.7 (25th-75th percentile, 3.8-5.2) years. 577 patients had follow-up longer than 1 year and were included in the analysis for estimated glomerular filtration rate (eGFR) decrease. Median follow-up was 3.2 (25th-75th percentile, 2.7-3.7) years. Predictors: Urine protein, albumin, and tubular damage markers in 24-hour urine samples. Outcomes: Death-censored graft failure and decrease in eGFR. Results: There were 42 patients with graft failure; mean eGFR change was -0.46 +/- 3.7 (standard deviation) mL/min/1.73 m(2)/y. The area under the receiver operating characteristic curve for death-censored graft failure showed that albuminuria (0.78; 95% CI, 0.59-0.76) was significantly higher than proteinuria (0.67; 95% CI, 0.59-0.76; P = 0.001), NGAL (0.63; 95% CI, 0.52-0.74; P = 0.02), and H-FABP (0.62; 95% CI, 0.53-0.73; P = 0.005) and not significantly different from KIM-1 (0.74; 95% CI, 0.66-0.82) and NAG (0.75; 95% CI, 0.67-0.83). Results were similar for the eGFR decrease outcome. Limitations: Single-center observational study. Conclusions: Measuring albuminuria may provide superior predictions for long-term renal outcomes after kidney transplant than total proteinuria. Additional assessment of urinary excretion of tubular damage markers may have limited value. Am J Kidney Dis. 57(5): 733-743. (C) 2011 by the National Kidney Foundation, Inc.