Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

Abstract Background and hypothesis Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. Methods From the KNOW-CKD cohort, we included 2099 patients diagnosed with CKD grades 1–5, who did not require kidney replacement therapy. We measured the spot urine albumin-to-creatinine ratio (mACR) and protein-to-creatinine ratio (PCR) and estimated the ACR (eACR) using PCR. Kidney Failure Risk Equation (KFRE) scores were calculated using the mACR, PCR, and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). Results The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating curve showed excellent predictive performance for all KFRE scores from the mACR, PCR, and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified etiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of PCR were greater than those of mACR. Conclusions The mACR, eACR, and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.