Elevated serum and urinary secreted protein acidic and rich in cysteine levels are novel biomarkers of kidney fibrosis severity

Interstitial fibrosis is the primary determinant of the progression of chronic kidney disease (CKD), and noninvasive identification of interstitial fibrosis is a major challenge. We aimed to explore the diagnostic value of secreted protein acidic and rich in cysteine (SPARC) in serum and urine in kidney fibrosis. Single-cell transcriptome analysis was used to measure SPARC expression in healthy reference kidneys and those of patients with CKD. A total of 674 patients with CKD who underwent renal biopsy served as the training cohort (n = 322) and the validation cohort (n = 352). Serum and urinary SPARC levels were measured at the time of kidney biopsy. In vivo and in vitro models of kidney fibrosis were also used to confirm the role of SPARC. Increased SPARC expression was detected in kidney fibrosis tissues. Higher serum SPARC levels were associated with increased severity of kidney fibrosis. Moreover, the area under the receiver operating characteristic curve (AUC-ROC) (AUC 0.86) was greater for the serum SPARC level than for the urinary SPARC level and estimated glomerular filtration rate (eGFR). The combination of the serum and urinary SPARC levels and eGFR increased the AUC-ROC for predicting kidney fibrosis from 0.86 to 0.90. The diagnostic performance of serum or urinary SPARC levels was consistent in the validation cohort. In vivo and in vitro models of kidney fibrosis also confirmed the upregulation of SPARC expression. Serum and urinary SPARC levels may be potential biomarkers for kidney fibrosis and may be useful for noninvasive diagnosis.