Increased urinary cystatin C reflects structural and functional renal tubular impairment independent of glomerular filtration rate

Objectives: The ratio of the urinary mass concentrations of cystatin C and creatinine (UcysC/Ucrea) ≥ 11.3 mg/mmol has recently been proposed as an accurate marker for the detection of GFR ≤ 60 mL/min/1.73 m². Design and methods: We prospectively evaluated the diagnostic performance of UcysC/Ucrea ≥ 11.3 mg/mmol and factors associated with increased UcysC/Ucrea in 72 children and adults with a wide variety of renal disorders. UcysC/Ucrea was calculated, and GFR wad estimated from serum creatinine and cystatin C by equations. Results: UcysC/Ucrea ≥ 11.3 mg/mmol had a low diagnostic value to detect GFR values ≤ 60 mL/min/1.73 m² estimated by creatinine or cystatin-C-based equations with sensitivities of 72% and 63%, and specificities of 42% and 34%. ROC curves for UcysC/Ucrea to detect GFR ≤ 60 mL/min/1.73 m² confirmed this with AUCs of 0.59 for creatinine and 0.57 for cystatin-C-based equations. Multivariate analysis identified tubular proteinuria, tubulointerstitial disease and heavy proteinuria, but not GFR ≤ 60 mL/min/1.73 m², as factors independently associated with increased UcysC/Ucrea. Conclusions: UcysC/Ucrea ≥ 11.3 mg/mmol is not an accurate marker to detect GFR ≤ 60 mL/min/1.73 m², but reflects tubular dysfunction and proteinuria due to heavy proteinuria and tubulointerstitial disease.