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Cystatin C and Estimates of Renal Function: Searching for a Better Measure of Kidney Function in Diabetic Patients

what is Cystatin C. Cystatin C is a small protein that belongs to the cystatin super-family of cysteine protease inhibitors. It is a nonglycosylated peptide consisting of 120 amino acids and is produced by virtually all nucleated cells. Cystatin C is present in all investigatedbody fluids and is not affected by age, gender, muscle mass or the inflammatoryprocess1. Cystatin C is removed from circulation by glomerular filtration and is completely reabsorbed and degraded in the tubules. Therefore, the plasma concentration of cystatin C is almost exclusively determined by the glomerular filtration rate (GFR) making cystatin C an excellent indicator of GFR. Cystatin C is amore sensitive screening test than serum creatinine for early changes in GFR. It has been reported that Cystatin C is a better predictor of GFR than serum creatinine for renal transplant , cancer, liver disease and a more practical monitor of GFR changes in the pediatric population.Measurement of Cystatin C aids in the diagnosis and treatment of renal diseases.

Current study: Early identification of impairment in renal function is crucial in diabetic patients. Serum cystatin C may be the most sensitive indicator of glomerular filtration rate (GFR) in the clinical setting.

Methods: We compared cystatin C with creatinine, the Cockcroft-Gault (C-G) formula, and the Modification of Diet in Renal Disease (MDRD) study equation for the assessment of early decreased renal function in 288 diabetic patients (125 type 1, 163 type 2) with renal impairment [GFR: 4–222 mL · min–1 · (1.73 m2)–1]. Relationships of Cystatin C , creatinine, and iohexol clearance were linearized by plotting their reciprocals in a simple regression model. Diagnostic efficiency was calculated from ROC curves.

Results: In this study population, cystatin C (P = 0.0013) was better correlated with GFR (r = 0.857) than were creatinine (r = 0.772), C-G (r = 0.750), and MDRD (r = 0.806), a result replicated in patients with normal renal function (P = 0.023, type 1; P = 0.011, type 2), but not in those with decreased GFR. Mean cystatin C concentrations showed step-by-step statistically significant increases as GFR decreased, allowing very early detection of reduction in renal function. At 90 mL · min–1 · (1.73 m2)–1 and 75 mL · min–1 · (1.73 m2)–1 cut-points, diagnostic efficiencies of cystatin C (89% and 92%) were better than those of the other variables (79%–82% and 85%–86%, respectively; P = 0.01).

Conclusions: All data supported the value of serum cystatin C compared with conventional estimates based on serum creatinine measurement for detecting very early reduction of renal function. Use of cystatin C to measure renal function will optimize early detection, prevention, and treatment strategies for diabetic nephropathy.

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