Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes

• Published in: Diabetic medicine 2010-12, Vol.27 (12), p.1358-1365
• Main Authors: Cherney, D. Z. I., Sochett, E. B., Dekker, M. G., Perkins, B. A.
• Format: Article
• Language: English
• Subjects: Adolescent; Biological and medical sciences; Biomarkers - blood; Blood Glucose - physiology; Creatinine - blood; Cystatin C - blood; cystatin C hyperglycaemia; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - blood; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - physiopathology; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glomerular Filtration Rate; Humans; Hyperglycemia - blood; Hyperglycemia - complications; inulin; Kidney Function Tests; Male; Medical sciences; Type 1 diabetes mellitus; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2010.03121.x

Diabet. Med. 27, 1358–1365 (2010) Aims  Systematic study of hyperfiltration in diabetic nephropathy has been hindered by the lack of a simple glomerular filtration rate (GFR) measure that is accurate in this range of renal function. Serum cystatin C (GFRCYSTATIN C) reflects long‐term trends in GFR in normal or elevated ranges. To test whether it can reflect acute changes, we examined the impact of clamped hyperglycaemia on GFRCYSTATIN C and GFRINULIN in subjects with Type 1 diabetes. Methods  GFRINULIN and GFRCYSTATIN C were measured in 32 normotensive, normoalbuminuric subjects during clamped euglycaemia and hyperglycaemia. For comparison, GFRMDRD was estimated according to the four‐variable equation. Results  During clamped euglycaemia, agreement between GFRCYSTATIN C and GFRINULIN was excellent, with mean bias +1.9 (90% distribution −29 to +31) ml min−1 1.73 m−2, while GFRMDRD had mean bias +11.4 (−45 to +51) ml min−1 1.73 m−2. With exposure to clamped hyperglycaemia, the mean increase in GFRCYSTATIN C (+17.5 ± 13.5 ml min−1 1.73 m−2) reflected that observed with GFRINULIN (+15.3 ± 28.1 ml min−1 1.73 m−2, P = 0.74), while GFRMDRD demonstrated a mean decline of −4.4 ± 33.6 ml min−1 1.73 m−2 (P = 0.01). In all 24 subjects in whom GFRINULIN increased in response to hyperglycaemia, GFRCYSTATIN C reflected a concordant change (sensitivity, 100%) while GFRMDRD increased in 10/24 (sensitivity, 42%). In the eight remaining subjects, specificity was 25 and 75% for GFRCYSTATIN C and GFRMDRD, respectively. Conclusion  GFRCYSTATIN C reflects normal and elevated renal function better than GFRMDRD even under the acute influences of hyperglycaemia, suggesting a role for cystatin C in clinical practice and research for the study of early renal function changes in Type 1 diabetes.