Cystatin C in the Diagnosis of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus

The aim of the investigation was to estimate the role of cystatin C in the diagnosis of chronic kidney disease in patients with type 2 diabetes mellitus (DM2).

Materials and Methods. The study involved 97 patients with DM2, their mean age being 57 [53; 63] years, DM2 duration — 7.7 [2.5; 12] years. In all patients we identified сystatin C level and calculated glomerular filtration rate using different methods.

Results. Cystatin C is a reliable marker of glomerular filtration rate in DM2 patients. It enables to diagnose chronic kidney disease in normal albumin excreted with urine, i.e. at early stages of diabetic nephropathy.

The determination of this value by cystatin C in boundary glomerular filtration rate level of under 60 ml/min/1.73 m² is more accurate than that calculated by Cockcroft–Gault and MDRD formulae.

1. Tonelle C.A, Edwards R.G., Stowe H.J., et al. Partial amino acid sequence of two forms of human post-gamma globulin. Biochemical Biophysical Research Communications 1979; 86(3): 613–619.
2. Rawlings N.D., Barrett A.J. Evolution of proteins of the cystatin superfamily. Journal of Molecular Evolution 1990; 30: 60–71.
3. Hall A., et al. Structural basis for the biological specificity of cystatin C. Journal of Biological Chemistry 1995; 270: 5115–5121.
4. Brown W.M., Dziegielewska K.M. Friends and relations of the cystatin superfamily — new members and their evolution. Protein Science 1997; 6: 5–12.
5. Chudleigh R.A., Ollerton R.L., Dunseath G., et al. Use of cystatin C-based estimations of glomerular filtration rate in patients with type 2 diabetes. Diabetologia 2009; 52: 1274–1278.
6. Newman D.J., Thakkar H., Edwards R.G., et al. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine for glomerular filtration rate. Kidney Int 1995; 47: 312–318.
7. Shlipak M.G. Cystatin C as a marker of glomerular filtration rate in chronic kidney disease: influence of body composition. Nat Clin Pract Nephrol 2007; 3(4): 188–189.
8. Vervoort G., Willems H.L., Wetzels J.F. Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation. Nephrol Dial Transplant 2002; 17: 1909–1913.
9. Pierrat A., Gravier E., Saunders C., et al. Predicting GFR in children and adults: a comparison of the Cockcroft–Gault, Schwartz and Modification of Diet in Renal Disease formulas. Kidney Int 2003; 64: 1425–1436.
10. Xie D., Joffe M.M., Brunelli S.M., et al. A comparison of change in measured and estimated glomerular filtration rate in patients with non-diabetic kidney disease. Clin J Am Soc Nephrol 2008; 3: 1332–1338.
11. Riordan S.E., Webb M.C., Stowe H.J., et al. Cystatin C improves the detection of mild renal dysfunction in older patients. Ann Clin Biochem 2003; 40: 648–655.
12. Fontsere N., Esteve V., Saurina A., et al. The search for a new marker of renal function in older patients with chronic kidney disease stages 3–4: usefulness of cystatin C-based equations. Nephron Clin Pract 2009; 112(3): 164–170.
13. Hojs R., Bevc S., Ekart R., et al. Serum cystatin C-based equation compared to serum creatinine-based equations for estimation of glomerular filtration rate in patients with chronic kidney disease. Clin Nephrol 2008; 70(1): 10–17.
14. Kravaritou M., Thanopoulou A., Karamanos B., et al. Evidence that even “normal” albuminuria may denote incipient GFR reduction in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2009; 85(3): 317–321.
15. Watanabe S., Okura T., Liu J., et al. Serum cystatin C level is a marker of end-organ damage in patients with essential hypertension. Hypertens Res 2009; 26: 895–899.
16. Grubb A., Bjork J., Lindstrom V., et al. A cystatin C-based formula without anthropometric variables estimates glomerular filtration rate better than creatinine clearance using the Cockcroft–Gault formula. Scand J Clin Lab Invest 2005; 65(2): 153–162.
17. Reinhard M., Erlandsen E.J., Randers E. Biological variation of cystatin C and creatinine. Scand J Clin Lab Invest 2009; 69(8): 831–836.
18. Mussap M., Dalla Vestra M., et al. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int 2002; 61(4): 1453–1461.
19. Herget-Rosenthal S., Bokenkamp A., Hofmann W., et al. How to estimate GFR-serum creatinine, serum cystatin C or equations? Clin Biochem 2007; 40(3–4): 153–161.
20. Stevens L.A., Coresh J., Schmid C.H., et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008; 51(3): 395–406.
21. Oddoze C., Morange S., Portugal H., et al. Cystatin C is not more sensitive than creatinine for detecting early renal impairment in patients with diabetes. Am J Kidney Dis 2001; 38(2): 310–316.
22. Tidman M., Sjostrom P., Jones I., et al. A Comparison of GFR estimating formulae based upon s-cystatin C and s-creatinine and a combination of the two. Nephrol Dial Transplant 2008; 23(1): 154–160.
23. Rigalleau V., Raffaitin C., Gin H., et al. Accounting for body composition does not improve cystatin C estimation of GFR in diabetic subjects with CKD. Am J Kidney Dis 2007; 49(4): 560.
24. Perlemoine C., Beauvieux M.C., Rigalleau V., et al. Interest of cystatin C in screening diabetic patients for early impairment of renal function. Metabolism 2003; 52(10): 1258–1264.
25. Jerums G., Premaratne E., Panagiotopoulos S., et al. New and old markers of progression of diabetic nephropathy. Diabetes Res Clin Pract 2008; 82(Suppl 1): 30–37.
26. Shestakova M.V. Sakharnyy diabet i khronicheskaya bolezn' pochek: sovremennaya diagnostika i lechenie [Diabetes mellitus and chronic kidney disease: modern diagnostics and management]. Vestnik RAMN — Herald of RAMS 2012; 1: 45–49.
27. Shestakova M.V., Dedov I.I. Sakharnyy diabet i khronicheskaya bolezn’ pochek [Diabetes mellitus and chronic kidney disease]. Moscow: OOO «Meditsinskoe informatsionnoe agentstvo»; 2009; 482 p.
28. Shestakova M.V. Sovremennoe ponyatie «Khronicheskaya bolezn’ pochek»: metody diagnostiki, klinicheskoe znachenie [Modern concept of “Chronic kidney disease”: diagnostic techniques, clinical relevance]. Sakharnyy diabet — Diabetes mellitus 2008; 2: 4–7.
29. Maslova O.V., Suntsov Yu.I., Shestakova M.V. i soavt. Rasprostranennost’ diabeticheskoy nefropatii i khronicheskoy bolezni pochek pri sakharnom diabete v Rossiyskoy Federatsii [The incidence of diabetic nephropathy and chronic kidney disease in diabetes mellitus in the Russian Federation]. Klinicheskaya nefrologiya — Clinical nephrology 2010; 3: 45–51.
30. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. National Kidney Foundation. Am J Kidney Dis 2007; 49(Suppl 2): L–180.

Yarkova N.А., Borovkov N.N., Zanozina О.V., Nosov V.P. Cystatin C in the Diagnosis of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus. Sovremennye tehnologii v medicine 2013; 5(4): 89