Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes.
OBJECTIVE
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 (GFR(CYSTATIN 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 GFR(CYSTATIN C) and GFR(INULIN) in subjects with Type 1 diabetes.


METHODS
GFR(INULIN) and GFR(CYSTATIN C) were measured in 32 normotensive, normoalbuminuric subjects during clamped euglycaemia and hyperglycaemia. For comparison, GFR(MDRD) was estimated according to the four-variable equation.


RESULTS
During clamped euglycaemia, agreement between GFR(CYSTATIN C) and GFR(INULIN) was excellent, with mean bias +1.9 (90% distribution -29 to +31) ml min(-1) 1.73 m(-2), while GFR(MDRD) had mean bias +11.4 (-45 to +51) ml min(-1) 1.73 m(-2). With exposure to clamped hyperglycaemia, the mean increase in GFR(CYSTATIN C) (+17.5 ± 13.5 ml min(-1) 1.73 m(-2) ) reflected that observed with GFR(INULIN) (+15.3 ± 28.1 ml min(-1) 1.73 m(-2), P = 0.74), while GFR(MDRD) 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 GFR(INULIN) increased in response to hyperglycaemia, GFR(CYSTATIN C) reflected a concordant change (sensitivity, 100%) while GFR(MDRD) increased in 10/24 (sensitivity, 42%). In the eight remaining subjects, specificity was 25 and 75% for GFR(CYSTATIN C) and GFR(MDRD), respectively.


CONCLUSIONS
GFR(CYSTATIN C) reflects normal and elevated renal function better than GFR(MDRD) 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.
Division of Nephrology, University Health Network, Hospital for Sick Children, University of Toronto, ON, Canada. david.cherney@uhn.on.ca
D Z I
DZ
Cherney
E B
EB
Sochett
M G
MG
Dekker
B A
BA
Perkins
D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000502:physiology; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications*; D007677:Kidney Function Tests; D008297:Male
D015415:Biomarkers; D001786:Blood Glucose; D055316:Cystatin C; D003404:Creatinine