Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.
BACKGROUND
Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk.


METHODS
Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol.


RESULTS
Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model.


CONCLUSIONS
Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.
School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden.
Per-Ola
PO
Sundin
School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden.
Per
P
Sjöström
School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden.
Ian
I
Jones
School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden.
Lovisa A
LA
Olsson
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
Ruzan
R
Udumyan
Department of Clinical Chemistry, Laboratory Medicine, University Hospital, Lund, Sweden.
Anders
A
Grubb
Department of Clinical Chemistry, Laboratory Medicine, University Hospital, Lund, Sweden.
Veronica
V
Lindström
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.|Clinical Epidemiology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Department of Epidemiology and Public Health, University College, London, UK.
Scott
S
Montgomery
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D015897:Comorbidity; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007472:Iohexol / Q000032:analysis*; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015996:Survival Rate; D055815:Young Adult
D015415:Biomarkers; D055316:Cystatin C; D007472:Iohexol; D003404:Creatinine
GFR; creatinine; cystatin C; epidemiology; prognosis