Is Cystatin C more sensitive than creatinine in detecting early chronic allograft nephropathy?
BACKGROUND
Cystatin C (CyC) has been suggested as a more accurate indicator of renal function than creatinine (Crea). CyC performance against graft histopathology has not been investigated.


OBJECTIVE
To compare CyC and Crea-based methods as predictors of chronic allograft damage index (CADI).


METHODS
105 protocol biopsies obtained at 6 months post-transplantation were classified with Banff'97 and CADI. CyC and Crea were measured concomitantly. Histology was correlated to CyC, Crea, their reciprocals, CyC-estimated GFR (Larsson), Cockroft and Gault (C&G) and abbreviated MDRD using Kendall's Tau. The area under ROC curve (ROC-auc),sensitivity/specificity, positive and negative predictive values were calculated at CADI cut-off of 2.


RESULTS
Mild histological changes were best revealed by Crea, although with modest sensitivity/ specificity. A Crea threshold of 111 micromol/l distinguished 74% of the patients with CADI > 2 and excluded this condition in 66%. For Crea, ROC-auc was 0.72 (p < 0.001). Crea and 1/Crea correlated best to CADI, chronic allograft nephropathy, chronic inflammation, tubular atrophy, vascular changes and glomerulopathy. Neither C&G nor MDRD improved Crea performance alone. CyC and Larsson formula performed the same (ROC-auc 0.67). A CyC threshold of 1.12 mg/l distinguished 69% of the patients with CADI > 2 and excluded it in 60%. Significant Tau correlation was found between CyC, 1/CyC and Larsson with CADI, chronic inflammation, tubular atrophy and chronic vascular changes.


CONCLUSIONS
CyC, 1/CyC and Larsson-estimated GFR did not offer significant advantages over Crea in predicting mild histological allograft changes. Protocol biopsy provides information that cannot be sensitively predicted by biochemical measurements used in clinical practice.
Ortiz
F
F
Division of Nephrology, Department on Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Harmoinen
A
A
Paavonen
T
T
Koskinen
P
P
Grönhagen-Riska
C
C
Honkanen
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003404:Creatinine / Q000378:metabolism*; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D013997:Time Factors
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003404:Creatinine