Doubling of serum creatinine: is it appropriate as the endpoint for CKD? Proposal of a new surrogate endpoint based on the reciprocal of serum creatinine.
BACKGROUND
The evaluation of the progression of renal insufficiency, or decline in glomerular filtration rate (GFR), has been approached more simply and precisely by converting measured serum creatinine value into the reciprocal of serum creatinine, estimated GFR, or other parameters. Doubling of serum creatinine (simple doubling) is conveniently used as a surrogate endpoint for progression of renal disease but is thought to be biased unfairly by the initial value of serum creatinine (Scr(Int)). We proposed the definite decline in the reciprocal of serum creatinine (2-4 doubling) as a surrogate endpoint, comparing simple doubling with this new endpoint to verify the effect of Scr(Int) on the endpoint.


METHODS
For the purpose of comparison between endpoints, 194 patients in a historical cohort of chronic glomerulonephritis were investigated. Kaplan-Meier survival analysis was performed with the composite endpoint of need for dialysis and either simple doubling or 2-4 doubling. Then, the distribution of Scr(Int) was compared between total patients and patients developing each endpoint.


RESULTS
The endpoint value of serum creatinine (Scr(End)) with 2-4 doubling was lower than that with simple doubling at Scr(Int) <2.00 mg/dl, and the difference of Scr(End) between simple doubling and 2-4 doubling was larger, as Scr(Int) became lower. In patients reaching simple doubling, Scr(Int) was higher than that of the total patients (1.66 vs. 1.07 mg/dl in median, respectively; p < 0.001). In patients reaching 2-4 doubling, there was no significant difference in Scr(Int).


CONCLUSIONS
Patients with low serum creatinine concentration at baseline had a tendency of prolonged development into simple doubling. In contrast, with 2-4 doubling, there was no bias of Scr(Int).
Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. noriko-takeuchi@graduate.chiba-u.jp
Noriko
N
Takeuchi
Emi
E
Takenoshita
Fumino
F
Kato
Tomoko
T
Terajima
Makoto
M
Ogawa
Satoshi
S
Suzuki
Takayuki
T
Fujii
Eriko
E
Kobayashi
Tomoya
T
Sakurada
Nobunori
N
Satoh
Shiro
S
Ueda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology*; D012189:Retrospective Studies; D055815:Young Adult
D003404:Creatinine