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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)., Conclusion: 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).

Unlabelled: Renal anemia is a serious complication of chronic kidney disease (CKD) and accelerates its progress. Recombinant human erythropoietin (rHuEPO) therapy not only improves anemia but also has a renoprotective effect. This study aimed to determine whether treatment with rHuEPO can retard the initiation of hemodialysis (HD) in patients with CKD., Methods: Clinical data of CKD patients who had already been treated with HD were analyzed retrospectively. Twenty-one patients who had received rHuEPO therapy constituted the treated group (EPO(+) group), and twenty-one other patients without rHuEPO constituted the non-treated group (EPO(-) group). The study start-point was the day of kidney function deterioration, judged as CKD stage 5. The end-point of the study was the initiation of HD., Results: During the evaluation period, mean values of hemoglobin (Hb) in the EPO(+) group remained lower than those in the EPO(-) group. Survival analysis limited to the two-year period from the beginning of evaluation showed that the renal survival rate of the EPO(+) group was significantly better than that of the EPO(-) group [EPO(+): 42.1% vs. EPO(-): 12.5%, p<0.05]. Duration of renal survival was 29.8 +/- 4.07 months in the EPO(+) group and 19.1 +/- 3.27 months in the EPO(-) group (p<0.05)., Conclusion: Although the mean values of Hb remained lower in the EPO(+) group than in the EPO(-) group during the observation period, the renal survival rate and duration of renal survival in the EPO(+) group were significantly superior than in the EPO(-) group. The study suggests that rHuEPO exerts a renoprotective effect via a mechanism other than the correction of anemia.