a Spearman’s rank correlation Crenolanib coefficient (r) = 0.0728, P = 0.3094. b Spearman’s rank correlation coefficient (r) = −0.0412, P = 0.5654. No significant relationship is seen between eGFR slope and age, or between

eGFR slope and initially measured eGFR. Mean observation time of eGFR was 4.2 ± 3.0 years In Table 2, 196 patients are grouped according to the CKD stage [13] depending on the initially measured eGFR. The advancement of CKD stages significantly related to increased age (P < 0.0001). Slopes of eGFR and 1/Cr were not statistically different among ATM Kinase Inhibitor clinical trial CKD stages, and even younger patients with relatively preserved kidney function in stage 1 had similar slopes of eGFR and 1/Cr to patients in advanced stages. The percent ratio of the decline in eGFR and 1/Cr in relation to the initially measured values progressively increased as the CKD stage advanced (P < 0.0001). Table 2 Age, eGFR slope and 1/Cr slope in relation to the CKD stages of initially measured eGFR   CKD stages Epigenetics inhibitor according to initially measured eGFRa (ml/min/1.73 m2) P value Stage 1 ≥90 Stage 2 89–60 Stage 3 59–30 Stage 4 + 5b ≤29 Initial eGFR (ml/min/1.73 m2) 113.8 ± 25.9 75.1 ± 7.9 45.0 ± 8.8

16.3 ± 8.0 – Patient number 32 62 71 31 – Age (years) 29.9 ± 11.4 42.4 ± 10.2 52.4 ± 12.1 55.0 ± 8.4 <0.0001 eGFR slopec (ml/min/1.73 m2/year) −4.2 ± 9.5 −3.5 ± 4.1 −3.1 ± 3.3 −2.8 ± 1.7 0.6775 eGFR slope/initial eGFR × 100 (%/year) −3.2 ± 8.0 −4.8 ± 5.4 −7.5 ± 8.5 −16.4 ± 10.3 <0.0001 1/Cr sloped (dl/mg/year) −0.04 ± 0.13 −0.05 ± 0.07 −0.06 ± 0.07 −0.05 ± 0.03 0.8982 1/Cr slope/initial 1/Cr × 100 (%/year) −2.2 ± 7.4 −4.0 ± 5.1 −6.7 ± 8.1 −15.1 ± 9.6 <0.0001 Data are presented as the mean ± SD. P values are calculated by ANOVA aPatients were staged according to the National Kidney Foundation Disease Outcomes Quality Initiative guidelines bESRD (dialysis and transplantation) is not included in stage 4 and 5 groups ceGFR slope is the annual change Cobimetinib of estimated GFR d1/Cr slope is the annual change of 1/Cr 1/Cr was plotted against age in 106 patients who had been followed for more than 3 years (Fig. 3). In the

supplementary figure, the plot of 1/Cr versus age is illustrated in all 255 patients. 1/Cr declined to a greater or lesser extent every year with a relatively constant decline rate for each patient at considerable variance among individuals. Neither figure shows that 1/Cr remains stable at a younger age than at an older age. For more detailed examination of the compensatory period of GFR, eGFR is plotted against age in 36 patients who had been followed up for more than 5 years (Fig. 4). Similar to 1/Cr, eGFR declined in each patient. In five patients shown by red lines, the declining curve changed from moderate to rapid during follow-up.