Study population
A total of 3861 very elderly patients (aged ≥ 75 years) were hospitalized between January 1, 2007 and December 31, 2018 at the National Clinical Research Center for Geriatric Diseases, and 760 developed AKI during hospitalization. Among these patients, 10 were excluded for hospital stays < 48 h, and 3 were excluded due to missing data. Therefore, 747 AKI patients were suitable for the subsequent analysis, including 685 (91.7%) patients with P-AKI and 62 (8.3%) patients with T-AKI. Of the 747 patients, we further excluded 54 patients due to death within 48 h post-AKI because the duration of AKI could not be determined. Consequently, 693 AKI patients were included in the final evaluation.
AKI
As shown in Table 1, the median age of the 693 participants was 88 years, and the majority (656, 94.7%) were male. Of these, T-AKI was documented in 62 (9.0%), and P-AKI in 631 (91.0%) according to our definitions, including 104 (15.0%) with AKI duration of 3–4 days, 140 (20.2%) with AKI duration of 5–7 days, and 387 (55.8%) with persistent AKI > 7 days. Among the 693 patients, 319 (46.0%) had KDIGO stage 1 AKI, 172 (24.8%) had stage 2 AKI, 202 (29.1%) had stage 3 AKI, and 4 (0.6%) needed dialysis. Among all patients, 209 (30.2%) died within 90 days, including 5 (8.1%) with T-AKI and 204 (32.3%) with P-AKI. Of the 484 survivors with AKI in whom eGFR recovery could be assessed, 362 (74.8%) recovered to the baseline level and 122 (25.2%) developed CKD. The study flow chart is presented in Fig. 1.
Clinical characteristics associated with T-AKI or P-AKI
The P-AKI group had a lower percentage of hypertension (71.8% vs. 83.9%, P=0.041), cardiovascular events (14.4% vs. 24.2%, P = 0.041), or surgical therapy compared with the T-AKI group (6.2% vs. 14.5%, P = 0.027; Table 2). Similarly, the P-AKI group more frequently required mechanical ventilation support (39.9% vs. 12.9%, P < 0.001). Laboratory results, such as Scr (129.0 vs. 116.1 μmol/L, P < 0.001) levels, peak Scr (146.3 vs. 117.9 μmol/L, P < 0.001) levels, BUN (12.7 vs. 9.3 mmol/L, P < 0.001) levels, peak BUN (18.5 vs. 10.8 mmol/L, P < 0.001) levels, uric acid (364.8 vs. 338.3 μmol/L, P = 0.017) levels, Na (140 vs 138 mmol/L, P=0.001) levels, Mg (0.9 vs. 0.9 mmol/L, P = 0.003) levels, albumin (34.3 ± 5.5 vs. 36.1 ± 5.3 g/L, P = 0.013) levels, and hemoglobin (112 ± 22 vs. 119 ± 20 g/L, P = 0.010) differed significantly between the two groups. More patients with P-AKI were evaluated by nephrologists than those with T-AKI (27.4% vs. 11.3%, P = 0.006). No significant differences were observed in age, gender, BMI, pre-existing comorbidities (coronary disease, COPD and diabetes) or baseline Scr and eGFR, mean arterial pressure, oliguria, BG, K, Ca, P, CRP, prealbumin, as well as the need for renal replacement therapy between the two groups.
Ninety-day mortality and new-CKD progression according to AKI duration and KDIGO stage
A total of 209 patients died within 90 days. Among the survivors, 25.2% experienced CKD progression and 74.8% did not. The 90-day mortality was 8.1% in patients with T-AKI and 32.3% in those with P-AKI (P < 0.001; Table 2). Accordingly, as shown in Table 3, the prevalence of P-AKI was significantly higher in the non-surviving group (97.6% vs. 88.2%, P < 0.001); AKI of medium or longer duration occurred more frequently among non-survivors than survivors (22.0% vs. 19.4% and 62.7% vs. 52.9%, respectively; P<0.001). The Kaplan–Meier survival plot demonstrated that 90-day survival was higher in the T-AKI group than in the P-AKI group. Furthermore, within the AKI groups, higher mortality was found in patients with a longer duration of AKI than those with a shorter AKI duration (log rank P = 0.002; Fig. 2).
Table 3 shows that the 90-day mortality rates were: 7.2%, 23.9%, and 68.9% for AKI stages 1, 2, and 3, respectively (P < 0.001). The Kaplan–Meier curves showed that 90-day mortality increased steadily with AKI severity (P<0.001, log-rank test; Fig. 3). Fig. 4 shows the 90-day mortality curves in the different AKI groups for each AKI stage. The 90-day mortality rates among the AKI groups for each AKI stage were significantly different (all P < 0.001, log-rank test), but there was no difference in T-AKI (duration 1–2 days) among the different AKI stage group (log-rank test: P = 0.104).
As shown in Table 3, the incidence rates of P-AKI were 96.7% in patients with new-onset CKD vs. 85.4% in the non-CKD group. Long-duration (> 7 days) AKI was more likely to be seen in new-onset CKD than in the non-CKD group (85.2% vs. 42.0%, P < 0.001). Fig. 5 shows the significant differences in new-onset CKD among the four groups (P < 0.001). Table 3 shows the relationship between the AKI stage and CKD progression. Surprisingly, AKI severity was not significantly associated with progression of new-onset CKD (63.9% vs. 62.4% for stage 1 patients, 23.0% vs. 26.0% for stage 2, and 13.1% vs. 11.6% for stage 3; P = 0.765 for the three stages).
Influence of AKI duration and KDIGO stage on 90-day patient mortality and new-onset CKD progression
When AKI duration was considered a binary variable (T-AKI and P-AKI), P-AKI was associated with 90-day mortality (hazard ratio [HR] = 2.522; 95% confidence interval [CI]: 1.028–6.186; P = 0.043) and the progression of new-onset CKD (odds ratio [OR] = 3.907; 95% CI: 1.331–11.463; P = 0.013) in a multivariate regression analysis (data not shown).
When AKI duration was considered an ordinal variable (1–2, 3–4, 5–7, and > 7 days), the independent risk factors for 90-day mortality were the following: duration of AKI (3–4 days: HR = 2.512; 95% CI: 1.021–6.181; P = 0.045, 5–7 days: HR = 3.154; 95% CI: 1.250–7.960; P = 0.015; > 7days: HR = 6.212; 95% CI: 2.383–16.192; P < 0.001), more advanced AKI stage (stage 2: HR = 7.365; 95% CI: 4.114–13.183; P < 0.001; stage 3: HR = 28.414; 95% CI: 16.360–49.350; P < 0.001), and low BMI (HR = 0.910; 95% CI: 0.870–0.953; P < 0.001) (Table 4). The independent risk factors for the progression of new-onset CKD were duration of AKI (3–4 days: OR = 0.982; 95% CI: 0.247–3.900; P = 0.980; 5–7 days: HR = 1.322; 95% CI: 0.381–4.592; P = 0.661; > 7 days: HR = 7.007; 95% CI: 2.417–20.311; P < 0.001) and baseline eGFR (OR = 0.928; 95% CI: 0.901–0.956; P < 0.001) (Table 4).