Abstract
Objective
Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients’ quality of life.
Methods
We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients’ baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3.
Results
A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4%), 73 (13.2%), and 229 (41.4%) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2% vs 26.0% or 22.7%; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery: 65.1% vs 27.4% or 22.7%; P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95% CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95% CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate >20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups.
Conclusion
The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.
Keywords: sepsis, acute kidney injury, recovery, outcomes, intensive care unit
Abstract
目的
急性肾损伤(acute kidney injury，AKI)是脓毒症的危重症患者常见的并发症之一，可增加患者死亡、心血管事件和慢性肾功能不全的发生风险。AKI持续时间和AKI后肾功能恢复状况可影响患者的预后，但是脓毒症AKI后患者的早期恢复情况是否与预后密切相关，目前仍存在争议。早期预测AKI后肾功能恢复状态有利于制订个体化的治疗策略和预防严重并发症的发生，然而如何在临床上早期识别脓毒症AKI患者中肾功能未恢复的高危患者尚不清楚。本研究旨在探讨危重症患者脓毒症AKI后早期恢复状态与预后的关系，并早期识别肾功能未恢复的危险因素，以提高患者的生存质量。
方法
回顾性分析2015年1月至2017年3月在中南大学湘雅二医院和湘雅三医院重症监护室(intensive care unit，ICU)住院且在进入ICU后48 h内发生AKI的脓毒症患者的临床资料。脓毒症的诊断根据第3版脓毒症与感染性休克定义国际共识(the Third International Consensus Definitions for Sepsis and Septic Shock，Sepsis-3)，AKI的诊断和分期根据2012年改善全球肾脏病预后组织(Kidney Disease: Improving Global Outcomes，KDIGO)指南。根据诊断AKI后第7天的恢复状态，将脓毒症AKI患者分为完全恢复、部分恢复和未恢复3组。收集患者的基线特征，包括人口学特征、合并症、进入ICU时的临床和实验室检查资料以及进入ICU后24 h内的干预情况。研究的主要结局为90 d时死亡和慢性透析的复合结局，次要结局包括ICU停留天数、住院天数和持续性肾功能不全。使用多因素回归分析评估AKI后早期恢复状态对90 d预后的预测价值，并确定AKI后肾功能未恢复的危险因素。此外，我们进一步分别对诊断AKI后第7天仍在院的患者、无慢性肾脏病病史的患者和AKI分期为2~3期的患者进行敏感性分析。
结果
在553例脓毒症AKI患者中，完全恢复组为251例(45.4%)，部分恢复组为73例(13.2%)，未恢复组为229例(41.4%)。与完全恢复组或部分恢复组患者相比，未恢复组患者90 d死亡(未恢复组vs部分恢复组、完全恢复组：64.2% vs 26.0%、22.7%；P<0.001)和复合结局(未恢复组 vs 部分恢复组、完全恢复组：65.1% vs 27.4%、22.7%；P<0.001)的发生率更高。此外，未恢复组患者与其他两组患者相比，住院时间更短，进展为持续性肾功能不全的比例更高。在校正了混杂因素后，与完全恢复组患者相比，未恢复组患者90 d死亡(HR=3.50，95% CI：2.47~4.96，P<0.001)和复合结局(OR=5.55，95% CI：3.43~8.98，P<0.001)发生的风险明显增加，而部分恢复组患者与完全恢复组比较差异无统计学意义(P>0.05)。男性、充血性心力衰竭、肺炎、呼吸频率>20 次/min、贫血、高胆红素血症、需要机械通气和AKI 3期是AKI后肾功能未恢复的独立危险因素。敏感性分析结果进一步支持在特定患者亚组中AKI后肾功能未恢复仍然是90 d死亡和复合结局的独立预测因素。
结论
危重症患者脓毒症AKI后早期恢复状态与预后不良密切相关，诊断AKI后7 d内肾功能未恢复是90 d死亡和复合结局的独立预测因素。男性、充血性心力衰竭、肺炎、呼吸增快、贫血、高胆红素血症、呼吸衰竭和严重AKI是AKI后肾功能未恢复的危险因素。因此，对于脓毒症AKI患者，应在早期阶段实时评估肾功能恢复状态，AKI后肾功能未恢复的患者则需要在住院期间持续评估肾功能，出院后加强随访，预防远期不良事件的发生。
Keywords: 脓毒症, 急性肾损伤, 恢复, 预后, 重症监护室
Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis[1-3]. Up to 60% of septic patients will develop AKI and sepsis accounts for about 50% of AKI cases[2]. Sepsis-associated AKI (SA-AKI) is an important cause for short- and long-term mortality, cardiovascular events, and progression into chronic kidney disease (CKD) or end-stage renal disease (ESRD). At present, the prevention or treatment for SA-AKI is still limited.
Recent studies[4-13] have focused on the association between the duration or renal function recovery of AKI and prognosis. Compared with non-AKI patients and SA-AKI patients who recovered before discharge, SA-AKI patients with unrecovered renal function at discharge were at higher risk of mortality and ESRD[5, 8, 12]. However, it is still controversial whether early recovery status after AKI is closely related to poor prognosis in SA-AKI patients. Some studies[4-5] suggested that the persistence of AKI was independently associated with short- and long-term mortality and morbidity. Similarly, a recent study[7] found that in-hospital mortality was higher in patients who remained unchanged or deteriorated than those who recovered on Day 7 after AKI. On the contrary, Perinel et al [11] found no independent relationship between persistent AKI and outcome when the AKI stage was taken into account. Another study[13] also showed no significant difference in death up to 1 year between patients with and without reversal within 7 days. In addition, early prediction of renal function recovery after AKI can contribute to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify patients at high risk of unrecovered renal function after AKI at an early stage.
In this study, we aim to provide an overview of early recovery status after AKI and determine its association with outcomes in critically ill patients with SA-AKI. Furthermore, we try to identify risk factors associated with unrecovered renal function after AKI in SA-AKI patients.
1. Subjects and methods
1.1. Study design
This was a retrospective cohort study in the Second Xiangya Hospital and Third Xiangya Hospital of Central South University in China. Adult patients admitted to the intensive care unit (ICU) with sepsis from January 2015 to March 2017 were enrolled. For patients with multiple ICU admissions, only patients with the first ICU admission were analyzed. Patients with ESRD, hospital stay <48 hours, missing serum creatinine (SCr) data, and non-AKI within the first 48 hours after ICU admission were excluded. We also excluded patients without follow-up SCr data after the diagnosis of AKI. In total, 553 SA-AKI patients were finally included in our study (Figure 1). Then eligible SA-AKI patients were assigned into 3 groups according to their early recovery status after AKI: A complete recovery group(the absence of AKI criteria), a partial recovery group (a decline in AKI stage) and an unrecovered group[14]. There were 251 (45.4%) patients in the complete recovery group, 73 (13.2%) in the partial recovery group, and 229 (41.4%) in the unrecovered group, respectively (Figure 1). This study was approved by the Medical Ethics Committee of the Second Xiangya Hospital of Central South University (2013-S061) and registered in Chinese Clinical Trial Registry (ChiCTR 1800019857).
Figure 1. Flow chart of patient selection.
1.2. Study variables and definitions
Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria as an acute change of ≥2 points on the Sequential Organ Failure Assessment (SOFA) score secondary to the infection[15]. AKI was defined and staged according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline[16]. Early recovery status after AKI was determined based on the presence and severity of AKI on Day 7 after the diagnosis of AKI. If SCr data on Day 7 were missing, we would use the data recorded on the day nearest to Day 7 but not later than Day 10. For patients who died or were discharged within 7 days, early recovery status after AKI was determined according to their last available data. Baseline SCr was defined as the most recent SCr value available from 365 to 7 days before ICU admission[17]. For patients lacking a reliable reference SCr value, baseline SCr was obtained by back estimation using the 4-variable modification of diet in renal disease equation with an estimated glomerular filtration rate (eGFR) of 75 mL/(min·1.73 m2)[16, 18].
Data were collected from the electronic medical record system and laboratory information system, including demographics, comorbidities, clinical and laboratory data on admission, and treatment within the first 24 hours. Premorbid CKD was defined as baseline eGFR <60 mL/(min·1.73m2). Hypotension was defined as systolic arterial pressure <90 mmHg (1 mmHg= 0.133 kPa), mean arterial pressure <65 mmHg or requiring vasopressors. We defined anemia as hemoglobin <100 g/L, thrombocytopenia as platelet <100×109/L, hypoalbuminemia as serum albumin <30 g/L, hyperbilirubinemia as bilirubin >34.2 μmol/L, hypoxemia as oxygenation index <300 mmHg, hyperkalemia as serum potassium >5.5 mmol/L, and lactic acidosis as lactate >5 mmol/L. Overt disseminated intravascular coagulation (DIC) was determined based on the International Society on Thrombosis and Haemostasis (ISTH) criteria[19]. Disease severity was evaluated using modified Acute Physiology and Chronic Health Evaluation (APACHE) II score and modified SOFA score, excluding central nervous system component[15, 20].
1.3. Study outcomes
The primary outcome was the composite of death and chronic dialysis at 90 days. Survival status was determined by query of the Chinese Center for Disease Control and Prevention cause-of-death reporting system. Chronic dialysis was determined by reviewing all relevant inpatient and outpatient medical records and making phone calls. Secondary outcomes included length of stay (LOS) in the ICU, LOS in the hospital, and persistent renal dysfunction (PRD). PRD was defined as a final inpatient SCr value ≥2.0 times baseline at hospital discharge or until Day 30[21].
1.4. Statistical analysis
To compare the baseline characteristics and outcomes between patients stratified by early recovery status after AKI, we used the Kruskal-Wallis test for continuous variables and the chi-square tests for categorical variables. Survival data were analyzed by Kaplan-Meier survival method and log-rank test. Multivariate Cox regression was used to characterize the association between early recovery status after AKI and 90-day mortality. Multivariate logistic regression was performed to assess the predictive value of early recovery status after AKI on 90-day composite outcome and to identify risk factors for unrecovered renal function after AKI. Variables considered clinically relevant or P<0.1 on univariable analysis were selected as covariates in the multivariate regression models.
To test the sensitivity of our findings, we further conducted sensitivity analyses. Firstly, we focused on patients who still stayed in hospital on Day 7 after the diagnosis of SA-AKI for the reason that data was not available up to Day 7 in patients who died or were discharged earlier. Secondly, the analysis was performed in patients without premorbid CKD to eliminate the influence of baseline renal insufficiency on poor prognosis. Thirdly, we restricted the study population to patients with AKI Stage 2 to 3, considering that the diagnosis of mild AKI was often missed in clinical practice.
We conducted statistical analyses using SPSS software, version 22.0 (IBM, Armonk, NY). P<0.05 was considered significant for single comparisons and P<0.017 was corrected by Bonferroni method for multiple comparisons.
2. Results
2.1. Baseline characteristics
Compared with the complete recovery group, the unrecovered group had a higher prevalence of congestive heart failure and premorbid CKD, had a higher proportion of tachypnea and anemia on admission, and were more likely to receive mechanical ventilation during the first 24 hours (Table 1). Additionally, the unrecovered group had more severe organ failure or renal dysfunction than the complete recovery group, as reflected by significantly higher modified APACHE II score, modified SOFA score, and percentage of AKI Stage 3.
Table 1.
Baseline characteristics of patients stratified by early recovery status after AKI
| Groups | n | Age/year | Sex, male/[No.(%)] | Comorbidities/[No.(%)] | Baseline creatinine/(μmol·L-1) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hypertension | Diabetes mellitus | Congestive heart failure | COPD | Cirrhosis | Malignancy | Immuno-suppression | Premorbid CKD | |||||
| P | 0.622 | 0.134 | 0.088 | 0.096 | <0.001 | 0.664 | 0.918 | 0.470 | 0.115 | 0.011 | 0.348 | |
| Complete recovery | 251 | 63(50-73) | 149(59.4) | 95(37.8) | 53(21.1) | 13(5.2) | 29(11.6) | 10(4.0) | 21(8.4) | 26(10.4) | 19(7.6) | 84(68-90) |
| Partial recovery | 73 | 64(52-79) | 42(57.5) | 29(39.7) | 19(26.0) | 8(11.0) | 8(11.0) | 3(4.1) | 4(5.5) | 3(4.1) | 11(15.1) | 85(69-93) |
| Unrecovered | 229 | 64(50-75) | 154(67.2) | 109(47.6) | 68(29.7) | 39(17.0)* | 32(14.0) | 11(4.8) | 23(10.0) | 29(12.7) | 37(16.2)* | 86(68-94) |
| Groups | Clinical data on admission/[No.(%)] | Modified SOFA score | Modified APACHE II score | AKI stage/[No.(%)] | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pneumonia | Abdominal infection |
Temperature >38 ℃ |
Heart rate >90 beats per minute | Respiratory rate >20 beats per minute | Hypotension | 1 | 2 | 3 | |||
| P | 0.051 | 0.278 | 0.094 | 0.026 | <0.001 | 0.932 | <0.001 | <0.001 | <0.001 | ||
| Complete recovery | 109(43.4) | 79(31.5) | 24(9.6) | 184(73.3) | 140(55.8) | 142(56.6) | 7(5-9) | 15(12-19) | 135(53.8) | 65(25.9) | 51(20.3) |
| Partial recovery | 29(39.7) | 21(28.8) | 9(12.3) | 50(68.5) | 39(53.4) | 43(58.9) | 8(6-10) | 18(15-21)* | 0(0.0)* | 23(31.5) | 50(68.5)* |
| Unrecovered | 121(52.8) | 57(24.9) | 37(16.2) | 187(81.7) | 164(71.6)*† | 132(57.6) | 9(6-11)* | 19(15-24)* | 39(17.0)*† | 38(16.6)*† | 152(66.4)* |
| Groups | Laboratory data on admission/[No.(%)] | Treatment within 24 hours/[No.(%)] | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Leucocytes >12 ×109/L | Anemia | Thrombocytopenia | Overt DIC | Hypoalbuminemia | Hyperbilirubinemia | Lactic acidosis | Hypoxemia | Hyper-kalemia | Mechanical ventilation | Vasopre-ssors | Renal replacement therapy | |
| P | 0.949 | 0.012 | 0.534 | 0.451 | 0.652 | 0.087 | 0.035 | 0.102 | 0.050 | 0.005 | 0.749 | <0.001 |
| Complete recovery | 133(53.0) | 108(43.0) | 99(39.4) | 70(27.9) | 176(70.1) | 44(17.5) | 53(21.1) | 178(70.9) | 12(4.8) | 150(59.8) | 137(54.6) | 22(8.8) |
| Partial recovery | 40(54.8) | 42(57.5) | 32(43.8) | 20(27.4) | 55(75.3) | 11(15.1) | 7(9.6) | 52(71.2) | 0(0.0) | 42(57.5) | 43(58.9) | 13(17.8) |
| Unrecovered | 124(54.1) | 126(55.0)* | 84(36.7) | 75(32.8) | 166(72.5) | 56(24.5) | 54(23.6)† | 181(79.0) | 15(6.6) | 166(72.5)*† | 131(57.2) | 78(34.1)*† |
COPD: Chronic obstructive pulmonary disease; CKD: Chronic kidney disease; SOFA: Sequential Organ Failure Assessment; APACHE: Acute Physiology and Chronic Health Evaluation; DIC: Disseminated intravascular coagulation.Continuous variables are presented as median (interquartile range) and categorical variables are presented as [No.(%)]. *P<0.05 vs the complete recovery group; †P<0.05 vs the partial recovery group.
2.2. Outcomes
The composite outcome of death and chronic dialysis up to 90 days was more frequent in the unrecovered group than that in the complete or partial recovery group (P<0.05). The 90-day mortality was higher in the unrecovered group than that in the other 2 groups (both P<0.05), but there was no significant difference between the partial and the complete recovery groups (P>0.05; Table 2, Figure 2). The complete or partial recovery group had prolonged LOS in the hospital than the unrecovered group (P<0.05), while there was no significant difference in LOS in the ICU among the 3 groups (P=0.119). Additionally, a larger percentage of patients with unrecovered renal function progressed into PRD at hospital discharge or until Day 30 (Table 2).
Table 2.
Outcomes of patients stratified by early recovery status after AKI
| Groups | n | ICU length of stay/d |
Hospital length of stay/d |
Persistent renal dysfunction/ [No.(%)] |
90-day adverse outcomes | ||
|---|---|---|---|---|---|---|---|
| Death/[No.(%)] | Chronic dialysis/[No.(%)] | Composite outcome/[No.(%)] | |||||
| P | 0.119 | 0.002 | <0.001 | <0.001 | 0.115 | <0.001 | |
| Complete recovery | 251 | 7(4-12) | 13(8-22) | 6(2.4) | 57(22.7) | 0(0) | 57(22.7) |
| Partial recovery | 73 | 8(5-15) | 15(10-24) | 16(21.9)* | 19(26.0) | 1(1.4) | 20(27.4) |
| Unrecovered | 229 | 8(4-15) | 10(5-22)*† | 171(74.7)*† | 147(64.2)*† | 2(0.9) | 149(65.1)*† |
*P<0.05 vs the complete recovery group; †P<0.05 vs the partial recovery group.
Figure 2. Kaplan-Meier survival curve of patients stratified by early recovery status after AKI.
In multivariate Cox regression analysis, the unrecovered group was at significantly increased hazard of death within 90 days (P<0.001), but the partial recovery group was not (P=0.59). After adjustment for potential confounders, the unrecovered group (P<0.001), but not the partial recovery group (P=0.61), was associated with significantly higher risk of 90-day composite outcome (Figure 3).
Figure 3. Association between the early recovery status after AKI and the outcomes.
A: Multivariate Cox regression of association between the early recovery status after AKI and the 90-day mortality in the overall cohort and by subgroups; B: Multivariate logistic regression of the association between the early recovery status after AKI and the 90-day composite outcome in the overall cohort and by subgroups.
2.3. Risk factors associated with unrecovered renal function after AKI
Multivariate logistic regression analysis revealed that the male sex (P=0.049), congestive heart failure (P=0.008), pneumonia (P=0.046), respiratory rate > 20 beats per minute (P=0.008), anemia (P=0.018), hyperbilirubinemia (P=0.007), need for mechanical ventilation (P=0.002), and AKI Stage 3 (P<0.001 vs AKI Stage 1) were independent risk factors for unrecovered renal function after AKI (Table 3).
Table 3.
Multivariate logistic regression analysis for risk factors associated with unrecovered renal function after AKI
| Factors | OR | 95% CI | P |
|---|---|---|---|
| Age | 1.00 | 0.99-1.02 | 0.718 |
| Sex, male | 1.52 | 1.00-2.30 | 0.049 |
| Hypertension | 1.22 | 0.77-1.93 | 0.396 |
| Diabetes mellitus | 1.38 | 0.87-2.18 | 0.167 |
| Congestive heart failure | 2.48 | 1.27-4.82 | 0.008 |
| Premorbid CKD | 1.67 | 0.91-3.08 | 0.097 |
| Pneumonia | 1.56 | 1.01-2.42 | 0.046 |
| Heart rate > 90 beats per minute | 1.46 | 0.89-2.39 | 0.135 |
| Respiratory rate > 20 beats per minute | 1.79 | 1.16-2.75 | 0.008 |
| Anemia | 1.64 | 1.09-2.46 | 0.018 |
| Hyperbilirubinemia | 1.98 | 1.20-3.24 | 0.007 |
| Hypoxemia | 0.86 | 0.53-1.42 | 0.556 |
Table 3.
(to be continued)
| Factors | OR | 95% CI | P |
|---|---|---|---|
| Mechanical ventilation | 2.01 | 1.28-3.16 | 0.002 |
| AKI Stage | |||
| 1 | 1.00 | reference | - |
| 2 | 1.59 | 0.90-2.79 | 0.110 |
| 3 | 6.58 | 4.03-10.75 | <0.001 |
CKD: Chronic kidney disease; AKI: Acute kidney injury.
2.4. Sensitivity analyses
Sensitivity analyses were conducted in patients who still stayed in hospital on Day 7 after the diagnosis of SA-AKI, patients without premorbid CKD, and patients with AKI Stage 2 to 3. The results in the subgroups were similar to those in the overall study cohort. The unrecovered renal function on Day 7 after AKI was independently cor related to a higher risk of 90-day mortality and composite outcome, whereas the partial recovery was not (Figure 3).
3. Discussion
In this study, we find that 41.4% of patients with SA-AKI have unrecovered renal function within the first 7 days after AKI diagnosis, while 45.4% and 13.2% of patients experienced early complete reversal and partial recovery, respectively. Unrecovered renal function after AKI is an independent predictor of 90-day mortality and composite outcome. Additionally, male sex, congestive heart failure, pneumonia, respiratory rate > 20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 are risk factors for unrecovered renal function after AKI.
AKI is now regarded as a clinical syndrome that can lead to long-term sequelae such as CKD, cardiovascular events, and death, and our study described the evolution of AKI in critically ill septic patients. Early studies[8, 12] have shown that SA-AKI patients with unrecovered renal function at hospital discharge have worse outcomes than those who recovered. Recently, the Acute Disease Quality Initiative 16 Workgroup proposed novel definitions for persistent AKI and acute kidney disease (AKD) to clarify clinical trajectories of renal function recovery after AKI[22]. Several recent studies have explored the effectiveness of the new definitions in SA-AKI patients. Uhel et al [4] find that persistent AKI is independently associated with mortality and host response aberrations compared with transient AKI in critically ill septic patients. Similarly, Ozrazgat-Baslanti et al[5] find that persistent AKI is associated with decreased long-term physical function and survival among patients with surgical sepsis. However, there have been no uniform conclusions on the relationship between clinical outcomes and AKD in septic patients[7, 13]. Our study further confirm the new AKD definition, as recovery status within the first 7 days after AKI is independently associated with poor prognosis. Moreover, unrecovered renal function, but not partial recovery, is an independent predictor for 90-day mortality and composite outcome in SA-AKI patients. We also find that most SA-AKI patients with unrecovered renal function on Day 7 develop PRD, while patients with partial recovery are more likely to experience delayed recovery later. Therefore, the evaluation of early recovery status after AKI is essential for timely intervention and management in SA-AKI patients. For patients with unrecovered renal function after AKI, additional in-hospital care is necessary, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment of renal function. In addition, they need more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events after discharge.
Many factors, including demographics, chronic comorbidities, multiple organ dysfunction, and severe AKI, can affect renal function recovery after AKI[14]. Consistent with our previous study[23], the male sex, respiratory failure, and AKI stage are independent risk factors associated with unrecovered renal function. Meanwhile, we find several novel risk factors for unrecovered renal function, including congestive heart failure, hyperbilirubinemia, and anemia. Congestive heart failure, characterized as the decline in cardiac output, may be caused by chronic diseases like hypertension and coronary artery disease or sepsis. The effects of heart failure on unrecovered renal function may include hemodynamic changes, systemic inflammation, and neurohumoral pathways[24]. A recent study[25] demonstrates that severe hyperbilirubinemia (bilirubin >2.0 mg/dL) is associated with a higher risk of contrast-related AKI. Anemia is commonly present in critically ill patients with severe acute renal failure and has been found to be an independent risk factor of mortality[26]. Our study demonstrates that hyperbilirubinemia and anemia are both related to early recovery status after AKI in SA-AKI patients.
Our study has 3 limitations. Firstly, it was a retrospective study conducted in 2 tertiary hospitals and the sample size was relatively small. Selection bias may exist to limit the generality of the results and the correlation between the variables identified in the study could not imply causality. Secondly, urine output criteria were not included in the diagnosis of AKI. A considerable proportion of patients with reduced urine output received diuretics in the early phase after ICU admission, which may affect the primary urine output of these patients compared with those who did not. Thirdly, many unmeasured potential factors may affect the prognosis, and the information on other endpoints (such as major adverse cardiac events) was not available during the follow-up period. Further large prospective studies are still required to investigate the epidemiology and pathophysiology of renal function recovery after AKI in septic patients.
In conclusion, unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome in critically ill patients with SA-AKI. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are identified as risk factors for unrecovered renal function after AKI. Our results emphasize the necessity of early risk stratification, timely estimation of the renal function, and effective follow-up for SA-AKI patients.
Contributions: LUO Xiaoqin Collected, analyzed, and interpreted data, drafted and revised the manuscript; YAN Ping, ZHANG Ningya Collected, analyzed, and interpreted data, reviewed and revised the manuscript; WANG Mei, DENG Yinghao, WU Ting, WU Xi, LIU Qian, WANG Hongshen, WANG Lin, KANG Yixin Interpreted data, reviewed and revised the manuscript; DUAN Shaobin Conceptualized and supervised the study, analyzed data, reviewed and revised the manuscript. All authors have approved the final version of this manuscript.
Funding Statement
This work was supported by the National Natural Science Foundation of China (81873607).
Conflict of Interest
The authors declare that they have no conflicts of interest to disclose.
Note
http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/202205535.pdf
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