Worsening or improving hypoalbuminemia during continuous renal replacement therapy is predictive of patient outcome: a single-center retrospective study

In total, 1895 patients received CRRT in our hospital between January 2016 and December 2020. We excluded 5 patients who were < 18 years of age, 304 patients who had end-stage kidney disease, 656 patients who received CRRT for < 72 h, 116 patients who remained in the hospital for > 100 days, and 21 patients who had no serum albumin data during CRRT. Thus, we included 793 patients in the analysis (Fig. 1).

Fig. 1figure 1

Flow diagram of the study population

The median age of the patients was 67.5 (56–77) years; 63.1% of the patients were men, and the mean BMI was 24.3 ± 12.9 kg/m2. The patients had a median of 1 (1–2) comorbidity; diabetes (41.8%), hypertension (51.9%), and congestive heart failure (26.6%) were the most common comorbidities. Liver cirrhosis was observed in 11.2% of the patients, and sepsis was diagnosed in 23.7% of the patients. The mean SOFA score at the initiation of CRRT was 10.34 ± 3.74.

The mean serum albumin level at the initiation of CRRT was 3.05 ± 0.67 g/dL. Serum albumin levels changed during the median of 5 (3–8) days of CRRT. Among the 793 included patients, serum albumin levels were persistently low in 299 (37.7%), increased in 85 (10.4%), decreased in 195 (24.6%), and persistently high in 214 (27.0%). Changes in the serum albumin level in each group are plotted in Fig. 2. In the decreasing and increasing groups, serum albumin levels started to change on the second day of CRRT, and on the third day (day 3) of CRRT, mean serum albumin levels were highest in the persistently high, followed by the increasing, decreasing, and the persistently low group. At the end of CRRT, the mean serum albumin level in the increasing group was similar to that in the persistently high group.

Fig. 2figure 2

Changes in serum albumin level during continuous renal replacement therapy in the four albumin groups: orange, persistently high; green, increasing; purple, decreasing; blue, persistently low. Numbers at the bottom of the figure indicate the number of data available for each group on each day

Thirty-seven of 793 (4.7%) patients received intravenous albumin during CRRT; 15 (5.0%) among the persistently low, 5 (5.9%) among the increasing, 9 (4.6%) among the decreasing, and 8 (3.7%) among the persistently high albumin group. No difference in proportion was detected.

Associations of patient characteristics and disease course with changes in serum albumin levels

In the initial normoalbuminemia group, congestive heart failure, COPD, and CKD were more common, whereas sepsis and the use of vasopressors were less common than in the initial hypoalbuminemia group. Mean arterial pressure was higher and SOFA score was lower in the initial normoalbuminemia group at the initiation of CRRT (Additional file 1: Table S1).

Among the patients with initial hypoalbuminemia, the increasing group received CRRT longer [8 (5–13.3) days] than did the persistently low group [6 (4–11) days, p < 0.001]. The initial laboratory findings and disease severity did not differ between the two groups, except for the lower CRP levels in the increasing albumin group. A greater proportion of patients in the increasing group transitioned to conventional HD (21.2% vs. 12.4, p = 0.041), while a smaller proportion of patients terminated CRRT because of low BP/DNR/death (41.2% vs. 53.2%, p = 0.049), compared to the persistently low group (Table 1).

Table 1 Baseline characteristics of patients by the serum albumin change pattern

Among the patients with initial normoalbuminemia, patients in the decreasing group were older [70 (61–77.5) years vs. 64 (52–75) years, p = 0.002] and were more likely to have cancer (21% vs. 11.7%, p = 0.010) than were patients in the persistently high group. Sepsis was more common (18.6% vs. 6.2%, p < 0.001), vasopressors were more frequently required (60.5% vs. 49.3%, p = 0.004), and CRP levels were higher in the decreasing group than in the persistently high group. The proportion of patients who terminated CRRT because of low BP/DNR/death was higher (39.5% vs. 29.9%, p = 0.042) in the decreasing group (Table 1).

In-hospital mortality according to changes in serum albumin levels

In total, 378 (47.9%) of the 789 patients died during their hospital stay. The in-hospital mortality rate was higher in the initial hypoalbuminemia group than in the initial normoalbuminemia group (Additional file 1: Fig. S1). Among the patients with initial hypoalbuminemia, the hazard ratio (HR) for in-hospital mortality was significantly lower in the increasing group than in the persistently low group (Fig. 3A, left); among the patients with initial normoalbuminemia, the HR for in-hospital mortality was significantly higher in the decreasing group than in the persistently high group (Fig. 3A, right). In the subgroup of patients with sepsis, cancer, COPD, or a higher SOFA score (SOFA score > 10), the HRs did not significantly differ between the increasing and persistently low groups or the decreasing and persistently high groups. Analysis of all patients showed that the in-hospital mortality rates were highest in the persistently low and decreasing groups, followed by the increasing and persistently high groups (log-rank p < 0.01) (Fig. 3B).

Fig. 3figure 3

A Hazard ratios for in-hospital mortality of the increasing group compared to the persistently low group (left), and the decreasing group compared to the persistently high group (right) stratified by age, sex, body mass index, diabetes, congestive heart failure, liver cirrhosis, chronic kidney disease, chronic obstructive pulmonary disease, sepsis, anuria, and SOFA score. B Kaplan–Meier survival analysis results of the four albumin change groups; orange, persistently high; green, increasing; purple, decreasing; blue, persistently low

Table 2 shows the HRs of the albumin groups for prediction of in-hospital mortality after adjustments for age, BMI, COPD, CKD, sepsis, SOFA score, and CRRT dose. The HRs for in-hospital mortality were 0.571 (0.340–0.958) in the increasing group and 0.565 (0.353–0.903) in the persistently high group compared to the persistently low group. The HR of the decreasing group for in-hospital mortality was 0.722 (0.455–1.146), which was similar to the HR of the persistently low group. Similar results were observed in the fully adjusted model (Additional file 1: Table S2). In addition to the change in serum albumin, old age [HR 1.014 (1.002–1.027)] and a higher SOFA score [HR 1.089 (1.036–1.45)] were significant predictors of in-hospital mortality (Table 2).

Table 2 Multi-variable Cox regression analysis results for predicting in-hospital mortality

As day 3 serum albumin levels clearly separated the four albumin groups, we further tested its performance in predicting in-hospital mortality. After adjusting for the parameters listed above, lower serum albumin on day 3 (HR 0.532; 0.377, 0.751) was significant for predicting in-hospital mortality (Table 2).

Lengths of ICU and hospital stays according to changes in serum albumin levels

The median length of ICU stay was 11 (6–20) days; it was longer in the decreasing group [16 (10–30) days] than in the increasing [10 (6–17) days] or persistently high [9.5 (6–15) days] groups (p < 0.001) (Additional file 1: Table S3). In the multivariable linear regression model adjusted for age, SOFA score, and CRRT duration, the median length of ICU stay was 3.55 (0.49–6.60) days longer in the persistently low group than in the persistently high group (p = 0.023) (Table 3).

Table 3 Impact of the albumin change pattern on length of stay at ICU or hospital

The median length of hospital stay was 22 (12–42) days; it was longer in the decreasing group [69 (16–58) days] than in the increasing group [21 (10–35) days] (Additional file 1: Table S3). However, the multivariable linear regression model adjusted for age, SOFA score, and CRRT duration revealed no differences in the length of hospital stay according to changes in serum albumin levels. In this study, the length of hospital stay was affected by age (mean difference, − 0.17 (− 0.31 to − 0.03) days) and CRRT duration (mean difference, 0.90 (0.56–1.21) days) (Table 3).

In the multivariable linear regression model, each 1 g/dL decrease in serum albumin level on day 3 predicted 3.96 (0.20, 7.89) days longer duration of hospital stay, whereas it was not predictive for the length of the ICU stay (Additional file 1: Table S4).

Changes in volume status during CRRT according to the serum albumin group

During the median 5 (3–8) days of CRRT, mean total input was 24.3 ± 34.8 L, the mean total output was 21.6 ± 24.9 L, and the mean total fluid balance was 2.1 ± 6.5L, which was 2.9 ± 9.8% of initial body weight. The mean changes in volume status per body weight in each group were 5.6 ± 9.5%/kg in the persistently low, 3.2 ± 9.2%/kg in the increasing, 3.2 ± 10.2%/kg in the decreasing, and − 0.2 ± 9.2%/kg in the persistently high group (Additional file 1: Table S5). The proportion of patients with more than a 2%/kg volume decrease was highest in the persistently high group (43.2%) followed by the increasing (27.0%), decreasing (22.7%), and persistently low groups (20.3%), whereas the proportion of patients with more than 2%/kg added volume was highest in the persistently low (58.6%) and decreasing (57.1%) groups followed by the increasing (50%) and persistently high (31.7%) albumin groups (Fig. 4).

Fig. 4figure 4

A The proportion of patients with a fluid reduction more than 2% of their initial body weight in the four albumin groups. B The proportion of patients with a fluid gain of more than 2% of initial body weight in the four albumin groups

Changes in CRP during CRRT according to the serum albumin group

Information for CRP was available in the 72.3%, 36.7%, and 46.6% of the groups at the start of CRRT, CRRT day 3, and upon stopping CRRT. As shown in Fig. 5, serum CRP levels were persistently high in the persistent low albumin group and significantly increased during CRRT in the decreasing albumin group. CRP levels were persistently low in the increasing albumin group, which was comparable to those in the persistently high albumin group.

Fig. 5figure 5

Changes in serum CRP levels during continuous renal replacement therapy in the four albumin groups: orange, persistently high; green, increasing; purple, decreasing; blue, persistently low. Numbers at the bottom of the figure show the number of data available for each group and each day

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