Part Two Effect Of Influenza Vaccination On The Outcomes Of Hospitalization For Kidney Disease in A Geriatric Population: A Propensity-score Matched Study

Results

The unmatched baseline characteristics of patients with KD who did or did not receive IV are shown in Table 1 (N = 22,590). After matching (Table 2), no differences in the baseline characteristics were observed between patients with KD who did or did not receive IV (N = 8772).

Before matching by propensity score (S1 Table), IV was associated with mortality (OR 0.66, 95% CI 0.50–0.88), septicemia (OR 0.83, 95% CI 0.76–0.92), and intensive care (OR 0.87, 95% CI 0.79–0.95). After propensity-score matching (Table 3), patients with KD and a previous IV had lower risks of septicemia (OR 0.77, 95% CI 0.68–0.87), need for intensive care (OR 0.85, 95% CI 0.75–0.96), and in-hospital mortality (OR 0.56, 95% CI 0.39–0.82), compared with the control group. The length of hospital stay (10.0±11.5 vs. 11.4±15.1 days, p<0.0001) and medical expenditures (1973±3157 vs. 2294±3580 US dollars, p<0.0001) were both lower in patients with KD who received IV than in non-IV controls. After propensity-score matching, the linear regression analyses showed that IV was associated with reduced length of hospital stay (beta = -1.4, p<0.0001) and medical expenditures (beta = -320.8, p<0.0001).

After propensity-score matching, the stratified analysis (Table 4) showed that receiving IV was associated with reduced adverse events during KD admission (including septicemia, intensive care, and mortality) among men (OR 0.72, 95% CI 0.60–0.87), women (OR 0.79, 95% CI 0.67–0.93), and patients aged 75–79 years (OR 0.78, 95% CI 0.62–0.98), 80–84 years (OR 0.67, 95% CI 0.51–0.87), and ≥85 years (OR 0.66, 95% CI 0.49–0.90). In addition, IV was associated with adverse events in patients with one medical condition (OR 0.61, 95% CI 0.50–0.74).

Discussion

As shown in the present study, elderly patients receiving IV within the previous 12 months had reduced risks of septicemia, intensive care, and mortality during hospitalizations for KD. A shorter length of hospital stay and lower medical expenditures were also noted in IV users compared to non-IV patients during KD admission. The beneficial effect of IV was especially significant in patients with KD aged ≥ 75 years. To our knowledge, this study is the first to focus on the short-term outcomes during KD admission, which provides an important clinical implication in the context of kidney failure.

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Few studies have investigated the relationship between IV and KD outcomes [20–24]. Compared with previous studies [20–24], we included a variety of kidney diseases and performed a comprehensive evaluation of critical outcomes in patients with KD to increase the generalizability of our results. A prior IV was associated with lower risks of all-cause mortality, septicemia, and the need for intensive care, consistent with previous studies [20–24]. Although the rates of pneumonia and stroke were lower in the vaccine cohort than in the control cohort, the association did not reach statistical significance, in contrast to some studies [13, 16, 17, 21]. This discrepancy is possibly attributable to our relatively shorter follow-up period compared with previous studies [13, 16, 21]. IV before hospitalization reduces the risks of mortality and readmission among geriatric populations admitted with pneumonia [25, 26]. Based on our results, the protective effect of IV may be generalizable to hospitalized patients with KD, irrespective of the types of kidney disease and different medical conditions. Notably, our stratified analyses showed that the association between IV and a reduced number of adverse events was stronger in the subgroup of age ≥ 75 years, consistent with some other studies [22, 23].

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We proposed the following explanations for the observed phenomena in this study. First, patients with influenza virus infection are susceptible to a secondary bacterial infection, which contributes to serious complications, such as mortality and the need for intensive care [27]. IV may protect against secondary bacterial infections by preventing influenza infection and improving the in-hospital outcome during KD admission. Second, previous studies suggested that IV reduces the risk of hospitalizations for influenza, pneumonia, cardiovascular diseases, and all-cause mortality [13–19, 22, 23, 25, 26]. Influenza infection might exacerbate coexisting diseases, especially in fragile patients with KD. The health condition of vaccine recipients may have been better than nonrecipients and hence improved in-hospital outcomes of KD hospitalization. Third, hospitalized patients are susceptible to nosocomial influenza and pneumonia [16, 28]. A prior IV might protect against possible nosocomial infections and thereby reduce overall mortality. Fourth, we found that IV was associated with fewer adverse events in patients aged ≥ 75 years but not < 75 years. Based on this finding, older people are more vulnerable to influenza infection and associated complications than younger people [29]. Therefore, older patients might have benefitted more from IV than their younger counterparts in this study. Finally, patients receiving IV annually might have higher levels of health consciousness, ambulatory independence, and support from family members and social networks than nonrecipients. Patients’ knowledge, attitudes, and practice of health behaviors and socioeconomic factors may influence the outcomes of patients with KD [30, 31].

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Our results indicate an urgent need to promote IV for elderly patients with KD. However, the administration of vaccines to this vulnerable population is challenging. Antibody responses to IV, measured as seroconversion and seroprotection, decrease with increasing age [32]. The immunogenicity of the influenza vaccine is also attenuated in patients with kidney failure [33]. Current guidelines highly recommend the annual administration of seasonal inactivated influenza vaccines to adults with KD [34]. Among geriatric patients with KD, a high-dose trivalent influenza vaccine may be safe and immunogenic [35, 36]. In addition, an MF59-adjuvanted influenza vaccine exhibited better immunogenicity in patients with end-stage renal disease in a previous study [37]. Regarding the optimal influenza vaccine schedules for patients with KD, sufficient scientific evidence from large-scale randomized trials is unavailable [35, 38].

Our study has some limitations. First, distinct serotypes of seasonal influenza vaccines and vaccine adjuvants may activate different levels of immunogenic reactions [37, 39]. Although the present study was unable to standardize types of vaccines, we used the stated serotypes of vaccines used each year. Second, our database did not contain information on host-related factors that may affect influenza vaccine responsiveness, such as preexisting immunity and genetic polymorphisms [40]. Third, baseline kidney function and the duration of KD for each subject were unknown due to data unavailability. Fourth, the cause of death was unclear, and a causal relationship between vaccination and a reduced mortality rate is difficult to infer. Fifth, we did not measure markers of inflammatory and immune responses and therefore were unable to elucidate the biological mechanism underlying the results of our statistical analyses. Finally, we admitted that residual confounding possibly existed in this study since we were unable to control all potential confounding factors in the current analysis.

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In conclusion, prior receipt of IV was significantly associated with reduced mortality, septicemia, and the need for intensive care in geriatric patients hospitalized for KD. Additionally, vaccine recipients had a shorter length of hospitalization and lower medical expenditures than nonrecipients. The protective effect of IV was especially significant in patients aged ≥75 years. These results provide evidence to promote the delivery of influenza vaccines to patients with KD as a prophylactic measure to protect against adverse events.

References

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Chien-Chang LiaoID1,2,3,4,5, Ying-Hsuan Tai3,6, Chun-Chieh Yeh7,8, Yung-Ho Hsu9 , TaLiang Chen2,3,10, Yih-Giun CherngID3,6

1 Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan,

2 Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan,

3 Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan,

4 Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan,

5 School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan,

6 Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan,

7 Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan,

8 Department of Surgery, University of Illinois, Chicago, Illinois, United States of America,

9 Department of Nephrology, Shuan Ho Hospital, Taipei Medical University, New Taipei City, Taiwan,

10 Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan