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[연구] 체내 산 축적 과도하면 사망위험 15배

국제학술지 <사이언티픽 리포츠> 최신호 게재

송보미 기자bmb@healthi.kr 입력 : 2019-04-17 14:32  | 수정 : 2019-04-17 14:32

네이버 페이스북 밴드 구글 트위터 핀터레스트 카카오스토리 카카오링크 인쇄 다운로드 확대 축소

대사성 산증환자와 정상환자의 사망률 및 질병 발병률 비교.
자료=분당서울대병원.

 

[헬스앤라이프 송보미 기자] 신장의 주요 조절 기능인 산염기 조절에 이상이 생기면 산성 유발 물질이 과도하게 축적되면서 사망 위험을 최대 15배까지 높인다는 연구결과가 발표됐다.

 

16일 분당서울대병원 신장내과 김세중 교수 연구팀에 따르면 대사성 산증이 신장의 만성적 악화가 아닌 ‘급성 신손상’과도 연관 있는지에 주목하면서 연구를 설계했다. 우선 2013년도에 입원한 분당서울대병원 전체 입원환자 중 1만7320명의 자료를 통해 입원당시 대사성 산증이 발생한 환자를 분류했고 신장 기능의 손상여부 및 사망률을 분석했다. 

 

김세중 분당서울대병원 신장내과 교수.
사진=분당서울대병원

분석대상 환자 중 입원시점에 대사성 산증이 발생한 환자는 25%(4488명)를 차지했다. 대사성 산증이 발생한 환자에서는 급성 신손상 발생위험이 1.57배 증가했고, 산증의 정도가 심할수록 급성 신손상 발생위험도 더욱 증가하는 것으로 확인됐다. 

 

또한 대사성 산증 환자에서는 사망위험 역시 증가했다. 정상 환자 대비 90일 사망률은 1.30배, 1년 사망률은 1.31배 높게 나타났다. 대사성 산증의 정도가 심할수록 사망률이 점점 더 증가하는 결과를 보였으며, 대사성 산증과 급성 신손상이 함께 나타난 경우에는 사망위험이 최대 15배 이상 증가하는 것으로 밝혀졌다.

 

김세중 교수는 “신장 기능과 관련된 다양한 이상신호를 종합해 보면 환자의 예후나 사망위험을 미리 확인할 수 있고, 그 만큼 보다 적절한 조치를 취할 수 있게 된다”며 “앞으로도 다각적인 임상 정보를 확보해서 이용한다면 파생 가능한 질병이나 예후를 정확하고 신속하게 예측할 수 있을 것”이라고 밝혔다. 

 

이번 연구결과는 국제학술지 <사이언티픽 리포츠>에 게재됐다.

 

아래는 해당 논문의 요약본과 관련 표 자료.

 

Short-term and long-term effects of low serum bicarbonate level at admission in hospitalised patients

 

Abstract

 

Although low serum bicarbonate level is known to be associated with adverse outcomes in patients with chronic kidney injury, it is unclear whether low serum bicarbonate level is associated with the development of acute kidney injury (AKI). The purpose of our study was to determine whether serum bicarbonate levels at admission could be a risk factor for AKI development and mortality in hospitalised patients. We retrospectively enrolled 17,320 adult patients who were admitted to the academic teaching hospital from January 2013 to December 2013. Patients were divided into 2 groups based on the first measurement of serum bicarbonate level at admission. The incidence of AKI was higher in patients with low serum bicarbonate level than in those with normal serum bicarbonate level (8.0% vs. 4.1%). Low serum bicarbonate levels at admission were significantly associated with the development of AKI. In addition, low serum bicarbonate levels also independently predicted the 90-day mortality. Pre-existing low bicarbonate levels and subsequent development of AKI increased in-hospital mortality by 15 times compared with that in patients with normal bicarbonate levels and no AKI. Low serum bicarbonate levels may be associated with the development of AKI and high mortality in hospitalised patients.

 

Results

 

A total of 17,320 patients were enrolled and divided into 2 groups according to the serum bicarbonate level. In the enrolled cohort, 25.91% (n = 4,488) were acidotic initially. During a median (interquartile range) hospital stay of 6.0 (3.0–10.0) days, AKI of all stages was detected in 882 (5.1%) patients, of whom 662 (3.8%) were in stage I and 220 (1.3%) were in stage II and stage III (Supplementary Table S1). Of the patients, 3.1% died of all causes within 90 days after admission. No patient died before the development of AKI.

 

 

Baseline characteristics according to serum bicarbonate level

 

The patient demographics and clinical parameters at the time of admission are summarised in Table 1. Patients with low serum bicarbonate level were older than those with normal serum bicarbonate level, and more likely to have pre-existing comorbidities such as diabetes, hypertension, cardiovascular disease, and heart failure, except cancer. However, there was no significant difference in the Charlson comorbidity index score between the 2 groups.

 

Table 1. Baseline characteristics of patients with low serum bicarbonate and normal serum bicarbonate. ICU, intensive care unit; RAS, renin-angiotensin system; BP, blood pressure; TWA-MAP, time-weighted average mean arterial pressure; eGFR, estimated glomerular fltration rate. Values are expressed as mean±standard deviation for continuous variables and n (%) for categorical variables. *Incomplete data. Te missing data rate was 8.9% in body mass index; 0.1% in systolic and diastolic BP; 1.2% in white blood cells, haemoglobin, and platelet; 45.6% in C-reactive protein; 2.2% in protein; 1.5% in albumin; 2.1% in cholesterol; and 2.2% in bilirubin.
자료=사이언티픽 리포츠

 

The median serum bicarbonate levels in the low serum bicarbonate group and normal serum bicarbonate group were 20.0 (7–21) and 24.0 (22–29) mmol/L, respectively. Additionally, patients with low serum bicarbonate level at admission were more likely to have higher serum creatinine and to develop AKI. Compared with patients with normal serum bicarbonate level, those with low serum bicarbonate level had lower serum sodium, albumin, and estimated glomerular filtration rate (eGFR) at admission.

 

 

Low serum bicarbonate, AKI, and mortality

 

A significantly higher rate of AKI development was observed in the low bicarbonate group than in the normal bicarbonate group (Fig. 1). Patients with AKI had lower serum bicarbonate levels than those without AKI. To evaluate the independent risk factors predicting the development of AKI, Cox regression analysis was performed (Supplementary Table S2, Table 2). Variables that were significant in univariate analysis, such as albumin, history of intensive care unit stay, hypertension, and diabetes mellitus, were included as adjusting covariates in multivariate analysis. As a result, lower serum bicarbonate level was independently associated with an increased risk of AKI development, with a hazard ratio (HR) of 1.574 (95% confidence interval [CI], 1.273–1.949; P < 0.001) in multivariate Cox proportional hazard regression analysis.

 

Figure 1. Clinical outcomes according to serum bicarbonate level. *P<0.001 compared with the non-acidosis group. AKI, acute kidney injury; ESRD, end-stage renal disease.
자료=사이언티픽 리포츠

 

Table 2 Hazard ratio for the development of AKI and 90-day mortality in multivariable Cox proportional hazard regression.

 

The low bicarbonate group also showed a statistically higher risk of severe AKI, end-stage renal disease at 1 year, and mortality of all causes within 90 days or 1 year after admission than the normal bicarbonate group (Fig. 1, Fig. 2a). Patients with AKI also had considerably higher risk of 90-day than those who did not develop AKI (Fig. 2b). As shown in Table 2, both low serum bicarbonate level and AKI were significant predictors of 90-day mortality in multivariate Cox proportional regression analysis (adjusted HR, 1.302; 95% CI, 1.008–1.682; P = 0.043 and adjusted HR, 2.472; 95% CI, 1.900–3.217; P < 0.001, respectively; Table 2). As low serum bicarbonate level was associated with the development of AKI, we assessed the interaction between low serum bicarbonate levels and AKI for mortality by using the relative excess risk due to interaction (Table 3). Compared with patients with normal serum bicarbonate level and without AKI, patients with low serum bicarbonate level and those with AKI had worse mortality (odds ratio [OR], 2.723; P < 0.001 and OR, 15.200; P < 0.001, respectively). In addition, patients in the low bicarbonate group with AKI had an increased risk of 90-day mortality by 18.863 times compared with patients in the normal bicarbonate group (P < 0.001). We also observed that the hazards of AKI and mortality decreased as the serum bicarbonate level increased in the restricted cubic regression models, and that higher serum  bicarbonate level within the normal range seemed beneficial with respect to avoiding the development of AKI and mortality (Fig. 3).

 

 

Cumulative survival rate according to serum bicarbonate level and acute kidney injury (AKI). (ac) Show the survival curves of serum bicarbonate, AKI, and combined serum bicarbonate and AKI groups for the 90-day mortality, respectively. *And indicate P < 0.001 when compared with normonatraemic patients without AKI and hyponatraemic patients without AKI, respectively; indicates P < 0.05 when compared with normonatraemic patients with AKI in the log-rank test.

 

 

 

※출처   <사이언티픽 리포츠> 2월 26일자 온라인판

 

 


bmb@haelthi.kr

 

#분당서울대병원 #신장내과 #김세중교수 #대사성산증 #신장 #신장질환 #급성신손상 #신장산성화 #의료계연구성과 #헬스앤라이프