A slight decrease in serum albumin level is associated with rapid progression of kidney dysfunction even within the normal range: The Yuport Health Checkup Center Cohort Study

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between serum albumin level and future decline of kidney function is unclear. We aimed to clarify the effect of serum albumin level on the decline of kidney function in the general population. Methods The data used were from 11,000 participants of a voluntary health checkup program between 1998 and 2006 conducted in Japan. The primary outcome for kidney function was a difference in estimated glomerular filtration rate (ΔeGFR) of ≥3 mL/min/1.73 m2/year. The association of the risk of decreased kidney function with albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4– 4.6 (n=5,427), and ≥4.7 (n=3,043). Results Of 11,000 participants, 346 had a ΔeGFR/year of ≥3. As compared with the participants with albumin levels of ≥4.7 g/dL, the risk of decline in kidney function was higher not only in those with albumin levels of ≤4.3 g/dL (adjusted OR = 2,29, 95% CI: 1.65–3.18) but also in 4.4-4.6 g/dL (adjusted OR = 1.60, 95% CI: 1.20–2.14). Conclusion Decreased albumin level is an independent risk factor for rapid decline in kidney function even within the normal range.

The number of patients with chronic kidney disease (CKD) has been increasing 4 in most parts of the world, and the disease is estimated to affect 200 million 5 individuals worldwide [1]. Furthermore, the increase in the number of patients 6 with CKD is expected to accelerate.
CKD creates a large burden and is 7 recognized as an important problem for both individuals and the society as a 8 whole. First, CKD is a risk factor for not only end-stage kidney disease (ESKD) 9 but also cardiovascular disease (CVD), which is the main cause of death 10 worldwide [2][3][4][5]. Second, the worldwide medical expenses associated with 11 hemodialysis due to ESKD is estimated to increase to a 1000 billion USD within 12 the next 10 years [6]. For these reasons, establishment of an effective measure 13 for CKD prevention is vital; in fact, this is one of the most important issues in 14 public and national health. 15 While accumulating evidence shows that some metabolic and lifestyle risk 16 factors of CKD, such as hypertension, dyslipidemia, and diabetes mellitus were 17 addressed [7-13], the effective measure for CKD prevention has not been 18 established yet. Therefore, risk factors other than the "conventional" risk factors 1 of CKD should be considered. 2 Previous studies suggested that a lower albumin level, even that within the 3 clinical normal range, is associated with high risks of CVD and mortality in the 4 general population [14,15]. However, studies that investigate the relationship 5 between the albumin level and decline of kidney function are completely lacking.

6
The aim of this study was to evaluate the effect of serum albumin level on the 7 decline of kidney function in the general population by using a large retrospective 8 cohort data set of the Japanese population. procedures were performed in the same manner, both during the baseline and 10 follow-up periods, including blood measurements. Height and weight were 11 measured to calculate body mass index (BMI), which was defined as weight 12 divided by height squared (kg/m 2 ). Blood pressure was measured by trained 13 nurses using a sphygmomanometer.

15
Kidney function 16 Kidney function was expressed as an estimated glomerular filtration rate (eGFR) 17 using the CKD Epidemiology Collaboration (CKD-EPI) modified for Japanese [17].

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GFR estimated by the coefficient-modified CKD-EPI equation was more closely 1 related to CVD incidence than that estimated by the Japanese GFR equation [18].

2
The coefficient-modified CKD-EPI equation is as follows.  The baseline characteristics of the participants according to abnormal decline in 4 kidney function status are shown in Table 1 Next, we evaluated the unadjusted and adjusted ORs and 95% confidence 10 intervals (CIs) for abnormal decline of kidney function according to albumin level.

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In the continuous variable evaluation, the albumin levels (per 0.1 g/dL) were

17
In the categorical variable evaluation, as compared with the participants with 18 albumin levels of ≥4.7 g/dL, the risk of abnormal decline in kidney function was 1 significantly higher not only in those with albumin levels of ≤4.3 g/dL but also in 2 those with 4.4-4.6 g/dL (Fig. 3A): This result means that lower serum albumin 3 level, even within the normal range, is related to rapid kidney function decline. 4 The results of the sensitivity analysis, in which a ΔeGFR of ≥5 mL/min/1. In this retrospective, population-based, cohort study, the relationship between 4 albumin level and decline in kidney function over time was investigated. A 5 decrease in albumin level was found to be the primary risk factor of abnormal 6 decline in kidney function. More importantly, our study suggests that even within 7 the normal range, those with albumin levels of ≤4.6 g/dL had a risk of decline in 8 kidney function. 9 Our study could not reveal the reason why relatively low but within normal limit  Most previous studies used abnormally lower albumin levels as an indicator 11 of malnutrition status for research [15,31]. However, our study showed that in our study, we included almost five times more subjects than that in the previous 2 study. 3 Our study showed that decreased albumin level was significantly associated be conducted to provide more insight. 8 In conclusion, our study showed that decreased serum albumin level is an   Data are expressed as mean and standard deviation, or percentage and number or median with 25th and 75th percentiles. Abbreviations: NGSP, National Glycohemoglobin Standardization Program