The relationship between urinary albumin to creatinine ratio and all-cause mortality in the elderly population in the Chinese community: a 10-year follow-up study

With the acceleration of aging, when the age structure of the population becomes less young, tools for predicting the risk of all-cause mortality in the middle-aged and elderly have become more and more important in research, policy, and clinical practice [1‐4]. Chronic kidney disease (CKD), defined as the presence of proteinuria and/or decreased renal function, is an /important risk factor for end-stage renal disease (ESKD), cardiovascular events and all-cause death [5]. In the general population, the association between proteinuria and all-cause death has received widespread attention. Albuminuria is highly prevalent among older adults, especially those with diabetes and hypertension [6‐9]. It is associated with several chronic diseases [10]. However, its overall impact on the health of the elderly, as well as on all-cause mortality in the community, has not been studied in detail [11, 12]. The urinary albumin to creatinine ratio is a new and reliable method for monitoring the excretion of urine protein. The measurement of the urinary albumin to creatinine ratio can reliably reflect the amount of urine protein in 24 h. It is fast, simple and accurate. Urinary albumin to creatinine ratio has become a clinically qualitative and quantitative diagnostic index for proteinuria that can replace the traditional 24-h urine protein quantification [13, 14]. Studies have shown that high levels of urinary albumin excretion are associated with an increase in cardiovascular (CV) mortality, especially in patients with diabetes, and hypertension, as well as those with a history of cardiovascular disease, but there are few studies on the prediction of all-cause mortality in community populations [15‐19]. In addition, in healthy people (UACR less than 30 mg/g), the urinary albumin to creatinine ratio as a risk indicator is controversial in predicting all-cause death in healthy people [20]. Their previous relationship and degree of association have not yet been specifically studied [2, 17, 21]. The few published studies on the urinary albumin to creatinine ratio and all-cause mortality are aimed at smaller populations, relying on retrospectively collected data, or the population is a special population with underlying diseases such as diabetes and hypertension [6‐9, 22‐24]. Therefore, in this study, we selected a relatively large cohort from the community population, followed up for 10 years, and studied the relationship between urinary albumin to creatinine ratio and all-cause mortality from multiple levels.

In this present study, after adjusting age, gender, height, weight, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, blood creatinine, blood uric acid, history of coronary heart disease, history of diabetes, history of drinking, taking group 1 as a reference, the hazard ratio of group 2 was 1.289 times that of group 1 (P = 0.048). The hazard ratio (HR value) of group 3 was 1.394 times that of group 1 (P = 0.037). The normal urine albumin-creatinine ratio recognized in our country is < 30 mg/g. Group 2 (10 mg/g < UACR< 30 mg/g) is a community population with a higher urine albumin-creatinine ratio within the normal range. Our results show that even if the urinary albumin and creatinine ratio is normal, if the UACR value is higher, it will still have a certain impact on all-cause death. This is the innovation of our research. Before our research, there have been reports at home and abroad that microalbuminuria (30 mg/g < UACR< 300 mg/g) can predict the risk of cardiovascular and all-cause death [22, 23, 29]. There is no doubt that UACR> 30 mg/g is proteinuria. Studies have divided proteinuria into microalbuminuria (30 mg/g < UACR< 300 mg/g) and massive proteinuria (UACR> 300 mg/g), and there is evidence that microalbuminuria can predict cardiovascular death and all-cause death [7, 30]. However, the research on the relationship between the normal high value of UACR (10 mg/g < UACR< 30 mg/g) and all-cause death is not detailed enough.

In 2020, another Chinese study showed that urinary albumin-creatinine ratio (UACR) within the normal range (less than 30 mg/g) would also increase the risk of cardiovascular disease. The optimal cut-off value of UACR for diagnosing diabetic left ventricular hypertrophy is 10 mg/g [27]. In our study to predict all-cause death, we used the same cut-off value, and the results were similar. In our study, the same cut-off value was used by us to predict all-cause death. The results are similar. The risk of all-cause death in the group with UACR< 10 mg/g is the lowest, and the results are statistically significant. The reason may be that kidney damage is a continuous process. In the process of the urinary albumin-creatinine ratio gradually increasing, the damage has already formed, which has a certain impact on the outcome of all-cause death. Therefore, the UACR range in the normal high value (10 mg/g < UACR< 30 mg/g) does not mean that it is healthy, and the damage has already occurred, which deserves more attention and research. A UK study in 2003 have shown that microalbuminuria (30 mg/g < UACR< 300 mg/g) can predict all-cause and cardiovascular disease mortality in men and women independently of other established cardiovascular risk factors. In all subjects Among them, compared with participants with normal albuminuria, individuals with microalbuminuria increased the risk of all-cause death by about 50%, and the risk of death from cardiovascular disease increased by about twice [17]. The results of our study are consistent with the study in the United Kingdom. There is a dose response relationship between the degree of proteinuria and the risk of death. However, the measurement unit range standard for the UACR used in the UK is different from that in China. In addition, unlike their research, our follow-up study time is longer, with an average of 9.87 years (18,407.3 person-years of follow-up). It makes our results more credible. Most importantly, the urine samples in their study were cryopreserved, and the measured urinary albumin to creatinine ratio may be inaccurate. Our data were all measured on-site during community surveys. A large-scale study in the Netherlands in 2002 pointed out that urine albumin excretion can predict cardiovascular and non-cardiovascular deaths in the general population [31]. The study included a population of 40,548 people with a large sample size. The results of the study showed that urinary albumin excretion increased twice, the relative risk of cardiovascular mortality was 1.29, and the relative risk of non-cardiovascular mortality was 1.12. The follow-up time of this study was only 3 years, so the mortality rate in the results was lower, and the relative risk of mortality was lower than the British study and our study.

In predicting the occurrence of cardiovascular disease, a 2005 study in the United States presented evidence that challenged the concept that UACR< 30 mg/g means normal [7]. This is the starting point for us to consider the relationship between normal UACR and all-cause death. The 2007 ESC-ESH Hypertension Management Guidelines stated: “In diabetic and non-diabetic hypertensive patients, microalbuminuria, even if it is below the currently considered threshold, has been proven to predict cardiovascular events.” [32] In the studies mentioned in the guidelines, the study population of Redon J et al. in 2002 and de Leeuw PW et al. in 2004 were mainly concentrated in the special hypertensive population [33, 34]. The study of Bigazzi R et al. in 1998, Jensen JS et al. in 2000, and Arnlöv J et al. in 2005 mainly explored the relationship between proteinuria and cardiovascular events [7, 16]. Although Gerstein HC et al. in 2001 and Jager A et al. in 1999 studied the relationship between proteinuria and death, their follow-up time was only 4.5 years and 5 years [6, 35].

Our study is the first time that groups within the range of normal urine albumin to creatinine ratio are used to predict all-cause mortality in community populations with 10-year follow-up. In terms of the pathological mechanism of the relationship between urine albumin-creatinine ratio and all-cause death, proteinuria may be an early sign of vascular endothelial dysfunction, which easily leads to the development of individual atherosclerosis [36]. Atherosclerosis and increased pulse pressure further damage vascular endothelial cells, forming a vicious circle, causing damage to the whole body. A study in Taiwan, China in 2018 also showed that there is a linear relationship between proteinuria and arterial stiffness in Chinese adults [37]. Arteriosclerosis is an important risk factor for cardiovascular and cerebrovascular diseases, which may be the pathological cause leading to all-cause death.

Compared with other studies, our study has a 10-year follow-up, a novel grouping standard, and enough community populations to prove the relationship between urine albumin-creatinine ratio and all-cause deaths in Chinese community populations. However, our study also has some shortcomings. First, most of our follow-ups are conducted through telephone consultation, and the degree of cooperation and response accuracy of the interviewed population may be biased. Secondly, in our study, 294 (13.7%) lost follow-up in 10 years. This tendency to attrition may have weakened our results. In the end, we had 1854 people included in the study, and the reduced sample size also reduced the robustness of our conclusions.

Previously, only in patients with hypertension and diabetes, doctors would pay attention to the patient’s urinary albumin to creatinine ratio, because many studies have shown that proteinuria is independently related to all-cause death. However, in the non-diabetic hypertensive population and the general community population, people pay insufficient attention to the ratio of urinary albumin to creatinine ratio. Through our research evidence, in clinical practice, doctors will pay more attention to the UACR indicator and have more choices in predicting the indicators and standards of death from all causes.