Global, regional, and national burden of kidney dysfunction from 1990 to 2019: a systematic analysis from the global burden of disease study 2019

Kidney dysfunction (KD) is defined as a state of decreased kidney function, caused by any conditions which is characterized by metabolite retention, imbalance of water, electrolyte and acid–base metabolism, and systemic symptoms over a period of time and ultimately leads to end stage renal disease (ESRD), dialysis or kidney transplantation [1, 2]. Over the past 40 years, KD has been classified into two distinct syndromes — acute kidney injury and chronic kidney disease (CKD) by nephrologists, both of which are delineated according to the serum creatinine concentration or the glomerular filtration rate (GFR) and important contributor to increased disability rate and mortality for non-communicable diseases. KD has also been identified as a significant risk factor for cardiovascular disease [3] and is a risk multiplier in patients with hypertension and diabetes [4, 5].

Nearly 10% of adults globally are being influenced by a variety of kidney diseases, however, firstly, as a “silent killer”, KD is often hardly detected at its early stage but can cause the lethal kidney failure in its late stage in both developed and developing countries [6, 7], besides, KD is diagnosed through biochemical testing to measure kidney function by estimating GFR and kidney damage through urinary albumin excretion which is not routine tested in daily life by adults, thus, both of above reasons together lead to a phenomenon that patients with KD are often not aware that they are suffering this disease [8]. Furthermore, due to the subdued economic development and health care system function in underdeveloped countries and territories, the prevalence, mortality and disability rate of KD is always underestimated universally [9].

The complexities of characterizing and quantifying the prevalence, mortality disability rate of KD varies across nations, however, previous researches mainly focused on the epidemiology and burden of CKD based on limited data [10], or finite regions [11],the prevalence and attributable burden of KD have not been documented well on a global scale yet, while the mortality and disability rate are significantly higher in KD than those in CKD according to GBD 2019 [12, 13]. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 systematically collected and integrated the risk data from 84 risk factors thus proving a chance to analyze the incidence, prevalence and attributable burden to KD in the global level [14, 15]. KD is defined as a risk factor in the GBD study which includes communicable, non-communicable and malignant diseases. Basing on the data of GBD 2019, the data of summary exposure value (SEV) and attributable burden of KD from 204 countries and territories were extracted for further analyzing the trends of the prevalence and attributable burden of KD from 1990 to 2019 at the global, regional and national levels. We also analysis their association with sex, age and sociodemographic development disparities to provide an up-to-date and comprehensive assessment about the health burden associated with KD and inform priorities for population-level interventions to alleviate the related burden.

In this study, we find that the global prevalence of KD has increased in the past thirty years, conversely most countries have decreasing trends of KD attributable burden. However, there exists large variations in the prevalence and attributable burden of KD across countries and territories, what’s noteworthy is that many countries, mainly location in low and low-middle SDI regions, had increasing burden from 1990 to 2019. Females are facing a higher SEV but a lower attributable burden compared with males and the gender gap is particularly in those older than 60 years old. The SDI was negatively correlated with SEV, ASMR and ASDR, indicating that low SDI regions had higher exposure levels and attributable burden of KD.

The increasing prevalence trend of KD in almost all regions and nations might be a result of the high-speed increasing population from 1990 to 2019 globally [12], however, the increase in the global age-standardized SEV for KD from 1990 to 2019 was not accompanied by corresponding increases in age-standardized mortality rate and disability rate, indicating high prevalence of non-fatal KD and the development and universality of renal replacement treatment of KD have achieved desirable outcomes, such as kidney transplantation, peritoneal dialysis and hemodialysis. In addition, we observed that the SEV, ASMR and ASDR for KD are all negatively correlated with SDI, suggesting that people in low-income countries are facing a higher possibility to KD than developed countries. Such correlation may be explained by lacking of health awareness, the low rate of routine medical examinations as well as the lack of medical resource and experienced nephrologists, we should note that not all patients with KD could receive renal replacement therapy, especially in developing countries, it is reported that 78% of patients with KD lived in low-income and middle-income countries, where resources, availability of dialysis, and kidney transplantations were unpleasant [19]. Although in nations with higher development level, the medical resource might be adequate enough to supply the need of renal treatment of KD, we should note that there is also a high age-standard SEV, ASMR and ASDR in high SDI nations such as America, Germany and Russia which leads to an increased burden of medical financial expenditure and financial working of these countries. Thus, there is an urgent need for all countries to pay more attention to KD and accelerate the process of prevention projection of KD in worldwide. Besides, in order to promoting the prevention of KD, the treatment of CKD also remains a big challenge in low-SDI countries, because the mortality and disability rate were also higher in these countries.

Developing status is a significant factor contributing to the age-standard SEV, ASMR and ASDR, compared regions with high and low SDI, high-middle, middle and low-middle SDI regions are facing a significantly larger SEV for KD, which might be explained by the limited number of populations in low SDI regions and the high medical care levels in high SDI regions, and nations with modest SDI had a higher increasing speed of population compared with low and high SDI regions. As for ASMR and ASDR, regions with higher SDI showed considerably lower value compared with those with lower SDI, which might because that people in higher-SDI regions have more opportunities to benefit from a well-developed healthcare system and policy priorities [17], besides, prolonged life expectancy and increased percentage of elderly people in high SDI regions may play a vital role, because that KD is an age-related condition which mainly affects the elderly [20]. Although all SDI regions exhibited an increasing trend of SEV for KD, the EAPC of SEV was negatively correlated with SDI, furthermore, the ASMR and ASDR fluctuated rather than reducing in lower SDI regions, both indicating the urgency of prevention and treatment of KD in all SDI regions especially in lower SDI regions. The findings at the national level were comparable to the regional level. From 2010 to 2019, there was a global decrease in ASMR and ASDR for KD. However, the situation of KD prevention and control varied from countries. Although most countries had decreased KD attributable burden, there saw upward trends in many countries, mainly in underdeveloped countries, such as Tajikistan, Uzbekistan, El Salvador, and Mexico. What’ more, it’s noteworthy that during the past thirty years, as the rate decreased globally, the absolute number of deaths and DALYs attributable to KD increased in almost all the countries, caused by the increasing population and the process of senescent universally, which will certainly upsurge the burden of medical and economy of the society, and greater challenges will come if efforts are not fully performed to deal with KD and CKD globally.

GBD 2019 defined IHD, CKD, stroke and gout as outcomes associated with KD, which might be able to explain why the mortality and disability of KD are significantly higher than those of CKD. IHD was once the most common outcome of ASMR for KD, however the ASMR and ASDR attributable to IHD has decreased in the past thirty years continuously. Reasons for such results are complicated, the invitation and update iterations of prevention medications permit the declining mortality rate and DALYs rate [21], in addition, the most important risk factor attributable to IHD was High systolic blood pressure, following by High LDL cholesterol and High fasting plasma glucose [22]. In addition, because of the same degree of progress in prevention mortality rate and DALYs rate of CKD as we have seen for many other important non-communicable diseases were not observed, a limited decline for CKD (2·8% change [95% UI − 1·5 to 6·3]) from 1990 to 2017 [10], resulting that CKD the ASMR and ASDR attributable to CKD continuously from 1990 to 2019 and had surpassed IHD to be the leading outcome of ASMR for KD and kept on the top outcome of ASDR for KD. The prevalence and attributable burden of stroke for KD was comparable with that of IHD.

Compared with females, despite lower level of exposure, males possessed higher ASMR and ASDR for KD, as evidenced by a 40% higher mortality rate and a 25% higher DALYs rate, however the gender difference are becoming more and more narrow in the past thirty years, which was in accordance with previously reported studies [23, 24]. The contribution of sex in different age groups was as similar as that of all ages however the gender difference of ASMR and ASDR held a different trend, which is particularly marked in females up to the age of 59 years, nevertheless this gender advantage is abruptly weakened while after 59 years, reflecting the remarkable protective effects of estrogen on the cardiovascular system prior to menopause [25]. People aged 70 + years make up the majority of IHD-related mortality while the majority of CKD-related mortality was mainly observed in those aged 60 + years old [10, 26], which was accordance with our results, we reported that the age-standard SEV, ASMR and ASDR were significantly higher in the elderly than the youngers, indicating the priority and urgency in preventing KD and KD-related outcomes, such as CKD, IHD and stroke, of elderly population.

Although the effect of KD on the burden of non-communicable diseases was not just limited in CKD and ESKD, it is reported that almost 7% total cardiovascular disease burden could be attributed to KD, it is reasonable to prevent severe adverse events and reduce mortality rate and DALYs rate due to KD in people at high risk and early population by routine examination of kidney function and standard treatment [27]. Previous studies has demonstrated that screening for CKD in both high-risk and early stage populations is a cost-effective method to delay the progression to CKD and ESKD [28, 29]. Dialysis plays a vital role in the treatment of CKD in the past decades, however, due to the limitation of health education and medical resource, poor adherence to dialysis treatment, the delay of treatment of primary disease, such as diabetes, hypertension and glomerulonephritis, fear of adverse effects and economic burden had resulted in insufficient treatment of KD, leading to the high ASMR and ASDR in worldwide especially in regions with low SDI [30, 31]. Peritoneal dialysis exists as the commonest measure of treatment of KD while peritonitis continues to be the major reason of mortality rate and DALYs rate in patients receiving peritoneal dialysis globally [32], however, as a preventable complication, there is plentiful evidence that the rate of peritonitis around the world have decreased considerably and the vast majority with KD would receive benefits from proper treatment of dialysis [33]. Public health also plays a vital role in decreasing the steadily rising rate of KD and CKD even ESKD by personal education of health, routine kidney function detection programmes, early administration of renal protective therapy and appropriate treatment of primary disease that affects kidney function [34]. In addition to dialysis and other renal replacement therapy, the access to laboratory diagnostic services, the awareness of KD treatment of health workers, medical consulting to patients and public health education on the harm of KD are all not sufficient enough universally especially in underdeveloped countries [35, 36], thus, more attention need to be paid to KD by policy-makers and more health education and supportive policies are in great urgency to alleviate the severe situation of KD.

To the best of our knowledge, this is the first study to explore the prevalence health burden of KD, stratified by age, sex and sociodemographic development thus providing a comprehensive description on it. However, there also exists some limitations that could not be ignored in our study. First of all, as suggested by KDIGO guidelines, repeat serum creatinine and urine ACR measurements over 3 months are required to confirm the chronicity of abnormalities [37], however, most involved studies reporting the prevalence of non-fatal CKD in GBD 2019 failed to provide such results and the nature of cross-sectional of these studies both result into a possible 25–50% overestimation of prevalence of CKD [38]. Hence, it is possible that an overestimation of KD prevalence was presented by the results of our analysis. The modeling of this study also leads to some internal limitations: Firstly, GBD 2019 failed to contain Mendelian randomisation studies in meta-regression, which might provide some unexpected new insights; Secondly, the data source effective size of KD on the outcome were mostly obtained from prospective observational studies and the authenticity and reliability of the estimates will be reduced by confounding factors in prospective observational studies. Besides, relative risks are often assumed as a function of exposure that are universal and consistent across regions and time periods, which will lead to inevitable bias [13].Due to the insufficient development in less-developed countries, high-quality primary data are sparsely acquired in these countries, nevertheless GBD must rely on statistical methods and predictive covariate values to generate final estimates. Furthermore, even when the data are available, the discrepancies of data in terms of quality, accuracy and comparability might also result into the deviations in the final estimated values [12, 13, 26].

Despite the fact that the high prevalence and attributable burden of KD, increasing prevalence however decreasing attributable burden had also been observed globally from 1990 to 2019. However, some countries, including many high-income countries, remains suffering from increasing trends of age-standard SEV, ASMR and ASDR for KD. In general, regions and nations of lower SDI are facing a higher prevalence and mortality and disability rate of KD. Compared with females, males have a lower prevalence however higher attributable burden of KD, the elderly are facing higher age-standard SEV, ASMR and ASDR for KD. With the progress of senescent, we will face more severe challenges of KD and this study provided an evidence-based guidance for policymakers to design and implement appropriate public health measures and interventions to alleviate the burden associated with KD.