Burden of chronic kidney disease and its risk-attributable burden in 137 low-and middle-income countries, 1990–2019: results from the global burden of disease study 2019

Chronic kidney disease (CKD) is a global public health concern [1], and a risk factor for adverse outcomes in other diseases [2, 3]. CKD can be defined as a sustained damage of renal parenchyma that leads to chronic deterioration of renal function and may gradually progress to end-stage renal disease (ESRD) [4]. Without kidney replacement therapy (dialysis or kidney transplantation), ESRD remains uniformly fatal [4]. Studies have shown that kidneys are linked to Coronavirus disease 2019 (COVID-19) infection [5]. COVID-19 has been declared as a global pandemic by the World Health Organization [5], and the incidence of acute kidney injury (AKI) in patients infected with COVID-19 is around 3–15% [6, 7]. AKI can cause ESRD directly, and increase the risk of developing incident CKD and worsening of underlying CKD [8]. According to the Global Burden of Disease (GBD) study, disability-adjusted life-years (DALYs) for CKD has risen from 29th in 1990 to 18th in 2019 [9]. The global burden of CKD is rapidly increasing and is projected to become the 5th most common cause of years of life lost worldwide by 2040 [10, 11], with the burden of CKD increasing faster in low - and middle-income countries (LMICs) [12]. The burden of CKD is studied predominantly in high-income countries, with few studies in LMICs, and even fewer studies on attributable disease burden [2]. In this study, we aimed to analyzed and compared the trends of disease burden of CKD as well as its attributable disease burden in LMICs from 1990 to 2019, by using the data from the GBD 2019 study.

CKD-related YLDs, YLLs and DALYs increased to varying degrees in various income regions from 1990 to 2019 (Table 1). In 2019, LICs had the highest age-standardized DALY rate at 692.25 per 100,000 people (95%UI: 605.14 to 785.67) in 2019, followed by Lower MICs (684.72% (95%UI: 623.56 to 746.12)), Upper MICs (447.55% (95%UI: 405.38 to 493.01)), while HICs (292.93% (95%UI: (263.61 to 322.94)) had the lowest rate. The age-standardized YLL rate was much higher than the YLD rate at the global level and in various income regions. From 1990 to 2019, the age-standardized YLD rate all showed an upward trend in various income regions(P < 0.001), while YLL rate decreased in LICs (AAPC = − 0.7, 95%UI: − 0.7 to − 0.7), P < 0.001) and Upper MICs (AAPC = -0.3, 95%UI: − 0.4 to − 0.2, P < 0.001). The age-standardized DALY rate showed a 6.27% increment in Global (AAPC = 0.3, 95%UI: 0.2 to 0.4, P < 0.001), 12.75% increment in HICs (AAPC = 0.6, 95%UI: 0.5 to 0.7, P < 0.001), 3.72% increment in Lower MICs (AAPC = 0.2, 95%UI: 0.0 to 0.3, P < 0.05), whereas decreased 13.70% from 802.15 per 100,000 people (95%UI: 716.50 to 893.68) in 1990 to 692.25 per 100,000 people (95%UI: 605.14 to 785.67) in 2019 in LICs (AAPC = -0.5, 95%UI: − 0.6 to − 0.5, P < 0.001), and 2.25% reduction in Upper MICs (AAPC = 0.1, 95%UI: 0.0 to 0.1, P = 0.150) (Tables 2 and 3).

In terms of gender, age-standardized YLD rate was higher in females than in males, whereas age-standardized rates of YLL and DALY of CKD were all higher in males than in females in globally and LMICs (Table 2). Additionally, the YLD, YLL and DALY rates of CKD increased with age in various income regions, which were higher in aged≥70 years (Fig. 1).

Among all 137 LMICs, the highest age-standardized YLD, YLL and DALY rates of CKD in 2019 were seen in Mexico 296.40 per 100,000 people (95% UI: 206.99 to 394.46), Micronesia (Federated States of) 1895.00 per 100,000 people (95% UI: 1313.85 to 2478.01) and Micronesia (Federated States of) 2162.73 per 100,000 people (95% UI: 1584.61 to 2761.55), respectively. Whereas the lowest age-standardized YLD, YLL and DALY rates were seen in Ukraine 56.53 per 100,000 people (95% UI: 39.81 to 75.38), Belarus 69.79 per 100,000 people (95% UI: 55.13 to 89.34) and Belarus 128.92 per100 000 people (95% UI: 104.56 to 156.45), respectively. From 1990 to 2019, the growth of age-standardized DALY rate varied from − 46.83% in Mongolia to 182.92% in El Salvador. The variations in other CKD burden metrics (YLDs, YLLs and DALYs) by country in 2019 can be found in Fig. 2 and Additional file.

There was much consistency in the PAF of CKD-related age-standardized DALYs for these risk factors in various income regions. In 2019, CKD-related risk factors with the top three PAF were high systolic blood pressure, high fasting plasma glucose and high body-mass index, which all are metabolic risks (Fig. 3). The PAF of CKD-related age-standardized DALYs for risk factors in 2019 were presented in Table 4.

From 1990 to 2019, there were upward trends in the PAF contributions of high fasting plasma glucose, high systolic blood pressure, and high body-mass index to age-standardized CKD DALY in Global, LICs, Lower MICs and Upper MICs (Table 4). Notably, the greatest increase in the PAF was attributed to high body-mass in various income regions, especially in Lower MICs (111.83% (95% UI: 66.28 to 196.48); AAPC = 2.7, 95%UI: 2.7 to 2.8, P < 0.001), followed by Upper MICs (73.58% (95% UI: 48.84 to 113.01); AAPC = 1.9, 95%UI: 1.9 to 2.0, P < 0.001) and LICs (70.37% (95% UI: 40.14 to 133.32); AAPC = 2.0, 95%UI: 1.8 to 2.2, P < 0.001). In addition, the PAF of age-standardized DALYs for high systolic blood pressure increased the most in Upper MICs (16.94% (95% UI: 12.55 to 22.01); AAPC = 0.6, 95%UI: 0.6 to 0.7, P < 0.001), whereas decreased in HICs (4.82% (95% UI: − 6.9 to − 2.81); AAPC = -0.3, 95%UI: − 0.3 to − 0.2, P < 0.001) (Fig. 4).

Chronic kidney disease (CKD) is a significant global health problem and one of the top 20 causes of death worldwide. It is a serious threat to people’s life and health [26, 27]. CKD DALYs is calculated by adding the YLLs and the YLDs, we found that the age-standardized YLL rate is much higher than the YLD rate at the global level and in various income regions, suggesting that premature death is the main cause of CKD burden. The age-standardized YLD rates all showed an upward trend in LICs, Lower MICs and Upper MICs, the age-standardized YLL rates decreased in LICs and Upper MICs, suggesting that future CKD treatment strategies should focus on improving the quality of life of CKD patients.

Our results show disparities in CKD burden were also observed in geographical regions and countries. LICs had the highest age-standardized DALY rate, followed by Lower MICs, which may be related to different exposures to risk factors, weak health systems, inadequate health care funding, access to effective health care interventions [28]. These findings call for increased planning and interventions, and developed novel and more appropriate solutions to address the burden of CKD in these areas [10]. The greatest decline in age-standardized DALY rates of CKD were all seen in LICs. This may be related to the improvement of medical technology and effective health care reform. However, the age-standardized DALY rate showed an upward trend in Lower MICs. If these trends continue, the disparities that exist in CKD burden between Lower MICs and LICs and Upper MICs will be further increased.

Furthermore, our results showed that the CKD burden showed homogeneity by gender among global and LMICs: age-standardized YLD rate was higher in females than in males, whereas age-standardized rates of YLL and DALY of CKD were all higher in males than in females. The disease burden of CKD is mainly due to premature death in males and disability in females. This difference may be related to physiological differences, estrogen levels and lifestyle between males and females [29]. This gender difference should also be taken into account by policy makers when planning future strategies and implementing preventive and control measures. Additionally, the YLD, YLL and DALY rates of CKD increased with age, which were higher in aged ≥70 years in various income regions, speculated this change is largely related to the aging population and the increase of the elderly population. More attention should be paid to the older adults in the prevention and treatment of CKD.

In 2019, except for age and other non-modifiable risk factors, high systolic blood pressure, high fasting plasma glucose, and high body-mass index remained the major causes attributable age-standardized CKD DALY in LMICs. Unfortunately, there was no remarkable decline in PAF of them since 1990. This may be related to the increased incidence and prevalence of hypertension, dyslipidemia, overweight and obesity and sedentary lifestyle in the population over the past 30 years [30]. Therefore, more efforts are needed to create healthy lifestyles. Moreover, there were upward trends in the PAF of DALYs contributions of high systolic blood pressure, high fasting plasma glucose, and high body-mass in LMICs from 1990 to 2019. Perhaps most concerning are high body mass index, especially in Lower MICs, so it is imperative that effective measures be taken to curb the rise of obesity. There is clear evidence that interventions to manage hypertension and promote weight loss are associated with reduced risks of developing CKD and better outcomes among those living with CKD [31‐33]. Therefore, it is important to develop relevant strategies and targeted measures to prevent and manage hypertension, diabetes, and obesity.

GBD 2019 for the first time included high and low temperatures exposure as a global risk factor [13]. This study indicated that the PAF attributable to low temperature exceeded the PAF attributable to high temperature in various income regions in 2019, but the PAF attributable to low temperature showed a downward trend. Generally, infrastructure, such as the spread of heating, housing insulation, and the prevalence of air conditioning are likely explanations [34]. In 1990, high temperatures displayed a protective effect, leading to a negative high-attributable PAF in LMICs. In the context of global climate change, however, the PAF of high temperatures induced CKD is increasing in various income regions, requiring more attention and intervention. Meanwhile, this study shows that LICs and Lower MICs have larger PAF due to high temperature in 2019. This may be because, compared to HICs and Upper MICs, LICs and Lower MICs has higher poverty ratios, fewer medical resources and temperature-control facilities, and most LICs and Lower MICs are in Africa having high exposure to heat [35, 36]. Climate warming may be a potential factor in exacerbating the inter-country health and socio-economic inequalities [35, 37]. Therefore, it is necessary to consider the impact of high temperature and take measures to improve climate resilience, especially in LICs and Lower MICs.

In addition to the seven risk factors for CKD quantified by GBD 2019, there are other potential and nontraditional factors that are likely to affect future global burden of CKD, for example, food insecurity, heavy metals, air pollution, persistent organic pollutants, war and displaced refugee populations and so on [38‐41]. Further study of potential risk factors for CKD is also necessary in order to facilitate the development of targeted interventions. In addition, in the context of the pandemic of coronavirus disease 2019, although COVID-19 predominantly affects the respiratory system, it also involves multiple organs, such as the cardiovascular system, the liver as well as the kidneys [42]. Adverse renal manifestations, such as acute kidney injury (AKI), have been reported as a result of COVID-19. Studies have shown that AKI can directly cause ESRD, and increase the risk of developing incident CKD and worsening of underlying CKD [8]. CKD has not been sufficiently recognized due to its inconspicuous course during COVID-19 infection, especially in the early stage [42]. As the pandemic continues, more precise prevention policies may be needed to guide patients with chronic kidney disease. COVID-19 is a huge medical challenge that health care providers should recognize early and take appropriate action as soon as possible.

This study has evaluated the burden of CKD and its risk-attributable burden in 137 LMICs from 1990 to 2019. CKD burden remains high in various income regions, especially in LICs and Lower MICs. More effective and targeted preventive policies and interventions aimed at mitigating preventable CKD burden and addressing risk factors are urgently needed, particularly in geographies with high or increasing burden.