沉浸式翻译

Abstract
抽象

Introduction: The burden of chronic kidney disease (CKD) varies across regions. This study provides comprehensive global, regional, and national estimates of total CKD and CKD due to four specific etiologies from 1990 to 2021. Methods: Data were extracted from the 2021 Global Burden of Disease study, categorized by sex, 20 age groups, 204 countries or territories, and 5 sociodemographic index (SDI) regions. Age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), age-standardized death rates (ASDRs), age-standardized disability-adjusted life year rates (ASDARs) and risk factor burdens for total CKD and four etiology-specific types were analyzed. Temporal trends were assessed using the estimated annual percentage change. Results: In 2021, CKD remained a significant global burden, with 673 million prevalent cases and 1.5 million deaths, primarily due to metabolic risk factors. The fastest growth in the ASPR and ASIR occurred in the middle-SDI regions, whereas the highest ASDR and ASDAR were observed in low-SDI regions. From 1990 to 2021, global ASIR increased for CKD caused by all four specific etiologies. The ASDR and ASDAR increased for CKD due to type 2 diabetes, glomerulonephritis, and hypertension, whereas there was a decline in CKD due to type 1 diabetes. Discussion: Between 1990 and 2021, CKD-related disability-adjusted life years (DALYs) and deaths increased substantially, with type 2 diabetes and hypertension accounting for half of the etiology-specific DALYs in 2021. Effective health policies are urgently needed to address CKD risk factors and implement prevention strategies.
引言：慢性肾脏病（CKD）的负担因地区而异。本研究提供了 1990 年至 2021 年四种特定病因导致的总 CKD 和 CKD 的全球、区域和国家综合估计值。方法：数据提取自 2021 年全球疾病负担研究，按性别、20 个年龄组、204 个国家或地区和 5 个社会人口指数（SDI）地区分类。分析了年龄标准化发病率（ASIR）、年龄标准化患病率（ASPR）、年龄标准化死亡率（ASDRs）、年龄标准化残疾调整生命年率（ASDARs）和总 CKD 和 4 种病因特异性类型的危险因素负担。使用估计的年度百分比变化评估时间趋势。结果： 2021 年，CKD 仍然是一个重大的全球负担，有 6.73 亿例流行病例和 1.500 万人死亡，主要是由于代谢风险因素。 ASPR 和 ASIR 的增长最快发生在中 SDI 区域，而最高的 ASDR 和 ASDAR 出现在低 SDI 区域。从 1990 年到 2021 年，由所有四种特定病因引起的 CKD 的全球 ASIR 都有所增加。 2 型糖尿病、肾小球肾炎和高血压引起的 CKD 的 ASDR 和 ASDAR 增加，而 1 型糖尿病引起的 CKD 下降。讨论：1990 年至 2021 年期间，CKD 相关的残疾调整生命年（DALY）和死亡人数大幅增加，其中 2 型糖尿病和高血压占 2021 年病因特异性 DALY 的一半。迫切需要有效的卫生政策来解决 CKD 风险因素并实施预防策略。

Introduction
介绍

As the global population ages, chronic kidney disease (CKD) has emerged as a critical public health crisis. In 2017, CKD affected approximately 9.1% of the global population, equating to 697.5 million cases, with India and China accounting for nearly one-third of the total cases (1). CKD compromises kidney function and leads to severe complications, such as cardiovascular diseases, anemia, bone disorders, metabolic acidosis, and hypertension, significantly impacting health and increasing mortality risks (2,3). Recent projections suggest that CKD-related deaths may double to 4 million by 2040 (1), underscoring the urgent need for effective preventive and interventional strategies.
随着全球人口老龄化，慢性肾病（CKD）已成为一场严重的公共卫生危机。2017 年，CKD 影响了全球约 9.1% 的人口，相当于 6.975 亿例，其中印度和中国占总病例的近三分之一（1）。CKD 损害肾功能并导致严重的并发症，如心血管疾病、贫血、骨骼疾病、代谢性酸中毒和高血压，严重影响健康并增加死亡风险（2,3）。最近的预测表明，到 2040 年，与 CKD 相关的死亡人数可能会翻一番，达到 400 万（1），这凸显了对有效预防和干预策略的迫切需求。

The global burden of CKD significantly varies due to differences in etiologies and risk factors. In developed countries, diabetes and hypertension are predominant causes, while glomerulonephritis and diseases of unknown origin are more prevalent in Asia and sub-Saharan Africa (4). Environmental factors, such as exposure to heavy metals and high levels of particulate matter of 2.5 µm, further elevate CKD risk (5). Despite its high prevalence and mortality, awareness of CKD remains critically low, with only 10% of at-risk individuals globally aware of their condition (6). This highlights the urgent need to improve public awareness and promote early screening initiatives.
由于病因和风险因素的差异，CKD 的全球负担差异很大。在发达国家，糖尿病和高血压是主要原因，而肾小球肾炎和不明原因的疾病在亚洲和撒哈拉以南非洲更为普遍（4）。环境因素，例如暴露于重金属和 2.5μm 的高水平颗粒物，进一步增加了 CKD 风险（5）。尽管 CKD 的患病率和死亡率很高，但对 CKD 的认识仍然极低，全球只有 10% 的高危人群知道自己的病情（6）。这凸显了提高公众意识和促进早期筛查举措的迫切需要。

Previous studies have largely focused on the general state of CKD or examined the effects of individual causes and risk factors in isolation, lacking integration and comparative insights. In this study, we aimed to address this gap by analyzing the prevalence of total CKD and CKD due to 4 specific etiologies and 15 risk factors, using data from the latest Global Burden of Disease (GBD) 2021 study (7–9). Additionally, we perform stratified analyses globally, regionally, and nationally, disaggregated by sex, age, and sociodemographic index (SDI), to inform more targeted prevention and control strategies.
以前的研究主要集中在 CKD 的一般状态上，或者孤立地检查个体原因和风险因素的影响，缺乏整合和比较见解。在这项研究中，我们旨在通过使用 2021 年最新全球疾病负担（GBD）研究（7-9）的数据分析由 4 种特定病因和 15 种风险因素引起的总 CKD 和 CKD 患病率来解决这一差距。此外，我们在全球范围内、区域和国家范围内进行分层分析，按性别、年龄和社会人口指数（SDI）分类，以制定更有针对性的预防和控制策略。

Materials and methods
材料和方法

Overview
概述

The GBD database, led by the Institute for Health Metrics and Evaluation at the University of Washington, represents the most extensive global health data resource to date. It provides detailed health data between 1990 and 2021 across 204 countries and territories worldwide. The database encompasses 371 diseases and injuries and 88 risk factors (8,9). Methodologies for estimating the burden of disease and risk factors have been described in the literature. This study was adherent to the Guidelines for Accurate and Transparent Health Estimates Reporting (10). Additionally, this research did not require ethical approval as we utilized available data from the GBD 2021 study. This invaluable resource is pivotal for deciphering and tackling the complexities of global health challenges. It serves as a critical tool for policymakers, researchers, and health professionals in their quest to improve well-being worldwide.
GBD 数据库由华盛顿大学健康指标与评估研究所领导，代表了迄今为止最广泛的全球健康数据资源。它提供了 1990 年至 2021 年间全球 204 个国家和地区的详细健康数据。该数据库包括 371 种疾病和损伤以及 88 个风险因素（8,9）。文献中描述了估计疾病负担和风险因素的方法。本研究遵守了准确和透明的健康估计报告指南（10）。此外，这项研究不需要伦理批准，因为我们利用了 GBD 2021 研究的可用数据。这一宝贵的资源对于破译和应对全球健康挑战的复杂性至关重要。它是政策制定者、研究人员和卫生专业人员寻求改善全球福祉的重要工具。

Data source
数据源

We gathered data from the Global Health Data Exchange query tool (http://ghdx.healthdata.org/gbd-results-tool), including annual incidence, prevalence, death, disability-adjusted life years (DALYs) cases, the age-standardized rates (ASRs) for incidence, prevalence, death, and DALYs of CKD, with 95% uncertainty intervals (UIs) according to country, region, etiology, age, and sex between 1990 and 2021. The data were meticulously organized by dividing ages into 20 cohorts, each spanning 5 years, to facilitate a detailed analysis across various life stages.
我们从全球健康数据交换查询工具（http://ghdx.healthdata.org/gbd-results-tool）收集了数据，包括 1990 年至 2021 年间根据国家、地区、病因、年龄调整生命年（DALY）病例、CKD 发病率、患病率、死亡和 DALY 的年龄标准化率（ASR），以及 95% 的不确定性区间（UI）。数据经过精心组织，将年龄分为 20 个队列，每个队列跨越 5 年，以便于对各个生命阶段进行详细分析。

SDI

The SDI is a composite measure derived from the geometric mean of lagged income per capita, average years of education, and fertility rate of female individuals aged <25 years. It serves as an indicator of socio-demographic development, with scores ranging from 0 to 1 points. Based on the SDI quintiles ranked from highest to lowest, the 204 countries and territories in the GBD were categorized into 5 tiers: high-, high-middle-, middle-, low-middle-, and low-SDI regions (11). This stratification allowed us to explore the relationship between the CKD burden and the socioeconomic development level.
SDI 是一个综合衡量标准，由年龄为 <25 岁女性个体的人均滞后收入、平均受教育年限和生育率的几何平均值得出。它是社会人口发展的指标，分数从 0 到 1 分不等。根据 SDI 五分位数从高到低排序，GBD 中的 204 个国家和地区分为 5 个等级：高、高中、中、低、中低和低 SDI 地区（11）。这种分层使我们能够探索 CKD 负担与社会经济发展水平之间的关系。

Estimates of CKD by cause
按病因划分的 CKD 估计值

We utilized two distinct datasets to model the etiological distribution of CKD (9). First, we used data from end-stage kidney disease (ESKD) registries to estimate the proportion of each etiology among patients undergoing renal replacement therapy. The results from all five etiology-specific models were adjusted such that the sum of the estimates for each cause was 100%. Then, these adjusted proportions were applied to DisMod-MR 2.1 model for end-stage renal disease dialysis and transplantation, to generate estimates for each etiology by location, year, age, and sex. The second dataset was obtained from the Geisinger Health System in Pennsylvania. It included age- and sex-specific etiological proportions for identifying patients with CKD stages 1–2, 3, 4, and 5 who were not receiving renal replacement therapy. For each patient with CKD, we used historical records of the International Classification of Diseases (ICD) codes to identify the primary nephropathy ICD codes. Patients with CKD without a history of primary kidney disease ICD code were classified as having CKD of unknown etiology (12).
我们利用两个不同的数据集来模拟 CKD 的病因分布（9）。首先，我们使用来自终末期肾病（ESKD）登记处的数据来估计接受肾脏替代治疗的患者每种病因的比例。对所有 5 个病因特异性模型的结果进行调整，使每个原因的估计值之和为 100%。然后，将这些调整后的比例应用于终末期肾病透析和移植的 DisMod-MR 2.1 模型，以按位置、年份、年龄和性别生成每种病因的估计值。第二个数据集来自宾夕法尼亚州的 Geisinger Health System。它包括年龄和性别特异性病因比例，用于识别未接受肾脏替代治疗的 CKD 1-2、3、4 和 5 期患者。对于每位 CKD 患者，我们使用国际疾病分类（ICD）代码的历史记录来识别原发性肾病 ICD 代码。无原发性肾病病史的 CKD 患者 ICD 代码被归类为病因不明的 CKD [12]。

Risk factors
风险因素

We assessed the impact of specific risk factors on the total CKD burden and utilized a data-driven approach to determine the risk factor–outcome pairs. For each risk-outcome pair, the relative risks of the given outcome as a function of exposure to the risk factor were estimated. For each risk factor, the overall exposure value representing the risk-weighted exposure prevalence and the theoretical minimum risk exposure level were estimated. The population-attributable fraction was calculated based on these estimates. The population-attributable fractions measured in DALYs were multiplied by the outcomes to determine the attributable years of life lived with a disability, years of life lost, and DALYs (9).
我们评估了特定风险因素对 CKD 总负担的影响，并利用数据驱动的方法来确定风险因素-结局对。对于每个风险-结果对，估计了给定结果的相对风险作为风险因素暴露的函数。对于每个风险因素，估计代表风险加权暴露率和理论最低风险暴露水平的总体暴露值。总体归因分数是根据这些估计值计算的。将 DALY 中测量的人口归因分数乘以结果，以确定残疾寿命的可归因年数、丧失的寿命年数和 DALY （9）。

Statistical analysis
统计分析

In this study, the ASRs based on the GBD global standard population were calculated. Prevalence, incidence, mortality, and DALYs were expressed as predicted values per 100,000 people, accompanied by 95% UI. The 95% UI was estimated using the 2.5th and 97.5th percentile values from 500 draws at each calculation stage (7). Furthermore, to assess the overall trends in the observed disease burden, we computed the estimated annual percentage change (EAPC) for the ASRs for incidence, prevalence, death, and DALYs, evaluating the epidemiological trends between 1990 and 2021. The natural logarithm of the rate is fitted to a linear regression model Y = α + βX + ε, where Y is equal to ln (rate), β indicates the positive or negative changing trends, X refers to calendar year, and ε is an error. Thus, the EAPC was calculated as 100×(eβ−1)100 \times (e^\beta - 1)100×(eβ−1), and its 95% confidence interval was derived from the linear regression model. If the EAPC and the lower bound of its 95% UI are both positive, the ASR is considered to exhibit an upward trend. Conversely, if the EAPC and the upper bound of its 95% UI are both negative, the ASR is classified as having a downward trend. If neither condition is met, the ASR is deemed stable (14). All analyses and graphical visualizations were conducted using R statistical computing software (version 3.5.2; R Software for Statistical Computing, Vienna, Austria).
本研究计算了基于 GBD 全球标准人群的 ASR。患病率、发病率、死亡率和 DALY 表示为每 100,000 人的预测值，并伴有 95% 的 UI。在每个计算阶段，使用 500 次抽奖的第 2.5 个和第 97.5 个百分位值估计 95% 的 UI （7）。此外，为了评估观察到的疾病负担的总体趋势，我们计算了发病率、患病率、死亡率和 DALY 的 ASR 的估计年百分比变化（EAPC），评估了 1990 年至 2021 年间的流行病学趋势。比率的自然对数拟合到线性回归模型 Y = α + βX + ε，其中 Y 等于 ln（比率），β表示正或负的变化趋势，X 表示日历年，ε 是错误。因此，EAPC 计算为 100×（eβ−1）100 \times （e^\beta - 1）100×（eβ−1），其 95% 置信区间来自线性回归模型。如果 EAPC 及其 95% UI 的下限均为正值，则 ASR 被视为呈上升趋势。相反，如果 EAPC 及其 95% UI 的上限均为负值，则 ASR 被归类为具有下降趋势。如果两个条件都不满足，则认为 ASR 稳定（14）。所有分析和图形可视化均使用 R 统计计算软件（版本 3.5.2;R Software for Statistical Computing， Vienna， Austria）。

Results
结果

Total CKD
总 CKD

In 2021, an estimated 673,722,703 individuals globally were affected by CKD (95% UI: 629,095,119–722,364,096), representing a significant rise from 350,962,674 cases in 1990 (95% UI: 326,973,785–376,155,723). Despite this increase, the age-standardized prevalence rate (ASPR) slightly declined from 8072.75 per 100,000 (95% UI: 7560.37–8634.07) in 1990 to 8,006 per 100,000 (95% UI: 7482.12–8575.62) in 2021, with an EAPC of 0.01 (95% UI: -0.02–0.04) (Table 1). Female individuals exhibited a higher ASPR for CKD than male individuals did, highlighting a sex-based disparity in prevalence by 2021. The ASPR increased with age, underscoring a positive correlation between advancing age and CKD risk (Figure 1A). Throughout the study period, the prevalence and ASR of CKD were consistently higher in female individuals than in male individuals (Supplementary Figure S1A, B). In 2021, middle- and low-SDI regions, particularly India, reported the highest ASPR, whereas high-SDI regions, notably Iceland, exhibited the lowest rates (Figure 2B, Supplementary Figure S1A). Older individuals formed a high-incidence group (Figure 3B). Among nations, the Republic of Korea demonstrated the greatest ASPR reduction between 1990 and 2021, whereas Guatemala showed the largest increase (Supplementary Table S1). All other SDI regions except the middle-SDI regions saw ASPR declines in 2021 compared to 1990 (Supplementary Table S2).
2021 年，全球估计有 673,722,703 人患有慢性肾病（95% UI：629,095,119–722,364,096），与 1990 年的 350,962,674 例（95% UI：326,973,785–376,155,723）相比大幅增加。尽管有所增加，但年龄标准化患病率（ASPR）从 1990 年的每 100,000 人 8072.75 人（95% UI：7560.37-8634.07）略微下降到 2021 年的每 100,000 人 8,006 人（95% UI：7482.12-8575.62），EAPC 为 0.01（95% UI：-0.02-0.04）（表 1）。女性个体的 CKD ASPR 高于男性个体，这凸显了到 2021 年基于性别的患病率差异。ASPR 随着年龄的增长而增加，强调了年龄增长与 CKD 风险之间的正相关（图 1A）。在整个研究期间，女性个体的 CKD 患病率和 ASR 始终高于男性个体（补充图 S1A、B）。2021 年，中低 SDI 地区，尤其是印度，报告的 ASPR 最高，而高 SDI 地区，尤其是冰岛，表现出最低的比率（图 2B，补充图 S1A）。老年人构成了高发病率组（图 3B）。在各国中，大韩民国在 1990 年至 2021 年期间的 ASPR 下降幅度最大，而危地马拉的增幅最大（补充表 S1）。与 1990 年相比，除 SDI 中间地区外，所有其他 SDI 地区在 2021 年的 ASPR 均有所下降（补充表 S2）。

The total number of CKD incident cases in 2021 was approximately 19,935,038 (95% UI: 18,702,793–21,170,794). The age-standardized incidence rate (ASIR) for CKD increased from 192.16 per 100,000 (95% UI: 178.69–207.34) in 1990 to 233.56 per 100,000 (95% UI: 220.02–247.24) in 2021, reflecting an EAPC of 0.64 (95% UI: 0.63–0.65) (Table 1). Similar to the ASPR, the ASIR demonstrated sex and age-related variations, with higher values among female individuals and a bell-shaped distribution across age groups (Figure 1A). Incident cases were predominantly concentrated among older adults. Although the ASIR decreased in some age groups compared with the past, rates increased for all other age groups relative to 1990, with the 15–19-year age group exhibiting the fastest growth except for those aged under 5 years (Supplementary Table S3). Among 204 countries and 5 SDI regions, China recorded the highest number of incident cases in 2021. In contrast, Saudi Arabia had the highest ASIR (Supplementary Table S5), and the high-SDI region displayed the highest ASIR, which was comparable to that of other SDI countries (Supplementary Figure S1A). Between 1990 and 2021, Estonia experienced the greatest annual percentage change in the ASIR, whereas Greece recorded the smallest change (Supplementary Table S5). Across all SDI regions, the ASIR in 2021 exceeded that in 1990, with the middle-SDI region showing the largest increase (Supplementary Table S2).
2021 年 CKD 事故病例总数约为 19,935,038 例（95% UI：18,702,793–21,170,794）。CKD 的年龄标准化发病率（ASIR）从 1990 年的 192.16/100,000（95% UI：178.69-207.34）增加到 2021 年的 233.56/100,000（95% UI：220.02-247.24），反映 EAPC 为 0.64（95% UI：0.63-0.65）（表 1）。与 ASPR 类似，ASIR 表现出与性别和年龄相关的差异，女性个体的值较高，年龄组呈钟形分布（图 1A）。事件病例主要集中在老年人中。尽管与过去相比，某些年龄组的 ASIR 有所下降，但相对于 1990 年，所有其他年龄组的 ASIR 都有所增加，其中 15-19 岁年龄组的增长最快，但 5 岁以下的年龄组除外（补充表 S3）。在 204 个国家和 5 个 SDI 地区中，中国在 2021 年记录的事件病例数最高。相比之下，沙特阿拉伯的 ASIR 最高（补充表 S5），而高 SDI 地区的 ASIR 最高，与其他 SDI 国家相当（补充图 S 1A）。1990 年至 2021 年期间，爱沙尼亚的 ASIR 年度百分比变化最大，而希腊的变化最小（补充表 S5）。在所有 SDI 地区中，2021 年的 ASIR 超过了 1990 年，其中 SDI 中部地区的增幅最大（补充表 S2）。

In 2021, CKD accounted for an estimated 1,527,639 deaths globally (95% UI: 1,389,377–1,638,914), marking an increase in the ASDR from 14.85 per 100,000 (95% UI: 13.64–16.38) in 1990 to 18.5 per 100,000 (95% UI: 16.72–19.85). This rise corresponds to an EAPC of 0.82 (95% UI: 0.76–0.89) (Table 1). Throughout the period, male individuals consistently exhibited higher ASDRs than female individuals did, with significant increases for both sexes compared to 1990 (Supplementary Figure S2A; Supplementary Table S6). Mortality rates were highest among the super-aged population, which also experienced the largest increases in the ASR (Figures 1A, B, 3C). In 2021, Mauritius had the highest ASDR, whereas Belarus reported the lowest (Supplementary Table S7). Low-SDI regions had the highest ASDR, whereas middle-SDI regions accounted for the largest absolute number of deaths (Supplementary Figure S1A, B). Compared to 1990, the United States experienced the fastest ASDR growth, whereas the greatest decrease was observed in Poland (Supplementary Table S7). Across all SDI regions, the ASDR for CKD significantly increased between 1990 and 2021 (Supplementary Table S2).
2021 年，全球估计有 1,527,639 例死亡（95% UI：1,389,377–1,638,914），这表明 ASDR 从 1990 年的每 100,000 人 14.85 例（95% UI：13.64-16.38）增加到每 100,000 人 18.5 例（95% UI：16.72-19.85）。这种上升对应于 0.82 的 EAPC（95% UI：0.76-0.89）（表 1）。在整个时期，男性个体的 ASDR 始终高于女性个体，与 1990 年相比，两性都显著增加（补充图 S2A; 补充表 S6）。超老年人口的死亡率最高，其中 ASR 的增幅也最大（图 1A、B、3C）。2021 年，毛里求斯的 ASDR 最高，而白俄罗斯报告的 ASDR 最低（补充表 S7）。低 SDI 区域的 ASDR 最高，而中 SDI 区域的绝对死亡人数最多（补充图 S1A、B）。与 1990 年相比，美国的 ASDR 增长最快，而波兰的下降幅度最大（补充表 S7）。在所有 SDI 地区，CKD 的 ASDR 在 1990 年至 2021 年期间显著增加（补充表 S2）。

The global burden of CKD in 2021 was further underscored by the DALYs, with an ASR of 529.62 per 100,000 (95% UI: 486.25–577.42). This represents a notable increase from 1990, with an annual percentage change of 0.37 (95% UI: 0.33–0.41) (Table 1). Male individuals had higher DALYs and ASDAR than female individuals did, with the sex disparity widening with age, particularly among individuals over 90 years (Figure 1A). The ASR of DALYs increased with age, and trends since 1990 reveal contrasting patterns: among individuals aged <35 years, younger age groups experienced steeper declines in the ASR, whereas for those aged >35 years, the ASR positively increased with age (Supplementary Table S3). Low-SDI regions exhibited the highest ASR of DALYs, whereas Finland reported the lowest rates. Middle-SDI regions, particularly India, bore the highest burden in terms of absolute DALYs attributed to CKD (Supplementary Table S8). Between 1990 and 2021, Lesotho and Ethiopia recorded the fastest increase in the ASR of DALYs among the 204 countries and 5 SDI regions, whereas Poland achieved the most significant decline (Supplementary Table S8). Within the SDI spectrum, reductions in the ASR of DALYs were noted in low- and upper-middle-SDI regions, whereas high-SDI regions experienced the largest increases (Supplementary Table S2).
残疾调整生命年进一步强调了 2021 年全球 CKD 负担，ASR 为 529.62/100,000（95% UI：486.25-577.42）。这比 1990 年有显著增长，年百分比变化为 0.37（95% UI：0.33-0.41）（表 1）。男性个体的 DALY 和 ASDAR 高于女性个体，性别差异随着年龄的增长而扩大，尤其是在 90 岁以上的个体中（图 1A）。DALY 的 ASR 随着年龄的增长而增加，自 1990 年以来的趋势揭示了截然不同的模式：在 <35 岁的个体中，较年轻的年龄组的 ASR 下降幅度更大，而对于 >35 岁的个体，ASR 随着年龄的增长而呈正上升（补充表 S 3）。低 SDI 地区的 DALY ASR 最高，而芬兰报告的 ASR 最低。中 SDI 地区，尤其是印度，在 CKD 归因于绝对 DALY 的负担方面承担了最高的负担（补充表 S8）。1990 年至 2021 年期间，莱索托和埃塞俄比亚在 204 个国家和 5 个 SDI 地区中记录了 DALY 的 ASR 增长最快，而波兰的下降幅度最大（补充表 S8）。在 SDI 光谱中，SDI 低和中上部区域观察到 DALY 的 ASR 降低，而高 SDI 区域的增长幅度最大（补充表 S2）。

CKD due to type 1 diabetes mellitus (T1DM)
1 型糖尿病（T1DM）引起的 CKD

In 2021, CKD due to T1DM affected an estimated 6,295,711 individuals worldwide (95% UI: 5,459,693–7,114,345), with 95,140 new cases (95% UI: 82,237–111,471) identified during the same year (Table 1). Across all age groups, female individuals exhibited a higher prevalence of CKD due to T1DM, compared with male individuals, with the most pronounced disparity observed in adolescents aged 20–34 years. Conversely, male individuals had a higher incidence of new cases. Notably, the incidence rate among infants and young children aged 0–5 years was significantly higher than in other age groups (Supplementary Figure 3A, B). Male patients also recorded higher ASDR and age-standardized DALY rates (ASDAR) than female patients did, particularly in the 45–64-year-old population (Supplementary Figure S3A). Among countries, Belarus reported the highest ASIR, Canada had the highest ASPR, and the United States recorded the highest ASDR and ASDAR (Supplementary Tables S10–S13). The middle-SDI regions led in ASR metrics for deaths and DALYs (Supplementary Table S14).
2021 年， 1 型糖尿病引起的 CKD 影响了全球估计 6,295,711 人（95% UI：5,459,693-7,114,345），同年发现了 95,140 例新病例（95% UI：82,237-111,471）（表 1）。在所有年龄组中，与男性个体相比，女性个体因 T1DM 导致的 CKD 患病率更高，其中在 20-34 岁的青少年中观察到的差异最为明显。相反，男性个体的新病例发生率更高。值得注意的是，0-5 岁婴幼儿的发病率显著高于其他年龄组（补充图 3A、B）。男性患者的 ASDR 和年龄标准化 DALY 率（ASDAR）也高于女性患者，尤其是在 45-64 岁的人群中（补充图 S 3A）。在国家/地区中，白俄罗斯报告的 ASIR 最高，加拿大的 ASPR 最高，美国的 ASDR 和 ASDAR 最高（补充表 S10-S 13）。中等 SDI 地区在死亡和 DALY 的 ASR 指标方面处于领先地位（补充表 S14）。

Globally, a comparison with 1990 data revealed an increase in both the ASIR and ASPR by 2021, whereas the ASDR and ASDAR showed a decline, albeit with some fluctuations around 2000. Between 1990 and 2021, the 0–5-year age group consistently exhibited high numbers of new cases, whereas other age groups showed relatively stable trends. For ASPR, a declining trend was observed exclusively in the population under 15 years of age (Supplementary Table S9). Over this period, male individuals consistently recorded higher ASIR, ASDR, and ASDAR than did female individuals. However, a downward trend in the ASDR and ASDAR among female individuals was observed during the survey period (Supplementary Table S15). By 2021, the United States experienced the most rapid escalation in the ASDR and ASDAR compared to 1990 (Supplementary Tables S12, S13). Across all SDI regions, both the ASIR and ASPR increased. Notably, only the high- and lower-middle-SDI regions displayed slight increases in the ASDR and ASDAR (Supplementary Table S14).
在全球范围内，与 1990 年数据的比较显示，到 2021 年，ASIR 和 ASPR 都有所增加，而 ASDR 和 ASDAR 则有所下降，尽管在 2000 年左右存在一些波动。在 1990 年至 2021 年期间，0-5 岁年龄组的新病例数量一直很高，而其他年龄组则表现出相对稳定的趋势。对于 ASPR，仅在 15 岁以下的人群中观察到下降趋势（补充表 S9）。在此期间，男性个体的 ASIR 、 ASDR 和 ASDAR 一直高于女性个体。然而，在调查期间，观察到 fe 男性个体的 ASDR 和 ASDAR 呈下降趋势（补充表 S15）。到 2021 年，与 1990 年相比，美国的 ASDR 和 ASDAR 升级速度最快（补充表 S12、S13）。在所有 SDI 区域中，ASIR 和 ASPR 都有所增加。值得注意的是，只有高中低 SDI 区域在 ASDR 和 ASDAR 中显示出轻微增加（补充表 S14）。

CKD due to type 2 diabetes mellitus (T2DM)
2 型糖尿病（T2DM）引起的 CKD

In 2021, CKD due to T2DM was the leading global cause of CKD, affecting approximately 107,559,955 individuals (95% UI: 99,170,797–115,994,732), with 2,012,025 new cases identified that year (95% UI: 1,857,800–2,154,288). This condition contributed to 477,273 deaths (95% UI: 401,541–565,951) and 11,278,935 DALYs (95% UI: 9,682,785–13,103,871) (Table 1). CKD due to T2DM was rare among individuals aged <15 years; however, elevated ASMR and ASDAR were observed in the older population (Supplementary Table S16). A consistent sex difference was observed, with male individuals exhibiting higher ASRs across incidence, prevalence, mortality, and DALYs compared with female individuals (Supplementary Table S17).
2021 年， 2 型糖尿病引起的 CKD 是全球 CKD 的主要原因，影响了大约 107,559,955 人（95% UI：99,170,797–115,994,732），当年发现了 2,012,025 例新病例（95% UI：1,857,800–2,154,288）。这种情况导致 477,273 人死亡（95% UI：401,541-565,951）和 11,278,935 名 DALY（95% UI：9,682,785-13,103,871）（表 1）。由 T2DM 引起的 CKD 在 <15 岁的个体中很少见;然而，在老年人群中观察到 ASMR 和 ASDAR 升高（补充表 S16）。观察到一致的性别差异，与女性个体相比，男性个体在发病率、患病率、死亡率和 DALY 方面表现出更高的 ASR （补充表 S17）。

Geographically, regions in North Africa and Western Asia reported higher ASIR and ASPR, whereas high-middle-SDI regions had the lowest ASDR and ASDAR (Supplementary Tables S18-S20). Conversely, high-SDI regions exhibited the highest ASIR, highlighting regional disparities (Supplementary Table S18).Between 1990 and 2021, CKD due to T2DM saw significant increases in the ASRs for incidence, mortality, and DALYs, with EAPCs of 0.61 (95% UI: 0.60–0.63), 1.17 (95% UI: 1.10–1.24), and 0.81 (95% UI: 0.75–0.87), respectively. However, the ASPR showed a modest decline of 0.17 (95% UI: 0.14–0.20) over the same period (Table 1). Across age groups, only individuals < 40 years exhibited declining trends in ASDAR and ADMR, while the most significant increase observed among individuals ≥ 80 years. For ASIR and ASPR, the burden decreased among individuals aged 15–34 years (Supplementary Table S16). Over the past three decades, males consistently demonstrated higher ASIR, ASPR, ASMR, and ASDAR values compared with females, along with a greater magnitude of changes in these indicators (Supplementary Table S17). The United States experienced the most rapid increases in the ASIR, ASDR, and ASDAR, reflecting its evolving burden of CKD due to T2DM (Supplementary Tables S19, S21, S22). High-SDI regions also demonstrated the steepest EAPCs for death and DALYs, a trend that aligns with global patterns observed in other regions (Supplementary Table S18).
从地理上看，北非和西亚地区报告的 ASIR 和 ASPR 较高，而中高 SDI 地区的 ASDR 和 ASDAR 最低（补充表 S18-S20）。相反，高 SDI 区域表现出最高的 ASIR，突出了区域差异（补充表 S18）。1990 年至 2021 年间，T2DM 引起的 CKD 的发病率、死亡率和 DALY 的 ASR 显着增加，EAPC 分别为 0.61（95% UI：0.60-0.63）、1.17（95% UI：1.10-1.24）和 0.81（95% UI：0.75-0.87）。然而，ASPR 在同一时期显示出 0.17 的小幅下降（95% UI：0.14-0.20）（表 1）。在各个年龄组中，只有个体 < 40 岁的 ASDAR 和 ADMR 呈下降趋势，其中在 80 ≥ 个体中观察到的增加最为显着。对于 ASIR 和 ASPR，15-34 岁个体的负担减轻（补充表 S16）。在过去的三十年中，与女性相比，男性始终表现出更高的 ASIR、ASPR、ASMR 和 ASDAR 值，以及这些指标的变化幅度更大（补充表 S17）。美国的 ASIR、ASDR 和 ASDAR 增长最快，反映了其因 T2DM 而造成的 CKD 负担不断演变（补充表 S19、S21、S22）。高 SDI 区域还显示出死亡和 DALY 最陡峭的 EAPC，这一趋势与在其他地区观察到的全球模式一致（补充表 S18）。

CKD due to glomerulonephritis
肾小球肾炎引起的 CKD

In 2021, CKD due to glomerulonephritis contributed to a significant health burden, with 6,959,758 DALYs (95% UI: 6,018,414–7,961,673) DALYs. The patient population totaled 10,735,809 (95% UI: 9,925,500–11,520,171) individuals, and the number of new patients was 357,288 (95% UI: 292,260–388,483) (Table 1). New cases were mainly concentrated in the 0–5-year age group and showed a degree of sex difference. Moreover, males exhibited higher overall burden indicators compared with females (Supplementary Tables S24). Across all age groups, with the ASMR and ASDAR being significantly elevated among older patients (Supplementary Tables S23). Nicaragua and Mauritius had the highest ASIR and ASPR, respectively, whereas the United Republic of Tanzania and El Salvador had the highest ASDR and ASDAR (Supplementary Tables S25–S28). Notably, regions with higher SDI, specifically the high- and high-to-middle-SDI regions, had lower ASDR and ASDAR. In contrast, the middle- and low-to-middle-SDI regions showed higher ASIR and ASPR (Supplementary Table S29).
2021 年，肾小球肾炎引起的 CKD 造成了重大的健康负担，有 6,959,758 个 DALY（95% UI：6,018,414–7,961,673）DALY。患者人数总计 10,735,809 人（95% UI：9,925,500–11,520,171）人，新患者人数为 357,288 人（95% UI：292,260–388,483）（表 1）。新病例主要集中在 0-5 岁年龄组，并表现出一定程度的性别差异。此外，与女性相比，男性表现出更高的总体负担指标（补充表 S24）。A 跨越所有年龄组，老年患者的 ASMR 和 ASDAR 显着升高（补充表 S23）。尼加拉瓜和毛里求斯的 ASIR 和 ASPR 最高，而坦桑尼亚联合共和国和萨尔瓦多的 ASDR 和 ASDAR 最高（补充表 S25-S28）。值得注意的是，具有较高 SDI 的区域，特别是高到中等 SDI 区域，具有较低的 ASDR 和 ASDAR。相比之下，中低到中等 SDI 区域显示出更高的 ASIR 和 ASPR（补充表 S29）。

During 1990–2021, a global uptick was observed in the ASR of incidence, prevalence, death, and DALYs for CKD due to glomerulonephritis, with EAPCs of 0.39 (95% UI: 0.36–0.43), 0.06 (95% UI: 0.04–0.08), 0.54 (95% UI: 0.50–0.59), and 0.28 (95% UI: 0.25–0.31), respectively (Table 1). The ASIR showed an upward trend across all age groups, with the 0–5-year age group leading in the ASIR despite a decline from the 1990 levels. A decrease was also observed in the ASPR, ASDR, and ASDAR for the 0–14-year age group (Supplementary Table S23). Males exhibited greater increases in ASIR and ASDAR compared with females, whereas the growth trends for ASPR and ASMR were lower in males than in females (Supplementary Table S24). Among the 204 GBD countries, South Korea achieved the most notable reduction in the ASDR and ASDAR, with EAPCs of -4.67 (95% UI: -5.43– -3.91) and -4.58 (95% UI: -5.21– -3.94), respectively (Supplementary Tables S27, S28). Compared with 1990, all SDI regions exhibited an increase in the ASIR, with the ASPR remaining relatively stable, and only the high-middle- and low-SDI regions reported a decrease in the ASDR and ASDAR (Supplementary Table S29).
在 1990-2021 年期间，观察到肾小球肾炎引起的 CKD 的发病率、患病率、死亡率和 DALY 的全球 ASR 呈上升趋势，EAPC 分别为 0.39（95% UI：0.36-0.43）、0.06（95% UI：0.04-0.08）、0.54（95% UI：0.50-0.59）和 0.28（95% UI：0.25-0.31）（表 1）。ASIR 在所有年龄组中均呈上升趋势，尽管与 1990 年的水平相比有所下降，但 0-5 岁年龄组在 ASIR 中处于领先地位。在 0-14 岁年龄组的 ASPR、ASDR 和 ASDAR 中也观察到下降（补充表 S23）。与女性相比，男性的 ASIR 和 ASDAR 增加幅度更大，而男性的 ASPR 和 ASMR 的增长趋势低于女性（补充表 S24）。在 204 个 GBD 国家中，韩国的 ASDR 和 ASDAR 下降最为显着，EAPC 分别为 -4.67（95% UI：-5.43– -3.91）和 -4.58（95% UI：-5.21– -3.94）（补充表 S27、S28）。与 1990 年相比，所有 SDI 区域的 ASIR 均表现出增加，ASPR 保持相对稳定，只有高、中、低 SDI 区域报告 ASDR 和 ASDAR 下降（补充表 S29）。

CKD due to hypertension
高血压引起的 CKD

In 2021, CKD due to hypertension emerged with 1,282,205 (95% UI: 1,195,230–1,366,296) new cases and 24,467,653 (95% UI: 22,861,634–26,230,869) individuals. This condition contributed to 10,850,728 (95% UI: 1,195,230–1,366,296) DALYs (Table 1). A notable sex difference that increased with age was observed in the ASIR and ASPR (Supplementary Figure S4A, B), and the ASDR and ASDAR were predominantly concentrated among older and super-aged patients (Supplementary Table S30). Mauritius exhibited the highest ASRs for both death and DALYs, whereas the United Arab Emirates and Nicaragua reported the highest ASIR and ASPR, respectively (Supplementary Tables S31–S34). A minimal variation was observed in the ASPR across all SDI regions, with the high-SDI region showing the highest ASIR and the low-SDI region bearing the highest ASDR and ASDAR (Supplementary Table S4).
2021 年，高血压引起的 CKD 出现 1,282,205 例（95% UI：1,195,230–1,366,296）新病例和 24,467,653 例（95% UI：22,861,634–26,230,869）个体。这种情况导致了 10,850,728 （95% UI： 1,195,230–1,366,296） DALYs（表 1）。在 ASR 和 ASPR 中观察到显着的性别差异，随着年龄的增长而增加（补充图 S4A、B），ASDR 和 ASDAR 主要集中在老年和超老年患者中（补充表 S30）。毛里求斯的死亡和 DALY 的 ASR 最高，而阿拉伯联合酋长国和尼加拉瓜分别报告了最高的 ASIR 和 ASPR（补充表 S31-S34）。在所有 SDI 区域的 ASPR 中观察到最小变化，高 SDI 区域显示最高的 ASR，而低 SDI 区域显示最高的 ASDR 和 ASDAR（补充表 S4）。

Compared to 1990, the ASPR for CKD due to hypertension saw a slight decline in 2021 by 0.16 (95% UI: 0.13–0.18). In contrast, the ASRs of incidence, death, and DALYs exhibited growth, with respective EAPCs of 0.66 (95% UI: 0.66–0.67), 0.97 (95% UI: 0.91–1.03), and 0.63 (95% UI: 0.58–0.67) (Table 1). Female individuals experienced greater changes in these metrics than male individuals did, among these metrics, only the ASPR exhibited a declining trend (Supplementary Table 35). In 2021, the ASIR increased across all age groups, compared with 1990, whereas a decrease was observed in the ASDR and ASDAR for individuals aged <35 years. Additionally, during the study period, the ASPR exhibited an upward trend among individuals aged 20–44 years (Supplementary Table S30). Among the 204 GBD countries, Ireland was the sole nation to record a decrease in the ASIR, with an EAPC of -0.09 (95% UI: -0.14– -0.04) (Supplementary Table S31). The United States experienced the most rapid increase in the ASDR (Supplementary Table S33). All other SDI regions witnessed an increase in the ASDR and ASDAR except for the low-SDI region, with the high-SDI region showing the most significant increase (Supplementary Table S4).
与 1990 年相比，2021 年高血压引起的 CKD 的 ASPR 略微下降了 0.16 （95% UI： 0.13–0.18）。相比之下，发病率、死亡和 DALY 的 ASR 表现出增长，EAPC 分别为 0.66 （95% UI： 0.66–0.67）、0.97 （95% UI： 0.91–1.03）和 0.63 （95% UI： 0.58–0.67）（表 1）。女性个体在这些指标上的变化比男性个体更大，在这些指标上，只有 ASPR 表现出下降趋势（补充表 35）。与 1990 年相比，2021 年所有年龄组的 ASIR 都有所增加，而 <35 岁个体的 ASDR 和 ASDAR 则有所下降。此外，在研究期间，ASPR 在 20-44 岁的个体中呈上升趋势（补充表 S30）。在 204 个 GBD 国家中，爱尔兰是唯一一个 ASIR 下降的国家，EAPC 为 -0.09（95% UI：-0.14– -0.04）（补充表 S31）。美国的 ASDR 增长最快（补充表 S33）。除低 SDI 区域外，所有其他 SDI 区域的 ASDR 和 ASDAR 均有所增加，其中高 SDI 区域显示最显着的增加（补充表 S4）。

Risk factors of total CKDs
总 CKD 的危险因素

Globally, CKD can be attributed to a constellation of 15 identifiable risk factors, which include three main categories: environmental factors, including high temperature, low temperature, and lead exposure; behavioral factors, such as a diet low in fruits, whole grains, and vegetables; diet high in red meat, sugar-sweetened beverages, sodium, and processed meats; and low physical and metabolic factors, including high fasting plasma glucose, high systolic blood pressure, high body mass index (BMI), and impaired kidney function. These factors collectively illuminate the complex interplay contributing to CKD, emphasizing the necessity of a holistic strategy for its prevention and treatment.
在全球范围内，CKD 可归因于一系列 15 个可识别的风险因素，其中包括三大类：环境因素，包括高温、低温和铅暴露;行为因素，例如水果、全谷物和蔬菜含量低的饮食;红肉含量高、含糖量高的饮食 ed 饮料、钠和加工肉类;以及低物理和代谢因素，包括高空腹血糖、高收缩压、高体重指数（BMI）和肾功能受损。这些因素共同阐明了导致 CKD 的复杂相互作用，强调了预防和治疗整体策略的必要性。

In 2021, the leading risk factors contributing to ASDAR in male patients with total CKD were impaired kidney function, high fasting plasma glucose levels, high systolic blood pressure, high BMI, and a low-fruit diet. For female individuals, the risk factors were largely aligned, with impaired kidney function and high fasting plasma glucose at the forefront, followed by high BMI, high systolic blood pressure, and a low-fruit diet. Notably, female individuals were more significantly affected by a high BMI than were male individuals (25.0% vs. 21.3%). These conclusions are also reflected in the ASDR (Supplementary Table S36). Across different SDI regions, the four most prevalent attributable risk factors for total CKD were consistent in both the ASDR and ASDAR: impaired kidney function, high fasting plasma glucose, high BMI, and high systolic blood pressure. Low-SDI regions were least affected by high BMI but were disproportionately impacted by impaired kidney function, indicating a stronger association with this risk factor in these areas (Supplementary Table S37).
2021 年，导致男性总 CKD 患者 ASDAR 的主要危险因素是肾功能受损、空腹血糖水平高、收缩压高、BMI 高和低水果饮食。对于女性个体，风险因素在很大程度上是一致的，肾功能受损和高空腹血糖最为突出，其次是高 BMI、高收缩压和低水果饮食。值得注意的是，女性个体受高 BMI 的影响比男性个体更显着（25.0% vs. 21.3%）。这些结论也反映在 ASDR 中（补充表 S36）。在不同的 SDI 区域中，导致 tal CKD 的 4 个最普遍的归因危险因素在 ASDR 和 ASDAR 中是一致的：肾功能受损、空腹血糖高、BMI 高和收缩压高。低 SDI 区域受高 BMI 的影响最小，但受肾功能受损的影响不成比例，表明这些区域与该风险因素的相关性更强（补充表 S37）。

During 1990–2021, the fastest increase in DALYs and deaths due to CKD was attributed to impaired kidney function, which has always been the leading cause of CKD. The subsequent risk factors, in descending order of impact, were high fasting plasma glucose levels, high BMI, and high systolic blood pressure. Other contributing risk factors showed relatively stable progression over the same period (Supplementary Tables S36, S38). Compared to the 1990 data, across all SDI regions, a noticeable decline was observed in the proportion of the ASDR and ASDAR due to impaired kidney function. Conversely, the influence of high fasting plasma glucose levels and high BMI increased. In more economically advanced areas, such as high- and high-middle-SDI regions, the proportion of risk attributed to high BMI remained above the global average. In contrast, in less economically developed low-SDI regions, the ASDR and ASDAR due to impaired kidney function and a diet low in fruits were notably higher than their global shares (Supplementary Tables S37, S39).
在 1990-2021 年期间，残疾调整生命年和 CKD 导致的死亡人数增长最快归因于肾功能受损，这一直是 CKD 的主要原因。随后的危险因素，按影响降序排列，是高空腹血糖水平、高 BMI 和高收缩压。其他影响风险因素在同一时期显示出相对稳定的进展（补充表 S36、S38）。与 1990 年的数据相比，在所有 SDI 区域中，由于肾功能受损，观察到 ASDR 和 ASDAR 的比例显着下降。相反，高空腹血糖水平和高 BMI 的影响增加。在经济较发达的地区，如 SDI 高和高中部地区，归因于高 BMI 的风险比例仍高于全球平均水平。相比之下，在经济欠发达的低 SDI 地区，由于肾功能受损和水果饮食不足而导致的 ASDR 和 ASDAR 明显高于其全球份额（补充表 S37、S39）。

4 Discussion
4 讨论

Globally, the number of individuals with CKD doubled during 1990–2021. The ASR of incidence, death, and DALYs for CKD has increased over the past three decades, indicating that CKD remains a serious global health issue that requires focused attention. Almost all countries experienced an increase in the ASIR between 1990 and 2021, and approximately 70% of them experienced an increase in the ASDARs. Demographically, older adults have the highest ASDARs, and male individuals have higher ASDAR than do female individuals, with the largest gap observed in CKD due to hypertension. Among all CKD cases, CKD due to T2DM has the highest ASDR and ASDAR and is growing at the fastest rate. Only CKD due to T1DM has shown a decrease in the ASDR and ASDAR since 1990. Among the four distinct CKD etiologies, those due to T1DM exhibited the most rapid increases in both the ASIR and ASPR. However, patients with CKD due to T2DM and hypertension experienced a decline in both the ASIR and ASPR. Moreover, the ASIR and ASPR for nephritis-related CKD remained relatively stable.
1990 年至 2021 年期间，全球 CKD 患者人数翻了一番。在过去三十年中，CKD 的发病率、死亡和 DALY 的 ASR 有所增加，这表明 CKD 仍然是一个严重的全球健康问题，需要引起关注。在 1990 年至 2021 年期间，几乎所有国家/地区的 ASIR 都有所增加，其中约 70% 的国家/地区的 ASDAR 有所增加。从人口统计学上看，老年人的 ASDAR 最高，男性个体的 ASDAR 高于女性，在高血压引起的 CKD 中观察到的差距最大。在所有 CKD 病例中，由 T2DM 引起的 CKD 具有最高的 ASDR 和 ASDAR，并且以最快的速度增长。自 1990 年以来，只有 1 型 DM 引起的 CKD 显示 ASDR 和 ASDAR 下降。在四种不同的 CKD 病因中，由 T1DM 引起的 ASIR 和 ASPR 均表现出最快速的增加。然而，由于 T2DM 和高血压引起的 CKD 患者的 ASIR 和 ASPR 均有所下降。此外，肾炎相关 CKD 的 ASIR 和 ASPR 保持相对稳定。

Risk factors for CKD include environmental influences, lifestyle choices, dietary habits, and metabolic conditions. Over the past 30 years, the ASDARs attributable to nearly all CKD risk factors have increased, indicating that efforts for the early diagnosis and prevention of CKD are insufficient. Among all the global risk factors in 2021, the DALYs caused by impaired kidney function were higher than those attributed to drug use, low physical activity, second-hand smoke, and diet (8). However, despite these risk factors, public health policymakers and the general population do not pay sufficient attention to kidney health. According to the latest research findings from the Global Atlas of Kidney Health, only 25% of the countries have developed national strategies for CKD, and 48% have identified CKD as a health priority (15). Additionally, the awareness rate of patients with early-stage CKD concerning their condition is extremely low (<5%), possibly because people mistakenly believe that CKD is merely a complication of diabetes or hypertension (16). Many patients seek medical help when they progress to ESKD. Once ESKD is achieved, life only can be sustained through renal replacement therapy or kidney transplantation. This transition imposes a heavy economic burden on patients and often triggers anxiety and fear of death due to uncertainty about prognosis. In response, many patients turn to spiritual beliefs, attempting to heal their illness through religion and attain inner peace. Studies have shown that for patients with ESKD, particularly those with lower socioeconomic status, seeking meaning in life through spirituality or religious connections can enhance psychological adaptation to severe illness (17). It is estimated that approximately 5.4 million patients will require renal replacement therapy by 2030 (18).Approximately 2–3.7 million people die prematurely due to the unavailability of this life-saving but expensive treatment (19). Therefore, effectively reducing the high incidence and mortality rates associated with CKD depends on early identification of CKD risk factors, timely diagnosis, and implementation of effective intervention measures to delay or prevent further deterioration of kidney function (20). In addition to conventional modern medical treatments, many countries—particularly China, South Korea, and Japan—are increasingly utilizing traditional herbal medicines or bioactive extracts in clinical practice to alleviate discomfort caused by toxin accumulation in patients with ESKD (21).
CKD 的危险因素包括环境影响、生活方式选择、饮食习惯和代谢状况。在过去的 30 年中，几乎所有 CKD 风险因素的 ASDAR 都有所增加，这表明 CKD 的早期诊断和预防努力不足。在 2021 年的所有全球风险因素中，由肾功能受损引起的 DALY 高于归因于药物使用、低体力活动、二手烟和饮食的 DALY （8）。然而，尽管存在这些风险因素，公共卫生政策制定者和普通民众并未对肾脏健康给予足够的重视。根据全球肾脏健康地图集的最新研究结果，只有 25% 的国家制定了 CKD 国家战略，48% 的国家将 CKD 确定为健康重点（15）。此外，早期 CKD 患者对其病情的知晓率极低（<5%），这可能是因为人们错误地认为 CKD 只是糖尿病或高血压的并发症（16）。许多患者在发展为 ESKD 时寻求医疗帮助。一旦达到 ESKD，只有通过肾脏替代疗法或肾移植才能维持生命。这种转变给患者带来了沉重的经济负担，并且由于预后的不确定性，经常引发焦虑和对死亡的恐惧。作为回应，任何患者都转向精神信仰，试图通过宗教治愈他们的疾病并获得内心的平静。研究表明，对于 ESKD 患者，尤其是那些社会经济地位较低的患者，通过灵性或宗教联系寻求生活意义可以增强对严重疾病的心理适应（17）。据估计，到 2030 年，约有 540 万患者将需要肾脏替代疗法（1， 8）。大约 2-3 个。由于无法获得这种挽救生命但昂贵的治疗方法，700 万人过早死亡（19）。因此，有效降低与 CKD 相关的高发病率和死亡率取决于早期识别 CKD 危险因素、及时诊断和实施有效的干预措施以延缓或防止肾功能的进一步恶化（20）。除了传统的现代医学治疗外，许多国家（尤其是中国、韩国和日本）在临床实践中越来越多地使用传统草药或生物活性提取物来缓解 ESKD 患者因毒素积累而引起的不适（21）。

Metabolic risk factors, including im
代谢危险因素，包括 impaired kidney function, high systolic blood pressure, high fasting
肾功能配对、高收缩压、高空腹plasma
血浆 glucose levels, and high BMI, have consistently been the primary causes of CKD between 1990 and 2021. This is partly attributed to sociodemographic ageing and lifestyle changes. Globally, CKD and kidney function impairment remain a heavy burden. When examining the correlation between the ASDR and ASDAR of CKD caused by kidney injury and SDI, a negative correlation was revealed between these metrics. Fortunately, the proportions of the ASDR and ASDAR attributable to kidney function impairment have decreased. This indicates the progress in healthcare services, preventive strategies, and disease management. High systolic blood pressure, the second-largest third-level contributor to the risk burden in 2021, along with high fasting
1990 年至 2021 年期间，血糖水平和高 BMI 一直是 CKD 的主要原因。这部分归因于社会人口老龄化和生活方式的改变。在全球范围内，CKD 和肾功能损害仍然是一个沉重的负担。在检查肾损伤引起的 CKD 与 SDI 的 ASDR 和 ASDAR 之间的相关性时，这些指标之间存在负相关。幸运的是，可归因于肾功能损害的 ASDR 和 ASDAR 比例已经下降。这表明医疗保健服务、预防策略和疾病管理方面的进展。高收缩压是 2021 年风险负担的第二大第三大因素，与高空腹并列plasma
血浆 glucose and high BMI, revealed a trend of increasing health burdens due to major metabolic risk factors (8). Over the past 30 years, high systolic blood pressure has consistently been a primary risk factor for the onset and progression of CKD (22). The burden of CKD attributed to high systolic blood pressure varies by region, with middle-high SDI areas having the lowest ASDAR and the smallest increase. In contrast, middle-low-SDI regions bear the heaviest ASDAR and experience rapid growth. This may be related to different dietary structures, preventive health policies, medical standards, and blood pressure management across regions. Elevated blood pressure is associated with kidney function progression, and reports have suggested that enhanced blood pressure control may lower the estimated glomerular filtration rate (eGFR) and increase the tubular biomarker levels (23). However, globally, only 23% of
葡萄糖和高 BMI 揭示了由于主要代谢风险因素而增加健康负担的趋势（8）。在过去的 30 年里，高收缩压一直是 CKD 发生和进展的主要危险因素（22）。归因于高收缩压的 CKD 负担因地区而异，中高 SDI 区域的 ASDAR 最低且增加最小。相比之下，中低 SDI 区域承载最重的 ASDAR 并经历快速增长。这可能与不同地区的饮食结构、预防性健康政策、医疗标准和血压管理有关。血压升高与肾功能进展有关，报告表明，加强血压控制可能会降低估计肾小球滤过率（eGFR）并增加肾小管生物标志物水平（23）。然而，在全球范围内，只有 23% 的female individuals
女性个体and 18% of
和 18%male individuals
男性个体have well-controlled blood pressure (24). Therefore,
血压控制良好（24）。因此 maintaining optimal blood pressure control is crucial for delaying kidney function decline and preventing complications in patients with CKD
保持最佳血压控制对于延缓 CKD 患者肾功能下降和预防并发症至关重要 (25). A high fasting
（25）. 高度禁食plasma
血浆 glucose level is a recognized risk factor for CKD. It progresses gradually into diabetic nephropathy and leads to impaired kidney function (26). This was confirmed in a previous
血糖水平是公认的 CKD 危险因素。它逐渐发展为糖尿病肾病，并导致肾功能受损（26）。这在之前的in vitro
体外 study, where high fasting
书房，其中高禁食plasma
血浆 glucose levels impaired mitochondrial respiration in mesangial and tubular cells (27). Owing to population ageing, rapid urbanization, and industrialization, unhealthy lifestyles are becoming more prevalent, including increased consumption of high-sugar and high-fat diets, reduced physical activity, and rising obesity rates, leading to a global increase in average fasting
葡萄糖水平损害系膜细胞和肾小管细胞的线粒体呼吸（27）。由于人口老龄化、快速城市化和工业化，不健康的生活方式变得越来越普遍，包括增加高糖和高脂肪饮食的消费、减少身体活动和肥胖率上升，导致全球平均禁食率增加plasma
血浆 glucose levels (28). Notably, middle-low-SDI regions have gradually replaced high-SDI regions by contributing to the highest ASDAR since 1990, whereas middle-low-SDI regions have become the areas with the lowest ASDAR through effective control. This highlights the need to recognize that the association between high fasting
葡萄糖水平（28）。值得注意的是，自 1990 年以来，中低 SDI 区域逐渐取代高 SDI 区域，贡献了最高的 ASDAR，而中低 SDI 区域通过有效控制成为 ASDAR 最低的区域。这突出表明需要认识到高禁食之间的关联plasma
血浆 glucose-induced CKD burden and the SDI should not be oversimplified or linearized (29). The burden of CKD owing to high BMI significantly increased in nearly all regions worldwide, with the ASDR and ASDARs positively correlated with the SDI in 2021. High and medium-high-SDI regions have high
葡萄糖诱导的 CKD 负荷和 SDI 不应过度简化或线性化（29）。全球几乎所有地区都因高 BMI 而导致的 CKD 负担显著增加，2021 年 ASDR 和 ASDAR 与 SDI 呈正相关。高和中高 SDI 区域具有较高的er obesity rates than low- and medium-low-SDI regions, potentially making relevant interventions more valuable in these areas (30). Simultaneously, economic development in low- and middle-income countries has prompted significant lifestyle changes, characterized by increased sedentary behavior and the adoption of Westernized dietary habits.
ER 肥胖率高于低和中低 SDI 区域，这可能使相关干预措施在这些领域更有价值（30）。与此同时，低收入和中等收入国家的经济发展促使人们的生活方式发生了重大变化，其特点是久坐行为的增加和采用西化的饮食习惯。These changes
这些更改 may
五月increase
增加exposure to
暴露于risk factors
风险因素 and
和exacerbate the global burden of CKD.
加剧了 CKD 的全球负担。Contributing factors
成因include obesity, physical inactivity, and unhealthy diets
包括肥胖、缺乏身体活动和不健康的饮食—particularly those deficient in fruits and vegetables
尤其是那些缺乏水果和蔬菜的人(31,32). Notably, many fruits and vegetables contain natural antioxidants,
值得注意的是，许多水果和蔬菜都含有天然抗氧化剂，which have been shown in
已在 multiple studies
多项研究to reduce
减少cellular oxidative damage, offering diverse health benefits
细胞氧化损伤，提供多种健康益处relevant to disease
与疾病相关prevention and treatment
预防和治疗 (33).

Geographically, significant differences are observed in the contribution of the CKD burden across regions and countries. The gap in the ASDAR between low-, medium-low-, and medium-SDI regions and high- and medium-high-SDI regions reflects inequalities in access to preventive care and renal replacement therapy due to varying levels of socio-economic development. Additionally, a sizeable amount of research data primarily originates from developed countries, which may be partly attributed to the limited access to comprehensive CKD testing in regions where medical resources and advanced laboratory diagnostic services are constrained, leading to incomplete diagnosis and data reporting of CKD in low- and middle-SDI regions (34). Therefore, CKD should receive greater attention in global health policy decisions, particularly in the low- and medium-SDI regions. Early screening and implementation of kidney-preserving treatments, including effective control of CKD risk factors (such as high systolic blood pressure and high fasting plasma glucose), can reduce the incidence of ESKD (35). Simultaneously, we should recognize that implementing screening and intervention measures in these countries may pose even greater challenges to their existing overburdened health resources.
从地理上看，不同地区和国家/地区的 CKD 负担贡献存在显著差异。低、中低和中 SDI 区域与高和中高 SDI 区域之间的 ASDAR 差距反映了由于社会经济发展水平不同，在获得预防保健和肾脏替代疗法方面存在的不平等。此外，大量研究数据主要来自发达国家，这可能部分归因于在医疗资源和先进实验室诊断服务受限的地区获得综合 CKD 检测的机会有限，导致低和中等 SDI 地区的 CKD 诊断和数据报告不完整（34）。因此，CKD 在全球卫生政策决策中应得到更多关注，尤其是在低和 SDI 中地区。早期筛查和实施保肾治疗，包括有效控制 CKD 危险因素（如高收缩压和高空腹血糖），可以降低 ESKD 的发生率（3， 5）。同时，我们应该认识到，在这些国家实施筛查和干预措施可能会对其现有的不堪重负的卫生资源造成更大的挑战。

Over the past 30 years, the ASIR of total CKD has consistently been higher in female individuals than in male individuals; however, the ASDAR has been lower in female individuals. However, among the four specific causes of CKD, the ASIR in male individuals exceeded that in female individuals, suggesting that, besides the known specific causes, female individuals are also affected by other unspecified factors, leading to a higher ASIR. Therefore, more screenings are required for female individuals. The simplest explanation is that female individuals generally live longer, and kidney function naturally declines with age, thus increasing the incidence of CKD (36). This sex difference highlights the role of sex hormones, such as the protective effect of premenopausal sex hormones. A longer reproductive period is associated with a lower risk of CKD, indicating that the cumulative protective effect of estrogen becomes apparent over time (37,38). Male individuals have higher ASDR and ASDAR, indicating that they may suffer more long-term health losses due to CKD. CKD poses a higher fatal risk to male individuals, meaning that they progress to ESKD faster. This may be related to androgenic effects, NO metabolism, and excessive oxidative stress (39). Additionally, previous studies have shown that the lifetime risk of kidney replacement therapy is higher in male individuals than that in female individuals, while the usage rate of kidney replacement therapy is also higher in male individuals. This indirectly supports the observation that male individuals with CKD tend to progress more rapidly than female individuals (40). These findings suggest that female patients are more likely to opt for conservative treatment approaches, potentially due to slower progression of CKD or other factors influencing treatment choices. Overall, the observed sex disparity in CKD incidence fundamentally represents the interplay of multiple biological mechanisms—specifically sex hormone regulation and aging processes—with clinical phenotypes including disease progression rate and treatment requirements, rather than being attributable to a singular risk factor.
在过去的 30 年中，女性个体总 CKD 的 ASIR 一直高于男性个体;然而，女性个体的 ASDAR 一直较低。然而，在 CKD 的 4 个具体原因中，男性个体的 ASIR 超过了女性个体，这表明，除了已知的特定原因外，女性个体还受到其他未明确因素的影响，导致 ASIR 更高。因此，需要对女性个体进行更多筛查。最简单的解释是女性个体通常寿命更长，肾功能会随着年龄的增长而自然下降，从而增加 CKD 的发病率（36）。这种性别差异突出了性激素的作用，例如绝经前性激素的保护作用。较长的生育期与较低的 CKD 风险相关，表明雌激素的累积保护作用随着时间的推移而变得明显（3 7,38）。男性个体的 ASDR 和 ASDAR 较高，表明他们可能会因 CKD 而遭受更多的长期健康损失。CKD 对男性个体构成更高的致命风险，这意味着他们更快地发展为 ESKD。这可能与雄激素作用、NO 代谢和过度氧化应激有关（3， 9）。此外，既往研究表明，男性个体接受肾脏替代疗法的终生风险高于女性个体，而男性个体接受肾脏替代疗法的使用率也较高。他间接支持男性 CKD 个体往往比女性个体进展更快的观察结果（40）。这些发现表明，女性患者更有可能选择保守治疗方法，这可能是由于 CKD 进展缓慢或其他影响治疗选择的因素。总体而言，他观察到 CKD 发病率的性别差异从根本上代表了多种生物学机制（特别是性激素调节和衰老过程）与临床表型（包括疾病进展速度和治疗要求）的相互作用，而不是归因于单一的风险因素。

In addition to exhibiting sex dimorphism, the CKD burden is most prominent in older adults. Regardless of total CKD or the four specific causes of CKD, the ASIR and ASDARs in older adults were higher than those in other age groups. The ASDARs peaked in 2010 and have remained stable since then, possibly related to the World Health Organization's implementation of the global strategy action plan for the prevention and control of non-communicable diseases (NCDs) around 2010 (41). Older adults have a higher prevalence of hypertension and diabetes, making them more susceptible to kidney damage. However, natural ageing also leads to structural changes in the kidneys, resulting in decreased eGFR. CKD and ageing influence each other; the prevalence of CKD is positively correlated with age, and CKD accelerates biological ageing through multiple mechanisms (42). In a longitudinal study of healthy populations, the urinary creatinine clearance rate decreased at approximately 0.75 mL/min per year (43). Therefore, according to the single standard definition of eGFR <60 mL/min/1.73 m², approximately half of the individuals aged >70 years may be diagnosed with CKD; however, it might just be physiological ageing rather than a disease (44). With age, reduced muscle mass can lead to a decrease in serum creatinine levels, which may mask a true decline in kidney function (45). Thus, the eGFR standard for diagnosing CKD should be modified based on age to account for the physiological decline in eGFR due to healthy ageing, thereby avoiding the overdiagnosis of CKD in older individuals (46).
除了表现出性别二态性外，CKD 负担在老年人中最为突出。无论总 CKD 或 CKD 的 4 个具体原因如何，老年人的 ASIR 和 ASDARs 都高于其他年龄组。ASDAR 在 2010 年达到顶峰，此后一直保持稳定，这可能与世界卫生组织在 2010 年左右实施预防和控制非传染性疾病（NCD）全球战略行动计划有关（4， 1）。老年人患高血压和糖尿病的患病率更高，使他们更容易受到肾脏损伤。然而，自然衰老也会导致肾脏的结构变化，从而导致 eGFR 降低。CKD 和衰老相互影响;CKD 的患病率与年龄呈正相关，CKD 通过多种机制加速生物衰老（4， 2）。在一项针对健康人群的纵向研究中，尿肌酐清除率下降了大约 0。每年 75 mL/min （43）。因此，根据 eGFR <60 mL/min/1 的单一标准定义。73 m²，大约一半的 >70 岁个体可能被诊断患有 CKD;然而，它可能只是生理衰老，而不是一种疾病（44）。随着年龄的增长，肌肉质量减少会导致血清肌酐水平降低，这可能掩盖了肾功能的真正下降（4， 5）。因此，诊断 CKD 的 eGFR 标准应根据年龄进行修改，以考虑健康老龄化导致 eGFR 的生理性下降，从而避免老年人对 CKD 的过度诊断（4， 6）。

NCDs have replaced infectious diseases as the most common causes of global morbidity and premature death (47–49). In response, the United Nations set a sustainable development goal to reduce premature mortality from NCDs by one-third by 2030. The impact of CKD on the NCD burden extends beyond ESKD or CKD itself; it often acts as a key risk factor for major NCDs (cardiovascular disease, hypertension, and diabetes), necessitating proactive prevention and treatment of this disease. The global ASDR for cardiovascular diseases, cancer, and chronic respiratory diseases decreased by 34.3%, 21.4%, and 36.7%, respectively, between 1990 and 2021. However, the ASDR for CKD has increased by 24.6% (50). Ample evidence supports the idea that the early diagnosis and timely treatment of CKD are key components of comprehensive national NCD strategies (51). Implementing cost-effective interventions for individuals aged ≥55 years, including those with a history of diabetes, hypertension, cardiovascular disease, and a family history of kidney disease, will reduce the risk of ESKD and cardiovascular diseases, thereby significantly alleviating the burden of CKD. Low-income, middle-income, and high-risk populations are primary beneficiaries.
非传染性疾病已取代传染病成为全球发病率和过早死亡的最常见原因（4， 7–4， 9）。作为回应，联合国设定了一项可持续发展目标，即到 2030 年将非传染性疾病导致的过早死亡率降低三分之一。CKD 对 NCD 负担的影响超出了 ESKD 或 CKD 本身;它通常是主要非传染性疾病（心血管疾病、高血压和糖尿病）的关键危险因素，需要积极预防和治疗这种疾病。1990 年至 2021 年期间，全球心血管疾病、癌症和慢性呼吸系统疾病的 ASDR 分别下降了 34.3%、21.4% 和 36.7%。然而，CKD 的 ASDR 增加了 24。6% （50）。大量证据支持这样的观点，即 CKD 的早期诊断和及时治疗是国家 NCD 综合战略的关键组成部分（5， 1）。对 ≥ 55 岁的个体实施具有成本效益的干预措施，包括有糖尿病、高血压、心血管疾病和肾病家族史的人，将降低 ESKD 和心血管疾病的风险，从而显着减轻 CKD 的负担。低收入、中等收入和高危人群是主要受益者。

However, this study has some limitations. First, the GBD relies on reporting data from different countries and regions, which may vary in quality and completeness. In areas where data collection is incomplete or inaccurate, GBD estimates may be biased. Moreover, GBD data typically exhibit a time lag, meaning that the latest data may not reflect current health conditions and may fail to capture the impact of sudden public health events on the disease burden. Second, different diagnostic criteria and methods may have been used across countries and periods, which can affect regional and temporal comparisons. Furthermore, changes in disease coding and classification systems, such as updates to ICD codes, can affect the consistency and comparability of data. Third, a GBD study employs complex statistical models to estimate disease burden, which are based on a series of assumptions that may affect the accuracy of the estimates. Fourth, GBD research primarily focuses on estimating the disease burden rather than the effectiveness of interventions, which may make it challenging to evaluate and accurately adjust public policy and health planning. These limitations highlight the importance of considering potential biases and constraints when developing public health policies and clinical practice guidelines, ensuring that the measures implemented effectively address both current and future health challenges.
但是，这项研究有一些局限性。首先，GBD 依赖于来自不同国家和地区的报告数据，这些数据的质量和完整性可能有所不同。在数据收集不完整或不准确的领域，GBD 估计值可能存在偏差。此外，GBD 数据通常表现出时间滞后，这意味着最新数据可能无法反映当前的健康状况，并且可能无法捕捉突发公共卫生事件对疾病负担的影响。其次，不同国家和时期可能使用了不同的诊断标准和方法，这可能会影响区域和时间比较。此外，疾病编码和分类系统的变化，例如 ICD 代码的更新，会影响数据的一致性和可比性。第三，GBD 研究采用复杂的统计模型来估计疾病负担，这些模型基于一系列可能影响估计准确性的假设。第四，GBD 研究主要侧重于估计疾病负担而不是干预措施的有效性，这可能使评估和准确调整公共政策和卫生计划变得具有挑战性。这些局限性凸显了在制定公共卫生政策和临床实践指南时考虑潜在偏见和限制的重要性，确保实施的措施有效应对当前和未来的健康挑战。