Global trends
Between 1990 and 2021, the global prevalence of CAKUT increased from 5,221,076 (95% UI: 4188738, 6516684) to 6,343,413 (95% UI: 5069614, 7900494) cases. The age-standardized prevalence rate (ASPR) rose from 86.34 (95% UI: 69.25, 107.63) per 100,000 individuals to 89.76 (95% UI: 71.86, 111.25) per 100,000 individuals. Conversely, the global incidence of CAKUT decreased from 1,167,139 (95% UI: 887687, 1554170) to 1,094,236 (95% UI: 823143, 1438205) cases, with the age-standardized incidence rate (ASIR) showing a slight decrease from 18.21 (95% UI: 13.85, 24.25) per 100,000 individuals to 17.69 (95% UI: 13.31, 23.25) per 100,000 individuals. The global number of deaths due to CAKUT significantly decreased from 9679 (95% UI: 6857, 15280) to 7495 (95% UI: 5175, 11712). Similarly, the age-standardized mortality rate (ASMR) decreased from 0.15 (95% UI: 0.11, 0.24) per 100,000 individuals to 0.12 (95% UI: 0.08, 0.19) per 100,000 individuals. The global DALYs attributable to CAKUT also showed a significant decrease, decreasing from 1,043,302 (95% UI: 775258, 1567968) to 882,185 (95% UI: 659007, 1258015). This trend was reflected in the age-standardized DALY rate (ASDR), which declined from 16.63 (95% UI: 12.38, 24.89) per 100,000 individuals to 13.56 (95% UI: 10.08, 19.57) per 100,000 individuals (Fig. 1; Table 1).
Trends in global numbers and ASRs of CAKUT prevalence (a), incidence (b), deaths (c), and DALYs (d) among different sexes, from 1990 to 2021. ASRs, age-standardized rates; ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate; DALYs, disability-adjusted life years
An in-depth analysis using APC and AAPC revealed diverse trends for CAKUT. ASPR demonstrated an overall increasing trend, as indicated by an AAPC of 0.13% (95% CI: 0.11%, 0.15%) (Supplementary Table 1). Notably, the period from 2005 to 2009 experienced the most pronounced decline, with an APC of -0.21% (95% CI: -0.28%, -0.14%). Conversely, the most significant increase in ASPR was observed from 2019 to 2021, with an APC of 1.09% (95% CI: 0.95%, 1.23%) (Supplementary Fig. 1a and Supplementary Table 2). ASIR exhibited a biphasic trend, initially decreasing from 1990 to 2016 before experiencing a subsequent increase. The rebound in ASIR was particularly evident from 2016 to 2021, with an APC of 1.67% (95% CI: 1.47%, 1.88%) (Supplementary Fig. 1b and Supplementary Table 2). The ASMR showed a consistent downward trend, reflected by an AAPC of -0.87% (95% CI: -0.96%, -0.77%) (Supplementary Table 1). The most substantial decrease in the ASMR was recorded between 2019 and 2021, with an APC of -2.90% (95% CI: -4.07%, -1.71%) (Supplementary Fig. 2a and Supplementary Table 2). Similarly, the ASDR exhibited a significant downward trend, with an AAPC of -0.63% (95% CI: -0.68%, -0.59%) (Supplementary Table 1). The most pronounced reduction in the ASDR was observed over the period from 2013 to 2021, with an APC of -1.49% (95% CI: -1.61%, -1.37%) (Supplementary Fig. 2b and Supplementary Table 2).
Regional trends in 21 GBD regions
At the level of 21 GBD regions in 2021, Southern Sub-Saharan Africa exhibited the highest ASPR and ASIR, reaching 164.25 (95% UI: 129.29, 206.02) and 28.41 (95% UI: 21.04, 38.86), respectively. The highest ASMR was observed in Central Latin America, at 0.27 (95% UI: 0.19, 0.35), while Southern Latin America recorded the highest ASDR at 26.21 (95% UI: 15.84, 35.22). Notably, East Asia and Southeast Asia had the lowest ASPR, ASIR, ASMR, and ASDR among all 21 GBD regions (Table 2).
Between 1990 and 2021, the EAPCs exhibited significant variation across the 21 GBD regions. In terms of the ASPR, 11 GBD regions showed a positive EAPC, with Andean Latin America and Oceania recording the highest EAPC values at 0.58% (95% CI: 0.56%, 0.59%) and 0.49% (95% CI: 0.44%, 0.53%), respectively. Conversely, Eastern Europe recorded the most substantial decline, with an EAPC of ASPR at -0.43% (95% CI: -0.46%, -0.39%). For the ASIR, only five GBD regions exhibited a positive EAPC. Andean Latin America and Oceania again showed the most pronounced increases, with EAPC of ASIR at 0.77% (95% CI: 0.67%, 0.86%) and 0.52% (95% CI: 0.47%, 0.58%), respectively. In contrast, the lowest EAPC of ASIR was observed in High-income Asia Pacific, at -1.22% (95% CI: -1.45%, -0.99%). The trends for the ASMR and the ASDR followed a similar pattern. Only seven regions—Oceania, Tropical Latin America, Central Latin America, Andean Latin America, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, and Southern Latin America—showed positive EAPC values, whereas the remaining 14 GBD regions exhibited negative trends. Eastern Europe recorded the most significant declines, with EAPC values of -3.66% (95% CI: -3.97%, -3.36%) for ASMR and − 2.57% (95% CI: -2.75%, -2.39%) for ASDR (Fig. 2 and Supplementary Table 3).
The EAPCs of ASPR (a), ASIR (b), ASMR (c), and ASDR (d) for CAKUT across the 21 GBD regions, from 1990 to 2021. Red indicates positive EAPC values and blue indicates negative EAPC values. EAPC, estimated annual percentage change; ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate
Regional trends by the SDI
In 2021, CAKUT prevalence was highest in the low-middle SDI region, with 987,898 (95% UI: 768661, 1274289) cases in males and 1,018,236 (95% UI: 807992, 1282828) in females. The high SDI region had the lowest prevalence, with 228,956 (95% UI: 184013, 281819) cases in males and 302,979 (95% UI: 250027, 360979) in females. In terms of incidence, the low-middle SDI region had the most cases (183421 [95% UI: 135901, 245776] males and 176231 [95% UI: 131100, 235270] females), whereas the high SDI region had the fewest cases (33805 [95% UI: 25729, 43301] males and 37430 [95% UI: 28801,48000] females). Mortality was also highest in the low-middle SDI region, with 1871 (95% UI: 844, 3642) male deaths and 946 (95% UI: 498, 1665) female deaths. DALYs followed a similar trend, with the largest burden in low-middle SDI regions (Fig. 3 and Supplementary Table 4).
On the other end of the spectrum, the low SDI region exhibited the highest ASPR, with rates of 100.36 (95% UI: 79.19, 126.15) for males and 109.75 (95% UI: 86.13, 137.70) for females. Interestingly, a notable sex-based disparity in ASPR was observed predominantly in high-middle SDI regions, where the rates were 60.01 (95% UI: 48.06, 74.17) for males and 98.76 (95% UI: 79.82, 120.94) for females. Similarly, the low SDI region recorded the highest ASIR, reaching 19.67 (95% UI: 14.70, 26.10) in males and 19.94 (95% UI: 14.87, 26.47) in females. Furthermore, with respect to mortality, the low-middle SDI region had the highest ASMR for both sexes, with 0.19 (95% UI: 0.09, 0.38) for males and 0.10 (95% UI: 0.05, 0.18) for females. The high-middle SDI region had the lowest ASMR, with rates of 0.09 (95% UI: 0.06, 0.13) for males and 0.05 (95% UI: 0.03, 0.08) for females. Finally, the ASDR was also highest in the low-middle SDI region, where males had an ASDR of 20.83 (95% UI: 11.07, 37.61), and females had an ASDR of 12.97 (95% UI: 8.20, 21.29). And the high-middle SDI region also had the lowest ASDR, at 9.84 (95% UI: 6.84, 13.52) for males and 8.06 (95% UI: 5.70, 11.42) for females (Fig. 3 and Supplementary Table 5).
The prevalence (a), ASPR (b), incidence (c), ASIR (d), deaths (e), ASMR (f), DALYs (g) and ASDR (h) for CAKUT among different sexes, stratified by SDI, in 2021. ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate; SDI, socio-demographic index
Between 1990 and 2021, the EAPCs showed substantial variation across five SDI regions. Regarding the ASPR, the most notable increase was observed in middle SDI region, with an EAPC of 0.16% (95% CI: 0.13%, 0.19%). In contrast, high-middle SDI region experienced the most significant decline in ASPR, with an EAPC of -0.16% (95% CI: -0.18%, -0.14%). For all five SDI regions, the ASIR, ASMR, and ASDR exhibited decreasing trends. Among them, the most pronounced reduction in ASIR occurred in high SDI region, with an EAPC of -0.57% (95% CI: -0.74%, -0.40%). The most significant declines in ASMR and ASDR were observed in high-middle SDI region, with EAPCs of -2.27% (95% CI: -2.46%, -2.08%) and − 1.81% (95% CI: -1.96%, -1.67%), respectively (Supplementary Fig. 3 and Supplementary Table 6).
National trends
In 2021, there was marked variation in the burden of CAKUT across 204 countries and territories. Botswana and South Africa recorded the highest ASPR at 166.81 (95% UI: 129.40, 208.57) and 165.63 (95% UI: 131.10, 206.68), respectively, whereas Indonesia and the Philippines had the lowest rates at 43.90 (95% UI: 34.28, 54.79) and 47.08 (95% UI: 37.19, 59.14), respectively. Concerning ASIR, South Africa and Singapore led with 30.99 (95% UI: 22.65, 41.90) and 30.33 (95% UI: 21.23, 42.66), whereas Paraguay and Ireland had the lowest ASIR at 8.08 (95% UI: 5.50, 11.13) and 8.48 (95% UI: 6.59, 10.97), respectively. Kuwait and Sudan reported the highest ASMR and ASDR, with Kuwait’s ASMR at 0.46 (95% UI: 0.26, 0.65) and ASDR at 46.24 (95% UI: 29.05, 63.20), whereas Sudan’s ASMR was 0.43 (95% UI: 0.22, 0.88) and the ASDR at 42.7 (95% UI: 23.02, 82.83) (Fig. 4 and Supplementary Table 7).
The ASPR (a), ASIR (b), ASMR (c), and ASDR (d) of CAKUT across 204 countries and territories in 2021. ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate
Correlations of age-standardized rates (ASRs) with the SDI
When the CAKUT metrics across 21 GBD regions were investigated, a nuanced correlation with the SDI emerged. Notably, there was a significant negative correlation between the ASPR and SDI (R = -0.25, P < 0.01), as well as between the ASIR and SDI (R = -0.38, P < 0.01). Conversely, the ASMR exhibited a negligible and nonsignificant slight negative association with the SDI (R = -0.05, P = 0.21). Additionally, a marginally significant weak negative correlation was found between the ASDR and SDI (R = -0.09, P = 0.01) (Fig. 5). Similarly, a broader analysis across 204 countries and territories confirmed significant negative correlations between the SDI and ASPR (R = -0.27, P < 0.01), ASIR (R = -0.35, P < 0.01), ASMR (R = -0.19, P < 0.01), and ASDR (R = -0.24, P < 0.01) (Supplementary Fig. 4).
Spearman correlation analysis between the SDI and ASPR (a), ASIR (b), ASMR (c), and ASDR (d) for CAKUT across 21 GBD regional levels from 1990 to 2021. ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate; SDI, socio-demographic index
Drivers of CAKUT epidemiology: population growth, aging, and epidemiologic changes
The decomposition analysis was performed across different genders and various SDI regions (Figs. 6 and 7). It is evident that between 1990 and 2021, population growth was the predominant contributor to the increase in CAKUT prevalence across both genders. Aging was identified as the primary driver behind the decline in CAKUT incidence. Epidemiological changes were the main factor responsible for the reduction in deaths, particularly among females. The synergistic effects of aging and epidemiological changes contributed to the decrease in CAKUT DALYs (Fig. 6).
Decomposition analysis of CAKUT prevalence (a), incidence (b), deaths (c), and DALYs (d) from 1990 to 2021, by sex. The black dot represents the overall change value of population growth, aging, and epidemiological change. DALYs, disability-adjusted life years
In the context of various SDI regions, population growth was the chief contributor to the increase in CAKUT prevalence, incidence, deaths, and DALYs within low SDI regions. Aging served as the principal cause of the decline in CAKUT incidence in other regions. Furthermore, epidemiological changes were the dominant factors leading to the marked reduction in deaths and DALYs in the high-middle and high SDI regions (Fig. 7).
Decomposition analysis of CAKUT prevalence (a), incidence (b), deaths (c), and DALYs (d) from 1990 to 2021, by SDI. The black dot represents the overall change value of population growth, aging, and epidemiological change. DALYs, disability-adjusted life years
BAPC prediction of CAKUT burden
From 2022 to 2036, the prevalence of CAKUT is predicted to continue increasing, a trend also reflected in the ASPR. Regarding incidence, the ASIR steadily declined from 1990 to 2019 but rebounded between 2019 and 2021. BAPC projections suggest that the incidence numbers and ASIR will continue to rise through 2036 (Fig. 8).
In terms of mortality and DALYs related to CAKUT, BAPC projections indicate that from 2022 to 2036, both male and female mortality, along with the ASMR, will continue to decline. Similarly, DALYs and ASDR for both sexes are expected to decrease steadily over the same period (Fig. 8).
Projected numbers and ASRs of prevalence (a), incidence (b), deaths (c), and DALYs (d) for CAKUT among different sexes, from 1990 to 2036 based on the BAPC model. ASPR, age-standardized prevalence rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized disability-adjusted life year rate; DALYs, disability-adjusted life years
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