Chronic kidney disease (CKD) is a pervasive and growing global health concern, affecting between 8% and 16% of adults worldwide. Traditionally, CKD has been associated with older populations, and much of the clinical focus has been directed toward addressing advanced stages of the disease. However, emerging research has highlighted an overlooked population at risk: younger adults experiencing modest reductions in kidney function. These reductions, while not meeting the current diagnostic threshold for CKD, are associated with a host of adverse outcomes, including cardiovascular events, kidney failure, and all-cause mortality. Addressing this gap in knowledge and clinical practice is critical for mitigating the long-term burden of CKD and its associated complications.
Diagnostic Limitations for Younger Adults
CKD is currently defined by structural kidney damage detected through albuminuria or a sustained reduction in estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m² for at least 90 days. This universal diagnostic threshold has been derived from epidemiological studies demonstrating elevated risks of adverse outcomes across all age groups below this eGFR level. However, this fixed threshold does not account for age-related variations in kidney function. Younger adults, particularly those under the age of 40, often have eGFR values exceeding 100 mL/min/1.73m² under normal conditions. As a result, they may experience significant kidney function decline before meeting the diagnostic criteria for CKD.
This limitation has profound implications. Early and sustained reductions in eGFR, even within the range of 60-100 mL/min/1.73m², may indicate underlying kidney dysfunction and heightened risk for adverse outcomes. The failure to recognise and address these risks in younger populations represents a critical gap in CKD management, particularly given the lifelong implications of progressive kidney disease.
Evidence on Early Kidney Function Decline
Recent large-scale studies have begun to illuminate the risks associated with modest eGFR reductions in younger adults. In a cohort study of 8.7 million adults, 17% of individuals aged 18-39 years were found to have eGFR values between 60 and 100 mL/min/1.73m². While these levels are above the current diagnostic threshold for CKD, they are below the expected range for this age group, where optimal eGFR values typically exceed 100 mL/min/1.73m².
The study demonstrated that these modest reductions in eGFR were significantly associated with adverse outcomes, including cardiovascular events, kidney failure, and mortality. Importantly, these risks were observed across all sexes, comorbid conditions, and repeated eGFR measurements, emphasising the robustness of the findings. Even a 20% reduction in eGFR relative to age-specific referents was associated with a substantial increase in the risk of adverse events. These results align with previous research, including findings from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which demonstrated a link between eGFR values below 110 mL/min/1.73m² in adults under 40 and increased coronary artery calcification, a key marker of cardiovascular risk, over a 10-year follow-up period.
Cardiovascular Risk and CKD
The cardiovascular risks associated with CKD have been well-documented, but the recognition of these risks in younger adults with modest eGFR reductions is a relatively new area of focus. Research has shown that eGFR values as high as 80-90 mL/min/1.73m² in younger adults are associated with elevated cardiovascular risks. These findings challenge the conventional focus on severe kidney function decline and highlight the importance of addressing early-stage CKD.
The public health implications of these findings are significant. Cardiovascular disease remains the leading cause of death worldwide, and its association with early kidney function decline suggests that even modest increases in cardiovascular risk in young adults could have far-reaching consequences. Given the long-life expectancy of this population, the cumulative burden of CKD-related cardiovascular complications is likely to be substantial, highlighting the need for early intervention and prevention strategies.
Gender and Comorbidities
The risks associated with early kidney function decline are not uniformly distributed across populations. Gender differences, in particular, have been observed in the progression and outcomes of CKD. In the recent cohort study, men aged 18-39 exhibited higher crude incidence rates of adverse outcomes, while women showed higher adjusted hazard ratios for the same outcomes. This suggests that while men may experience faster progression to severe disease or mortality, women may have a slower decline but still face significant risks.
Comorbid conditions such as diabetes and hypertension further exacerbate these risks. Both conditions are well-established risk factors for CKD progression and were associated with higher adverse outcome rates across all eGFR levels in the cohort study. Additionally, elevated albumin-to-creatinine ratio (ACR), a key marker of kidney damage, was strongly linked to adverse outcomes even when eGFR remained relatively intact. Despite its clinical importance, ACR testing remains underutilised, with only 4% of participants in the study having an ACR measurement. This gap underlines the need for more comprehensive and proactive approaches to CKD screening and risk assessment.
Implications for Screening and Intervention
Proactive screening and intervention are critical for addressing the risks associated with early kidney function decline in younger adults. Routine eGFR and ACR testing could enable earlier detection of kidney dysfunction and inform targeted interventions. Current screening practices, however, often overlook younger adults, focusing instead on older populations and those with advanced stages of CKD. This approach fails to recognise the potential for early-stage interventions to prevent disease progression and reduce long-term complications.
Emerging therapeutics, such as sodium-glucose co-transporters (SGLTs), offer promising avenues for reducing CKD-related risks in high-risk populations. Lifestyle modifications, including dietary changes, increased physical activity, and smoking cessation, could also play a critical role in mitigating risk factors. Raising awareness among both patients and healthcare providers about the importance of early detection and intervention is essential for improving outcomes.
Public Health and Policy Implications
From a public health perspective, the under-recognition of CKD in younger adults represents a missed opportunity to address a major contributor to long-term morbidity and mortality. While the absolute risks associated with modest eGFR reductions in young adults may appear small, their extended life expectancy means that the cumulative impact of CKD-related complications can be substantial. Addressing these risks through enhanced screening, early intervention, and patient education could significantly reduce the burden of CKD on individuals and healthcare systems alike.
Policy changes are needed to support these efforts. Revising CKD diagnostic criteria to account for age-specific variations in eGFR could improve the early detection of kidney dysfunction in younger adults. Additionally, incorporating ACR testing into routine clinical practice and increasing access to preventive care for high-risk populations could help mitigate the long-term impact of CKD.
Strengths and Limitations of Current Research
While recent studies have provided valuable insights into the risks associated with early kidney function decline, several limitations must be acknowledged. For example, the reliance on single eGFR measurements to define baseline kidney function may not fully capture the chronicity of CKD. However, sensitivity analyses using repeated measures have confirmed the consistency of these findings.
Other limitations include potential misclassification of comorbidities in administrative data and the absence of data on medication use, which may influence kidney function. Despite these limitations, the large cohort size and alignment with previous research lend credibility to the findings and highlight the importance of addressing modest eGFR reductions in younger adults.
Conclusion
Chronic kidney disease in younger adults is an under-recognised public health challenge that demands greater attention from researchers, clinicians, and policymakers. Modest reductions in eGFR, even within the range of 60-100 mL/min/1.73m², are associated with significant risks of cardiovascular events, kidney failure, and mortality. These findings challenge the traditional focus on advanced stages of CKD and emphasise the need for earlier detection and intervention.
By adopting proactive screening strategies, raising awareness of CKD risks, and exploring targeted interventions, healthcare systems can better support younger adults at risk of kidney function decline. Addressing this gap in clinical practice and policy is critical for reducing the long-term burden of CKD and improving outcomes for millions of individuals worldwide. Early recognition and action today could prevent significant health consequences in the future.
References
Hussain, J., Grubic, N., Akbari, A., Canney, M., Elliott, M. J., Ravani, P., Tanuseputro, P., Clark, E. G., Hundemer, G. L., Ramsay, T., Tangri, N., Knoll, G. A., & Sood, M. M. (2023). Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study. BMJ (Clinical Research Ed.), 381, e075062. https://doi.org/10.1136/bmj-2023-075062
Bansal, N., Lin, F., Vittinghoff, E., Peralta, C., Lima, J., Kramer, H., Shlipak, M., & Bibbins-Domingo, K. (2016). Estimated GFR and subsequent higher left ventricular mass in young and middle-aged adults with normal kidney function: The Coronary Artery Risk Development in Young Adults (CARDIA) study. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 67(2), 227–234. https://doi.org/10.1053/j.ajkd.2015.06.024