Unmasking the silent epidemic: Mortality trends in diabetic nephropathy

Abstract

Diabetes mellitus is a major contributor to kidney failure, with diabetic nephropathy being a common microvascular complication. The increasing prevalence of diabetes and its complications suggests a rise in associated morbidity and mortality. Recent studies highlight increased mortality related to diabetic kidney disease, with disparities across demographic and geographic groups. Novel pharmacological treatments, including sodium-glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 agonists, offer promise in slowing disease progression and reducing renal mortality. However, the growing epidemics of obesity and diabetes necessitate prioritizing public health policies focused on primary and secondary prevention, along with comprehensive multidisciplinary care.

Core Tip: The rising incidence of diabetes and its complications, including diabetic nephropathy, underscores the urgent need for comprehensive strategies. While new pharmacological treatments offer benefits, prioritizing public health policies focused on prevention and multidisciplinary care is crucial to effectively reduce the progression of chronic kidney disease and its associated mortality.

TO THE EDITOR

Diabetes mellitus imposes a significant economic burden on society and healthcare systems due to direct healthcare costs, productivity loss, premature mortality, and intangible expenses. Additionally, more than half of these costs are attributed to diabetes and its complications[1]. According to data from the Centers for Disease Control and Prevention, type 2 diabetes mellitus is the leading cause of kidney failure, and its prevalence has more than doubled over the past two decades[2]. Additionally, diabetic nephropathy is one of the most common microvascular complications in patients with diabetes. A meta-analysis published in 2024 reported the prevalence of diabetic nephropathy to be 24% in the United States and 31% in Canada and Mexico[3].

The rising incidence of diabetes in recent decades, coupled with the well-documented high incidence of microvascular complications and the fact that diabetes mellitus is the leading cause of kidney failure, suggests an expected increase in morbidity and mortality associated with diabetic nephropathy, particularly if healthcare systems and public health policies remain inadequate. A previous study published in 2024 already highlighted an increase in mortality related to chronic kidney disease and diabetes[4]. This study found higher mortality rates among men and African Americans, as well as regional disparities in mortality.

Similarly, the study by Muhammad et al[5] analyzes mortality trends using death certificate data from 1999 to 2020, focusing on diagnoses related to diabetes with renal complications. Notably, the authors identified a significant increase in mortality, with disparities observed across demographic and geographic groups. Higher mortality rates were reported among men, American Indian/Alaska Native, and African American populations. Furthermore, regional differences were evident, with the highest mortality rates observed in the Western region.

The advent of novel pharmacological treatments with demonstrated benefits in slowing the progression of diabetic nephropathy and reducing renal mortality, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 (GLP-1) agonist-based therapies, offers hope for a more comprehensive treatment approach for this population, preventing the onset of chronic kidney disease while also decreasing its progression and associated mortality in this high-risk group[6-9].

GLP-1 receptor agonists, non-steroidal MRAs, and SGLT2 inhibitors each target distinct yet complementary pathways that contribute to improved outcomes and reduced mortality in diabetic nephropathy. SGLT2 inhibitors reduce intraglomerular pressure through afferent arteriole vasoconstriction, decrease hyperfiltration, and promote natriuresis and glycosuria, which lead to improved glycemic and hemodynamic profiles. GLP-1 receptor agonists exert cardio-renal protective effects by improving glycemic control, promoting natriuresis, reducing inflammation and oxidative stress, and lowering blood pressure and body weight. Non-steroidal MRAs, such as finerenone, attenuate renal and cardiovascular fibrosis by selectively blocking mineralocorticoid receptors in a tissue-specific manner, reducing inflammation and albuminuria with fewer electrolyte disturbances compared to steroidal MRAs. Collectively, these mechanisms mitigate the progression of diabetic kidney disease and reduce the risk of cardiovascular events and mortality.

However, it is crucial to recognize that as long as diseases such as obesity and diabetes continue to grow as global epidemics, the priority should be the implementation of public health policies focused on primary and secondary prevention. With the rising incidence of these conditions, pharmacological interventions alone are insufficient to meet the needs of such a large population, nor will they be adequate to effectively control the progression of chronic kidney disease and its associated mortality. It is essential to prioritize public health policies that emphasize primary prevention strategies to reduce the incidence and progression of diabetic nephropathy. Additionally, comprehensive programs targeting the global diabetic population should be developed, incorporating multidisciplinary care and evidence-based pharmacological interventions.

Preventive health programs have shown measurable impact in reducing the burden of type 2 diabetes and its complications, including diabetic nephropathy. For example, the PREVENIMSS program in Mexico, implemented by the Mexican Institute of Social Security, focused on early detection, lifestyle modification, and risk factor control[10]. An interrupted time-series analysis suggested that this program may have helped stabilize and modestly reduce diabetes-related mortality among insured populations, compared to increasing trends in the uninsured population. Similarly, the United States-based Diabetes Prevention Program demonstrated that structured lifestyle interventions could reduce the incidence of type 2 diabetes. Long-term follow-up studies also indicated reduced microvascular complications, including kidney disease[11]. These examples highlight the potential of national preventive strategies to reverse or slow current trends in diabetic nephropathy-related mortality. We hope this publication encourages the scientific community to critically evaluate current policies for managing diabetes and its complications.