New blood markers predict kidney disease and mortality in diabetes

Kidney complications in diabetes often progress silently, putting patients at risk of life-threatening outcomes long before any symptoms appear. Identifying individuals with diabetes who are at risk of rapid kidney function decline or early death has challenged doctors for decades, with traditional markers like serum creatinine and urinary albumin falling short of accurately predicting these risks.

Fortunately, a new study that was made available online on July 23, 2025, and published in Volume 16, Issue 4 of the Journal of Cachexia, Sarcopenia and Muscle on August 1, 2025, offers a promising solution. A team of researchers led by Associate Professor Tomohito Gohda from the Department of Nephrology, Juntendo University Faculty of Medicine, Japan, found that two simple blood markers-estimated glomerular filtration rate difference (eGFRdiff) and growth differentiation factor-15 (GDF-15) levels-can independently predict kidney disease progression and mortality in people with diabetes. "Currently, eGFR and urinary albumin, which are commonly used in routine clinical practice, are not sufficient to accurately predict kidney outcomes in individuals with diabetes," says Dr. Gohda. "The development of novel biomarkers that complement these existing markers may allow for the earlier and more convenient identification of patients at high risk for kidney disease progression and mortality."

The research team analyzed data from 638 Japanese adults living with diabetes mellitus. Participants were observed for a period of more than 5 years, during which 11.8% experienced significant kidney function decline and 6.9% died from various causes. Blood samples were used to calculate eGFRdiff, a measure that reflects differences between cystatin C- and creatinine-based kidney function estimates, and to determine serum levels of GDF-15, a protein increasingly recognized as a marker of inflammation and frailty. The analysis revealed a powerful link: patients with lower eGFRdiff values faced a dramatically higher risk of chronic kidney disease (CKD) progression, while those with elevated GDF-15 levels were at higher risk of increased mortality. Specifically, every 10-unit increase in eGFRdiff reduced the risk of CKD progression by 33%, while higher GDF-15 levels were strongly linked to an increased risk of death by 235%.

"eGFRdiff may contribute to early risk stratification in diabetic kidney disease and assist in developing personalized treatment strategies, potentially leading to improved quality of life for individuals with diabetes and reduced healthcare costs," explains Dr. Gohda.

Importantly, this research demonstrated that these two markers provide complementary insights. eGFRdiff, which can reflect muscle mass loss and metabolic changes, was more strongly associated with kidney disease progression. On the other hand, GDF-15, a stress-responsive cytokine linked to inflammation, better predicted mortality risk. This distinction suggests that using the two markers together could enhance precision in identifying which patients are most vulnerable to serious complications.

Globally, diabetes is a leading cause of CKD, which can progress to end-stage kidney disease requiring dialysis-a treatment with profound impacts on patients' lives and high costs for healthcare systems. Early detection of kidney risk using eGFRdiff and GDF-15 could enable clinicians to tailor interventions sooner, slowing or even preventing disease progression and potentially saving lives.

"Our results suggest that frailty and sarcopenia, driven by inflammation and metabolic abnormalities, may contribute to CKD progression and mortality in individuals with diabetes mellitus," concludes Dr. Gohda. "eGFRdiff assessment may enhance the identification of high-risk individuals."

By identifying these simple yet powerful markers, this study offers hope for improved personalized and proactive care in diabetes-a critical advancement as diabetes rates and their complications continue to increase worldwide.