Predicting kidney risk and survival in diabetes

Scientists reveal how simple blood markers predict risks of kidney disease and death in people with diabetes mellitus

Peple with diabetes often develop kidney disease without warning, leading to life-threatening complications. Now, researchers have discovered that two simple blood markers, estimated glomerular filtration rate difference (eGFRdiff) and growth differentiation factor-15 (GDF-15), can independently predict who is at an elevated risk of kidney function decline and early death. The findings could help clinicians identify vulnerable patients sooner, paving the way for timely, personalised treatments that slow disease progression, and improve outcomes for millions living with diabetes.

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.

However, a new observational study, published recently in the Journal of Cachexia, Sarcopenia, and Muscle, 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 – eGFRdiff, a measure that reflects differences between cystatin C- and creatinine-based kidney function estimates, and GDF-15, a protein increasingly recognised as a marker of inflammation and frailty – 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,” said 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 analysed data from 638 Japanese adults living with diabetes mellitus. Participants were observed for a period of more than five years, during which 11.8 per cent experienced significant kidney function decline and 6.9 per cent died from various causes. Blood samples were used to calculate eGFRdiff and to determine serum levels of GDF-15.

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 per cent, while higher GDF-15 levels were strongly linked to an increased risk of death by 235 per cent.

“eGFRdiff may contribute to early risk stratification in diabetic kidney disease and assist in developing personalised treatment strategies, potentially leading to improved quality-of-life for individuals with diabetes and reduced healthcare costs,” explained 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. Future research should focus on identifying modifiable factors that contribute to lower eGFRdiff values and elucidating their clinical implications.

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 sarcopaenia, driven by inflammation and metabolic abnormalities, may contribute to CKD progression and mortality in individuals with diabetes mellitus,” concluded Dr Gohda. “eGFRdiff assessment may enhance the identification of high-risk individuals.”