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.
Reference
Authors |
Tomohito Gohda1, Nozomu Kamei2,3, Marenao Tanaka4, Masato Furuhashi4, Tatsuya Sato4,5, Mitsunobu Kubota6, Michiyoshi Sanuki3, Takeo Koshida1, Shinji Hagiwara1, Yusuke Suzuki1, and Maki Murakoshi1 |
Title of original paper |
Association of Difference Between eGFR from Cystatin C and Creatinine and Serum GDF-15 with Adverse Outcomes in Diabetes Mellitus |
Journal |
Journal of Cachexia, Sarcopenia and Muscle |
DOI |
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Affiliations |
1Department of Nephrology, Juntendo University Faculty of Medicine 2Department of Endocrinology and Metabolism, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital 3Institute for Clinical Research, NHO Kure Medical Center and Chugoku Cancer Center 4Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine 5Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine 6Department of Endocrinology and Diabetology, NHO Kure Medical Center and Chugoku Cancer Center |
About Associate Professor Tomohito Gohda
Dr. Tomohito Gohda is an MD and Associate Professor in the Department of Nephrology at Juntendo University Faculty of Medicine, Tokyo. He earned his medical degree from Juntendo University and has over 20 years of experience in clinical and experimental nephrology. With more than 100 published articles, his research focuses on diabetic kidney disease, biomarkers, and inflammation‑driven renal decline. Notably, his work on circulating TNF‑receptors and early kidney‑function decline—alongside recent studies like the eGFRdiff/GDF‑15 project—has advanced early risk stratification in diabetic nephropathy.
