Check the clues to developing a treatment for diabetic kidney disease...Risk of progression faster as complement protein increases

Jun 26, 2025

Progress probability of diabetic kidney disease according to complement score. When other clinical variables were corrected, patients with high complement scores had a more than 2-fold higher risk of rapid progression of diabetic kidney disease, and this result was the same in the Korean and U.S. cohorts.

Some patients with diabetic kidney disease (diabetic kidney disease) continue to suffer from decreased renal function despite medication, and there is no way to prevent it completely yet. Recently, an international joint study with the United States confirmed that the innate immune system 'complex system' is closely involved in the rapid progression of diabetic kidney disease. The complement proteins that make up the complement system can be used to identify diabetic kidney disease with poor prognosis, and the applicability of complement activity inhibitors currently used as treatments in other diseases can also be expected.

The complement system refers to the innate immune system that is finally activated when the inflammatory response becomes severe, and various complement proteins are involved in the activity of the system.

A joint research team of professors Han Seung-seok and Yoon Dong-hwan of the Department of Nephrology at Seoul National University and Maryam Afkarian of UC Davis University announced on the 25th that they confirmed this through targeted and non-target urine proteomics analysis of Seoul National University Hospital and a cohort of diabetic kidney disease in the United States.

Diabetic kidney disease causes proteinuria as the glomerulus and renal tubules are damaged due to hyperglycemia and accompanying diseases, and renal function gradually decreases. The prognosis is worse compared to other kidney diseases, and half of current dialysis patients originate from diabetic kidney disease. With the recent increase in the number of diabetic patients and elderly people, the prevalence of diabetic kidney disease is also increasing, increasing the social burden.

The disease has different rates of disease progression from patient to patient, and its cause is not yet clearly known. In particular, some patients develop diabetic kidney disease even if they receive drug treatment that slows the progression of the disease, and sometimes they receive dialysis treatment within 3-5 years after diagnosis. However, there is no way to select and treat these high-risk groups early, so there is an urgent need to develop a biomarker that can target diabetic kidney disease with a poor prognosis.

Existing studies on diabetic kidney disease have been mainly based on blood analysis, but the research team noted that more than 70% of protein in urine is directly related to kidney damage. Accordingly, a non-targeted proteomics analysis was conducted on 64 Korean patients with diabetic kidney disease who clearly identified kidney damage due to diabetes in biopsy and thoroughly examined the entire protein in the urine.

The cluster was then divided according to the expression pattern of urine protein and analyzed the prognosis of diabetic kidney disease and protein expression pathway. As a result, the activity of complement system-related pathways was highest in clusters with rapidly deteriorating renal function, and complement proteins were relatively abundant. This suggests that 'complementary protein' is closely associated with rapid progression of diabetic kidney disease.

In addition, the research team developed a 'complement score' that quantifies the characteristics and expression level of complement proteins and calculated figures for each patient. As a result of the analysis, the patient group with high complement scores had more severe kidney tissue damage than the group with low complement scores, and the risk of rapidly worsening diabetic kidney disease was more than twice as high even after all other clinical variables were corrected.

These results were also shown to be the same in a targeted proteomics analysis of 282 patients with diabetic kidney disease from the American Multiracial Chronic Kidney Disease cohort (CRIC). This reaffirmed the fact that complement systems are strongly involved in the rapid progression of diabetic kidney disease, and demonstrated that complement proteins are potential biomarkers to identify these high-risk patients.

Professor Seung-Seok Han (Department of Nephrology) stated that "complementary system inhibitors are used in some kidney diseases and are showing therapeutic effects, but unfortunately, there is still a lack of clear evidence for diabetic kidney disease, so related studies were needed." Based on the results of this study, we confirmed the possibility that complementary system inhibitors will be effective in patients with rapidly progressing diabetic kidney disease, and we plan to continue follow-up studies for clinical application of related drugs in the future."

Meanwhile, the findings were published in the latest issue of the `Kidney International Reports' of the International Kidney Society.