Immune System in Diabetic Kidney Disease

NCT ID: NCT07292493

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-12-31

Study Completion Date

2028-12-31

Brief Summary

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Diabetes is a chronic condition marked by long-term elevated blood glucose levels. There are more types of diabetes; the majority of patients have type 1 or type 2 diabetes. Over long period of time, high blood sugar damages blood vessels and organs. One of the most common complications is diabetic kidney disease, which can slowly lead to kidney failure. People with this condition also have a much higher risk of heart and blood vessel diseases.

Newer research shows that the immune system, especially the complement system (a group of proteins that help defend the body), may also play a role in worsening kidney disease in diabetes. High blood sugar can activate these proteins, and they have been found in kidney tissue of patients with diabetic kidney disease.

The goal of this study is to find out how much the complement system contributes to kidney damage in diabetes, whether it affects different groups of patients differently, and whether it is linked to blood vessel health or the stage of kidney disease. The study will also assess if improved diabetes control is linked to reduced complement system activity.

Detailed Description

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Diabetes is a chronic disease characterized by long-term elevated blood glucose levels. Several types of diabetes are known, with most affected individuals having type 1 or type 2 diabetes. Long-term elevation of blood glucose affects various organs in the body, a condition referred to as chronic complications of diabetes. Since elevated blood glucose damages both small and large blood vessels, complications are classified as microvascular (damage to small vessels) and macrovascular (damage to large vessels). Diabetic kidney disease is the main microvascular complication in both type 1 and type 2 diabetes and is also the leading cause of kidney failure.

Changes in the kidneys develop over many years. Gradual deterioration of kidney function is monitored using laboratory parameters. Along with declining kidney function, blood pressure also increases, and cardiovascular diseases begin to develop- the risk of these rises exponentially with worsening kidney function. Cardiovascular diseases represent the leading cause of mortality among people with diabetes.

Traditionally, diabetic kidney disease was considered as non-inflammatory condition. Its development was attributed to impaired glucose metabolism and elevated blood pressure. Consequently, achieving optimal blood glucose and blood pressure values has been regarded as key to preventing chronic complications. However, diabetes itself represents an additional risk factor for cardiovascular disease compared with individuals without diabetes. Thus, individuals with diabetic kidney disease are even more prone to cardiovascular events. In these patients it is especially important to follow treatment guidelines and to treat elevated blood glucose and blood pressure as intensively as possible. For individuals with diabetic kidney disease, medications from the group of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are prescribed for the treatment of high blood pressure. Both medication groups also have a protective effect on the kidneys and slow the decline of kidney function. Angiotensin is a substance in the body responsible for raising blood pressure-when its action is inhibited, blood pressure decreases.

The investigators now know that inflammation and the immune system also play a role in the development of chronic diabetic complications. The complement system (a group of proteins in the blood involved in immune responses) is becoming recognized for its importance. Current studies do not suggest that the complement system plays a key role in the onset of the disease; however, its role in the progression of diabetic kidney disease and possibly in the occurrence of different forms of the disease has become evident. Hyperglycaemia increases the activity of certain complement proteins and activates specific pathways, while the hyperglycaemic environment also impairs the regulation of some proteins. Kidney biopsies of individuals with diabetic kidney disease have shown the presence of complement proteins in kidney tissue, and gene expression analyses have identified activation of complement-related genes.

The purpose of this study is to determine whether and to what extent activation of the complement system contributes to diabetic kidney disease and to define potential differences among different groups of individuals with diabetes. Additionally, the investigators aim to determine whether there is a connection between complement system activation and arterial function, as well as between complement system activation and the stage of kidney disease. The investigators will also investigate whether diabetes control influences complement system activation and whether previous kidney biopsy findings correspond with laboratory results.

Conditions

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Diabetes Diabetic Kidney Disease Complement System

Keywords

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C3b C5a new antidiabetic drugs diabetes diabetic kidney disease complement system C3 CD59 MAC MBL C3a

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Patients with type 1 diabetes without chronic kidney disease

The investigators will include male and female patients aged between 40 and 65 years, who have diagnosis of diabetes for at least 10 years and no more than 25 years, with a body mass index below 30 kg/m², and without known macrovascular complications (coronary artery, peripheral arterial, or cerebrovascular disease). All participants must be treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at the highest tolerated dose. Individuals without known chronic kidney disease must meet kidney function criteria with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min and a urine albumin-to-creatinine ratio (UACR) \< 3 g/mol.

No interventions assigned to this group

Patients with type 1 diabetes and chronic kidney disease

The investigators will include male and female patients aged between 40 and 65 years, who have diagnosis of diabetes for at least 10 years and no more than 25 years, with a body mass index below 30 kg/m², and without known macrovascular complications (coronary artery, peripheral arterial, or cerebrovascular disease). All participants must be treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at the highest tolerated dose. Individuals diagnosed with chronic kidney disease must meet the criteria of kidney function eGFR \< 60 ml/min and UACR \> 3 g/mol, or UACR \> 30 g/mol regardless of eGFR.

No interventions assigned to this group

Patients with type 2 diabetes and chronic kidney disease

The investigators will include male and female patients aged between 40 and 65 years, who have diagnosis of diabetes for at least 10 years and no more than 25 years, with a body mass index below 30 kg/m², and without known macrovascular complications (coronary artery, peripheral arterial, or cerebrovascular disease). All participants must be treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at the highest tolerated dose. Individuals diagnosed with chronic kidney disease must meet the criteria of kidney function eGFR \< 60 ml/min and UACR \> 3 g/mol, or UACR \> 30 g/mol regardless of eGFR.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* body mass index below 30 kg/m²
* unknown macrovascular complications
* treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at the highest tolerated dose

Exclusion Criteria

* a body mass index above 30 kg/m²
* macrovascular complications
Minimum Eligible Age

40 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Centre Ljubljana

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Miodrag Janić

Role: PRINCIPAL_INVESTIGATOR

Locations

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University Medical Centre Ljubljana

Ljubljana, , Slovenia

Site Status

Countries

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Slovenia

References

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Li MR, Sun ZJ, Chang DY, Yu XJ, Wang SX, Chen M, Zhao MH. C3c deposition predicts worse renal outcomes in patients with biopsy-proven diabetic kidney disease in type 2 diabetes mellitus. J Diabetes. 2022 Apr;14(4):291-297. doi: 10.1111/1753-0407.13264. Epub 2022 Mar 24.

Reference Type BACKGROUND
PMID: 35322566 (View on PubMed)

Ostergaard JA, Thiel S, Lajer M, Steffensen R, Parving HH, Flyvbjerg A, Rossing P, Tarnow L, Hansen TK. Increased all-cause mortality in patients with type 1 diabetes and high-expression mannan-binding lectin genotypes: a 12-year follow-up study. Diabetes Care. 2015 Oct;38(10):1898-903. doi: 10.2337/dc15-0851. Epub 2015 Jul 15.

Reference Type BACKGROUND
PMID: 26180106 (View on PubMed)

Hansen TK, Tarnow L, Thiel S, Steffensen R, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A. Association between mannose-binding lectin and vascular complications in type 1 diabetes. Diabetes. 2004 Jun;53(6):1570-6. doi: 10.2337/diabetes.53.6.1570.

Reference Type BACKGROUND
PMID: 15161763 (View on PubMed)

Flyvbjerg A. The role of the complement system in diabetic nephropathy. Nat Rev Nephrol. 2017 May;13(5):311-318. doi: 10.1038/nrneph.2017.31. Epub 2017 Mar 6.

Reference Type BACKGROUND
PMID: 28262777 (View on PubMed)

Other Identifiers

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20250187

Identifier Type: -

Identifier Source: org_study_id