Immune System in Diabetic Kidney Disease (KID-CODE)

February 19, 2026 updated by: University Medical Centre Ljubljana

The Role of Complement in Diabetic Kidney Disease

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.

Study Overview

Status

Enrolling by invitation

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • University Medical Centre Ljubljana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with type 1 and type 2 diabetes, who are being treated at the diabetology outpatient clinic of the Department of Endocrinology, Diabetes, and Metabolic Diseases, University Medical Centre Ljubljana.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of complement system activation
Time Frame: An additional visit to the diabetes outpatient clinic is planned within one year, where this will be determined.

The investigators will determine components of the complement system in blood and urine samples.

  • Blood parameters:

    • S compl. component C3: 0.6-1.3 g/L, ↓ consumpt.; ↑ inflam.,
    • S compl. component C4: 0.1-0.3 g/L,↓ classical/lectin | ↑ inflam.,
    • S fact. B: 166-399 mg/L, ↓ AP (alter. path.) consumpt. | ↑ AP act.,
    • S fact. H: 380.6-674.9 mg/L, ↓ regul. | ↑ compensation,
    • S fact. I: 21.2-42.1 mg/L, ↓ regul. | ↑ compensation,
    • S soluble C5b-9 lytic complex (sC5b-9): 127-303 ng/mL, ↑ terminal compl.,
    • S fact. B fragment Bb: 0.49-1.42 µg/mL, ↑ AP act.,
    • S fact. H antibodies (anti-FH): < 10 U/mL, ↑ AP dysreg.,
    • S C1q antibodies (anti-C1q): < 10 U/mL, ↑ classical pathway,
    • S C3a: man.ref., ↑ compl. act.,
    • S C3c: man. ref., ↑ C3 breakdown,
    • S C5a: man. ref., ↑ strong act.

  • Urine parameter :

    • Urinary soluble C5b-9 lytic complex (sC5b-9): < 30 ng/mL, ↑ renal compl. act.

Expressed in different mass units (mg,g,µg,ng) or activity units (U) per volume units of blood serum (mL,L).
An additional visit to the diabetes outpatient clinic is planned within one year, where this will be determined.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
IMT thickness
Time Frame: An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.
The investigators will measure the intima-media thickness (IMT) with ultrasound. Result will be expressed in millimetres. A thickness greater than 1.0 mm is considered pathological.
An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.
Carotid-femoral pulse wave velocity (PWV)
Time Frame: An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.
The investigators will evaluate arterial stiffness and central hemodynamics non-invasively using applanation tonometry and pulse wave analysis. Results will be expressed in metres per second (m/s). Higher PWV values indicate increased arterial stiffness and reduced arterial elasticity. Augmentation Index (AIx), or AIx@75, represents the contribution of the reflected pulse wave to central systolic pressure and reflects arterial compliance and wave reflection. Higher AIx values indicate increased arterial stiffness and enhanced wave reflection. Because AIx is influenced by heart rate, it is commonly adjusted to a standardized heart rate of 75 beats per minute (AIx@75).
An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.
Endothelial Function
Time Frame: An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.

The investigators will use peripheral arterial tonometry . The measurement is performed using a finger-mounted pneumatic probe, which detects pulsatile volume changes in the fingertip. The device's software analyses the change in pulse amplitude before and after occlusion, calculating the Reactive Hyperemia Index (RHI), which serves as a quantitative marker of endothelial function and has no unit. Lower RHI values indicate endothelial dysfunction and impaired nitric oxide-mediated vasodilation.Higher RHI values reflect preserved endothelial function.

Augmentation Index (AIx), derived from EndoPAT, reflects arterial stiffness and wave reflection in peripheral arteries. Higher AIx values indicate increased arterial stiffness and adverse vascular properties. Lower AIx values suggest better arterial compliance.
An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Centre Ljubljana

Investigators

  • Principal Investigator: Miodrag Janić

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

December 5, 2025

First Posted (Actual)

December 18, 2025

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20250187

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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