Immune System in Diabetic Kidney Disease

NCT07292493 | Enrolling By Invitation

• 1 other identifier: 20250187
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes; Diabetic Kidney Disease; Complement System

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Level of complement system activation

  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 Outcomes (3)

• IMT thickness

  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)

  An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.

• Endothelial Function

  An additional visit to the diabetes outpatient clinic is planned within one year, where the examination will be performed.

Study Arms (3)

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.

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• a body mass index above 30 kg/m²
• macrovascular complications

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (4)

• 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.

  PMID: 35322566 BACKGROUND

• 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.

  PMID: 26180106 BACKGROUND

• 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.

  PMID: 15161763 BACKGROUND

• 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.

  PMID: 28262777 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Nephropathies; Complement Component 3 Deficiency, Autosomal Recessive

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Study Officials

• Miodrag Janić

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 18, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 23, 2026

Record last verified: 2025-11

Locations

SL (1)