Exploring the role of the gut-kidney axis in type 1 diabetes
| ISRCTN | ISRCTN14636038 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14636038 |
| FLPP, Latvia | lzp-2025/1-0280 |
| Sponsors | University of Latvia, Pauls Stradiņš Clinical University Hospital |
| Funder | Latvijas Zinātnes Padome |
- Submission date
- 05/01/2026
- Registration date
- 16/02/2026
- Last edited
- 16/02/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Type 1 diabetes is a long-term autoimmune disease that leads to high blood sugar levels and can cause serious complications over time. One of the most important complications is diabetic kidney disease, which can progress to kidney failure and increase the risk of heart disease and early death. Many people with type 1 diabetes also experience digestive problems, such as abdominal pain, bloating, diarrhoea or constipation, but the causes of these symptoms are not fully understood.
Recent research suggests that changes in the gut, including increased intestinal permeability (“leaky gut”), inflammation, and changes in gut bacteria, may contribute to kidney disease progression. This study aims to better understand how changes in the gut may be linked to kidney damage in people with type 1 diabetes.
Who can participate?
Patients aged 18 years and over with type 1 diabetes who have had the disease for at least 8 years, have mild to moderate kidney disease, and have clinical indications for gastrointestinal endoscopic examination can participate. A control group of adults without diabetes, matched for age and sex and with indications for gastrointestinal endoscopy, will also be included.
What does the study involve?
Participants will attend a screening visit, complete a questionnaire about gastrointestinal symptoms, and provide blood, urine, and stool samples. If clinically indicated, they will undergo a sigmoidoscopy or colonoscopy, during which small tissue samples (biopsies) from the intestine will be taken. These samples will be analysed to assess intestinal inflammation, immune activity, and gut barrier integrity. Blood and urine samples will be used to measure markers of kidney damage and inflammation.
What are the possible benefits and risks of participating?
Participants may benefit from detailed medical assessments of their gut and kidney health, which may provide useful clinical information. Risks include temporary discomfort related to blood sampling and endoscopic procedures. All procedures will be performed by experienced specialists following standard safety guidelines.
Where is the study run from?
The study is conducted at the University of Latvia and Pauls Stradiņš Clinical University Hospital in Riga (Latvia).
When is the study starting and how long is it expected to run for?
The study is expected to start after ethical approval and will run for 36 months (3 years).
Who is funding the study?
The study is funded by the Latvian Council of Science under the Fundamental and Applied Research Projects Programme (FLPP, LZP).
Who is the main contact?
Dr Polina Zalizko, polina.zalizko@lu.lv
Contact information
Scientific, Public, Principal investigator
Jelgavas iela 3
Riga
LV1004
Latvia
| Phone | +371 (0)26876636 |
|---|---|
| polina.zalizko@lu.lv |
Public, Scientific
Jelgavas iela 3
Riga
LV1004
Latvia
| Phone | +371 (0)28323196 |
|---|---|
| jelizaveta.sokolovska@lu.lv |
Study information
| Primary study design | Observational |
|---|---|
| Observational study design | Cohort study |
| Scientific title | In individuals with type 1 diabetes, how modulation of the gut–kidney axis compared with usual gut–kidney axis function affects kidney function and the development of diabetic kidney disease |
| Study acronym | GUTKIDNEY-T1D |
| Study objectives | |
| Ethics approval(s) |
Approved 05/12/2025, Central Medical Ethics Committee of the Republic of Latvia (Brīvības iela 72 k-1, Riga, LV1011, Latvia; +371 (0)67876182; pasts@vm.gov.lv), ref: Nr. 01-29.1.2/5494 |
| Health condition(s) or problem(s) studied | Type 1 diabetes mellitus and diabetic nephropathy |
| Intervention | Population-based cross-sectional case-control study based on the longitudinal LatDiane cohort (Latvian Diabetic Nephropathy Study, initiated 2013). Participants: Adults with type 1 diabetes mellitus (n = 50), subdivided into those with progressive diabetic nephropathy and stable kidney disease. Control group (n = 20) of age-, gender-, and race-matched individuals with normal glucose metabolism. Inclusion/exclusion criteria ensure participants are suitable for gastrointestinal investigation and have no confounding conditions (e.g., inflammatory bowel disease, eGFR<45 ml/min/1.73m²). Recruitment and screening: Eligible participants are identified from LatDiane and the PSCUH outpatient clinic based on clinical and laboratory records. Screening includes a gastrointestinal symptom questionnaire, medical history review, and lab tests. Endoscopic evaluation (colonoscopy) is performed in participants with gastrointestinal indications. Data and sample collection: Biological samples: blood (serum), urine, stool; processed and stored at -80°C for biomarker analysis. Laboratory analyses: fecal markers (calprotectin, IgA, albumin, elastase), intestinal permeability markers in serum (LPS activity, zonulin, I-FABP, EndoCAb, LPB, KIM-1, NGAL, indoxyl sulfate, p-Cresyl sulfate) measured by ELISA or validated assays. Colon biopsies: collected during endoscopy, analyzed morphologically and immunohistochemically for immune cell markers (CD4, CD20) and intestinal integrity markers (zonula occludens 1, claudin-1, claudin-2, occludin). Statistical analysis: Descriptive statistics for baseline characteristics. Non-parametric tests (Kruskal-Wallis) for group comparisons. Multiple linear and logistic regression to assess associations between gut markers and kidney outcomes. Odds ratios, relative risks, 95% confidence intervals reported. Study powered at 80% to detect significant differences in I-FABP between progressive and stable DKD. Data management: FAIR principles will guide data handling. Analysis documentation stored in a DataverseLV repository for reproducibility. Study setting: Recruitment and sample collection at University of Latvia, Faculty of Medicine and Pauls Stradins University Hospital, Riga, Latvia. |
| Intervention type | Other |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) | |
| Completion date | 31/12/2028 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 20 |
| Total final enrolment | 70 |
| Key inclusion criteria | 1. Type 1 diabetes mellitus with a duration of least 8 years 2. Available data on DKD progression in the last 3 years or more 3. Indications for colonoscopy |
| Key exclusion criteria | 1. eGFR <45 ml/min/1.73m2 2. Nephrotic range proteinuria (more than 3.0 g/day) 3. Hematuria in more than two consecutive urine samples 4. Histologically proven other type of glomerular disease 5. Inflammatory bowel disease 6. Coeliac disease 7. Pregnancy 8. Intestinal infection within 1 month of planned endoscopy and faecal collection 9. Gastrointestinal “alarm symptoms”: bleeding, severe weight loss, fever, abrupt onset of symptoms, anemia |
| Date of first enrolment | 01/01/2026 |
| Date of final enrolment | 31/12/2028 |
Locations
Countries of recruitment
- Latvia
Study participating centres
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Editorial Notes
07/01/2026: Study's existence confirmed by the Latvian Central Ethics Committee.
