Diabetic Nephropathy in People With Diabetes. Prevalence and Predictive Factors (PRIMETIME2)

February 27, 2024 updated by: Marie Møller, Herlev Hospital

Biopsy-proven Diabetic Nephropathy in People With Type 2 Diabetes. Prevalence and Predictive Factors

a prospective, observational, multi-center study with a cohort of 300 patients with Type 2 diabetes and macroalbuminuria. Prospectively we will collect kidney biopsies and analyse the transciptome of the kidney tissue and other biomarkers from blood, faeces, urine, proteomic- and metabolomic profiles and DNA-variants. Thereby we hope to be able to discover molecular and clinical profiles, that can help us in the diagnosis of DKD, and to identify different risks of progression that can benefit from different forms of personalized treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The PRIMETIME project is made to bring together molecular, translational and clinical scientists to create collaborations and build a scientific bridge between diabetology, nephrology, clinical biochemistry, and pathology. The ultimately goal is to bring forward an improved understanding of the most frequent cause of end stage renal disease: DKD. We aim to improve the diagnostic accuracy as well as the treatment precision by investigating in detail the features of histology and protein expression in both retrospective(WP1) and prospective(WP2) kidney biopsy material.

PRIMETIME WP2 is a prospective, observational, multi-center study with a cohort of 300 patients. We plan to create a systematically unselected cohort of patients with Type2 diabetes and macroalbuminuria as a sign of kidney injury. Prospectively we will collect research kidney biopsies and other biomarkers from blood, faeces, urine, proteomic- and metabolomic profiles and DNA-variants. The biopsies will be thoroughly investigated with cutting-edge molecular technologies and associated to the biomarkers, disease course and clinical outcome. The participants will afterward be followed in 20 years.Thereby we hope to be able to discover molecular and clinical profiles, that can help us in the diagnosis of DKD, and to identify different risks of progression that can benefit from different forms of personalized treatment.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Recruiting
        • Aalborg Universitetshospital
        • Contact:
          • Charlotte Strandhave, MD PhD
        • Contact:
          • Peter Vestergaard
      • Gødstrup, Denmark
        • Recruiting
        • Regionshospitalet Gødstrup
        • Contact:
          • Frank H Mose
      • Herlev, Denmark, 2730
        • Recruiting
        • Herlev Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Iain Bressendorff, MD, PhD
        • Sub-Investigator:
          • Bo Broberg, MD
      • Hillerød, Denmark, 3400
      • Holbæk, Denmark, 4300
      • Køge, Denmark, 4600
        • Recruiting
        • Sjællands Universitetshospital, Køge
        • Contact:
      • Odense, Denmark
        • Recruiting
        • Odense Universitetshospital
        • Contact:
          • Karoline Schousboe
      • Roskilde, Denmark, 4000
        • Recruiting
        • Sjællands Universitetshospital, Roskilde
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Bjarne Ørskov, MD, PhD
      • Slagelse, Denmark, 4200
    • Aarhus
    • Gentofte
    • København Ø
      • Copenhagen, København Ø, Denmark, 2100
        • Recruiting
        • Rigshospitalet
        • Contact:
        • Contact:
          • Thomas Almdal, MD, MDSc
    • Nykøbing F
      • Nykøbing Falster, Nykøbing F, Denmark, 4800

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

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

People with type 2 diabetes, albuminuria and eGFR > 30 who are willing to undergo a kidney biopsy

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Written informed consent
  • Diagnosis with T2DM according to the American diabetes Association (20)
  • eGFR >30 mL/min/1.73 m2 (maximum six months old)
  • urine-albumin/creatinine-ratio (uACR) > 700 mg/g or 24 hours urine albumin >700 mg on more than one measurement

Exclusion Criteria:

  • Signs of acute kidney failure according to the KDIGO classification (21) at the time for kidney biopsy or the last 6 months before kidney biopsy

  • Factors that increases the risk of complications due to kidney biopsy:

    • Hemoglobin < 6 mmol/L
    • INR >1,4 at the time for biopsy
    • Platelet count < 100 x 109/l
    • Uncontrolled high blood pressure (defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg)
    • Only one functioning kidney
    • Evidence of urinary tract obstruction or hydronephrosis at the time of biopsy
    • Multiple bilateral kidney cysts
    • Kidney infection, peri-renal infection, or cutaneous infection that overlies the kidney at time for biopsy
    • Unwilling to receive blood transfusion
    • Unable to lie flat in bed six hours after biopsy
    • Any other contra-indications for percutaneous kidney biopsy according to local clinical guidelines
  • Unable to understand written and oral information
  • Kidney transplant recipient
  • Previous medical kidney biopsy
  • Women who are pregnant or planning to become pregnant before the kidney biopsy is performed
  • Treatment with Marcoumar (all other anticoagulants are accepted)

  • High thromboembolic risk combined with held in anticoagulation therapy according to the report "Perioperative regulation of antithrombotic treatment" (PRAB) (22)

    • mechanical heart valve
    • atrial fibrillation AND CHA2DS2-VASc> 5 and/or stroke within the last three months
    • recurrent venous thromboembolism OR venous thromboembolism within the last three months
    • less than 6 weeks after uncomplicated Acute Coronary Syndrome (ACS) with or without revascularization (Percutaneous Coronary Intervention (PCI)) with Bare Metal Stents (BMS) or Coronary Artery Bypass Grafting (CABG))
    • less than 3 months after uncomplicated ACS with revascularization (PCI with Drug Eluting Stent (DES))
    • less than 9-12 months after complicated ACS (e.g. reinfarction or stent thrombosis)
    • less than 1 month after revascularization in individuals with stable Coronary Artery Disease (CAD) (PCI with BMS or CABG)
    • less than 3 months after revascularization in individuals with stable CAD (PCI with DES)
    • less than 3 months after stroke, or Transient Ischemic Attack (TIA)
  • Inability to withdraw nonsteroidal anti-inflammatory drugs (NSAID) 7 days before biopsy

If a participant meets one or more exclusion criteria, that are reversible, the participant can be rescreened later on, to evaluate whether or not the participant now is qualified for participation.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Peolpe with T2DM and albuminuria
Prospectively we will collect research kidney biopsies and other biomarkers from blood, faeces, urine, proteomic- and metabolomic profiles and DNA-variants. The biopsies will be thoroughly investigated with cutting-edge molecular technologies and associated to the biomarkers, disease course and clinical outcome.
Procedure: Kidney Biopsy
Harvesting of kidney tissue from people with type 2 diabetes and albuminuria for subsequent analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence
Time Frame: From baseline to end inclusion (3 years)
To investigate the prevalence of biopsy-proven diabetic nephropathy in individuals with T2DM with severe albuminuria; urine albumin/creatinine ratio (UACR) >700 mg/g.
From baseline to end inclusion (3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improved clinical diagnosis
Time Frame: From baseline to end inclusion (3 years)
To investigate whether clinical variables, transcriptomic, proteomic and/or metabolomic profiles as well as genetic variation can predict the presence of diabetic nephropathy in a kidney biopsy.
From baseline to end inclusion (3 years)
diabetic retinopathy
Time Frame: From baseline to end inclusion (3 years)
To describe the sensitivity and specificity of diabetic retinopathy in predicting biopsy-proven diabetic nephropathy
From baseline to end inclusion (3 years)
Kidney Biopsy
Time Frame: From baseline to end of followup (20 years)
describe the prognostic value of different histological and molecular findings on kidney biopsy in individuals with biopsy-proven diabetic nephropathy
From baseline to end of followup (20 years)
non-diabetic nephropathy vs. biopsy-proven diabetic nephropathy
Time Frame: From baseline to end of followup (20 years)
describe the prognostic value of different histological and molecular findings on the kidney biopsy in individuals with non-diabetic nephropathy compared to biopsy-proven diabetic nephropathy.
From baseline to end of followup (20 years)
proteomic and metabolomic
Time Frame: From baseline to end of followup (20 years)
describe the prognostic value of the proteomic and metabolomic profiles in biopsy-proven diabetic nephropathy.
From baseline to end of followup (20 years)
genetic variants
Time Frame: From baseline to end of followup (20 years)
describe the prognostic value of different forms of genetic variation in biopsy-proven diabetic nephropathy
From baseline to end of followup (20 years)
Microbiome
Time Frame: From baseline to end of followup (20 years)
describe the prognostic value of different compositions of the microbiome and its relation to biopsy and clinical findings
From baseline to end of followup (20 years)
Annual changes in kidney status
Time Frame: From baseline to end of followup (20 years)
Annual changes in kidney status (defined by yes/no: initiation of dialysis, kidney transplantation, renal death or decrease in eGFR > 40 % compared to eGFR at baseline)
From baseline to end of followup (20 years)
Annual decline in eGRF
Time Frame: From baseline to end of followup (20 years)
Annual decline in eGRF
From baseline to end of followup (20 years)
Annual changes in albuminuria.
Time Frame: From baseline to end of followup (20 years)
Annual changes in albuminuria.
From baseline to end of followup (20 years)
Annual events of cardiovascular disease
Time Frame: From baseline to end of followup (20 years)
Events of cardiovascular disease (fatal CV events, non-fatal stroke, non-fatal myocardial infarction, hospitalization for heart failure, PCI or bypass surgery (heart or legs), amputations due to ischemia, and unstable angina)
From baseline to end of followup (20 years)
Death
Time Frame: From baseline to end of followup (20 years)
Death (any cause).
From baseline to end of followup (20 years)

Collaborators and Investigators

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

Sponsor

Herlev Hospital

Collaborators

Odense University Hospital
Zealand University Hospital
Novo Nordisk A/S
Aarhus University Hospital
Rigshospitalet, Denmark
Hillerod Hospital, Denmark
Steno Diabetes Center Copenhagen
Aalborg University Hospital
Holbaek Sygehus
Gødstrup Hospital
Nykøbing Falster County Hospital
Steno Diabetes Center Sjaelland
The Novo Nordisk Foundation Center for Basic Metabolic Research
Slagelse Sygehus
Steno Diabetes Center Nordjylland
Gubra ApS
Michigan Kidney Translational Medical Center

Investigators

  • Study Chair: Frederik Persson, MD, PhD, Steno Diabetes Center Copenhagen

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)

August 10, 2021

Primary Completion (Estimated)

December 31, 2043

Study Completion (Estimated)

December 31, 2043

Study Registration Dates

First Submitted

June 1, 2021

First Submitted That Met QC Criteria

June 1, 2021

First Posted (Actual)

June 7, 2021

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 27, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRIMETIME2
  • H-20080050 (Other Identifier: National Ethical Committee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

This topic is still up for discussion. We do plan to share most of the data, but how, time and place are still undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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