Clinical trial NCT04916132: Diabetic Nephropathy in People With Diabetes. Prevalence and Predictive Factors
Official title: Biopsy-proven Diabetic Nephropathy in People With Type 2 Diabetes. Prevalence and Predictive Factors
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Kidney Diseases
Albuminuria
Diabetic Kidney Disease
Diabetic Nephropathies
Diabetes type2
Molecular Sequence Variation
Kidney Biopsy
Keywords: diabetic nephropaty
precision medicine
kidney biopsy
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Hillerod Hospital, Denmark
name: Zealand University Hospital
name: Holbaek Sygehus
name: Slagelse Sygehus
name: Nykøbing Falster County Hospital
name: Aarhus University Hospital
name: The Novo Nordisk Foundation Center for Basic Metabolic Research
name: Novo Nordisk A/S
name: Gubra ApS
name: Odense University Hospital
name: Aalborg University Hospital
name: Gødstrup Hospital
name: Steno Diabetes Center Copenhagen
name: Steno Diabetes Center Sjaelland
name: Steno Diabetes Center Nordjylland
name: Michigan Kidney Translational Medical Center
First posted: 2021-06-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People with type 2 diabetes, albuminuria and eGFR \> 30 who are willing to undergo a kidney biopsy

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prevalence
timeFrame: From baseline to end inclusion (3 years)
Secondary outcomes:
measure: Improved clinical diagnosis
timeFrame: From baseline to end inclusion (3 years)
measure: diabetic retinopathy
timeFrame: From baseline to end inclusion (3 years)
measure: Kidney Biopsy
timeFrame: From baseline to end of followup (20 years)
measure: non-diabetic nephropathy vs. biopsy-proven diabetic nephropathy
timeFrame: From baseline to end of followup (20 years)
measure: proteomic and metabolomic
timeFrame: From baseline to end of followup (20 years)
measure: genetic variants
timeFrame: From baseline to end of followup (20 years)
measure: Microbiome
timeFrame: From baseline to end of followup (20 years)
measure: Annual changes in kidney status
timeFrame: From baseline to end of followup (20 years)
measure: Annual decline in eGRF
timeFrame: From baseline to end of followup (20 years)
measure: Annual changes in albuminuria.
timeFrame: From baseline to end of followup (20 years)
measure: Annual events of cardiovascular disease
timeFrame: From baseline to end of followup (20 years)
measure: Death
timeFrame: From baseline to end of followup (20 years)
Other outcomes:
Locations:
city: Skejby
country: Denmark
facility: Aarhus Universitetshospital, Skejby
state: Aarhus
city: Copenhagen
country: Denmark
facility: Steno Diabetes Center Copenhagen
state: Gentofte
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: København Ø
city: Nykøbing Falster
country: Denmark
facility: Nykøbing Falster Sygehus
state: Nykøbing F
city: Aalborg
country: Denmark
facility: Aalborg universitetshospital
city: Gødstrup
country: Denmark
facility: Regionshospitalet Gødstrup
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Hillerød
country: Denmark
facility: Kristine D Schandorff
city: Holbæk
country: Denmark
facility: Holbæk Hospital
city: Køge
country: Denmark
facility: Sjællands Universitetshospital, Køge
city: Odense
country: Denmark
facility: Odense universitetshospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital, Roskilde
city: Slagelse
country: Denmark
facility: Slagelse Sygehus
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Frederik Persson, MD, PhD
role: STUDY_CHAIR
References: