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

Sponsor

Herlev Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04916132

Collaborator

Rigshospitalet, Denmark (Other), Hillerod Hospital, Denmark (Other), Zealand University Hospital (Other), Holbaek Sygehus (Other), Slagelse Sygehus (Other), Nykøbing Falster County Hospital (Other), Aarhus University Hospital (Other), The Novo Nordisk Foundation Center for Basic Metabolic Research (Other), Novo Nordisk A/S (Industry), Gubra ApS (Other), Kidney Precision medicine Project (Other), Odense University Hospital (Other)

300

Enrollment

Locations

268.7

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Albuminuria Diabetic Kidney Disease Diabetic Nephropathies Diabetes type2 Molecular Sequence Variation Kidney Biopsy	Procedure: Kidney Biopsy

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 Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Aug 10, 2021

Anticipated Primary Completion Date :

Dec 31, 2043

Anticipated Study Completion Date :

Dec 31, 2043

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Prevalence [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.

Secondary Outcome Measures

Improved clinical diagnosis [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.
diabetic retinopathy [From baseline to end inclusion (3 years)]
To describe the sensitivity and specificity of diabetic retinopathy in predicting biopsy-proven diabetic nephropathy
Kidney Biopsy [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
non-diabetic nephropathy vs. biopsy-proven diabetic nephropathy [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.
proteomic and metabolomic [From baseline to end of followup (20 years)]
describe the prognostic value of the proteomic and metabolomic profiles in biopsy-proven diabetic nephropathy.
genetic variants [From baseline to end of followup (20 years)]
describe the prognostic value of different forms of genetic variation in biopsy-proven diabetic nephropathy
Microbiome [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
Annual changes in kidney status [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)
Annual decline in eGRF [From baseline to end of followup (20 years)]
Annual decline in eGRF
Annual changes in albuminuria. [From baseline to end of followup (20 years)]
Annual changes in albuminuria.
Annual events of cardiovascular disease [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)
Death [From baseline to end of followup (20 years)]
Death (any cause).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aarhus Universitetshospital, Skejby	Skejby	Aarhus	Denmark	8200
2	Steno Diabetes Center Copenhagen	Copenhagen	Gentofte	Denmark	2820
3	Rigshospitalet	Copenhagen	København Ø	Denmark	2100
4	Nykøbing Falster Sygehus	Nykøbing Falster	Nykøbing F	Denmark	4800
5	Herlev Hospital	Herlev		Denmark	2730
6	Kristine D Schandorff	Hillerød		Denmark	3400
7	Holbæk Hospital	Holbæk		Denmark	4300
8	Sjællands Universitetshospital, Køge	Køge		Denmark	4600
9	Sjællands Universitetshospital, Roskilde	Roskilde		Denmark	4000
10	Slagelse Sygehus	Slagelse		Denmark	4200