Diabetic Nephropathy in People With Diabetes. Prevalence and Predictive Factors

Chronic Kidney Diseases Clinical Trial

— PRIMETIME2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04916132
• Other study ID #: PRIMETIME2
• Secondary ID: H-20080050
• Status: Recruiting
• Start date: August 10, 2021
• Est. completion date: December 31, 2043

Study information

• Verified date: February 2024
• Source: Herlev Hospital
• Contact: Marie Møller
• Phone: +4561695364
• Email: marie.moeller[@]regionh.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2043
• Est. primary completion date: December 31, 2043
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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.

Related Conditions & MeSH terms

• Albuminuria
• Chronic Kidney Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetes type2
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Biopsy
• Kidney Diseases
• Molecular Sequence Variation
• Renal Insufficiency, Chronic

Intervention

Procedure:
• Kidney Biopsy
Harvesting of kidney tissue from people with type 2 diabetes and albuminuria for subsequent analysis

Locations

Country	Name	City	State
Denmark	Aalborg universitetshospital	Aalborg
Denmark	Rigshospitalet	Copenhagen	København Ø
Denmark	Steno Diabetes Center Copenhagen	Copenhagen	Gentofte
Denmark	Regionshospitalet Gødstrup	Gødstrup
Denmark	Herlev Hospital	Herlev
Denmark	Kristine D Schandorff	Hillerød
Denmark	Holbæk Hospital	Holbæk
Denmark	Sjællands Universitetshospital, Køge	Køge
Denmark	Nykøbing Falster Sygehus	Nykøbing Falster	Nykøbing F
Denmark	Odense universitetshospital	Odense
Denmark	Sjællands Universitetshospital, Roskilde	Roskilde
Denmark	Aarhus Universitetshospital, Skejby	Skejby	Aarhus
Denmark	Slagelse Sygehus	Slagelse

Sponsors (18)

Lead Sponsor

Collaborator

Herlev Hospital

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

Country where clinical trial is conducted

Denmark, 

Outcome

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