Diabetic Nephropathy in People With Diabetes. Prevalence and Predictive Factors

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Prevalence [Срок оценки: From baseline to end inclusion (3 years)]

Вторичные конечные точки (12)

• Improved clinical diagnosis [Срок оценки: From baseline to end inclusion (3 years)]
• diabetic retinopathy [Срок оценки: From baseline to end inclusion (3 years)]
• Kidney Biopsy [Срок оценки: From baseline to end of followup (20 years)]
• non-diabetic nephropathy vs. biopsy-proven diabetic nephropathy [Срок оценки: From baseline to end of followup (20 years)]
• proteomic and metabolomic [Срок оценки: From baseline to end of followup (20 years)]
• genetic variants [Срок оценки: From baseline to end of followup (20 years)]
• Microbiome [Срок оценки: From baseline to end of followup (20 years)]
• Annual changes in kidney status [Срок оценки: From baseline to end of followup (20 years)]
• Annual decline in eGRF [Срок оценки: From baseline to end of followup (20 years)]
• Annual changes in albuminuria. [Срок оценки: From baseline to end of followup (20 years)]
• Annual events of cardiovascular disease [Срок оценки: From baseline to end of followup (20 years)]
• Death [Срок оценки: From baseline to end of followup (20 years)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Дания · 13 центров

• Aarhus Universitetshospital, Skejby — Skejby
• Steno Diabetes Center Copenhagen — Copenhagen
• Kristine D Schandorff — Hillerød
• Holbæk Hospital — Holbæk
• Rigshospitalet — Copenhagen
• Sjællands Universitetshospital, Køge — Køge
• Nykøbing Falster Sygehus — Nykøbing Falster
• Sjællands Universitetshospital, Roskilde — Roskilde
• … и ещё 5 центров

Публикации

• Moller M, Borg R, Bressendorff I, Fink LN, Gravesen E, Jensen KH, Hansen T, Krustrup D, Persson F, Rossing P, Sembach FE, Thuesen ACB, Hansen D. Rationale and design of a prospective, clinical study of kidney biopsies in people with type 2 diabetes and severely increased albuminuria (the PRIMETIME 2 study). BMJ Open. 2023 Jun 6;13(6):e072216. doi: 10.1136/bmjopen-2023-072216. PMID 37280026

Идентификаторы

NCT: NCT04916132 · PRIMETIME2 · H-20080050

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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