Validation of New Markers of Glomerular Filtration Rate: Dota Gadolinium and Calcium EDTA (MultiGFR)

Assistance Publique - Hôpitaux de Paris

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Kidney Diseases; Renal Insufficiency, Chronic

Treatments: Drug: Gd-DOTA; Drug: Calcium EDTA

Study type: Interventional

Funder types: Other

Identifiers

NCT02286258

P100151

Details and patient eligibility

About

The purpose of this study is to validate in comparison to a reference method (inuline) two novel non-radioactive biomarkers for glomerular filtration rate (GFR) measurement in chronic-kidney disease (CKD) patients and in healthy volunteers: Calcium-EDTA and Gd-DOTA.

Full description

Research on estimation and measurement of renal function has been greatly stimulated by the international concept of chronic kidney disease (CKD) and its classification into stages of severity based on the level of glomerular filtration rate (GFR) (National Kidney Foundation KDOQI and ANAES in 2002, KDIGO conference in 2005), and by the development of recommendations for clinical practice according to this stages. Many efforts have focused on the validation of new formula to estimate GFR from endogenous markers. Nevertheless, the performance of these formula is limited by a large inter individual variability, that requires in many cases the use of GFR measurement using exogenous tracers (extreme anthropometric characteristics, abnormal production of endogenous tracers, potential kidney donors, dose adjustment, nephrotoxicity monitoring...). The use of GFR measurement is burdened by a lack of availability due to methodological, biological and regulatory (for radioactive tracers) constraints. That's why a need exists for new validated tracers that will be more accessible and easier to use. Moreover, there are differences between the measurement techniques: single injection of the tracer or concentration equilibrium obtained by continuous infusion; plasma or urinary clearance.

Two new tracers for GFR measurement are here offered for validation: Gd-DOTA and Calcium-EDTA. Gd-DOTA is a macrocyclic paramagnetic contrast product, which can be measured using an ELISA type immunoassay. Although being widely used in radiology with higher doses than those that will be used for GFR measurement in the multi-GFR study, Gd-DOTA has never been involved in systemic nephrogenic fibrosis cases (ProFinest study). Calcium-EDTA has been used for many years for the chelation of heavy metals. Recently, a colorimetric assay for Calcium-EDTA measurement has been developed. Gd-DOTA and Calcium-EDTA clearance for GFR measurement will be compared to inuline clearance in healthy volunteers (25 for each new tracer) and CKD patients (150 for each new tracer).

Enrollment: 166 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Patients :

Inclusion Criteria:

• males or females without pregnancy
• age : 18-75
• stable chronic kidney disease stages 1 to 4 (MDRD KDIGO 2005), estimated GFR > 15 mL/min/1.73m²
• clinical GFR measurement indication

Exclusion Criteria:

• kidney transplantation
• allergic
• acute disease leading to acute change in GFR
• heavy metals poisoning (treated or not)
• gadolinium contrast agent in the previous month

Healthy volunteers :

Inclusion criteria

• males, 18-35 years old
• weight : 60-100 kg , BMI 18-27 kg/m²
• estimated GFR > 90 mL/min/1.73 m² (MDRD)
• acute diseases in the previous 7 days

Exclusion criteria :

• uro-nephrological disease (past or present)
• nephrotoxic drug chronic use in the previous 2 months
• allergic
• systemic disease (acute or chronic)

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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166 participants in 2 patient groups

Inuline - Calcium EDTA

Experimental group

Description:

Calcium EDTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).

Treatment:

Drug: Calcium EDTA

Inuline - Gd-DOTA

Experimental group

Description:

Gd-DOTA clearance for GFR measurement is compared to inuline clearance in healthy volunteers and CKD patients (stage 1 to 4).

Treatment:

Drug: Gd-DOTA