Neutrophil Gelatinase-associated Lipocalin (NGAL) and Contrast Media Induced Nephropathy

Study Overview
=================
Brief Summary
-----------------
Introduction: Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated Lipocalin (NGAL), a new biomarker predictive for acute renal injury has been shown to be capable for earlier diagnosis of acute contrast media induced nephropathy (CIN) in patients undergoing cardiac surgery. Intravenous volume load is a widely accepted prophylaxis. In this randomized and controlled study, only patients with the need for an intra-arterial contrast media (CM) application will be included and receive a standardized, weight-based, intravenous hydration before investigation. It is the aim of this study: to evaluate the magnitude of a risk for contrast media induced nephropathy (CIN) following intra-arterial angiography in a well defined group of high-risk patients. to use urinary Neutrophil gelatinase-associated Lipocalin (NGAL) as an early predictor of contrast media induced nephropathy (CIN) after contrast media (CM) application. to evaluate the clinical benefit of an early post-procedural i.v. hydration as compared to only pre-procedural volume expansion. Patients with markedly increased urinary Neutrophil gelatinase-associated Lipocalin (NGAL) after investigation will be randomized into one of two study groups: Patients of Group A will undergo standard treatment consisting of unrestricted oral fluid intake. Patients of Group B will additionally receive 3-4 ml/kg BW/h 0.9 % saline intravenously for 6 hours. Endpoints: Primary endpoint: contrast media induced nephropathy (CIN) defined by an increase greater than 25% of baseline serum creatinine. Secondary endpoint: NGAL, Cystatin C, and creatinine values, need for renal replacement therapy, death.

Detailed Description
-----------------
Introduction: Over the last decades the growing demand for appropriate diagnosing and intervention in all fields of modern medicine has increased the necessity for use of iodinated contrast media (CM). Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN) and consecutively have a greater risk of death. To date, a reliable laboratory value or test that recognizes acute renal damage before serum creatinine increases is still sought for. It would be a most helpful tool to initiate proper treatment on time. Neutrophil gelatinase-associated Lipocalin (NGAL), a new biomarker predictive for acute renal injury has been shown to be capable for earlier diagnosis of contrast media induced nephropathy (CIN) in patients undergoing cardiac surgery. So far, an intravenous volume load is the only fairly proven and widely accepted prophylaxis. However, the optimal intravenous fluid regimen regarding the type, amount, route and duration of volume application has remained controversial. Habits of giving pre- and post-procedural volume have been widely differing throughout all randomized trials and, thus, are not comparable in the available studies. Unfortunately, most studies were also lacking statistical power, used different types of contrast media (CM) and definitions of contrast media induced nephropathy (CIN) or allowed for additional prophylactic measures, such as N-acetylcysteine or sodium bicarbonate in a varying percentage of their patients. In our randomized and controlled study, only patients with the need for an intra-arterial contrast media (CM) application will be included. Patients scheduled for a diagnostic angiography and/or endovascular intervention will receive a standardized, weight-based, intravenous hydration before investigation. Only one type of contrast media (CM) and neither sodium bicarbonate, nor N-acetylcysteine is used throughout the study. The study will be performed according to the Consort-Statement 2010 for clinical trials. It is the aim of our study: to evaluate the magnitude of a risk for contrast media induced nephropathy (CIN) following intra-arterial angiography in a well defined group of high-risk patients. to use urinary Neutrophil gelatinase-associated Lipocalin (NGAL) as an early predictor of contrast media induced nephropathy (CIN) after contrast media (CM) application. to evaluate the clinical benefit of an early post-procedural i.v. hydration as compared to only pre-procedural volume expansion. Patients with markedly increased Neutrophil gelatinase-associated Lipocalin (NGAL) values (criteria for randomization into one of two treatment groups see below) at 4 to 6 hours after investigation will be randomized into one of two study groups: Patients of Group A will additionally receive 3-4 ml/kg BW/h 0.9 % saline intravenously for 6 hours. Patients of Group B will undergo standard treatment consisting of unrestricted oral fluid intake, at least 500 ml tea or water provided by the ward, but no intravenous fluid application. Criteria for Randomization (after 2nd NGAL testing): Patients with NGAL levels > 150 ng/ml, if baseline was below 75 ng/ml. Patients with doubling of NGAL values, if baseline was between 75 and 150 ng/ml. Endpoints: Primary endpoint: contrast media induced nephropathy (CIN) defined by an increase greater than 25% of baseline serum creatinine. Secondary endpoint: NGAL, Cystatin C, and creatinine values, need for renal replacement therapy, death.

Official Title
-----------------
Early Detection and Intervention of Acute Contrast Media Induced Nephropathy Using Neutrophil Gelatinase-associated Lipocalin (NGAL) May Improve Renal Outcome: A Study in Patients Undergoing Intra-arterial Angiography.

Conditions
-----------------
Contrast Media Induced Nephropathy (CIN)

Intervention / Treatment
-----------------
* Other: application of intravenous volume
* Other: oral fluid application


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with the need for intra-arterial angiography/angioplasty Patients older than 18 years Patients with clinically stable chronic renal insufficiency stage 2 and more (calculated GFR < 70 ml/min/1,73 m2)(65) Written informed consent Exclusion Criteria: Pre-existing clinical and/or laboratory evidence of acute renal failure at the time of enrollment Evidence of rhabdomyolysis Patients on renal replacement therapy (34) Patients with life-threatening underlying disease (sepsis, MOF, SIRS) Contraindication for volume therapy Pregnancy Contrast media application within 7 days prior to intervention

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: intravenous hydration<br>intravenous application of 0.9% saline | Other: application of intravenous volume<br>* weight based intravenous application of volume<br>|
| Active Comparator: oral hydration only<br> | Other: oral fluid application<br>* oral fluid application<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contrast media induced nephropathy (CIN) defined by an increase greater than 25% of baseline serum creatinine. |  | 4 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NGAL, neutrophil gelatinase-associated Lipocalin, contrast media nephropathy, CIN, volume expansion, acute kidney injury, contrast media