Furosemide forced diuresis with matched hydration vs Standard care of treatment in the prevention of contrast mediated nephropathy (CIN) due to percutaneous transluminal angioplasty (PTA): a randomized controled trial

Recent publications regarding the Renalguard showed a reduction in the
incidence of CIN among patients who received a PCI and where known with chronic
kidney failure. This study indicates that this relatively new technique is safe
and effective in the prevention of CIN. Marenzi et al. showed that the use of
the Renalguard in 87 patients is not associated with device related
complications. In this study an absolute reduction of 75% was evident in the
incidence of CIN, when compared to regular pre-hydration therapy (4.6% vs 18%).
These studies where all conducted in cardiac patients requiring endovascular
treatment. Up to now there are no randomised studies studying hydration therapy
with the Renalguard in patients with renal function impairment whom require
endovascular treatment of the lower limbs.

We hypothesise the following;
1. Lowering the incidence of contrast induced nephropathy is possible when the
diuresis is increased up to >300 ml/hour during the intervention (PTA) and is
continued up to 4hours after the revascularizing procedure, using furosemide
matched hydration aided by the the Renalguard.

2. The development of CIN can be detected in an early stage by detecting
certain urine biomarkers postoperative on the general ward, whereas diagnosing
CIN is nog possible after 72h postoperative in the detection of increased serum
creatinine.

Endpoints regarding;
Hypothesis 1.
Primary (clinical) success is defined as a 50% reduction in contrast induced
nephropathy (CIN) using the Renalguard combined with furosemide forced
diuresis.
Secondary outcomes are the CIN related adverse events, in-hospital events such
as; acute pulmonic oedema, cardiogenic shock, additional treatment due to CIN
and the mortality within 1 month.

Hypothesis 2.
Primary success is defined as an area under de curve greater than 0.70 of the
urine biomarkers for early detection of CIN.
Secondary we will determine the optimal cut-off point for the detection of CIN
with the biomarkers and calculate the sensitivity and specificity.

The objective of the study can be defined into two goals

1. Reduction of CIN using the Renalguard with furosemide forced diuresis in
patients known with chronic kidney failure whom require an endovascular
intervention of the lower
limbs.
2. Early detection of CIN by sampling the urine biomarkers; NGAL, KIM-1 and
IL-18 15 minutes after ending the revascularizing procedure on
the general ward. Comparing to the golden standard in detecting CIN,
rise of serum creatinine 72h after surgery.

To summarize, the aim of this study is to verify if the incidence of CIN can
be reduced by using the Renalguard with furosemide forced diuresis in patients
with chronic kidney failure who receive an endovascular intervention, when
compared to the standard care of treatment.
Secondly we would like to study whether certain urine biomarkers can detect CIN
in an early stage. The urine biomarkers that will be used are; NGAL, KIM-1 and
IL-18. We will evaluate if increase in these urine biomarkers postoperatively
are predictive in the development of CIN diagnosed 72hours postoperatively
using serum creatinine.

The previously mentioned study and hypothesis gave rise to the following study
design. The study is designed as an open randomised controlled trial. Blinding
of patient or investigator is nt possible. Pre-operative the patient will
sign the informed consent form, after which the patient will be randomised in
to either one of the two groups. Group one will include patients who will
receive pre- and post-hydration following hospital protocol. Group two will
include patients who will be hydrated perioperative using the Renalguard system
in combination with furosemide forced diuresis. An urine sample will be
collected 4 hours postoperative in both groups. For further information
regarding the randomisation process I would like to refer you to paragraph 8.2
of the study protocol.

Percutaneous transluminal angioplasty of the lower limbs. One group will
receive pre-hydration as is common regarding hospital protocol. The
intervention group will be hydrated perioperative using the Renalguard.

The study procedures are not related to additional burden or risks for the
patients. However to increase the diuresis the patient will receive a bolus of
furosemide (0.5mg/kg) and might experience some of the side-effects. The
following side effect are known to occur and are published online on the
*farmacotherapeutisch kompas*:

Very often (>10%): dehydration, hypovolemia, disturbance of electrolytes,
increased serum creatinine, increased serum triglycerides.

Often (1-10%): haemoconcentration leading to: hypo- sodium, -potassium, or -
chloride. Liver encephalopathy. Increased diuresis, increased cholesterol.
Increased uric acid in serum which might lead to a gout-attack.

Not so often (0.1-1%): thrombocytopenia. Hearing impairment, such as tinnitus
(often temporary), deafness (sometimes irreversible). Nausea. Itchiness,
urticaria, dermal rash, erythema multiforme, bullous dermatitis, pemphigoid,
exfoliative dermatitis, purpura, fotosensibilitation. Increased levels of urea
in serum, decreased glucose tolerance.