An Old Idea with a Modern Twist: Preventing Contrast-Induced Nephropathy

with Induced Diuresis and Matched Replacement

CIN Remains a Problem

Caused by a combination of factors: - Ischemia/hypoxia, viscosity/clogging, direct cellular toxicity/

apoptosis Risks increasing:

-Seeing sicker patients (CKD ↑, Diabetes ↑) - Dye loads increasing (CTO, TAVI, etc)

Outcomes for patients who develop CIN remain poor: - Increases mortality - Worsens cardiac outcomes - Speeds progression of chronic kidney disease

Induced Diuresis to Prevent CIN

Theory: Inducing diuresis flushes contrast out of the kidney, reducing concentration, preventing clogging and hypoxia.

Results: Induced diuresis alone found to be worse than control.

What happened? All patients who received induced diuresis lost fluid relative to control patients.

PRINCE Study1 found matching hourly urine output could reduce CIN rate 50% in patients who achieved 150 ml/hr urine output, but most patients did not achieve that urine rate.

Guidelines now encourage 150 ml/hr urine output, but provide no predictable guidance for achieving that rate.

RenalGuard® enables the benefits of high urine flows while preventing the negative effects of dehydration. RenalGuard Therapy®:

Provides automated matched fluid replacement in real-time, reducing risk of over- or under-hydration

Creates and maintains high urine output Prevents contrast agents from clogging

tubules Limits toxin exposure in kidneys Fits into normal cath lab flow: begins 1 hr

before catheterization, continues during procedure and for 4 hours afterwards.

Answer: RenalGuard Therapy

University of Modena Study5 RenalGuard vs. Sodium Bicarbonate vs. CVVH

RenalGuard Therapy Overview

MYTHOS3

RenalGuard Therapy vs. Overnight Hydration

RG Control P

Diabetes 38 (44%) 29 (35%) 0.24

eGFR

(ml/min) 38±11 41±10 0.17

Contrast

volume

(ml)

181±104 158±109 0.17

REMEDIAL II4

RenalGuard Therapy vs. Sodium Bicarbonate

RG

(N=146)

Control

(n=146) P

Diabetes 69% 71% 0.51

eGFR

(ml/min) 32±7 41±10 0.83

Contrast

volume

(ml)

145±79 135±76 0.29

Pilot Study Urine Rates2

23 Patient, Single-arm pilot trial

Average urine rates from the 23 patients enrolled in US Pilot Study. Average eGFR 39.1 +/- 9.3. All patients reached the 300 ml/hr urine rate shown to reduce incidence of CIN. The rapid increase and wide variation in urine rates demonstrates need for the automated matched replacement RenalGuard provides.

118

474684

638

523450

390348 324

353314

111

407

742

601 562

437377

325 310

411

312

0

200

400

600

800

1000

1200

0:30 1:00 2:00 3:00 4:00 5:00 6:00 7:00 8:00 9:00 10:00

ml/

hr

Time since RenalGuard Therapy Started (h:mm)

Urine Rate Infusion Rate

Investigators treated 100 consecutive patients with sodium bicarbonate (32 pts), CVVH (35 pts) and RenalGuard Therapy (33 pts).

Problem: Contrast-Induced Nephropathy (CIN)

Results: Four Clinical Reports

BR00035 Rev A

1 Stevens et al. J Am Coll Cardiol 1999;33(2):403-11 2 Dorval J-F, et al. International Journal of Cardiology. Dec 2011. 3 Marenzi et al. JACC Cardiovasc Interv. 2012;5(1):90-7. 4 Briguori et al. Circulation 2011;124(11):1260-9. 5 Bertelli et al. J Am Coll Cardiol 2012;59(13):E96.

For More information visit www.plcmed.com

RenalGuard System is CE-marked for the intended use of temporary (up to 14 days) replacement of urine output by infusion of a matched volume of sterile replacement solution to maintain a patient’s intravascular fluid volume, and has demonstrated accurate matched replace-ment and an appropriate safety profile with normal saline in limited human use. In the U.S., RenalGuard System and RenalGuard Therapy are limited to investigational use only. PLC, RenalGuard and RenalGuard Therapy are trademarks of PLC Systems Inc.