Journal Club Rakesh Latchamsetty October 5, 2007

Renal Protection for Coronary Angiography in Advanced Renal Failure Patients by Prophylactic Hemodialysis Lee P, Chou K, Liu C, Mar G, Chung H, et al. JACC, Sept. 11, 2007

Why is Renal Impairment Important? CKD is associated with 3 year increased mortality and increased CV events 1 Background 1 Go AS, Hsu C, et al. NEJM :

3 Year Outcomes with CKD Background Go AS, Hsu C, et al. NEJM :

Why is Renal Impairment Important? Renal insufficiency increases mortality in patients admitted with ACS 2 Background 2 Eagle KA, Fox KA et al. JAMA :

Background Eagle KA, Fox KA et al. JAMA :

Even Temporary ARF has Worse Prognosis Background 6 month mortality in patients admitted with ACS is worse with acute renal failure, regardless of improvement in function 3 3 Latchamsetty R, Eagle KA, et al. AJC (7)

6 Month outcomes following ACS admission A – no change in creatinine B – Temporary rise in Cr C – Sustained rise Cr Background A B C Latchamsetty R, Eagle KA, et al. AJC (7)

ARF Following PCI has Worse Prognosis 4 Background 4 Rihal CS, Holmes DR, et al. Circulation (19):

Mechanism of CIN Background Multifactorial process -Vasoconstriction at the corticomedullary junction -Impairs autoregulatory capacity of kidney through loss of NO production -Direct tubular toxicity -Osmotic diuresis

Risk Factors for Developing CIN Background Pre-existing renal disease Diabetes Amount and type of contrast

Mechanism of CIN Background Tumlin J, McCullough P, et al. AJC (6A)

Methods to reduce CIN: – IVF – Low-osmolality contrast – Double dose mucomyst – Reducing contrast – Sodium Bicarbonate – CVVH Background

Low Osmolar Contrast Originally ionic monomers: hyperosmolar – 1500 to 1800 mOsm/kg Low-osmolar monomers of iodinated benzene rings (iohexol/omnipaque, iopamidol) – 600 to 850 mOsm/kg Nonionic dimer of benzene rings (iodaxinol/visipaque) – 290 mOsm/kg Background

N-Acetylcysteine Background Scavenges oxygen free radicals Shown to reduce incidence of CIN, dose- dependent effect 6 Some data on mortality reduction 6 6 Marenzi G, Bartorelli A, NEJM (26):

CVVH Previous study showing CVVH can reduce renal failure and improve outcomes in CKD 7 – Only elective cath/pci – Compared to NS alone Primary endpoint: 25% increase in Cr – 5 vs 50% (P<.001) One year mortality also decreased – 10 vs 30% (p=.01) Background 7 Marenzi G, Bartorelli A, et al. NEJM :

To determine whether prophylactic hemodialysis reduces CIN after coronary angiogram Objective

Inclusion Criteria Consecutive patients at Kaohsiung Veterans GH, Taiwan referred for coronary angiography > 20 years old Creatinine >3.5 mg/dl Methods

Exclusion Criteria Pregnancy or lactation Contrast in last 7 days Metformin or NSAIDs in last 48 hrs ESRD or renal txp Unstable new diabetes “Severe concomitant disease” Adverse contrast reaction in the past Methods

Protocol All given NS 6 hours before and 12 hours after cath Randomized to HD or not (control) Dialysis catheter placed before angiography Cath performed with nonionic iohexol (omnipaque) Dialysis performed as soon as possible after cath No fluid removal during dialysis Methods

Measurements CrCl by 24 hour urine before and on 4 th day after Serum creatinine on admission, day 4, and throughout hospitalization Need for emergent dialysis – Oliguria for 48 hours despite 1,000mg lasix per day – K + > 6 mEq/L Methods

Statistics Study was designed for significance of 5% and 90% power Required about 34 subjects in each group To compare baseline values: – Fisher exact test for categorical – Student unpaired t test for continuous Multiple regression to analyze variables affecting decrease in CrCl Methods

Endpoints Primary endpoint: change in CrCl between baseline and day 4 Secondary enpoints: – Change in Cr between baseline and day 4 – Peak Cr level – Cr level at discharge – Requirement of emergent or permanent dialysis Methods

Sample Space 3,724 consecutive patients receiving cath - 3,406 without CKD with ESRD with Cr < refused received NSAIDs/mucomyst/contrast 82Enrolled Results

Demographics The 2 groups were well matched Results

Change in Creatinine Clearance Results

Change in Creatinine Results

Factors associated with change in creatinine… Results

Further Outcomes 1 vs 14 needed temporary dialysis 5 control patients required permanent dialysis after discharge 2 vs 18 had increase in creatinine greater than 1 at discharge Results

Statistically Speaking… Cr increased > 1 at discharge: – control (45%) vs dialysis (5%), p<.001 – NNT = 2.5 Required maintenance dialysis after discharge: – control (13%) vs dialysis (0%) – NNT = 8 Results

Other Data/Outcomes Length of stay: DialysisControl 6 +/- 3 days13 +/- 18 daysp=0.017 No major complications in dialysis group Results

Limitations Limited sample size Single center Study not blinded Not compared to double dose mucomyst Did not use visipaque Only chose advanced renal disease Strong Endpoints? Discussion

Prophylactic HD in Advanced CKD Following Coronary Angiography: – Reduces discharge and maximum creatinine values – Probably reduces hospital stay – Probably prolongs need for permanent dialysis Conclusions

Prophylactic HD in Advanced CKD Following Coronary Angiography: – ? Effects on mortality, CV events – ? Effects on long term dialysis needs Conclusions

Will This Change How You Practice? Discussion