Journal Club

Rakesh LatchamsettyOctober 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 events1

Background

1Go AS, Hsu C, et al. NEJM 2004. 351: 1296-1305.

3 Year Outcomes with CKD

Background

Go AS, Hsu C, et al. NEJM 2004. 351: 1296-1305.

Why is Renal Impairment Important?

• Renal insufficiency increases mortality in patients admitted with ACS2

Background

2Eagle KA, Fox KA et al. JAMA 2004. 291: 2727-2733

Background

Eagle KA, Fox KA et al. JAMA 2004. 291: 2727-2733

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 function3

3Latchamsetty R, Eagle KA, et al. AJC 2007. 99(7) 939-942.

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 2007. 99(7) 939-942.

ARF Following PCI has Worse Prognosis4

Background

4Rihal CS, Holmes DR, et al. Circulation 2002. 105(19): 2259-2264.

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 2006. 98 (6A) 21-26.

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 effect6

• Some data on mortality reduction6

6Marenzi G, Bartorelli A, NEJM 2006. 354(26):2773-2782.

CVVH• Previous study showing CVVH can reduce

renal failure and improve outcomes in CKD7

– 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

7Marenzi G, Bartorelli A, et al. NEJM 2003. 349:1333-1340.

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 4th 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 318

- 88 with ESRD 230-122 with Cr <3.5 108 - 18 refused 90 - 8 received NSAIDs/mucomyst/contrast 82 Enrolled

Results

Demographics• The 2 groups were well matched

Results

Change in Creatinine ClearanceResults

Change in CreatinineResults

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:Dialysis Control6 +/- 3 days 13 +/- 18 days p=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