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WELCOME TO JOURNAL
PRESENTATION….
Dr. Hasan Mahmud Iqbal
MD Cardiology Thesis Part.
NHFH&RI
1
JACC February 2017
2
INTRODUCTION
Contrast-induced acute kidney injury (CI-AKI), also
known as contrast-induced nephropathy, is a
frequent complication following angiographic
procedures with significant impact on health care
costs and a powerful predictor of unfavourable early
and long-term outcomes.
3
•Contrast induced acute kidney injury is defined as a
rise in serum creatinine (SCr) of 0.5 mg/dl (44.2 mmol/l)
or a 25% relative rise in SCr within 72 h of contrast
exposure in the absence of an alternative cause.
•Because accumulation of SCr is relatively slow, it
requires 48 to 72 h to identify many cases of CI-AKI.
•Acute kidney injury up to 7 days post–contrast
administration could be considered CI-AKI.
4
•Incidence of CI-AKI - 1% to 2%.
•Incidence significantly higher in patients with
diabetes mellitus and pre-existing renal impairment.
•Patients usually have symptoms such as anuria,
electrolyte imbalance, hypotension, or hypertension
and may need renal replacement therapy(RRT).
5
• In patients with pre-existing renal impairment, the
risk for CI-AKI - as high as 50%.
•It is also procedure dependent, with 14.5% overall in
patients undergoing PTCA compared with 1.6% to
2.3% for diagnostic intervention.
•In patients undergoing percutaneous coronary
intervention, each 100 ml of contrast was associated
with a 12% increased risk for CI-AKI.
6
•The optimal treatment for preventing CI-AKI has
not yet been defined : trials of N-acetylcysteine,
diuretic agents, dopamine, calcium-channel
blockers, atrial natriuretic peptides, aminophylline,
statins, and endothelin antagonists have yielded
contrasting results.
•Only periprocedural hydration is widely accepted
to prevent contrast nephropathy.
7
8
Recently, a novel system aimed at reducing CI-AKI was
introduced.
The RENALGUARD SYSTEM delivers intravenous fluids
matched to urine output with a combination of hydration
with normal saline at an initial bolus dose plus a low dose
of furosemide and continuous monitoring for a urine
output flow of >300 ml/h sustained for 6 h.
The aim of this systematic review and meta
analysis was to evaluate if furosemide with
matched hydration using the RenalGuard System
effectively decreases the incidence of CI-AKI in
patients undergoing interventional procedures.
9
METHODS
•Investigators independently searched PubMed,
Embase, and the Cochrane Central Register of Clinical
Trials (last updated October 1, 2016) for appropriate
reports.
•The search strategy aimed to include any randomized
study ever performed with furosemide with matched
hydration with the RenalGuard System compared with
any control group in adult in interventional cardiology
settings.
10
Study Flow Diagram
1 11
STUDY SELECTION
Eligible studies met the following PICOS criteria:
1. Population: adult hospitalized patients undergoing
interventional procedures;
2. Intervention: furosemide with matched hydration with
the RenalGuard System;
3. Comparison intervention: any type of control group;
4. Outcome: incidence of CI-AKI;
5. Study design: randomized controlled trials.
12
•The exclusion criteria were overlapping
populations and pediatric studies.
•Two investigators independently assessed
selected studies for the final analysis, with
eventual divergences finally resolved by
consensus with a third investigator.
13
•The primary outcome of the present review
was the incidence of CI-AKI.
•The secondary outcomes were need for RRT,
mortality at longest follow-up available, acute
coronary syndromes, stroke or transient
ischemic attack, and adverse events.
•The outcomes were reported as per-study
definition
14
STUDY CHARACTERISTICS
Data Analysis:
•To analyze the binary outcome, investigators calculated
odds ratio (OR) with 95% confidence interval (CI).
•Investigators also calculated the number needed to
treat in case of statistically significant results.
•To assess between-study heterogeneity, investigators
used the Cochran Q statistics.
15
16
A total of 33,463 patients from 147 studies were
eligible for inclusion. Treatments including:
•saline (reference
treatment),
•saline plus N-acetylcysteine,
•sodium bicarbonate,
• sodium bicarbonate plus N-
acetylcysteine,
• ascorbic acid,
• statins,
• furosemide,
• probucol,
• methylxanthines,
• fenoldopam,
• device-guided matched
hydration,
• renal replacement
therapy,
• nebivolol,
• natriuretic peptides,
• mannitol,
• prostaglandins,
• trimetazidine and
• LVEDP-guided hydration,
117
RESULT:
•The large majority of cardiovascular invasive procedures
were coronary angiographies with or without
percutaneous coronary intervention.
• The study mean age of participants was 65.0 years.
• On average, 142.80 mL of contrast agent per procedure
was administered.
•The number of patients and events for single pair wise
comparisons are shown in Table.
18
RESULT
All trials used the RenalGuard System for the
prevention of CI-AKI in patients undergoing coronary
artery procedures or transcatheter aortic valve
replacement.
All trials administered specific treatments as control:
isotonic saline, intravenous sodium bicarbonate plus
N-acetylcysteine, or sodium bicarbonate plus isotonic
saline plus N-acetylcysteine plus vitamin C.
19
RESULT
Overall, RenalGuard therapy was associated with a lower
incidence of CI-AKI compared with control treatment.
(The level of evidence according to GRADE was
moderate).
RenalGuard therapy was associated with a lower need
for RRT. (The level of evidence according to GRADE was
low).
20
RESULT
The efficacy of the RenalGuard system was confirmed to
patients with GFRs <60 ml/min who underwent elective
coronary procedures or urgent coronary procedures for
non–ST-segment elevation acute myocardial Infarction.
Furosemide with matched hydration was associated with
a lower incidence of acute kidney injury also in TAVR
21
SAFETY PROFILE AND ADVERSE
EVENTS
•No life threatening adverse events were reported in
patients undergoing RenalGuard therapy.
•Because of the nature of the intervention, perioperative
pulmonary edema could be considered one of the
worrying adverse events.
•However, the meta-analysis for perioperative pulmonary
edema showed no difference between the RenalGuard
and control groups.
22
RESULT
•Other potential adverse effects include electrolyte
imbalance due to the high volume of saline administered
with furosemide forced diuresis.
•However, the trials reported no symptomatic
electrolyte disorders.
•The meta-analysis of asymptomatic hypokalemic events
did not find significant differences between RenalGuard
and control group.
•Length of hospital stay was not different between the
two groups.
23
Forest plots for effect sizes of treatment strategies
compared with saline, for mortality, dialysis,
myocardial infarction and heart failure.
24
25
Forest plots comparing effect of treatment strategies compared
with saline, for mortality & acute coronary syndrome.
26
RenalGuard therapy was found to significantly decrease both
contrast-induced acute kidney injury (CI-AKI) and renal
replacement therapy
27
Forest plots comparing effect of treatment strategies
compared with saline, for stroke /TIA, Pulmonary Oedema.
KEY POINTS :
•Contrast media have direct toxic effect on renal tubular
cells, causing vacuolization and altered mitochondrial
function.
•As a consequence, nitric oxide–mediated mechanism
and prostaglandin induced vasodilatation are inhibited,
leading to vasoconstriction and consequently to ischemia
of the vascular supply of kidney medulla.
28
KEY POINTS…
The mechanism of action of the RenalGuard is not yet
fully elucidated, but one can postulate that the high urine
output (>300 ml/h) maintained during the procedure has
a direct protective effect on the tubular cells and
improves simultaneously renal medulla perfusion, thus
counterbalancing the direct and the ischemic effects
induced by the contrast media.
However, there remains much to be learned about the
mechanisms of possible effects of this system on renal
function.
29
KEY POINTS…
Generally, CI-AKI follows a benign course, and persistent
renal impairment and dialysis dependence are rare.
In that regard, seldom is there considerable risk for RRT in
CI-AKI, with need for dialysis only in <1% of patients with
CI-AKI and in about 3% of patients undergoing primary
PCI for acute coronary syndromes.
In some patients, such as those with chronic kidney
disease or diabetes mellitus, however, up to 7% require
transient dialysis.
30
KEY POINTS…
Another crucial point is RenalGuard’s safety.
Particular attention should be paid to
the systemic effect related to volume and diuretic agent
administration ie, pulmonary congestion and electrolyte
Imbalance.
Urological complications related to the Foley’s catheter,
because urological problems might have potential serious
consequences, particularly in men undergoing interventions
with the use of antithrombotic drugs.
31
CONCLUSION…
•The main findings of this meta-analysis is that
furosemide with matched hydration by the
RenalGuard System seems to reduce the
incidence of CI-AKI and RRT in high-risk patients
undergoing interventional procedures.
•Further independent high-quality multicenter
randomized trials should elucidate the safety of
the RenalGuard System in the intevertional
procedures.
32
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Prevention of contrast nephropathy,CIN.

  • 1. WELCOME TO JOURNAL PRESENTATION…. Dr. Hasan Mahmud Iqbal MD Cardiology Thesis Part. NHFH&RI 1
  • 3. INTRODUCTION Contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy, is a frequent complication following angiographic procedures with significant impact on health care costs and a powerful predictor of unfavourable early and long-term outcomes. 3
  • 4. •Contrast induced acute kidney injury is defined as a rise in serum creatinine (SCr) of 0.5 mg/dl (44.2 mmol/l) or a 25% relative rise in SCr within 72 h of contrast exposure in the absence of an alternative cause. •Because accumulation of SCr is relatively slow, it requires 48 to 72 h to identify many cases of CI-AKI. •Acute kidney injury up to 7 days post–contrast administration could be considered CI-AKI. 4
  • 5. •Incidence of CI-AKI - 1% to 2%. •Incidence significantly higher in patients with diabetes mellitus and pre-existing renal impairment. •Patients usually have symptoms such as anuria, electrolyte imbalance, hypotension, or hypertension and may need renal replacement therapy(RRT). 5
  • 6. • In patients with pre-existing renal impairment, the risk for CI-AKI - as high as 50%. •It is also procedure dependent, with 14.5% overall in patients undergoing PTCA compared with 1.6% to 2.3% for diagnostic intervention. •In patients undergoing percutaneous coronary intervention, each 100 ml of contrast was associated with a 12% increased risk for CI-AKI. 6
  • 7. •The optimal treatment for preventing CI-AKI has not yet been defined : trials of N-acetylcysteine, diuretic agents, dopamine, calcium-channel blockers, atrial natriuretic peptides, aminophylline, statins, and endothelin antagonists have yielded contrasting results. •Only periprocedural hydration is widely accepted to prevent contrast nephropathy. 7
  • 8. 8 Recently, a novel system aimed at reducing CI-AKI was introduced. The RENALGUARD SYSTEM delivers intravenous fluids matched to urine output with a combination of hydration with normal saline at an initial bolus dose plus a low dose of furosemide and continuous monitoring for a urine output flow of >300 ml/h sustained for 6 h.
  • 9. The aim of this systematic review and meta analysis was to evaluate if furosemide with matched hydration using the RenalGuard System effectively decreases the incidence of CI-AKI in patients undergoing interventional procedures. 9
  • 10. METHODS •Investigators independently searched PubMed, Embase, and the Cochrane Central Register of Clinical Trials (last updated October 1, 2016) for appropriate reports. •The search strategy aimed to include any randomized study ever performed with furosemide with matched hydration with the RenalGuard System compared with any control group in adult in interventional cardiology settings. 10
  • 12. STUDY SELECTION Eligible studies met the following PICOS criteria: 1. Population: adult hospitalized patients undergoing interventional procedures; 2. Intervention: furosemide with matched hydration with the RenalGuard System; 3. Comparison intervention: any type of control group; 4. Outcome: incidence of CI-AKI; 5. Study design: randomized controlled trials. 12
  • 13. •The exclusion criteria were overlapping populations and pediatric studies. •Two investigators independently assessed selected studies for the final analysis, with eventual divergences finally resolved by consensus with a third investigator. 13
  • 14. •The primary outcome of the present review was the incidence of CI-AKI. •The secondary outcomes were need for RRT, mortality at longest follow-up available, acute coronary syndromes, stroke or transient ischemic attack, and adverse events. •The outcomes were reported as per-study definition 14 STUDY CHARACTERISTICS
  • 15. Data Analysis: •To analyze the binary outcome, investigators calculated odds ratio (OR) with 95% confidence interval (CI). •Investigators also calculated the number needed to treat in case of statistically significant results. •To assess between-study heterogeneity, investigators used the Cochran Q statistics. 15
  • 16. 16 A total of 33,463 patients from 147 studies were eligible for inclusion. Treatments including: •saline (reference treatment), •saline plus N-acetylcysteine, •sodium bicarbonate, • sodium bicarbonate plus N- acetylcysteine, • ascorbic acid, • statins, • furosemide, • probucol, • methylxanthines, • fenoldopam, • device-guided matched hydration, • renal replacement therapy, • nebivolol, • natriuretic peptides, • mannitol, • prostaglandins, • trimetazidine and • LVEDP-guided hydration,
  • 17. 117
  • 18. RESULT: •The large majority of cardiovascular invasive procedures were coronary angiographies with or without percutaneous coronary intervention. • The study mean age of participants was 65.0 years. • On average, 142.80 mL of contrast agent per procedure was administered. •The number of patients and events for single pair wise comparisons are shown in Table. 18
  • 19. RESULT All trials used the RenalGuard System for the prevention of CI-AKI in patients undergoing coronary artery procedures or transcatheter aortic valve replacement. All trials administered specific treatments as control: isotonic saline, intravenous sodium bicarbonate plus N-acetylcysteine, or sodium bicarbonate plus isotonic saline plus N-acetylcysteine plus vitamin C. 19
  • 20. RESULT Overall, RenalGuard therapy was associated with a lower incidence of CI-AKI compared with control treatment. (The level of evidence according to GRADE was moderate). RenalGuard therapy was associated with a lower need for RRT. (The level of evidence according to GRADE was low). 20
  • 21. RESULT The efficacy of the RenalGuard system was confirmed to patients with GFRs <60 ml/min who underwent elective coronary procedures or urgent coronary procedures for non–ST-segment elevation acute myocardial Infarction. Furosemide with matched hydration was associated with a lower incidence of acute kidney injury also in TAVR 21
  • 22. SAFETY PROFILE AND ADVERSE EVENTS •No life threatening adverse events were reported in patients undergoing RenalGuard therapy. •Because of the nature of the intervention, perioperative pulmonary edema could be considered one of the worrying adverse events. •However, the meta-analysis for perioperative pulmonary edema showed no difference between the RenalGuard and control groups. 22
  • 23. RESULT •Other potential adverse effects include electrolyte imbalance due to the high volume of saline administered with furosemide forced diuresis. •However, the trials reported no symptomatic electrolyte disorders. •The meta-analysis of asymptomatic hypokalemic events did not find significant differences between RenalGuard and control group. •Length of hospital stay was not different between the two groups. 23
  • 24. Forest plots for effect sizes of treatment strategies compared with saline, for mortality, dialysis, myocardial infarction and heart failure. 24
  • 25. 25 Forest plots comparing effect of treatment strategies compared with saline, for mortality & acute coronary syndrome.
  • 26. 26 RenalGuard therapy was found to significantly decrease both contrast-induced acute kidney injury (CI-AKI) and renal replacement therapy
  • 27. 27 Forest plots comparing effect of treatment strategies compared with saline, for stroke /TIA, Pulmonary Oedema.
  • 28. KEY POINTS : •Contrast media have direct toxic effect on renal tubular cells, causing vacuolization and altered mitochondrial function. •As a consequence, nitric oxide–mediated mechanism and prostaglandin induced vasodilatation are inhibited, leading to vasoconstriction and consequently to ischemia of the vascular supply of kidney medulla. 28
  • 29. KEY POINTS… The mechanism of action of the RenalGuard is not yet fully elucidated, but one can postulate that the high urine output (>300 ml/h) maintained during the procedure has a direct protective effect on the tubular cells and improves simultaneously renal medulla perfusion, thus counterbalancing the direct and the ischemic effects induced by the contrast media. However, there remains much to be learned about the mechanisms of possible effects of this system on renal function. 29
  • 30. KEY POINTS… Generally, CI-AKI follows a benign course, and persistent renal impairment and dialysis dependence are rare. In that regard, seldom is there considerable risk for RRT in CI-AKI, with need for dialysis only in <1% of patients with CI-AKI and in about 3% of patients undergoing primary PCI for acute coronary syndromes. In some patients, such as those with chronic kidney disease or diabetes mellitus, however, up to 7% require transient dialysis. 30
  • 31. KEY POINTS… Another crucial point is RenalGuard’s safety. Particular attention should be paid to the systemic effect related to volume and diuretic agent administration ie, pulmonary congestion and electrolyte Imbalance. Urological complications related to the Foley’s catheter, because urological problems might have potential serious consequences, particularly in men undergoing interventions with the use of antithrombotic drugs. 31
  • 32. CONCLUSION… •The main findings of this meta-analysis is that furosemide with matched hydration by the RenalGuard System seems to reduce the incidence of CI-AKI and RRT in high-risk patients undergoing interventional procedures. •Further independent high-quality multicenter randomized trials should elucidate the safety of the RenalGuard System in the intevertional procedures. 32
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