Contrast Induced Nephropathy

Contrast Induced Nephropathy

CIN

CIN

What is CIN?• Contrast-Induced Nephropathy (CIN) is a form

of Acute Renal Failure that is caused by exposure to contrast media during image-guided cardiology and radiology procedures.

• These less invasive, image-guided medical procedures require the use of an iodine-based radio-contrast media, or dye, to facilitate the capture and display of x-ray images, which are known to be toxic to the kidney.

CIN

Although the exact mechanisms of CIN pathogenicity is not fully elucidated, several causes have been described:

• Concentrated contrast agents in the collecting duct , will become increasingly viscous and can lead to tubular obstruction , ending with high tubular and intrarenal tissue pressure.

• This will result, in decreasing of the renal perfusion pressure for the renal medulla (17mmHg)and critical kidney areas , which end with hypoxic injury.

• Ischemia in the deeper portion of the outer medulla due to vasoconstriction induced with increased production of adenosine, endothelin, and free radical, and reduction in nitric oxide, and prostaglandin induced vasodilatation.

• Finally, Contrast Media also increase resistance to blood flow by increasing blood viscosity and by decreasing red cell deformability.

• This intravascular sludging generates local ischemia and causes activation of reactive oxygen species that result in tubular damage at a cellular level.

CIN

How is CIN determined?• In clinical practice, CIN is usually defined as an

increase in serum creatinine concentration of >0.5 mg/dL (>44 μ mol/L) or 25% above baseline within 48 hours after contrast administration (some references say up to 7days after a procedure).

• CIN rates vary widely depending on the patient population and baseline risk factors.

CINWhat factors may affect a patient's risk of

acquiring CIN?• There are many factors that may increase a

patient's risk of acquiring CIN. • These risk factors are the parameters of a risk

score for prediction of CIN after percutaneous coronary intervention which has been reported by Mehran et al.

Mehran Scoring system

So the incidence of CIN increases with :• Renal Insufficiency ( eGFR; GFR in mL/min per

1.73 m2).IF eGFR is POINTS

60-40 2

40-20 4

<20 6

Mehran Scoring system• Congestive Heart Failure (5 points, if class

III/IV, or history of pulmonary oedema).• Hypotension (5 points, if systolic blood

pressure <80 mm Hg for at least 1 hour requiring inotropic support).

Mehran Scoring system

Mehran Scoring systemscore Risk of CIN

A risk score of <6 7.5%

6 to 10 14%

11 to 16 26%

>16 57%

CINWhat are the potential consequences?CIN is associated with increased:• Major adverse in-hospital cardiac events;• In-hospital mortality rates;• Long-term mortality;• Risk of acceleration toward end-stage renal

disease (dialysis);• Longer and more frequent hospital stays.These consequences usually lead to higher health

care costs.

Development of Renal insufficiency • CIN is normally a transient process, with renal

functions reverting to normal within 7-14 days of contrast administration.

• Less than one-third of patients develop some degree of residual renal impairment.

CIN

• The risk of CIN is directly proportional to the severity of pre-existing renal insufficiency.

• Patients with renal insufficiency are easily identified with : serum creatinine, and estimated Glomerular Filtration Rate (eGFR).

• According to the National Kidney Foundation, eGFR is the best estimate of kidney function.

CINstage Description eGFR

1 Kidney damage (protein in the urine) and normal GFR

More than 90

2 Kidney damage and mild decrease in GFR

60-89

3 Moderate decrease in GFR 30-59

4 Severe decrease in GFR 15-29

5 Kidney failure (dialysis or kidney transplant needed)

Less than 15

• Dialysis is required in less than 1% of patients, with a slightly higher incidence in patients with underlying renal impairment (3.1%) and in those undergoing primary PCI for myocardial infarction (MI) (3%).

• Diabetic and severe CKD patients have a rate of dialysis up to 12%.

• 18% of Dialyzed patients, end up on permanent dialysis therapy.

CIN

Mortality

• According to Marenzi, et al, hospitalized patients who received contrast media and who acquired CIN, had significantly higher mortality rate (31% vs. .6%) than patients who did not acquire CIN.

• There is a complicated relationship between CIN, co-morbidity, and mortality.

• Most patients who develop CIN do not die from renal failure.

• Death, if it does occur, is more commonly from either a pre-existing none renal complication or a procedural complication.

• Patients who require dialysis have a considerably worse mortality rate, with reported rates of 35.7% in hospital mortality (compared with 7.1% in the non dialysis group) and a 2-year survival rate of only 19%.

• CIN by itself may be an independent mortality risk factor.

• Following invasive cardiology procedures, patients with normal baseline renal function who develop CIN have reduced survival compared with patients with baseline chronic CKD who do not develop CIN.

Are there any effective prevention methods?

• "No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing the risk of CIN.“


• The lack of effective treatment to prevent CIN remains problematic for patients with renal-insufficiency.

• Most studies of measures to prevent CIN have either been neutral, found deleterious effects, or have reported conflicting results.


• Specifically, prevention strategies involving calcium-channel blockers, endothelin receptor antagonists, theophylline, prostaglandins, diuretics, anti-oxidants, or other reno-protective drugs have been shown to have no benefit or to have little consistent effect.


• Current evidence does not support the use of post procedural haemodialysis for prevention of CIN (3 of 58 patients [5%] ).

• However, periprocedural hemofiltration given in an intensive care unit setting appears to be effective in preventing CIN ( 28 of 56 patients [50%]), which is associated with improved in-hospital and long-term outcomes.


• However, periprocedural hemofiltration is an invasive and costly procedure that is not directly applicable to all high-risk patients who are exposed to contrast agents for simpler procedures.


Hydration Therapy:• The first study revealing the benefit of

hydration in CIN prevention came from Solomon et al.

• Current evidence supports peri-procedural hydration with preferably intravenous administration of 0.9% isotonic saline or an isotonic sodium bicarbonate solution, without furosemide, mannitol, or dopamine.


• Adequate intravenous volume expansion with isotonic crystalloids (1-1.5 mL/kg/h), 3-12 hours before the procedure and continued for 6-24 hours afterward, decreases the incidence of CIN in patients at risk.

• Post procedure volume expansion is more important than pre-procedure hydration.


• For hospitalized patients, volume expansion should begin 6 hours prior to the procedure and be continued for 6-24 hours post procedure.

• For outpatients, administration of fluids can be initiated 3 hours before and continued for 12 hours after the procedure.


• It has been suggested that a urine output of 150 mL/h should guide the rate of intravenous fluid replacement (not very ipmortant).

• Normal saline has been found to increase delivery of sodium to the distal nephron, prevents rennin-angiotensin activation, and thus maintains increased renal blood flow.


• CHF poses a particular challenge. • Patients with compensated CHF should still be

given volume, albeit at lower rates.• Uncompensated CHF patients should undergo

hemodynamic monitoring, if possible, and diuretics should be continued.


• In emergency situations, one’s clinical judgment should be used, and, in the absence of any baseline renal function, adequate post-procedure hydration should be carried out.

• What is interesting, however, is that, while hydration remains the cornerstone for CIN prevention, a randomized, controlled trial comparing a strategy of volume expansion with no volume expansion has not been performed to date.


Bicarbonate Therapy:• Bicarbonate protocols most often include

infusion of sodium bicarbonate at the rate of 3 mL/kg/hour an hour before the procedure, continued at 1 mL/kg/hour for 6 hours after.

• Some investigators have used 1 mL/kg/hour for 24 hours, starting 12 hours before the procedure.


• The exact duration, however, remains a matter of debate.

• Hydration with sodium bicarbonate has been found by some researchers to be more protective than normal saline alone


• Bicarbonate therapy alkalinizes the renal tubular fluid and, thus, prevents free radical injury (hydroxide ion), through Harber-Weiss reaction, which is activated in an acidic environment.

• It also scavenges reactive oxygen species (ROS) from NO, such as peroxynitrite.


Treatment controversy• A 2008 retrospective cohort study at the Mayo Clinic

assessed the risk of CIN associated with the use of sodium bicarbonate, NAC, and the combination of sodium bicarbonate with NAC and found that, compared with no treatment, sodium bicarbonate used alone was associated with an increased risk of CIN. NAC alone or in combination with sodium bicarbonate did not significantly affect the incidence of CIN.

• The results were obtained after adjusting for confounding factors, including total volume of hydration, medications, baseline creatinine, and contrast iodine load.


Statins therapy:• Statins are widely used in coronary artery disease

(CAD) for their pleiotropic effects (favorable effects on endothelin and thrombus formation, plaque stabilization, and anti-inflammatory properties).

• It was believed that, given the vascular nature of CIN, they might have similar reno-protective effects.

• The data for statin use, however, are retrospective and anecdotal; they are taken mostly from patients already on statins who underwent PCI.


• A significantly lower incidence of CIN was found in patients treated with statins preoperatively (CIN incidence of 4.37% in the statin group vs 5.93% in the nonstatin group).

• However, prospective trials looking at statin use in patients undergoing noncardiac procedures are needed to better qualify this initial promise.


Type of contrast:• Gadolinium-based CM (used for magnetic

resonance imaging [MRI]), when compared with iodine-based CM, have a similar, if not worse, adverse effect profile in patients with moderate CKD and eGFR of less than 30 mL/min.

• Their use has been implicated in the development of nephrogenic systemic fibrosis, a chronic debilitating condition with no cure


• The risk factor profile is similar to that for iodinated CM; increased incidence of acute renal failure is seen in older patients and in those with lower baseline creatinine clearance, diabetic nephropathy, anemia, and hypoalbuminemia.


• Many physicians seek to reduce the toxicity of contrast by reducing the volume given to at-risk patients in a procedure.

• For more complex procedures, a physician may stage procedures, or perform 2-3 procedures over a period of days, allowing for a reduction in the amount of contrast put into the vascular system at one time.


• A physician may endeavor to limit the amount of contrast used in a single procedure.

• These methods may present limitations for patients requiring imaging procedures to advance their care.

• Finally, and most important, a physician may decide that the risk of complications related to the use of contrast outweighs the benefit of a diagnosis or intervention.

Summary

• CIN is a common cause of acute renal functional impairment and accounts for significant morbidity and mortality.

• Patients with CKD, DM, congestive HF, elderly, hypotension, and anaemia are at particular risk.

• The primary goal should be to avoid contrast media to prevent CIN, if at all possible, and low-osmolar or iso-osmolar contrast media should be used to prevent CIN in at-risk patients.

Summary

History• Patients usually present with a history of

contrast administration 24-48 hours prior to presentation, having undergone a diagnostic or therapeutic procedure (eg, PCI). The renal failure is usually non-oliguric.

Summary

Physical examination• A physical examination is useful for ruling out

other causes of acute nephropathy.

• Patients may have evidence of volume depletion or may be in decompensated CHF.

The differential diagnosis of CIN include the following: • Atheroembolic renal failure - More than 1 week after

contrast, blue toes, livedo reticularis, transient eosinophilia, prolonged course, and lower recovery

• Acute renal failure (includes prerenal and postrenal azotemia) - There may also be associated dehydration from aggressive diuresis, exacerbated by preexisting fluid depletion; the acute renal failure is usually oliguric, and recovery is anticipated in 2-3 weeks

• Acute interstitial nephritis (triad of fever, skin rash, and eosinophilia) - Also eosinophiluria; the nephritis is usually drug induced: such as penicillin, cephalosporin's, and nonsteroidal anti-inflammatory drugs (NSAIDs)

• Acute tubular necrosis - Ischemia from prerenal causes; endogenous toxins, such as haemoglobin, myoglobin, and light chains; exogenous toxins, such as antibiotics, chemotherapeutic agents, organic solvents, and heavy metals.

How to approach:• S.Cr concentration usually begins to increase

within 24 hours after contrast, peaks between 3-5days, and returns to baseline in 7-10 days.

• Serum cystatin C (which has been suggested as a surrogate marker of renal function in lieu of SCr) is increased in patients with CIN.

• Nonspecific urine findings include epithelial cells, pigmented granular casts, urate crystals, and debris can be found which do not correlate with severity.

• Urine osmolality tends to be less than 350 mOsm/kg.

• The fractional excretion of sodium (FENa) may vary widely. In the minority of patients with oliguric CIN, the FENa is low in the early stages, despite no clinical evidence of volume depletion.

Histology• CM cause direct toxic effects on renal tubular

epithelial cells, characterized by cell vacuolization, interstitial inflammation, and cellular necrosis.

• In a study, these characteristic changes, called osmotic nephrosis, were observed in 22.3% of patients undergoing renal biopsy, within 10 days of contrast exposure

REFERENCES :

• PLC , medical system website.• Contemporary Reviews in Cardiovascular Medicine; Contrast-

Induced Nephropathy-A Clinical and Evidence-Based Approach; Martin Tepel, MD; Peter Aspelin, MD; Norbert Lameire, MD.

Health & Medicine

Contrast Induced Nephropathy