OUTLINE

1. CONTRAST INDUCED NEPHROPATHYPRESENTING UNIT: NEPHROLOGYPRESENTER: UGWUNZE TOSAN JENNIFERDATE: 12/02/2014

2. OUTLINE • INTRODUCTION • EPIDEMIOLOGY • BASIC PRINCIPES OF CONTRAST MEDIA • CONTRAST PHARMACOLOGY • ETIOLOGY • RISK FACTORS • PATHOGENESIS • RISK STRATIFICATION SCORING SYSTEM • DIAGNOSIS • DIFERENTIAL DIAGNOSIS • TREATMENT • PROGNOSIS • PREVENTION

3. INTRODUCTION • Association of contrast use with renal impairment was first made with use of Iodopyracet, a di-iodinated pyridine derivative more than 50 years ago. • In 2008, contrast – induced AKI [CI-AKI] was proposed as the concensus name for what was formerly called “contrast induced nephropathy”.

4. DEFINITION • Contrast induced nephropathy/contrast induced AKI[CIN/CI-AKI] is defined as impairment of renal function that is measured as either a 25% increase in serum creatinine (SCr) from baseline or • 0.5 mg/dL (44 µmol/L) increase in absolute value, within 48-72 hours of intravenous contrast administration in the absence of any other apparent cause.

5. EPIDEMIOLOGY • Occurrence in the United States • CIN is the third leading cause of hospital-acquired renal failure. • Reported incidence is 3.1-31%. • Incidence generally depends on pre existing risk factors and type of procedure undertaken. • In patients without risk factors, the incidence may be as low as 2%.

6. EPIDEMIOLOGY • With the introduction of risk factors, like diabetes, the number rises to 9%, • Incidence is as as high as 90% in diabetics with CKD. • Incidence is 14.5% overall in patients undergoing coronary interventions compared to 1.6-2.3% for diagnostic intervention.

7. Race- and age-related demographics • Race has not been found to be a risk factor for CIN. • The incidence of CIN in patients older than age 60 years has been variously reported as 8-16%.

10. CONTRAST MEDIA

11. CONTRAST MEDIA • Although the data is by no means uniform, they seem to suggest that the iso-osmolar contrast agent iodixanol may be associated with smaller increases in SCr and lower rates of CIN when compared with low-osmolar agents, especially in patients with CKD and in those with CKD and diabetes mellitus.

12. CONTRAST MEDIA • Guidelines from the American Heart Association (AHA)/American College of Cardiology (ACC) for the management of acute coronary syndromes patients with CKD recommend the use of IOCM.

13. CONTRAST MEDIA • 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.

15. RISK FACTORS

16. RISK FACTORS

17. RISK STRATIFICATION[Mehran et al]

18. AETIOPATHOGENESIS

25. CLINICAL FEATURES • CI-AKI occurs after 24 to 48 hrs of contrast administration. • Cr peaks in 3 to 5 days and normalizes in 7 to 10 days[70%]. • In 30% ,it takes 3 weeks to return to baseline or progress to CKD. • CI-AKI presents predominantly as non –oliguric AKI and with mild proteinuria.

26. LABORATORY INVESTIGATIONS • S/U/E/Cr. • Serum cystatin C (which has been suggested as a surrogate marker of renal function in lieu of SCr) is increased in patients with CIN. • Plasma levels of asymmetrical dimethylarginine (ADMA), which is an endogenous inhibitor of all NO synthaseisoforms, can be used as a marker of CIN, especially in patients with unfavorable outcomes.

27. LAB INVX • Urine osmolality tends to be less than 350 mOsm/kg. • The fractional excretion of sodium (FENa) may vary widely but mostly shows low fractional excretion of sodium . • Urine analysis:shows • renal tubular epithelial cells, • pigmented granular casts, • urate crystals, • debris.

28. Histology: is characterized by • Cell vacuolization, • Interstitial inflammation, • Cellular necrosis. • These changes are called osmotic nephrosis.

29. DIFFERENTIAL DIAGNOSIS Atheroembolic renal failure – • More than 1 week after contrast, • blue toes, • livedoreticularis, • transient eosinophilia, • prolonged course, and lower recovery .

30. Acute renal failure (from other causes e.g prerenal and postrenalazotemia) – • There may also be associated dehydration from aggressive diuresis, exacerbated by preexisting fluid depletion; • the acute renal failure is usually oliguric, • recovery is anticipated in 2-3 weeks.

31. Acute interstitial nephritis (triad of fever, skin rash, and eosinophilia) – • Also eosinophiluria; • the nephritis is usually from drugs such as penicillin, cephalosporins, and nonsteroidal anti-inflammatory drugs (NSAIDs).

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

33. TREATMENT Mainly supportive: • Monitoring and correction of electrolyte imbalance • Correction of volume overload. • Treatment of metabolic acidosis. • Initiation of renal replacement therapy when indicated.

35. Hydration therapy is the cornerstone of CIN prevention. • Renal perfusion is decreased for up to 20 hours following contrast administration. • Intravascular volume expansion maintains renal blood flow, preserves nitric oxide production, prevents medullary hypoxemia, and enhances contrast elimination.

36. Normal saline has been found to be superior to half-normal saline in terms of its enhanced ability in intravascular volume expansion. • It also causes increased delivery of sodium to the distal nephron, prevents rennin-angiotensin activation, and thus maintains increased renal blood flow. • In terms of route of administration, oral fluids, while beneficial, are not as effective as intravenous hydration.

37. The CIN Consensus Working Panel found that 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.

38. For hospitalized patients, volume expansion should begin 6 hours prior to the procedure and be continued for 6-24 hours postprocedure. • For outpatients, administration of fluids can be initiated 3 hours before and continued for 12 hours after the procedure.

39. Postprocedure volume expansion is more important than preprocedure hydration. • It has been suggested that a urine output of 150 mL/h should guide the rate of intravenous fluid replacement

40.  Bicarbonate Therapy • Bicarbonate therapy alkalinizes the renal tubular fluid and, thus, prevents free radical injury. • 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. • Hydration with sodium bicarbonate has been found by some researchers to be more protective than normal saline alone.

42. 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).

43. N-acetylcysteine • NAC is acetylated L-cysteine, an amino acid. • Its sulfhydryl groups make it an excellent antioxidant and scavenger of free oxygen radicals. • It also enhances the vasodilatory properties of nitric oxide. • latest controversy relating to NAC therapy questioned the parameter on which its effectiveness was based. It was suggested that the beneficial effect of NAC in CIN is related to its SCr-lowering ability rather than to improved GFR.

44.  Renal Replacement Therapy • Less than 1% of patients with CIN ultimately go on to require dialysis, the number being slightly higher in patients with underlying renal impairment (3.1%) • And in those undergoing primary PCI for MI (3%). • However, in patients with diabetes and severe renal failure, the rate of dialysis can be as high as 12%.

45. RRT • Patients who get dialyzed do considerably worse, with inhospital mortality rates of 35.7% (compared with 7.1% in the nondialysis group) and a 2-year survival rate of only 19%.

46. HAEMODIALYSIS • CM can be effectively and efficiently removed by hemodialysis (HD). • Factors that influence CM removal include blood flow, membrane surface area, molecular size, transmembrane pressure, and dialysis time. • High-flux dialysis membranes with blood flows of between 120-200 mL/min can remove almost 50% of iodinated CM within an hour and 80% in 4 hours.

47. HD • Even in patients with CKD, in whom contrast excretion is delayed, it was found that 70-80% of contrast can be removed by a 4-hour HD treatment. • In view of the limited benefit of therapies such as hydration, bicarbonate and NAC, dialysis may seem like the definitive answer. • Dialysis immediately after contrast administration has been suggested for patients already on long-term HD and for those at very high risk of CIN

48. HD • However, an excellent meta-analysis by Cruz et al indicated that periprocedural extracorporeal blood purification (ECBP) does not significantly reduce the incidence of CIN in comparison with standard medical therapy.