ACUTE KIDNEY INJURY

1. ACUTE KIDNEY INJURY Prof. Dr. Gülçin Kantarcı, MD InternalMedicineandNephrology

2. REFERENCE &SUGGESTED READING • http://accessmedicine.com Current Medical Diagnosis and Treatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. Chapter 22. Kidney Disease (ACUTE RENAL FAILURE: GENERAL) Current Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson Chapter 9-11-14ACUTE RENAL FAILURE • http://www.uptodate.com (Overview of the management of acute kidney injury, Diagnostic approach to the patient with acute kidney injury (acute renal failure) or chronic kidney disease, Definition of acute kidney injury, Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury, Crush-relatedacutekidneyinjury )

3. CONTENTS • Definitions of Acute Kidney Injury (AKI). • Staging of AKI • Diagnostic Work-Up for AKI • Management of AKI • Therapeutic approach to AKI • Case presentations

4. Acute Kidney Injury (AKI) • Acute kidney injury (AKI) is the abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. • The term AKI has largely replaced acute renal failure (ARF), reflecting the recognition that smaller decrements in kidney function that do not result in overt organ failure are of substantial clinical relevance and are associated with increased morbidity and mortality. • The term ARF is now reserved for severe AKI, usually implying the need for renal replacement therapy.

5. AKI is defined as any of the following • Increase in SCr by >0.3 mg/dl within 48 hours; or • Increase in SCr to >1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or • Urine volume <0.5 ml/kg/h for 6 hours. 2012 KDIGO

6. Staging of AKI 2012 KDIGO

7. AKIN (Acute Kidney Injury Network) Mehta et al.Critical Care 2007

8. RIFLE kriterleri(ADQI workgroup Crit Care 2004)

9. The change in serum creatinine was specified as occurring over not more than seven days. Subsequent to publication of RIFLE, it was noted that the change in serum creatinine concentrations do not correlate with the percent decrease in GFR that is cited in the RIFLE classification; a 1.5-fold increase in serum creatinine corresponds to a 33 rather than 25 percent decrease in GFR. • However, given the absence of readily available methods for measurement of GFR when serum creatinine is not in steady state, as is the case during AKI, changes in GFR are not included in the Acute Kidney Injury Network (AKIN) and KDIGO 2012 classification system .

11. Risk factors that have been identified to enhance the likelihood of AKI • Elderly patients • Diabetes mellitus • Volume depletion • Vascular surgery • Chronic renal failure • Multiple antibiotics, NSAIDs • Multiple insult ( Kidney stones, malignant diseases,etc)

12. Symptoms of Acute KidneyInjury • anorexia, nausea, vomiting. • Seizures and coma may occur if the condition is untreated. • Fluid, electrolyte, and acid-base disorders develop quickly. • Hypovolemia can cause states of low blood flow to the kidneys, sometimes termed prerenal states, whereas hypervolemia can result from intrinsic or postrenal disease. • Pericardial effusions can occur with uremia, and a pericardial friction rub can be present

13. symptoms of prerenal AKI (60%) symptoms related to hypovolemia, including thirst, decreased urine output, dizziness, and orthostatic hypotension. How can we distinguish Prerenal AKI? • Ask about volume loss from vomiting, diarrhea, sweating, polyuria, or hemorrhage. • Patients with advanced cardiac failure leading to depressed renal perfusion may present with orthopnea and paroxysmal nocturnal dyspnea. • Insensible fluid losses can result in severe hypovolemia in patients with restricted fluid access and should be suspected in elderly patients and in comatose or sedated patients.

14. CluesforRenal ARF (35%) Glomerular diseases: Nephritic syndrome of hematuria, edema, and HTN indicates a glomerular etiology of AKI. Query about prior throat or skin infections. Tubular diseases: ATN should be suspected in any patient presenting after a period of hypotension secondary to cardiac arrest, hemorrhage, sepsis, drug overdose, or surgery. • A careful search for exposure to nephrotoxins(Vanco. /aminogli. /NSAID/ Amphoterisin-B, Radiocontrast)should include a detailed list of all current medications and any recent radiologic andangiographicexaminations • Pigment-induced AKI should be suspected in patients with possible rhabdomyolysis(muscular pain, recent coma, seizure, intoxication, excessive exercise, limb ischemia) or hemolysis (recent blood transfusion). • Allergic interstitial nephritis should be suspected with fevers, rash, arthralgias, and exposure to certain medications including NSAIDs and antibiotics.

15. Diagnostic Work-Up for AKI • History and physical examination • Urinalysis: urine microscopy,urine chemistry • Response to treatments (volume) • Imaging (U/S) • Serologies • +/- Kidney biopsy

16. Diagnostic Work-Up for AKI

18. Management of AKI

19. most cases of community-acquired AKI’s are secondary to volume depletion, as many as 90% of cases are estimated to have a potentially reversible cause. • Hospital-acquired AKI often occurs in an ICU setting and is commonly part of multiorgan failure.

20. RADIOCONTRAST NEPHRO. • Risk Factors • Preexistingrenalfailure • DN • >2ml/kg Radiocontrast • volumedepletion • Age>60 • Hyperuricemia • Hepaticfailure • What can we do? • Crcontrolsbeforetheexposure • Non-Nephrotoc. Contrastmedia • Lowerthecontrastdose • Hydration (Before12 hour)%0.45 NaCL 100ml/hour • Oral theophylline (200mg; 2x1) • Onehourbefore-48 hours • N-acetylcystein (600mg; 2x1) • 24 hourbefore-48 hours

21. Sodium bicarbonate solution for prevention of contrast-induced nephropathy • I.V. infusion: 154 mEq/L sodium bicarbonate in D5W solution: 3 mL/kg/hour for 1 hour immediately before contrast injection, then 1mL/kg/hour during contrast exposure and for 6 hours after procedure • To prepare solution, remove 154 mL from 1000 mL bag of D5W; replace with 154 mL of 8.4% sodium bicarbonate; resultant concentration is 154 mEq/L

22. CRUSH SYNDROME • Severe systemic manifestation of trauma and ischaemia involving soft tissues, principally skeletal muscle, due to prolonged severe crushing. • Crush injuries and prolonged compression of limbs are the most important types of trauma encountered in earthquake victims • It leads to increased permeability of the cell membrane and to the release of potassium, enzymes, and myoglobin from within cells. Ischaemic renal dysfunction secondary to hypotension and diminished renal perfusion results in acutekidneyinjury.

23. CRUSH SYN.PREVENTION from AKI • The general goals for preventive therapy in all cases of heme pigment-induced AKI are the correction of volume depletion, if present, and prevention of intratubular cast formation. In the case of disaster crush victims preventive measures should be applied at the disaster field, in the field hospitals, and after admission to regular hospitals. • The most important preventive measure at the disaster field is the correction of volume depletion. • The approach to prevention of AKI in the patient with rhabdomyolysis due to crush syndrome varies based upon the location of the patient and ability to closely monitor the victim. Kantarci G, Vanholder R, Tuglular S, et al. Am J Kidney Dis. 2002 Oct;40(4):682-9.Acute renal failure due to crush syndrome during Marmara earthquake.

25. ‘Acute on Chronic Renal Failure Causes: • Hypovolemi • Nephrotox. • Infection • Obstruction • Congestive heart failure • Accelerated HT

26. Prevention Earlydetection

27. Biomarkers of AKI • Early diagnosis is essential for AKI because AKI is more readily reversible in early stages • Diagnosis relies on functional parameters (Cr, UOP) • Even very small incremental increases (>0.3 mg/dL) in SCr cause significant loss of function and increased morbidity and mortality • Need a more sensitive biomarker to detect early injury • Permit early targeted interventions to reverse or ameliorate AKI • Cystatin C, urinary NGAL(Neutrophil gelatinase associated lipocalin), IL-18, KIM-1(Kidney injury molecule)

28. Maintaining Renal Perfusion Pressure • vasoconstrictors, vasopressor medications (eg, norepinephrine) should be used only to treat arterial hypotension (dopamine ,norepinephrine) • target mean arterial pressure 60 to 65 mm Hg (patients with long-standing hypertension and/or renal vascular disease may require substantially higher pressures to maintain renal perfusion) • intra-abdominal hypertension is associated with decreased renal perfusion and may result in AKI.

29. Immediatetherapy • The management of life-threatening fluid and electrolyte abnormalities due to acute kidney injury (AKI) should be started immediately. Common complications of AKI include the following: ●Fluid overload ●Hyperkalemia (serum potassium >5.5 mEq/L) or a rapidly increasing serum potassium ●Signs of uremia, such as pericarditis, or an otherwise unexplained decline in mental status ●Severe metabolic acidosis (pH <7.1) • Patients with any of these complications despite appropriate medical therapy generally require urgent dialysis

30. Pharmacologic Strategies for AKI Prevention • LoopDiuretics (?) • Mannitol (an osmoticdiuretic ) (?) • Dopamine (increases GFR bydirectvasodilationthroughdopaminergicreceptors, byincreasingthecardiacoutputbyβ-adrenergicstimulationorbyincreasingperfusionpressurebyα-stimulation ) • Fenoldopam (dopamine-1 receptoragonist ) • NatriureticPeptides (ANP, BNP) • preglomerularvasodilation • postglomerularvasoconstriction • natriuresisanddiuresis • increasethe GFR

31. Therapoetic approach to AKI • Prerenal  Management of hypovolemia and hypoperfusion. • Renal  Theraphy of causes, plasmaferesis, immunsup. • Post renal  obstruction

32. INDICATIONS FOR INITIATION OF DIALYSIS IN AKI • Refractory fluid overload • Hyperkalemia (plasma potassium concentration >6.5 mEq/L) or rapidly rising potassium levels • Signs of uremia, such as pericarditis, neuropathy, or an otherwise unexplained decline in mental status • Metabolic acidosis (pH less than 7.1) • Certain alcohol and drug intoxications

33. Mortality/Morbidity • AKI is not a benign disease. In a recent study, a 31% mortality rate was noted in patients with AKI not requiring dialysis, ICU mortality 50-69 % • Mortality rates are generally lower for nonoliguric AKI (>400 mL/d) than for oliguric (<400 mL/d) AKI, reflecting the fact that nonoliguric AKIis usually caused by drug-induced nephrotoxicity and interstitial nephritis

35. CASE 1 • A 68 year old man is admitted to Yeditepe U. MF hospital. He has been complaining of decreased urine output over the last two days. He has Type 2 Diabetes for 12 years. • Had coronary angiography 5 days ago-uneventfully • No symptoms of BPH • Pre-angiographic S.Cr- 2 mg/dl • History of 20 years hypertension + NIDDM • No extra fluids before or after procedure

36. PHYSICAL EXAMINATION • BP: 160/100mmHg; P:98/min/R W: 79 kg • The number of breaths per minute: 24/min • Raised JVP • Pretibial Edema (+) • Orthopneic • Dyspneic with crackles over the lung bases

37. LABORATORY • S. Cr: 4.5 mg/dl ; BUN:50 mg/dl, Na 134 mEq/L • What other features would you like to see?

38. Serum Potassium • Serum Sodium • Urinesodium • Ultrasound • Chest –X ray • Glycemicevaluation

39. AKI duetocontrastnephropathy

40. Preventionfor CIN • Main risk factors for CIN are estimated GFR < 50 mL/min/1.73m2, diabetes, hypovolemia • Other risk factors include age over 75, HF, cirrhosis, hypertension, proteinuria, concomitant use of NSAIDs, intra-arterial injection of contrast, and high doses of contrast • Serum creatinine levels peak at 3 days postexposure and usually return to baseline within 10 days. • It is not clear how to best prevent CIN • The lowest dose of contrast possible should be used. • Low osmolar contrast agents may be better. • Hydration with IV 0.9 normal saline may be preventive; the optimal duration of hydration is not clear. • Although N-acetylcysteine and IV sodium bicarbonate are sometimes used, the data demonstrating efficacy are inconsistent.

41. CASE 2 A 77-year-old male is admitted to the hospital with chief complaint of generalized weakness and potassium level of 6.5 mEq/L. The patient has had poor PO intake of fluids and food for the last 2 days. The patient has severe osteoarthritis and takes high-dose nonsteroidal antiinflammatory drugs (NSAIDs). Past medical history (PMH)Obesity, obstructive sleep apnea (OSA), hypertension (HTN), osteoarthritis (OA).Medicationsibuprofen, acetaminophen, lisinopril

42. Physicalexamination • Drymucosalmembranes (MM).Chest: ClearChestsounds.( Bronchovesicular )CVS: Aritmia +Abdomen: Soft, NT, ND, +BS.Extremities: noedema. Laboratory • Hb: 14.7g/dl Htc:46% • Na: 149mEq/L K: 6.5 mEq/L • Serum BUN: 48mg/dl ;Kr: 2.8mg/dL

43. What is the most likely diagnosis? • How to confirm the diagnosis? • What other tests would you order?

44. UNa x SCr FENa, percent = ——————— x 100 SNa x UCr

45. What is the most likely diagnosis? Prerenal ARF due to volume depletion • How to confirm the diagnosis? *Urine analysis *Urinary sodium and creatinine to calculate the fractional excretion of sodium (FENA) • What other tests would you order? Renal ultrasound to rule out urinary obstruction and nephrolithiasis

46. Urinary Na: 12 mEq/L ; Cr: 27mg/dL

48. Kidney US

49. What treatment would you start for this patient? • Insulin 10 units IV with D50, 1amp. IV x 1. • Kayexalate 45 gm po x 1.(880 mg polistiren sulfonat kalsiyum 2x1, 3x1) • Foley catheter. • Strict I/O. • Isotonic NaCl at 150 cc/hr x 2 L, then 125 cc/hr, adjust the rate of IVF according to I/O, avoid fluid overload. • Hold ACEi and NSAIDs

50. What did we learn from this case? • The fractional excretion of sodium (FENa) is useful in diagnosing pre-renal ARF. • FENa is less than 1 % in many patients with prerenal ARF. Intravenous hydration is the mainstay of treatment.