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 The change in serum creatinine was specified as occurring over not more than seven days. 2012 KDIGO

7. AKIN (Acute Kidney Injury Network) ADQI workgroup Crit Care 2004 Mehta et al.Critical Care 2007

9. 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)

10. Symptoms of Acute KidneyInjury • Anorexia, nausea, vomiting. • Seizures and coma may occur if the condition is untreated. • Fluid, electrolyte, and acid-base disorders • 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

11. Prerenal AKI (60%) • Symptomsrelated to hypovolemia (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.

12. Renal AKI (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.

13. Clues for Renal AKI • Nephrotoxinexposure ? (Vanco. /aminogli. /NSAID/ Amphoterisin-B, Radiocontrast) • Possiblity of rhabdomyolysis ? Pigment-induced AKI should be suspected in patients with (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.

14. Diagnostic Work-Up for AKI Imaging (US)

16. indicates BUN/CR ratio >20 BUN/CR <15

17. 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.

18. Contrast-associated nephropathy. • Contrast nephropathy can be defined as an acute impairment of renal function that follows exposure to radiocontrast media

19. Contrast-associated nephropathy • Risk Factors • nephrotoxicagents (NSAIDs, angiotensin-convertingenzymeinhibitorsandangiotensin II receptorblockers, metformin) • preexistingchronickidneydisease (eGFR <60 ml/min/1.73 m2 • diabetesmellitus • cirrhosis • heartfailureorothercauses of impairedrenalperfusion

20. PREVENTION OF CONTRAST-ASSOCIATED ACUTE KIDNEY INJURY • Identify patients at risk and consider alternative imaging in patients at risk, discontinuation of nephrotoxic medications • Use lowest dose of contrast media, • Use low-osmolar or iso-osmolar contrast media, • i.v. volume expansion with crystalloid solutions (6–12 h before contrast media administration, and 1l for 12 h during and following administration.) - oralternative regimen: bicarbonate solution • Pharmacologic prevention, Oral NAC,Theophyllin,VitaminC,Statins, • Prophylactic hemofiltration.

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 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. Fluidandelectrolyteabnormalities • The management of life-threatening fluid and electrolyte abnormalities due to acute kidney injury (AKI) should be started immediately. Common fluid and electrolyte abnormalities of AKI: ●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. PharmacologicStrategiesfor AKI Prevention- Management • preglomerularvasodilation • postglomerular vasoconstriction • natriuresis and diuresis • increase the GFR • LoopDiuretics (?) • Mannitol (an osmoticdiuretic ) (?) • Dopamine (increases GFR bydirectvasodilationthroughdopaminergicreceptors, byincreasingthecardiacoutputbyβ-adrenergicstimulationorbyincreasingperfusionpressurebyα-stimulation ) • Fenoldopam (dopamine-1 receptoragonist ) • NatriureticPeptides (ANP, BNP)

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. • 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, no History of Blood transfusion • Pre-angiographic S.Cr- 2 mg/dl • History of 20 years hypertension + NIDDM • No extra fluids before or after procedure

36. PHYSICAL EXAMINATION • Oriented, cooperative • Afebril, BP: 160/100mmHg; P:98/min/R W: 79 kg • The number of breaths per minute: 24/min • Raised JVP • Pretibial Edema (+), no ichterus • Orthopneic • Dyspneic with crackles over the lung bases • CVS S1, S2 (+), no murmur • Abdomen soft, mild hepatomegaly

37. LABORATORY • S. Cr: 4.5 mg/dl ; • BUN:50 mg/dl, • Na 134 mEq/L

38. Risk factors? • preexisting chronic kidney disease (eGFR <60 ml/min/1.73 m2 • diabetes mellitus

39. What other features would you like to see? • Serum Potassium • Serum Sodium • Urinesodium • Ultrasound • Chest –X ray • Glycemicevaluation

40. AKI duetocontrastnephropathy

41. 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.

43. 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

44. Physicalexamination • Oriented, cooperative, Drymucosalmembranes (MM). • Afebril, BP: 160/100mmHg; P:98/min/R W: 79 kg • Thenumber of breathsperminute: 24/min • noichterus • CVS S1, S2 (+), nomurmur, arytmia + • Abdomen soft, mildhepatomegaly

45. LABORATORY • Hb: 14.7g/dl Htc:46% • Na: 149mEq/L K: 6.5 mEq/L • Serum BUN: 48mg/dl ;Kr: 2.8mg/dL

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

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

48. What is the most likely diagnosis? Prerenal AKI duetovolumedepletion • 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

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