Acute Kidney Injury

1. Acute Kidney Injury Prof.Dr.Gülçin Kantarcı Yeditepe UniversityNephrologyDepartment

2. Aims& objectives • State the definition, pathophysiology, clinical findings and prevention methods of acute kidney injury

3. Reference 1. CurrentMedicalDiagnosisandTreatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. http://accessmedicine.com/resourceTOC.aspx?resourceID=1 Chapter 22. KidneyDisease (ACUTE RENAL FAILURE: GENERAL) 2. Bates' Guide toPhysicalExamination & HistoryTaking 11th edition, Bickleys LS, Szilagyi PG; Lippincott Williams andWilkins¸ 3. Kumar andClark'sClinicalMedicine, 8th edition; Kumar & Clark, Elsevier 4. AndreoliandCarpenter'sCecil Essentials of Medicine 8th edition, AndreoliandCarpenter, Elsevier PART 11: RENAL AND GENITOURINARY DISEASES 122: AcuteKidneyInjury , Bruce Molitoris Editor: Goldman, Lee 5. CURRENT Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson (ACUTE RENAL FAILURE Chapter 9-11-14)

4. PRESENTATION TOPICS • Essentials of Diagnosis • General Considerations • Clinical Findings • Classification & Etiology

5. ACUTE KIDNEY INJURY (Acute renal failure) • also known as acute renal failure, is defined as a sudden decrease in kidney function, resulting in an inability to maintain acid-base, fluid and electrolyte balance and to excrete nitrogenous wastes • It often results from major trauma, illness, or surgery but is sometimes caused by a rapidly progressive, intrinsic renal disease.

6. Kidney Disease: Improving Global Outcomes. Clinical practice guideline on acute kidney injury. 2011. www.kdigo.org • Serum creatinine rises ≥ 1.5 fold from the reference value, which is known or presumed to have occurred within one week or • urine output is < 0.5ml/kg/hr for >6 consecutive hours • If a reference serum creatinine value is not available within 3 months (acceptable up to one year) and AKI is suspected • repeat serum creatinine within 24 hours • a reference serum creatinine value can be estimated from the nadir serum creatinine value if patient recovers from AKI

7. Symptoms of Acute Kidney Injury • 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

8. Fluid overload in ARF

9. Diagnosis • based on laboratory tests of renal function, including serum creatinine. • urinary sediment, and imaging are needed to determine the cause.

10. CLINICAL CRITERIA • RIFLE criteria(ADQI workgroup Crit Care 2004) • AKIN (Acute Kidney Injury Network) (Mehta et al.Acute Kidney Injury Network Crit Care 2007)

11. RIFLE kriterleri(ADQI workgroup Crit Care 2004)

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

15. Prerenal azotemia • inadequate renal perfusion. • causes ECF volume depletion • cardiovascular disease. Main cause of AKI

16. PRE-RENAL (%55-60) • Intravascular volume depletion -Hemorrhage -GI losses -Renal losses -Skin and mucous membrane losses -Third space losses • Renal vasodilation • Systemic vasodilaton • Decreased cardiac output • Pharmocologic agent that acutely impair autoregulation & GFR

17. symptoms of prerenal AKI (ARF) 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.

18. Renal causes of AKI ( 35-40 %) intrinsic renal disease or damage • most common causes: - prolonged renal ischemia (post ischemic ATN) -nephrotoxins. • RPGN Wegener / PAN/ Goodpasture • Nephrotoc. Vanco. /aminogli. /NSAID/ Amphoterisin-B, Radiocontrast • Acute pyelonephritis • Acute tubulointertisiselnephrithis (ATIN) • Cholesterol crystal embolism • Contrast nephropathy

19. Renal ARF 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.

20. Postischemic acute tubular necrosis (ATN) • Postischemicacutetubularnecrosis (ATN) can resultfromprolongedhypotensionduemostcommonlyto: •Majorsurgery (particularlycardiacsurgery, abdominalaorticaneurysmsurgery, andsurgerytocorrectobstructivejaundice) •Sepsis •Markedhypovolemia •Severe pancreatitis

21. Pathophysiology of Postischemic acute tubular necrosis (ATN) • Endothelial injury from vascular perturbations • Ischemia/hypoxemia (including re-perfusion injury) • Tubular cell necrosis/apoptosis • Shed into lumen, tubular obstruction • Decreased tubular flow • Tubulo-glomerular back-leak leads to decreased GFR • Formation of inflammatory mediators • Oxidative stress, cytokine release • Abolishment of renal autoregulation • Intrarenal vasocontriction > vasodilatation

22. Pathophysiology 2 • AKI involves both vascular and tubular effects • AKI that secondary to sepsis;sympathetic system and renin-angiotensin-aldosterone system are stimulated and cause renal vasoconstriction

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

26. Nephrotoxicity • Hemodynamic disregulation • ACEI • ATII RB • Cyclosporin • NSAID • Radiocontrast Nephrotoxicity • Acute tubuler injury • Aminoglycosides • Acyclovir • Indinavir • Cysplatin • Cyclosporin • cephalosporines • Amphotericin Acute int. nephritis All drugs

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

28. Sodiumbicarbonatesolutionforpreventionof contrast-inducednephropathy • 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

30. CRUSH SYNDROME

31. Crushtrauma of themuscles • MYOGLOBIN Glomerular filtrate • Dehidratation • Tubular obstruction is depens upon the death cell and gelous Myoglobin

32. Crush Syndrome • Hypovolaemic shock(due to sequestration of water in the injured muscle cells) • Dark urine(Duetohighconcentration of myoglobin in thegloemerularfiltratewhichcomesfromtheswollenmuscles) • Hyperkalemia (release of cellular potassium by the injured muscle cells) This can also lead to: • Metabolic acidosis (release of cellular phosphate and sulphate by the injured muscle cells) • Acute KidneyInjury • Disseminated intravascular coagulation (DIC)

33. 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.

34. Fluid Replacement • Normotension %0.45 NaCl • Hypotension  Cause ? • Bleeding ? E.S • Dehidratation? %0.9 NaCl • Compartment Syn? Mannitol To prevent ARF: • i.v.fluid 1L/hr( During first hours 1-1.5 lt ) • Fluid %0.45 NaCl

35. Postrenal azotemia • obstructive nephropathyis due to various types of obstruction in the voiding and collecting parts of the urinary system

36. POST-RENAL (<%5) • Early diagnosis is important • Urinary obstr. • Bilateral obstruction of the ureter, pelvis • BPH, Prostate Ca • Cervix, ovarian Ca • uretral masses, Stones • Ureteral obstrustion (stone, mass) • DM papillary nec.

37. AKI In 748 AKI patients • ATN —% 45 • Prerenal —% 21 • Acute on Chronic — %13 • Urinary tract — %10 • GN or vasculitis— %4 • AIN — %2 • Atheroembolism — %1 Liano, F, Pascual, J, and the Madrid Acute Renal Failure StudyGroup. Epidemiology of acute renal failure: A prospective, multicenter, community-based study. Kidney Int 1996.

38. ‘Acute on Chronic Renal Failure • Causes: • Hypovolemi • Nephrotox. • Infection • Obstruction • KKY • Accelerated HT

39. ARF IN ICU ARF ın ICU is the part of MOF Kidney Int 1998;53: S16-S24

41. AKI in ICU • AKI requiring dialysis reduced survival %50, • Hospital mortality %69 • After 6-12 months %70 still survived

42. MORTALTY IS CORRELATED WITH NUMBER OF ORGANS Kidney Int 1998;53: S16-S24

43. Diagnosis of AKI • Diagnosis relies on functional parameters (Cr, UOP) • AKI is more readily reversible in early stages • 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) • Even very small incremental increases (>0.3 mg/dL) in SCr cause significant loss of function and increased morbidity and mortality • Early diagnosis is essential

44. Diagnostic Work-Up for AKI

45. THERAPHY • Prerenal Management of hypovolemia and hypoperfusion. • Renal Theraphy of causes, plasmaferesis, immunsup. • Post renal obstruction

46. 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.

48. 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 AKI is usually caused by drug-induced nephrotoxicity and interstitial nephritis

49. SUGGESTED READING CURRENT Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson (ACUTE RENAL FAILURE Chapter 9-11-14)