Risk factors and diagnosis of AKI IN ICU

Dr. V. Naresh Consultant Critical Care Medicine Sunshine Hospital, Madhapur, Hyderabad

Acute Renal Failure

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Definition:

A syndrome characterized by rapid decline in glomerular filtration rate (hrs. to days), retention of nitrogenous waste products, perturbation of extra cellular fluid volume and electrolytes and acid-base homeostasis.

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RIFLE Criteria for Acute Kidney Dysfunction R

isk

GFR Criteria* Increased creatinine x 1.5 or GFR decrease >25% Urine Output Criteria UO <.5ml/kg/h x 6 hrs High Sensitivity I

njury

Increased creatinine x 2 or GFR decrease >50% UO <.5ml/kg/h x 12 hrs F

ailure

Increase creatinine x 3 or GFR dec >75% or creatinine



4mg/dl (Acute rise of



0.5 mg/dl

)

UO <.3ml/kg/h x 24 hrs or anuria x 12 hrs High Specificity L

oss

E

SRD

Persistent AKD** = complete loss of renal function > 4 weeks End Stage Renal Disease

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Bellomo R, et al. Crit Care. 2004;8:R204 –R212.

AKIN Definition….

 An abrupt (with in 48 hrs.) reduction in kidney function,  Currently defined as a absolute increase in serum creatinine of either >0.3 mg/dl or 50 % increase in creatinine value  Increase in 1.5 times base line creatinine  Reduction in U/O <0.5 ml/kg/hr for 6 hrs.

AKIN modification in RIFLE Criteria

GFR Criteria* Urine Output Criteria STAGE I STAGE II

Increased creatinine by 50%,x 1.5 or GFR decrease >25% , >

0.3mg/dl

Increased creatinine x 2 or GFR decrease >50% UO <.5ml/kg/h x 6 hrs UO <.5ml/kg/h x 12 hrs

High Sensitivity STAGE III

Increase creatinine x 3 or GFR dec >75% or creatinine  4mg/dl (Acute rise of  0.5 mg/dl) UO <.3ml/kg/h x 24 hrs or anuria x 12 hrs

High Specificity

www.ADQI.net

Bellomo R, et al. Crit Care. 2004;8:R204 –R212.

GFR Calculation…….

Modified diet in renal disease (MDRD) Estimated GFR (ml/min/1.73m

2 ) = 1.86 x (P cr ) -1.154 x (age) -0.203

Multiply by 0.742 for female Cockcroft Gault Estimated creatinine clearance ml/min = (140-age x body weight in kgs) 72 x S .Cr

Multiply by 0.85 for female

Additional caveats were proposed by the AKIN group:  Time limit of 48 hrs.

 The diagnostic criteria should be applied only after volume status had been optimized  Urinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criterion

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Acute Kidney Injury

 AKI better represents the full spectrum of acute disorders of renal function, especially in regards to reversible injury (Palevsky, 2008)  Issue of pre-renal, obstructive etiologies not entirely clear in AKI definition, but classically held to exist in this framework  Despite these attempts, Sr. Creatinine, oliguria trends still suboptimal in outcomes, treatment measurement  Need “Troponin” analogue

Limitation of conventional Sr. Creatinine in measuring kidney function         Sr. Creatinine : not sensitive in detecting the decline in GFR ,in early stages of AKI.

Not show significant increase until approximately 50% kidney function is lost.

It takes 12 to 24hrs, Creatinine accumulation lags behind.

10 – 40 % clearance occurs by tubular secretion.

Drugs impair creatinine secretion : trimethoprim, cimetidine Variable with age, sex, dietary intake ,muscle mass, malnutrition, and muscle injury Reduce accuracy with ketoacidosis, cefoxitin, flucytosine Does not depict real time change in GFR

Newer biomakers

 Several biomarkers are being researched for the early diagnosis  Serum cystatin C     NGAL Urinary IL 18 Tubular enzymes  N acetyl β glucosaminidase, alanine aminopeptide Transmembrane protein  kidney injury molecule 1

Diagnostic approach to acute kidney injury includes

 Careful history & record review  Thorough physical examination  Judicious interpretation of  Laboratory data  Examination of the urinary sediment  Urinary chemistry

 Base line risks

Risk factors:

 Acute clinical conditions  Nephrotoxic agents

Baseline risks

         Elderly patients Diabetes mellitus Heart failure Liver failure Previous renal insufficiency Arterial vascular disease Hypoalbuminemia Male sex Race and genetic variation

Acute clinical conditions

        Sepsis Hypotension / Shock Volume depletion Cardiac / Vascular surgeries Rhabdomyolysis Non renal solid organ transplantion Abdominal compartmental syndrom Mechanical ventilation

Nephrotoxic agents

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Contrast media

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Anti microbial agents

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Chemotherapeutic agents

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NSAIDS

AKI in Sepsis

        BEST investigators says sepsis is most common cause of AKI in critically ill patients (47.5%).

19% AKI in moderate, 23% in severe, 51% in septic shock Septic AKI has higher in hospital mortality than with non septic AKI Oliguria is more common Early detection with NGAL, CYSTATIN C, IL 18, KIM I Components – Ischemic reperfusion injury, direct inflammatory injury, coagulation and endothelial cell dysfunction and apoptosis.

Hypotension does not correlate with AKI in septic patients Reduction in cortical microvascular perfusion in SIRS

Protective strategies:

Early goal directed therapy IAP MAP > 65, CVP> 8-12/ 12-15 for ventilated patient svo2 >70% Fluid choice crystalloids/ albumin/gelatin but no to hydroxyethyl starch Choice of vasopressors noradrenaline, early vasopressin Tight glucose control Low tidal volume ventilation Fenoldopam Mesylate NAC Natriuretic peptide Higher 35 to 45 ml/kg/hr CVVH group Extracorporeal purification of blood

PRERENAL

Acute Kidney Injury

AKI INTRINSIC POSTRENAL

Acute Kidney Injury

 PRERENAL: 40-80%     Volume loss/Sequestration Decrease intake Impaired Cardiac Output Systemic vasodilation    Hepatorenal Renal vasoconstriction Impaired auto regulation  Net result: glomerular hypoperfusion

Acute Kidney Injury

INTRINSIC: 10-30%      Vascular disorders:  small vessel  large vessel Glomerulonephritis or vasculitis Interstitial disorders:  Allergic   Infection Inflammation  intercalative processes Tubular necrosis:    Ischemia Infection Toxic Intra tubular obstruction

Acute Kidney Injury

 POSTRENAL: 5-15%  Intrarenal  Crystals  Proteins  Extrarenal  Pelvis/Ureter  Bladder/Urethra

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AKI IN ICU

Common risk factors in ICU

       Extra cellular volume depletion Postoperative (particularly cardiac surgery) Severe ventricular dysfunction or cardiogenic shock Sepsis Pancreatitis Trauma Burns

 Nephrotoxicity and drug-induced ARF  Myoglobinuric ARF  Radiocontrast nephropathy  Drugs  Acute bilateral cortical necrosis  Renal vascular disease Major vessel disease Renal artery embolism or thrombosis Renal vein thrombosis Microvascular disease Atheroembolism Vasculitis Scleroderma

 Cancer-related Obstructive uropathy Hypercalcemia Tumor-lysis syndrome ATN secondary to chemotherapy  Renal dysfunction with liver disease Pre-renal azotemia ATN Hepatorenal syndrome

AKI: Diagnostic studies-urine

  Urinalysis for sediment, casts Urine Na; FENa FENa (%) = U Na x Sr. Cr x 100 Sr. Na x U Cr   FENa < 1%: Pre-renal   FENa 1-2%: Mixed FENa > 2%: ATN Albumin / creatinine ratio

Urinalysis in Acute Kidney Injury Normal/bland Abnormal sediment Hematuria RBC casts proteinuria WBC WBC casts Eosinophils RTE cells Pigmented casts Crystalluria Non albumin proteinuria Prerenal Postrenal Oncotic AKI Glomerulopathy Vasculitis Thrombotic MA Pyelonephritis Interstitial nephritis AIN Athero embolic AKI ATN Myoglobin Hemoglobin Uric acid Toxins Drugs Plasma cell dyscrasia

Acute Kidney Injury

LABORATORY DATA  Creatinine; also BUN/Cr ratio     CBC: anemia, thrombocytopenia HCO3ˉ: anion gap, lactic acid, ketones Electrolytes pottasium, calsium,phosphates CPK/LDH/Uric acid/liver panel   Serologies:  Complement  ESR, RF, ANA, ANCA, AntiGBM  Electrophoresis Toxicology studies

Acute Kidney Injury

IMAGING STUDIES  Ultrasound: evaluates renal size, able to detect masses, obstruction, stones   CT: detects masses, stones; caveat exists when IVCD is considered MRI/MRA: can detect RAS; use of Gadolinium carries uncertain R/B ratio in AKI 2° potential hemodynamic changes similar to IVCD, and NFD In the AKI setting, U/S provides most information with the most favorable R/B ratio

AKI: Acute Tubular Necrosis

     Non-oliguric vs. Oliguric  Prognosis worse with oliguric ATN in most series Ischemic insult: medulla most susceptible to hypoxic event, cellular ATP depletion, oxidative injury AKI/ARF phase of ATN: 7-21 days on average Recovery phase of ATN: also known as diuretic phase  High urine output (>3-4 L)  K, Mg, PO4 wasting Associated with high FENa

AKI: Rhabdomyolysis

 Precipitated by trauma/crush injury, extreme exertion, statins, cocaine, envenomation, hypoK, hypoPO4  Multifold injury, with volume depletion, direct tubular toxicity, and obstructing pigment casts  UA: granular casts, (+) bld on dipstick but (-) microscopy due to myoglobin pigment  CK levels not always consistent in predicting AKI, but general consensus is that low likelihood exists with CK levels less than 5k 10k

Rhabdomyolysis

Endotoxin cascade Hypovolemia, CV suppression due to hi K, lo Ca, Met Acidosis Activation of ET NO scavengin g Muscular vasodilatation and uptake of ECF in damaged muscles Increased load of PO4 and urate Myoglobinemia Hyperuricemia Myoglobinuria Uricosuria

Renal vasoconstriction, ischemia Pigment nephrotoxicity Tubular cast formation and stasis

Depletion of ATP stores, synergistic tubular damage ATN Zager RA, Kidney Int 1996; 49: 314-326

AKI: Rhabdomyolysis

 Treatment is via forced saline diuresis: goal of UOP > 200-300 mL/hr  Early hydration: in crush victims, IV begun in field, advised even before full extrication (Turkey earthquake, 1999)  Urinary alkalization  Treatment for symptomatic hypocalcemia only: watch for hyperkalaemia

AKI: Radiocontrast Nephrotoxicity

 Well-recognized adverse outcome, but incidence varies widely, because of problems in defining AKI historically, as well as competing factors in pathogenesis  Improved with iso-osmolar agents  Onset of rise in Sr. Cr occurs within 24 hr; peak/fall within 3-5 days   Many studies with diuretics, osmolar agents, dopaminergic agents, etc..

Hydration, NAC, Bicarbonate therapy benificial effect with out harm.

Atheroembolic (AE) AKI

 Renal and systemic AE occur in patients with diffuse atheroscerotic disease  Risk factors include manipulation of the aorta or other large arteries during angiography or CV surgery  Also can occur spontaneously with ulcerated plaques  Destabilization of plaque may be enhanced in the setting of anticoagulation or thrombolytic therapy

AKI due to acute interstitial nephritis

        Onset usually 3-5 days with most drugs, but may be sooner with rifampin, or much later with NSAIDS Rising SCr which resolves upon d/c of offending drug Fever, hematuria, pyuria: Urine eosinophils Mild to moderate proteinuria; much higher to NS in NSAIDS Eosinophilia and morbilliform rash also s/sx in AIN Occasionally see hyperkalemia and distal RTA Bx not usually necessary for dx, assuming reversal of sx’s; may be needed for complicated cases Prednisone 40 mg PO x 2 wks sometimes utilized to shorten AKI interval

Acute Kidney Injury: AIN causes

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DRUGS

ACEI Allopurinol Cephalosporins Cimetidine Fluoroquinolones Loop diuetics NSAIDS PCN Phenytoin Rifampin Sulfonamides Tegretol Thiazides  

INFECTION

Bacterial     Viral Agents causing pyelonephritis Legionella Brucella Yersinia    Hantavirus HIV CMV,EBV,HSV

AKI: Glomerulonephritis (RPGN)/Systemic Vasculitis 

Immune-Complex Mediated

   SLE Cryoglobulinemic vasculitis Henoch-Schönlein purpura  Post-strep GN 

Direct Ab attack

 Anti-GBM disease  Goodpasture’s syndrome 

Pauci-immune vasculitis

   Microscopic polyangiitis Wegener’s granulomatosis Churg-Strauss syndrome 

Thrombotic Microangiopathy

     TTP HUS Scleroderma renal crisis Preeclampsia Malignant hypertension

Acute Glomerulonephritis (RPGN)        Accounts for a minority of AKI: ~5% May have severe morbidity, mortailty Extra-renal manifestations may be present  Pulmonary   Dermal GI  Hematologic HTN may be present, especially in absence of prior Hx UA: differentiates from ATN, AIN  Dysmorphic RBC, RBC casts, proteinuria > 0.5gm/24h Serologies, complement activation Need for specific therapy to reduce Ab critical towards attenuating/reversing AKI

Systemic Lupus Erythematosus (SLE)

      SLE nephritis diagnosis based on pathology, serology, extrarenal manifestations: 4/11 criteria by ARA WHO Class I-V of SLE nephritis: histopathology Variable s/sx of renal disease, but Class IV (diffuse proliferative GN) most often seen in AKI ANA, anti-DNA Ab, hypocomplementemia Role of Bx to guide therapy Immunosuppression   Steroids cyclophosphamide

Anti-GBM disease/Goodpasture’s

      Pulmonary hemorrhage distinguishes Goodpasture’s from anti-GBM disease Bimodal peak incidence  3 rd decade: men, pulmonary hemorrhage with AKI (Goodpasture’s)  6 th -7 th decade: women, anti-GBM Ab AKI, no pulm involvement Ab targets type IV collagen Aggressive course of AKI typically seen; pulm hemorrhage seen more often in smokers, exposure Anti-GBM present in >95% cases Predisone plus cyclophosphamide; TPEx indicated daily until circulating Ab titers undetectable

Pauci-immune vasculitis         Microscopic polyangiitis, Wegener’s granulomatosis, Churg-Strauss syndrome RBC casts with proteinuria, ESR elevated; crescentic GN on Bx Respiratory tract involvement may vary  Alveolar hemorrhage   Sinusitis, nodular lesions (Wegener’s) Asthma, eosinophilia (Churg-Strauss) ANCA hallmark of disease spectrum (90 %) MPO (+) in microscopic polyangiitis, Churg-Strauss PR3 (+) in Wegener’s Prednisone/Cytoxan; TPEx used in pulm hemorrhage Renal survival associated with entry-level SCr

Thrombotic Microangiopathy

Hemolytic-uremic Syndrome

     Predominately occurs in children Associated with diarrheal prodrome, Shigatoxin (verotoxin): E. coli O157:H7 Predominance of uremic signs/symptoms Hallmark of endothelial damage from verotoxin Supportive care

Thrombotic thrombocytopenic purpura

     Predominately in adults No inciting pathogen, GI prodrome Predominance of CNS signs, symptoms Hallmark of circulating Von- Willebrand factor-induced damage: defect in protease Plasma exchange

Acute Kidney injury

Crystal-induced AKI:  Common factors include high excretion in urine, and low solubility in acidic urine; exacerbated by hypovolemia; examination of urine critical to Dx   Common agents  Uric acid    Acyclovir Sulfa Methotrexate  Ethylene glycol Pre-exposure hydration, Urinary alkalinization

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Thank u…….