Acute Kidney injury

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Acute Kidney Injury

Acute Renal Failure (ARF): Abrupt decrease of renal function retention of nitrogenous waste products, loss of regulation of extracellular volume and electrolytes Creatinine (SCr): not sensitive in detecting the early decline in GFR in early stages of ARF

Creatinine: unreliable indicator during AKI

Variability of serum Cr Levels can vary with age, sex, muscle mass, medication and hydration status Late change of Scr May not change until about 50% of kidney function has been lost Overestimation of renal function At low GFR, the amount of tubular secretion of creatinine results in overestimation of renal function

Intensive Care Med 30:3337

 Not accurately depict kidney function during acute change of GFR During acute changes in GFR, SCr does not accurately depict kidney function until steadystate equilibrium has been reached

Acute Kidney Injury

2001 : Acute Dialysis Quality Initiative (ADQI) Risk: 1.5x inc in SCr, GFR dec 25%, UOP<0.5 ml/kg/h x 6h Injury: 2x inc SCr, GFR dec 50%, UOP<0.5 ml/kg/h x 12h Failure: 3x inc SCr, GFR dec 75%, UOP<0.5/kg/h x 24h Also anuria x 12 hr Loss: complete loss (inc need for RRT) > 4 wks ESRD: complete loss (inc need for RRT) > 3 months 2007: Acute Kidney Injury Network (AKIN) Modified RIFLE to include SCr 0.3 mg/dL from baseline, within 48hr, based on 80% mortality risk 2007: Acute Kidney Injury proposed by AKIN

RIFLE

Outcome

AKIN

Comparison between RIFLE and AKIN classifications

RIFLE classification
Risk, Injury, and Failure Loss and End stage renal disease describe renal outcome after acute kidney injury episode

AKIN classification
Stages 1, 2 and 3 Not used

Uses change in creatinine or glomerular filtration rate, in addition to urine output criteria
Risk: increased creatinine 1.5 or glomerular filtration rate decrease >25%

Uses change in creatinine, in addition to urine output criteria

Stage 1: increased creatinine 1.5 or 0.3 mg/dl Patients starting renal replacement therapy are classified as Stage 3, regardless of serum creatinine or urine output Acute kidney injury diagnosis is based on a change between two creatinine values within a 48-hour perioda Diagnostic criteria to be used only "after an optimal state of hydration has been achieved"

Stage not specified for patients starting renal replacement therapy

Proposed timeframe of 1 week specified for making diagnosis of acute kidney injury

Not specified

aAlthough

the diagnosis of acute kidney injury is based on changes over the course of 48 hours, staging occurs over a slightly longer timeframe. One week was the timeframe proposed by the Acute Dialysis Quality Initiative group Cruz et al. Critical Care 2009 13:211 doi:10.1186/cc7759

Risk for all-cause mortality by severity of AKI (n = 71,527)

Presenting manifestations of AKI

1. 2.

Serum Cr / BUN Urine output (abrupt)

Oliguria (< 400 ml/day) Anuria (< 100 ml/day)

3. Uremic symptoms:
Clinical: Fluid overload; mental alterations Anorexia, vomiting Pericarditis Lab: + anemia, hyperkalemia, acidemia Hypocalcemia, hyperphosphatemia

Pathophysiology of reduced GFR in ATN

intrinsic AKI Hx, PE, U/A

Renal vascular disorder Glomerular disease Acute interstitial nephritis

(BUN /Serum Cr without GFR)

Nonrenal factors altering urea Increased

Hypovolemia GI bleeding Severe catabolic state Hyperalimentation Corticosteroid Tetracycline

Decreased
Hepatocellular failure Low protein intake Water excess(SIADH)

Nonrenal factors altering creatinine Increased Decreased Overproduction Decreased Rhabdomyolysis muscle mass
Large meal, meat

Blocked secretion
Trimethoprim Cimetidine

Hepatocellular failure

Chemical interference
Cefoxitin Alphamethyldopa Acetone, acetoacetic a.

Acute vs. Chronic kidney disease

Review old values of Scr - most reliable
Hx : edema, hematuria, passing stone, nocturia, Uremic symptoms underlying dis. (DM,HT, renal disease) PE : anemia, dry skin & itching, hyperpigmentation, symptom not correlate with high BUN/Cr, peripheral neuropathy

Lab - Hct, rate of Cr rise U/A : broad casts Plain KUB, US - small kidney size* Renal osteodystrophy*

Acute VS Chronic kidney disease

Acute
Hx Oliguria Uremic symptoms Anemia Skin: dry, itching Peripheral neuropathy Kidney size Short (days-wk) + Earlier -

Chronic
Longer (mo-Yr) - (except ESRD) Not correlate with high BUN,Cr + + + + Small*

Renal osteodystrophy Normal

* Large kidney: DN, infiltrative kidney disease, ADPKD

Postrenal causes of ARF

Ureteric/pelvic obstruction Intrinsic obstruction: tumor, stones, blood clot, pus, fungal ball Extrinsic obstruction: retroperitoneal or pelvic malignancy, ureteric ligation, retroperitoneal fibrosis Bladder Impaired contractility: Neurogenic bladder (DM, spinal cord lesion), Drugs with anticholinergic activity Chronic bladder outlet obstruction Bladder neck obstruction: tumor, stones, BPH, prostatic carcinoma, obstructed indwelling catheter Urethra obstruction Phimosis, congenital posterior urethral valve, stricture, tumor

 Anuria (< 100 ml/day) Bilateral completed urinary tract obstruction Severe ATN, acute cortical necrosis Severe glomerulonephritis or AIN Vascular lesions

AKI
Glomerular

Tests
Hx/PE Sediment, ANA, C3, ANCA Biopsy + Hx/PE Eosinophilia Eosinophiluria Sediment Biopsy + Hx/PE MAHA Nuclear scan Arteriogram + Hx

Differential Dx
2 GN: SLE, Infectious RPGN Idiopathic Allergic Pyelonephritis Crystals Myeloma Malignant HT Microangiopathy Thrombosis/embolism Cholesterol embolic Vasculitis Ischemia Toxic

Interstitial

Vascular

ATN

Clinical clue to glomerular causes of renal failure

Acute Nephritic diseases 10 Glomerular dis. - Idiopathic crescentic GN - Ig A Nepfropathy - Membranoproliferative GN 20 Glomerular dis. - Poststreptococcal GN - GN due to BE, VA shunt - LE - Polyarteritis nodosa - Wegeners granulomatosis - Henoch-Schnlein purpura - Essential cryoglobulinemia Clinical Clue CS, flu-like prodrome Recurrent gross hematuria triggered by URI Partial lipodystrophy, SGOT Sore throat, impetigo, 1-3 Wk latent period CS, multisystem sx CS, upper or lower respiratory sx, multisystem Purpuric rash, arthralgias, GI pain or bleeding CS, purpuric rash, joint sx, LFT, hepatomegaly, multisystem sx

Nephrotic Diseases Rapid Progression of Dis. DN, Amyloidosis, HIV nephropathy Sequela of NS Renal vein thrombosis Chronic glomerular Dis. Proteinuria(+/- hematuria), Scr(over several mo.)

Glomerular causes of renal failure

1. Acute nephritic diseases - hematuria, proteinuria, RBC cast - acute or subacute renal failure 2. Nephrotic - Rapid progression of underlying dis. - Sequelae of NS Tubulointerstitial nephritis in lipoid nephrosis Hypovolemia from severe hypoalbuminemia Renal vein thrombosis - NSAIDs

Dysmorphic RBC
Vary in size, shape & Hb - Acanthocyte - Ring form: doughnut - Ruined forms: distorted cell Dwarf forms

Isomorphic RBC
Similar size, shape & Hb content

Heme cast

RBC cast

Glomerulonephritis

Interstitial causes of renal failure

Acute interstitial nephritis Drugs: Penicillin, Sulfonamides, Rifampicin, Cimetidine, Captopril, Thiazide, furosemide, allopurinol, NSAIDs, Chinese Herb Infections: Leptospirosis, CMV, typhoid fever, pyelonephritis, infectious mononucleosis Systemic diseases: connective tissue disease Neoplastic interstitial infiltration Lymphoma Solid tumor Idiopathic

Interstitial causes of renal failure

Hx drugs exposure Fever,rash, arthritis Lymphadenopathy Labs: CBC: Eosinophilia U/A: Eosinophile in urine

Vascular causes of renal failure

Large vessel involvement Renal arteries: thrombosis, atheroembolism, thromboembolism, dissection, vasculitis (e.g. Takayasu) Renal Veins: thrombosis, compression Small renal vessel (renal microvasculature) Scleroderma, Malignant HT, Toxemia of pregnancy HUS, TTP DIC, hyperviscosity syndrome

Vascular causes of renal failure

Hx Claudication, post-cardiac catheterization Flank pain and hematuria acute renal vein thrombosis BP, eye ground PE Pluses all extremities, Abdominal bruits Livedo reticularis Cutaneous infarction, toe gangrene Labs: anemia + MAHA+ platelet (HUS, TTP) Atheroembolism: (low complement, eosinophilia, eosinophiluria)

Urine sediment
Bland or Scant finding - Vasculitides: preglomerular vasculitis, HUS, SSS -Prerenal azotemia -Postrenal azotemia Granular casts - ATN : pigmented coarsely granular casts RBC & RBC casts - GN - small vessel vasculitis - Interstitial nephritis or ATN - rarely seen Epithelial & WBC or WBC casts - Eosinophiluria present : AIN - Eosinophiluria absence : AIN still possible - Pyelonephritis (severe, with abscess) Crystalluria Uric acid : Tumor lysis syndrome Calcium oxalate: Glycol toxicity

Tubular disorder
ATN (prominent injury to renal tubule) Ischemic: caused by prolonged prerenal and hypotension Nephrotoxic: Exogenous: antibiotics (aminoglycoside, vancomycin) amphotericin-B, pentamidine, foscanet anticancer agents (cisplatin) Heavy metals (mercury,cadmium, arsenic) organic solvent, herbiside Endogenous: hemoglobin,Myoglobin Myeloma light chains Intratubular deposition or obstruction Myloma protein, uric acid (tumor lysis syndome) acyclovir IV, methotrexate, sulfonamides,

Hemorrhage Volume depletion (vomiting, diarrhea, over diuresis, burns)

Prerenal

Cardiogenic shock Distributive shock (sepsis, anaphylaxis)

NSIADs/selective cox2 inhibitors ACEi/ARB Abdominal aortic aneurysm Renal artery stenosis Hepatorenal syndrome

Cardiac failure Hepatic cirrhosis Nephrotic syndrome

Clinical clue to prerenal renal failure

Recent volume loss - GI, Renal, insensible - 3rd space loss Recent cardiac insult, cirrhosis Fever or other signs of sepsis Orthostatic symptoms BP < usual level, JVP Urine volume Urine sp. gr. >1.020 BUN/Cr > 20:1 Albumin < 3 g/dl without edema Cr < 4 mg/dL fluctuation Scr

Urine indices: Prerenal & ATN Parameter

Urine Sp. gr. Uosm (mosmol/kg) U/P Cr Plasma BUN/Cr Urine Na (mEq/L) FENa Renal failure index

Prerenal
> 1.020 > 500 > 40 > 20 < 20 < 1% <1

Renal
< 1.010 < 350 < 20 < 10 > 40 > 1-2% >1

Use only in oliguria, no diuretic, no underlying renal disease, urine sample collected before treatment

FENa < 1%
Prerenal azotemia Severe renal vasoconstriction
hepatorenal syndrome NSAID, cyclosporin, contrast media Disease of afferent arteriole - TTP, Scleroderma

Acute glomerulonephritis Atheroembolic renal disease Early obstructive uropathy 10-15% of nonoligulic ATN

FENa > 1% 1. ATN 2. Diuretic use 3. Non reabsorbable solute 4. Bicarbonate, Glucose, Mannitol 5. Late obstructive uropathy 6. Mineralocorticoid deficiency

Management ARF
1. Correct causes & prerenal state 2. Drug - convert to non-oliguria: Furosemide 3. Prevent further damage - monitor & optimize hemodynamic - avoid hypotension & nephrotoxic drugs 4. Supportive Px & complications - Fluid (urine + extrarenal loss + 500-600 ml/d) (insensible loss water metabolism = 500 ml/d) - Electrolyte management (K, P, HCO3) - Drugs adjustment - Sepsis, GI bleeding - Dialysis if indicated 5. Nutrition 6. Recovery phase: fluid & electrolyte balance, drugs dose adjust

Indication of dialysis
1. 2. 3. 4. 5. Hyperkalemia Not response Volume overload to conservative Severe metabolic acidosis (pH < 7.2) Rx Uremia: encephalopathy, nausea, vomiting Uremic pericarditis hemorrhagic pericarditis (cardiac temponade) BUN & serum Cr level - BUN > 100 mg/dL; Cr > 10 mg/dL - In hypercatabolic ARF: BUN > 70 mg/dL; Cr > 7 mg/dL

6.

Non-catabolic & hypercatabolic ARF

Non catabolic Catabolic

BUN (mg/dl) Cr (mg/dl) Serum K Serum bicarbonate 10 - 20 0.5 -1.0 < 0.5 <1 > 20 >2 1 -2 >2

 Drugs therapy - Try diuretics once to identify less severe ARF - Do not use renal dopamine - Start specific agent based upon etiology of ARF - Start dialysis when indicated
- Choose therapy (mode, dialyzer) based upon co-morbid illnesses - Measure delivered dialysis dose