Acute Kidney Injury (AKI)

Definitions

  • General Definition: sudden decline in kidney function causing disturbances in fluid, electrolyte, and acid-base balance because of a loss in small solute clearance and decreased glomerular filtration rate (GFR)
  • Acute Kidney Injury Network (AKIN) Definition: abrupt (within 48 hrs) reduction in kidney function, defined as an absolute increase in serum Cr of greater than or equal to 0.3 mg/dL, a percentage increase in serum Cr of greater than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of <0.5 mL/kg/hr for >6 hrs

Physiology

  • Kidneys normally receive up to 25% of CO and are exquisitely sensitive to hypoperfusion
  • In AKI, the kidney’s ability to auto-regulate (maintain constant renal blood flow over a wide range of renal perfusion pressures) is compromised

Epidemiology

  • Incidence of AKI
    • Hospitalized Patients: occurs in 7% of hospitalized patients
    • ICU Patients: occurs in 36-67% of ICU patients
    • Incidence of AKI is increasing
    • 5-6% of ICU patients with AKI require HD
  • Morbidity of AKI in the ICU:
    • Increased ICU length of stay
    • Increased risk of CKD (however, true incidence of CKD following AKI is unknown)
  • Mortality of AKI in the ICU:
    • Mortality in severe AKI (requiring HD): 50-70%
    • Mortality is correlated with severity of AKI
    • Even small changes in serum Cr in hospitalized patients are correlated with increased mortality
  • Etiology of AKI in the ICU:
    • AKI is commonly multi-factorial in the ICU, resulting from hypoperfusion + sepsis + medications
    • Nephrotoxic medications have been implicated in up to 25% of all AKI cases in the ICU

Staging of AKI: RIFLE Staging

(Acute Dialysis Quality Initiative, 2002 Staging: excludes patients with primary kidney disease, such as glomerulonephritis)

  • Risk: Cr increase >1.5x or urine output <0.5 mL/kg/hr x 6 hrs
  • Injury: Cr increase >2x or urine output <0.5 mL/kg/hr x 12 hrs
  • Failure: Cr increase >3x or urine output <0.5 mL/kg/hr x 24 hrs (or anuria x 12hrs)
  • Loss: persistent loss of kidney function for >4 wks
  • End-Stage Kidney Disease: persistent loss of kidney function for >3 mo

Staging of AKI: Acute Kidney Injury Network (AKIN) Staging

  • Stage 1 (similar to Risk): Cr increase at least 0.3 mg/dL (or at least 1.5-2x increase from baseline) or urine output <0.5 mL/kg/hr for >8 hrs
  • Stage 2 (similar to Injury): Cr increase at least 2-3x from baseline or urine output <0.5 mL/kg/hr for >12 hrs
  • Stage 3 (similar to Failure): Cr increase at least 3x from baseline (or Cr at least 4 mg/dL with an acute rise of at least 0.5 mg/dL) or urine output <0.5 mL/kg/hr for 24 hrs (or anuria x 12 hrs)

Etiology: Pre-Renal

Hypovolemia

  • Contrast Nephropathy (see Contrast Nephropathy, [[Contrast Nephropathy]])
    • Epidemiology: uncommonly, some cases of contrast nephropathy manifest pre-renal urine studies, especially early during the oliguric phase
    • Physiology: possible mechanisms include contrast-induced renal vasospasm, increased blood viscosity with decreased renal blood flow, or acute tubular obstruction due to contrast-induced precipitates of Tamm-Horsfall protein
  • Hemorrhage/Hemorrhagic Shock (see Hemorrhagic Shock, [[Hemorrhagic Shock]])
  • Hypovolemia/Hypovolemic Shock (see Hypovolemic Shock, [[Hypovolemic Shock]])

Low Cardiac Output State

  • Cardiogenic Shock (see Cardiogenic Shock, [[Cardiogenic Shock]]): decreased CO state
  • General Anesthesia: causes systemic vasodilation and decreased CO

Increased Renal : Systemic Vascular Resistance Ratio

  • Abdominal Compartment Syndrome (see Abdominal Compartment Syndrome, [[Abdominal Compartment Syndrome]]): due to decreased renal perfusion
  • Amphotericin B (see Amphotericin, [[Amphotericin]]): due to renal vasoconstriction
  • Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]]): due to systemic vasodilation
  • Cyclosporine A (CSA) (see Cyclosporine A, [[Cyclosporine A]]]: due to renal vasoconstriction and direct toxicity
  • Epinephrine (see Epinephrine, [[Epinephrine]]): due to renal vasoconstriction
  • General Anesthesia: due to systemic vasodilation and decreased CO
  • Hepatorenal Syndrome (see Hepatorenal Syndrome, [[Hepatorenal Syndrome]]): cirrhosis (with protal HTN + ascites) is characterized by renal vasoconstriction, increased plasma volume, effective hypovolemia, and systemic vasodilation
  • Hypercalcemia (see Hypercalcemia, [[Hypercalcemia]]): due to renal vasoconstriction
  • Interleukin-2 (IL-2) (see Interleukin-2, [Interleukin-2]]): due to systemic vasodilation and capillary leak
  • Norepinephrine (see Norepinephrine, [[Norepinephrine]]): due to renal vasoconstriction
  • Sepsis (see Sepsis, [[Sepsis]]) (accounts for up to 50% of AKI cases in ICU, most common single etiology of AKI in a general ICU): due to systemic vasodilation
  • Tacrolimus (see Tacrolimus, [[Tacrolimus]])
  • Vasodilators: due to systemic vasodilation
    • Anti-Hypertensives
    • Epoprostenol (Flolan, Veletri) (see Epoprostenol, [[Epoprostenol]])

Renal Hypoperfusion with Impaired Renal Autoregulation

Hyperviscosity Syndromes


Etiology: Renal (Intrinsic)

Renovascular Obstruction

Glomerular/Renal Microvasculature Disease

Acute Tubular Necrosis (ATN)

Ischemic Acute Tubular Necrosis (Due to Hypotension/Shock)

Toxic Acute Tubular Necrosis

Drug-Induced Acute Tubular Necrosis
  • Acetaminophen (Tylenol) (see Acetaminophen, [[Acetaminophen]])
  • Aminoglycosides (see Aminoglycosides, [[Aminoglycosides]]): due to direct tubular toxicity/necrosis
  • Amphotericin B (see Amphotericin, [[Amphotericin]]): AKI occurs in 25-30% of cases -> liposomal amphotericin B is preferred because of reduced nephrotoxicity (19% vs 34%)
  • Cephalosporins (see Cephalosporins, [[Cephalosporins]])
  • Cisplatin (see Cisplatin, [[Cisplatin]])
  • Colistin (Colistimethate Sodium, Polymyxin E) (see Colistin, [[Colistin]])
  • Contrast Nephropathy (Contrast Nephropathy, [[Contrast Nephropathy]]): direct tubular toxicity with local ischemia
  • Cyclosporine A (see Cyclosporine A, [[Cyclosporine A]]): due to renal vasoconstriction and direct toxicity
  • Enflurane (see Enflurane, [[Enflurane]])
  • Foscarnet (see Foscarnet, [[Foscarnet]])
  • Illegal Abortifacients
  • Polymyxin B (see Polymyxin B, [[Polymyxin B]])
  • Tacrolimus (Prograf) (see Tacrolimus, [[Tacrolimus]])
Toxin-Induced Acute Tubular Necrosis
Pigment-Induced Acute Tubular Necrosis
Crystal-Induced Acute Tubular Necrosis
Multiple Myeloma (see Multiple Myeloma, [[Multiple Myeloma]])

Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])

Drug-Induced (Allergic) Interstitial Nephritis

Anti-Inflammatories
  • Antipyrine
  • Azathioprine (Imuran) (see Azathioprine, [[Azathioprine]])
  • Gold (see Gold, [[Gold]])
  • Interferons (see Interferons, [[Interferons]])
  • Non-Steroidal Anti-Inflammatory Drugs (NSAID’s) (see Non-Steroidal Anti-Inflammatory Drug, [[Non-Steroidal Anti-Inflammatory Drug]]): including selective COX-2 inhibitors
Antibiotics
Diuretics
Proton Pump Inhibitors (PPI’s)
  • Omeprazole (Prilosec) (see Omeprazole, [[Omeprazole]])
  • Lansoprazole (Prevacid) (see Lansoprazole, [[Lansoprazole]])
Other
  • Allopurinol (see Allopurinol, [[Allopurinol]])
  • α-Methyldopa (see α-Methyldopa, [[α-Methyldopa]])
  • Bismuth (see Bismuth, [[Bismuth]])
  • Captopril (see Captopril, [[Captopril]])
  • Clofibrate (Atromid-S) (see Clofibrate, [[Clofibrate]])
  • Coumadin (see Coumadin, [[Coumadin]])
  • Etanercept (see Anti-TNF Therapy, [[Anti-TNF Therapy]])
  • H2-Histamine Receptor Antagonists (see H2-Histamine Receptor Antagonists, [[H2-Histamine Receptor Antagonists]])
    • Cimetidine (Tagamet) (see Cimetidine, [[Cimetidine]]): cimetidine is the H2 blocker most associated with acute interstitial nephritis
    • Ranitidine (Zantac) (see Ranitidine, [[Ranitidine]]): only rare cases have been reported
  • Indinavir (Crixivan) (see Indinavir, [[Indinavir]])
  • Mesalamine (see Mesalamine, [[Mesalamine]])
  • Phenindione
  • Phenylpropanolamine (see Phenylpropanolamine, [[Phenylpropanolamine]])
  • Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]])
  • Probenecid (see Probenecid, [[Probenecid]])

Infectious Interstitial Nephritis

Viral
Bacterial
  • Acute Pyelonephritis (see Urinary Tract Infection, [[Urinary Tract Infection]])
  • Brucellosis (see Brucellosis, [[Brucellosis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Chlamydia (see Chlamydia, [[Chlamydia]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Diphtheria (see Diphtheria, [[Diphtheria]])
  • Enterococcus (see Enterococcus, [[Enterococcus]])
  • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
  • Legionellosis (see Legionellosis, [[Legionellosis]])
  • Leptospirosis (see Leptospirosis, [[Leptospirosis]]
  • Mycoplasma Pneumoniae (see Mycoplasma Pneumoniae, [[Mycoplasma Pneumoniae]])
  • Renal Tuberculosis (see Tuberculosis, [[Tuberculosis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Rocky Mountain Spotted Fever (see Rocky Mountain Spotted Fever, [[Rocky Mountain Spotted Fever]])
  • Staphylococcus (see Staphylococcus, [[Staphylococcus]])
  • Streptococcus (see Streptococcus, [[Streptococcus]])
  • Syphilis (see Syphilis, [[Syphilis]])
  • Tularemia (see Tularemia, [[Tularemia]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Yersinia (see Yersinia, [[Yersinia]])
Fungal
  • Candidiasis (see Candida, [[Candida]])
  • Coccidioidomycosis (see Coccidioidomycosis, [[Coccidioidomycosis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Histoplasmosis (see Histoplasmosis, [[Histoplasmosis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
Parasitic
  • Leishmaniasis (see Leishmaniasis, [[Leishmaniasis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation
  • Toxoplasmosis (see Toxoplasmosis, [[Toxoplasmosis]])
    • Produces a Histologic Variant of Acute Interstitial Nephritis with Associated Granuloma Formation

Infiltrative Interstitial Nephritis

Vasculitis-Associated Interstitial Nephritis

Other Etiologies of Interstitial Nephritis

  • Acute Renal Allograft/Transplant Rejection (see Renal Transplant, [[Renal Transplant]])
  • Immunoglobulin G4-Related Disease (IgG4-Related Disease) (see Immunoglobulin G4-Related Disease, [[Immunoglobulin G4-Related Disease]])
    • Epidemiology: acute interstitial nephritis is the most common renal manifestation of IgG4-related disease
  • Intravenous Drug Abuse (IVDA)
  • Radiation Nephritis (see Radiation Therapy, [[Radiation Therapy]])
  • Idiopathic Interstitial Nephritis

Intratubular Deposition and Obstruction

Renal Allograft/Transplant Rejection (see Renal Transplant, [[Renal Transplant]])

  • xxx

Nephrotic Syndrome (see Nephrotic Syndrome, [[Nephrotic Syndrome]])

  • Crescentic Glomerulonephritis
  • Focal Segmental Glomerulosclerosis
  • Focal Segmental Proliferative Glomerulonephritis
  • Membrano-Proliferative Glomerulonephritis Type 1
  • Membrano-Proliferative Glomerulonephritis Type 2
  • Membranous Glomerulonephritis
  • Mesangio-Proliferative Glomerulonephritis
  • Minimal Change Disease
  • Osmotic Nephrosis

Etiology: Post-Renal

Ureteral Obstruction

  • External Ureteral Compression
    • Inadvertent Ureteral Ligation During Surgery
    • Retroperitoneal Fibrosis
  • Sloughed Papillae
  • Ureteral Blood Clot
  • Ureteral Calculi
  • Ureteral Cancer

Bladder Neck Obstruction

Urethral Obstruction

  • Phimosis
  • Urethral Congenital Valve
  • Urethral Stricture

Multifactorial Etiologies

  • Post-Cardiac Surgery/Cardiopulmonary Bypass (occurs in up to 42% of cases without pre-existing kidney disease): associated with increased morbidity and mortality
  • Trauma (occurs in 31% of cases): due to [[Hemorrhagic Shock]], [[Rhabdomyolysis]], and [[Abdominal Compartment Syndrome]]

Diagnosis

Urinalysis (see Urinalysis, [[Urinalysis]])

Urine Microscopy

  • General Comments
    • Nephrologist Review of Urine Microscopy is Superior to Clinical Laboratory Review [MEDLINE]: nephrologists were likely to recognize the presence of renal tubular epithelial cells, granular casts, renal tubular epithelial cell casts, and dysmorphic red blood cells in urine
  • Urinary Scoring System [MEDLINE]: urine microscopy is highly predictive to differentiate prerenal azotemia from acute tubular necrosis
  • Pre-Renal Azotemia
    • Normal/Near Normal Urine Microscopy: hyaline or fine granular casts may be present
  • Acute Tubular Necrosis (ATN)
    • Muddy-Brown (Brown Pigmented) Granular Casts and Renal Tubular Epithelial Cell Casts
      • However, the presence of muddy brown granular casts and renal tubular epithelial cell casts are usually seen relatively late and thus are not sensitive for the early detection of AKI
      • In addition, the absence of casts deos not exclude the diagnosis of ATN: cell sloughing and cast formation may be less prominent in patients with less severe disease and non-oliguric ATN
  • Glomerular Injury
    • Cellular Casts
  • Acute Interstitial Nephritis
    • Eosinophiluria
      Urate Nephropathy
    • Uric Acid Crystals
  • Atheroembolic AKI

Serum Creatinine

  • Creatinine is limited as an real-time estimate of GFR in critically ill patients (as creatinine is not in steady state in these patients)
    • Rate of Cr production, apparent volume of distribution of creatinine, and rate of creatinine elimination are all variable
    • Some medications (trimethoprim, dronedarone, cimetidine) impair creatinine secretion
  • Use of creatinine lacks sensitivity and underestimates the degree of kidney dysfunction in critically ill patients
  • Increases in serum creatinine lag behind reductions in GFR -> large changes in GFR result in only small changes in creatinine (due to non-linear, exponential relationship of GFR and creatinine)

Biomarkers for the Early Detection of Acute Kidney Injury

Neutrophil Gelatinase-Associated Lipocalin (NGAL)

  • General Comments
    • NGAL Rapidly Increases in Response to Renal Ischemia: it may function to attenuate tubular toxicity by increasing the normal proliferation of renal tubular cells and by inducing heme oxygenase (which provides additional tubular cell protection)
    • NGAL is More Sensitive than Serum Creatinine for the Detection of Early AKI
    • Urine and Serum NGAL are Correlated with Increasing Length of ICU and Hospital Stay [MEDLINE]
  • Serum NGAL
  • Urinary NGAL
    • Sensitivity/Specificity (Using Cutoff Value of 50 microg/L) [MEDLINE]: sensitivity 100%/specificity 98%

Serum or Urinary Cystatin C

  • General Comments
    • Cystatin C is More Sensitive than Serum Creatinine for the Detection of Early AKI
  • Serum Cystatin C
  • Urinary Cystatin C

Kidney Injury Molecule-1 (KIM-1)

  • xxx

Urinary IL-18

  • xxx

Fractional Excretion of Sodium (FENa) (see xxx)

  • FENa is frequently useful for differentiating “pre-renal” (diminished renal perfusion, FENa <1%) from “intra-renal” (ischemia or nephrotoxins, FENa >2%)
  • However, pre-renal and intra-renal causes often co-exist in critically ill patients

Fractional Excretion of Urea (FE Urea) (see xxx)

  • xxx

Urinary Uric Acid:Urinary Creatinine Ratio

  • Ratio >1 -> suggests urate nephropathy
  • Ratio <1 -> suggests AKI due to other causes

Urine Osm

  • Contrast Nephropathy: urine osm around 300 (isosthenuria)

Diagnostic Volume Challenge

  • May be useful to determine if AKI is pre-renal

Renal Biopsy

  • Not necessary in contrast nephropathy (diagnosis is clinical)
  • May be useful in cases of GN or vasculitis

Prevention of Acute Kidney Injury (AKI)

  • In contrast to community-acquired AKI, ICU-acquired AKI is usually associated with more than one insult -> since the first insult may not predictable, much of prevention effort is aimed at preventing second or concurrent insults
    • Predictable causative events: cardiopulmonary bypass, contrast dye exposure, large volume paracentesis, nephrotoxic exposure, or chemotherapy

Prevention of Contrast Nephropathy

  • Hydration: meta-analyses provide strong evidence that sodium bicarbonate is superior to isotonic saline to decrease incidence of contrast nephropathy
    • Mix 3 amps bicarb in 1 L D5W -> run at 3 cc/kg/hr x 1 hr prior to contrast -> run at 1cc/kg/hr x 6 hrs after contrast
  • N-Acetylcysteine (Mucomyst): 600 mg BID on the day before and day of the administration of contrast (alternatively, can use IV mucomyst)
    • Free radical scavenger
    • Conflicting data in prevention of contrast nephropathy
  • Use of Low-Volume, Non-Ionic, Low-Osmolar or Iso-Osmolar Contrast Agents: proven to decrease risk of contrast nephropathy, as compared to high-osmolar agents
    • Although these agents have lower osmolality (600 to 850 mOsm/kg H2O) than first-generation ionic contrast agents (1,500 to 1,800 mOsm/kg H2O), they are significantly hyperosmolar relative to plasma
    • Studies of a new iso-osmotic (approximately 290 mOsm/kg H2O) contrast medium, iodixanol, have demonstrated decreased nephrotoxicity as compared to iohexol (3% vs 26%, respectively)
  • Avoid Concurrent Angiotensin Converting Enzyme Inhibitor Exposure (see Angiotensin Converting Enzyme Inhibitors, [[Angiotensin Converting Enzyme Inhibitors]]): might increase risk of contrast nephropathy
  • Peri-Procedural Ultra-Filtration or Hemodialysis: might decrease the risk of contrast nephropathy (however, studies are limited by fact that the clinical endpoint, Cr, is decreased by the intervention itself) -> not recommended without further studies
  • Fenoldopam (see Fenoldopam, [[Fenoldopam]]): selective dopamine-1 receptor agonist -> renal vasodilato
    • Currently approved for the treatment of hypertensive crisis
    • No benefit in prevention of contrast nephropathy
  • Theophylline (see Theophylline, [[Theophylline]]): no clear benefit in prevention of contrast nephropathy

Prevention of Alcoholic Hepatitis-Associated AKI

  • Pentoxifylline (see Pentoxifylline, [[Pentoxifylline]]): decreases incidence of AKI in setting alcoholic hepatitis
    [Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119:1637–1648]

Prevention of End-Stage Liver Disease-Associated AKI in Setting of SBP

  • Albumin (see Albumin, [[Albumin]]): decreases incidence of AKI in setting of SBP
    [Intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. NEJM 1999; 341:403– 409]

Prevention of ESLD-Associated AKI in Setting of Large-Volume Paracentesis

  • Albumin (see Albumin, [[Albumin]]): decreases incidence of AKI after large-volume paracetesis
    [Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 1988; 94: 1493–1502]

Prevention of ESLD-Associated AKI

  • Albumin + Terlipressin (a splanchnic vasoconstrictor, not available in US): may decrease mortality in hepatorenal syndrome
    [Terlipressin for hepatorenal syndrome. Cochrane Database Syst Rev 2006:CD005162]
    [Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: Results of a prospective, nonrandomized study. Hepatology 2002; 36:941–948]
  • Terlipressin or Norepinephrine (vasoconstrictors): improve renal function in hepatorenal syndrome (however, mortality benefit was demonstrated only in subset of patients who were “responders”)
    [A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008; 134:1360-1368]
    [Beneficial effects of terlipressin in hepatorenal syndrome: A prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol 2003; 18:152-156]
    [Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: A randomized study. Gastroenterology 2008; 134: 1352-1359]
    [Noradrenalin vs terlipressin in patients with hepatorenal syndrome: A prospective, randomized, unblinded, pilot study. J Hepatol 2007; 47:499 –505]
    [An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol 2008; 103:1689-1697]
  • Vasopressin: improves renal function, as compared to octreotide alone
    [Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: A retrospective study. Nephrol Dial Transplant 2005; 20:1813–1820]
  • Octreotide + Midodrine + Albumin (OMA) Therapy: midodine + octreotide improve mortality and may result in reversal of hepatorenal syndrome
    [Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology 1999; 29:1690-1697]
    [Octreotide/Midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007; 52:742-748]
    [Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome. J Clin Gastroenterol 2009; 43:680-685]

Maintenance of Renal Perfusion

  • Goal: maintain MAP greater than or equal to 65 (although actual MAP required in AKI is unknown and depends on age, underlying vascular disease, etc) using fluids/pressors
  • Renal-Dose Dopamine: may cause a trasient increase in urine output, but does not decrease incidence of AKI, need for HD, or improve outcome in AKI
    • Renal-dose dopamine may worsen renal perfusion in AKI, increases myocardial O2 demand, increase incidence of atrial fibrillation, and produce negative immunomodulatory effects
  • Crystalloid vs Colloid -> SAFE trial demonstrated no mortality difference or need for HD between crystalloid vs colloid groups
    [A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247–2256]

    • Higher mortality with colloid in subgroup with traumatic brain injury
    • Trend toward lower mortality with colloid in subgroup with septic shock
  • Hydroxyethyl Starches
    • Systematic review demonstrated increased risk of AKI in setting of sepsis
      [Systematic review of randomized clinical trials on the use of hydroxyethyl starch for fluid management in sepsis. BMC Emerg Med 2008; 8:1]
    • SOAP Study: no adverse effect of hydroxyethyl starches on incidence of AKI or need for HD
      [Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006; 34: 344 –353][Effects of hydroxyethyl starch administration on renal function in critically ill patients. Br J Anaesth 2007; 98:216 –224]
    • Lowest molecular weight starches appear to be the safest
  • Fluid-Conservative Management Strategy in ARDS (CVP <4, PCWP <8) does not impact ALI/ARDS mortality, as compared to fluid-liberal management strategy (CVP 10-14, PCWP 14-18)
    [The NHLBI Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. New Engl J Med 2006;354(24):2564-2575]

    • However, fluid-conservative management improves oxygenation, ventilator-free days, and ICU-free days
    • No increase in shock, nonpulmonary organ failure, or need for HD in the fluid-conservative group of patients

Management of Hyperglycemia

  • Tight Glucose Control: multiple studies have demonstrated a decreased incidence of AKI and a decreased requirement for HD
    [Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354:449-461]
    [Intensive insulin therapy in the critically ill patients. N Engl J Med 2001; 345: 1359-1367]
    [Tight blood glucose control is renoprotective in critically ill patients. J Am Soc Nephrol 2008; 19:571–578]
    [Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients. Crit Care 2008; 12:R154]
  • Tight Glucose Control: however, recent large trial did not demonstrate decreased need for HD (although the incidence of AKI was not reported in this study)
    [Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283-1297]

Fenoldopam (see Fenoldopam, [[Fenoldopam]])

  • Selective dopamine-1 receptor agonist -> renal vasodilator
  • Currently approved for the treatment of hypertensive crisis
  • Low-Dose Fenoldopam (less than 1 ug/kg/min): increases renal blood flow without systemic effects
  • In Sepsis: fenoldopam had no impact on need for HD (despite a smaller increase in Cr)
    [Prophylactic fenoldopam for renal protection in sepsis: A randomized, double-blind, placebo-controlled pilot trial. Crit Care Med 2005; 33:2451–2456]
  • In At-Risk Patients: meta-analyses demonstrated that fenoldopam decreased mortality and need for HD
    [Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Am J Kidney Dis 2007; 49:56–68]

    • Trials in cardiac surgery patients are ongoing [clinicaltrials.gov ID: NCT00557219]

Clinical Manifestations

Neurologic Manifestations

Renal Manifestations

  • Anuria: rare in contrast nephropathy cases
  • Creatinine Elevation: usually peaks at 1 wk in contrast nephropathy cases
  • Normal Osmolal Gap (see Serum Osmolality, [[Serum Osmolality]]): variable
    • May be elevated in cases where AKI results from an intoxication (such as ethylene glycol, methanol, etc)
  • Oliguria: present in 50% of contrast nephropathy cases

Other Manifestations

  • xxx

Prognosis

  • Contrast nephropathy is associated with a risk-adjusted odds rato of death of 5.5

Treatment

Diuretics

  • Diuretics increase Na excretion and may increase urine output in AKI
  • Oliguric AKI has worse outcome than non-oliguric AKI
    [Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group. J Am Soc Nephrol 1998; 9:692– 698]

    • However, there is no evidence that diuretics convert oliguric -> non-oliguric AKI
  • Diuretics do not improve mortality, shorten duration of AKI, or decrease the need for HD
    [The role of diuretic agents in the management of acute renal failure. Contrib Nephrol 2001: 158 -170]
  • Failure to Respond to Diuretics: associated with increased mortality and non-recovery of renal function
    [Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002; 288:2547–2553]
  • In patients in recovery from AKI (after receiving HD), furosemide increased urine output but did not impact renal recovery
    [van der Voort PH, Boerma EC, Koopmans M, et al. Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: A double-blind randomized controlled trial. Crit Care Med 2009; 37:533-538]

Optimization of Nutrition

  • See [[Nutrition]]

Renal Replacement Therapy (RRT)

  • Types of RRT
    • Peritoneal Dialysis (PD):
    • Hemodialysis (HD):
    • Ultrafiltration (UF):
    • Continuous Renal Replacement Therapy (CRRT): also known as continuous veno-venous HD (CVVHD)
    • Slow Low-Efficiency Dialysis (SLED): slower solute and fluid removal than CRRT
  • Indications for HD
    • Hyperkalemia
    • Uremia
    • Acidemia
    • Volume Overload
    • Drug Intoxications: ethylene glycol, etc
  • Timing of RRT
    • Studies are controversial as to effect of early vs late initiation of HD
  • RRT Modality
    • CRRT (CVVHD) has lower mortality rate than PD
      *[Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. N Engl J Med 2002; 347:895-902]
    • There is no evidence that the form of dialysis (CRRT vs intermittent HD vs SLED), affects mortality or renal recovery
    • Daily dialysis is not better than intermittent
    • Continuous therapies are consistently more expensive than intermittent therapies
  • Dose of RRT
    • There is a suggestion that the minimum dose of each dialysis treatment may have an impact on mortality -> studies suggest that a UF rate of at least 35 ml/kg/hr had lower mortality rate (43%) than 20 ml/kg/hr (59%)
  • Heparin vs Citrate Anticoagulation
    • Citrate may have same filter life and lower bleeding risk and mortality rate than heparin -> citrate is probably preferred

Atial Natriuretic Peptide (ANP) (Experimental)

  • ANP decreases the need for HD and improves dialysis-free survival in post-cardiopulmonary bypass-associated AKI without pre-existing CKD
    [Recombinant human atrial natriuretic peptide in ischemic acute renal failure: A ran- domized placebo-controlled trial. Crit Care Med 2004; 32:1310–1315]

Erythropoetic Agents (Experimental)

  • The endothelium plays a central role in the initiation and maintenance phases of AKI
  • Animal models demonstrate a renal-protective effect of erythropoietin on endotoxin-related kidney injury
  • Decreased severity of AKI is proposed to occur through tubular regeneration from the direct effects of erythropoietin on tubular epithelial cells
  • Trials are ongoing (clinicaltrials.gov NCT00476619).

Renal Tubule Assist Device (Experimental)

  • Ongoing trials

Hemofiltration for Sepsis (Experimental)

  • Ongoing trials

Stem Cells (Experimental)

  • Ongoing trials

References

General

  • Acute kidney injury in the intensive care unit: An update and primer for the intensivist. Crit Care Med 2010; 38:261-275

Diagnosis

  • Comparison and interpretation of urinalysis performed by a nephrologist versus a hospital-based clinical laboratory. Am J Kidney Dis 2005; 46:820–829 [MEDLINE]
  • Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.  Lancet 2005; 365:1231-1238 [MEDLINE]
  • Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008;36(4):1297-1303 [MEDLINE]
  • Diagnostic value of urine microscopy for differential diagnosis of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 2008; 3:1615–1619 [MEDLINE]
  • N-GAL: Diagnosing AKI as soon as possible. Critical Care 2007;11:1 [MEDLINE]
  • Diagnostic value of urine microscopy for differential diagnosis of acute kidney injury in hospitalized patients.  Clin J Am Soc Nephrol 2008; 3:1615-1619 [MEDLINE]
  • Biomarkers of acute kidney injury: an evolving domain. Anesthesiology 2010; 112(4): 998-1004 [MEDLINE]
  • The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: A multicenter pooled analysis of prospective studies.  J Am Coll Cardiol  2011; 57:1752-1761 [MEDLINE]

Contrast Nephropathy

  • Low Fractional Excretion of Sodium With Contrast Media-Induced Acute Renal Failure. Arch Int Med 1980; 140: 531-533
  • Prevention of contrast media-induced nephropathy by isotonic sodium bicarbonate: A meta-analysis. Wien Klin Wochenschr 2008; 120:742–748
  • Use of isotonic sodium bicarbonate to prevent radiocontrast ne- phropathy in patients with mild pre- existing renal impairment: A meta-analysis. Anaesth Intensive Care 2008; 36:646 – 653
  • Current role of sodium bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: A meta-analysis. Am Heart J 2008; 156: 414 – 421
  • Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: A meta-analy- sis. BMC Med 2009; 7:23
  • Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: A systematic review and meta-analysis. Am J Kidney Dis 2009; 53:617-627
  • Sodium bicarbonate vs sodium chloride for the prevention of contrast medium-induced nephropathy in patients undergoing coronary angiography: A randomized trial. JAMA 2008; 300:1038 –1046
  • Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343: 180 –184
  • Meta-analysis: Effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med 2008; 148:284-294
  • A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: Unsupervised clustering to resolve heterogeneity. BMC Med 2007; 5:32
  • The value of N-acetylcysteine in the prevention of radiocontrast agent-induced ne- phropathy seems questionable. J Am Soc Nephrol 2004; 15:407– 410
  • N-Acetylcysteine does not artifactually lower plasma creatinine concentration. Nephrol Dial Transplant 2008
  • Prevention of contrast media-associated nephropathy. Arch Intern Med 2002; 162:329-336.
  • A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract 2003; 93:C29-C34
  • Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003; 362:598-603.
  • Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: A meta-analysis of randomized, controlled trials. Am J Kidney Dis 2004; 43:1-9
  • Systemic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney Int 2004; 65:1366-1374.
  • Fenoldopam mesylate for the prevention of contrast-induced nephropathy: A randomized controlled trial. JAMA 2003; 290:2284-2291.
  • Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003; 348:491-499.
  • Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful. Am J Med 2001; 111:692-698.

Dialysis

  • Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. N Engl J Med 2002; 347:895-902
  • A randomized clinical trial of continuous versus intermittent hemodilaysis for acute renal failure. Kidney Int 2001; 60:1154-1163
  • Continuous versus intermittent renal replacement therapy: a meta analysis. Intensive Care Med 2002; 28:29-37
  • Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis 2002; 40:875-885
  • Effects of different doses of continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomized trial. Lancet 2000; 356:26-30
  • Daily hemodialysis and the outcome of acute renal failure. N Engl J Med 2002; 346:305-310
  • Renal replacement therapy in patients with acute renal failure. JAMA. 2008;299:793-805
  • Intensity of renal support in critically ill patients with acute kidney injury. N Engl Med. 2008;359:7- 20
  • Continuous venous-venous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet. 2006;368:379-85
  • Renal Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl Med 2009;361:1627-1638
  • Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: A double-blind randomized controlled trial. Crit Care Med 2009; 37:533-538