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April 08, 2008

Acute Renal Failure

Acute Renal Failure


Acute Renal Failure - ARF (Acute Kidney Injury - AKI) is defined as an abrupt or Rapid Decline in Renal Filtration Function. This condition is usually Marked by a Rise in Serum Creatinine Concentration or Azotemia (a rise in Blood Urea Nitrogen [BUN] concentration).

  • Renal Injury
    • However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production.
  • Without Renal Injury
    • Rise in the creatinin level - Medications (eg. cimetidine, trimethoprim),
    • Rise in the BUN level - GI or mucosal bleeding, steroid use, or protein loading.
A careful inventory must be taken before determining if a kidney injury is present.


ARF may occur in 3 clinical patterns, including the following :

  1. As an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons. (Prerenal ARF)
  2. In response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage. (Renal / Intrinsic ARF)
  3. With obstruction to the passage of urine. (Post Renal ARF)

Patients who develop ARF also can be classified into oliguric ARF or nonoliguric ARF :

  1. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure.
  2. Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, is suggestive of bilateral obstruction or catastrophic injury to both kidneys.
Stratification of renal failure along these lines helps in decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.


Prerenal ARF

  • The most common form of kidney injury and often leads to intrinsic ARF if not corrected.
  • Etiology :
    • Volume loss from GI, renal, cutaneous (eg, burns), and internal or external hemorrhage can result in this syndrome,
    • Decreased renal perfusion in patients with heart failure or shock (eg, sepsis, anaphylaxis),
    • Special classes of medications (induce prerenal ARF) in volume-depleted states are angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs),
    • Hypercalcemic states (induce arteriolar vasoconstriction),
    • The use of radiocontrast agents, onsteroidal anti-inflammatory drugs (NSAIDs), amphotereicin, calcineurin inhibitors, norepinephrine, and other pressor agents,
    • The hepatorenal syndrome can also be considered a form of prerenal ARF because functional renal failure develops from diffuse vasoconstriction in vessels supplying the kidney.
Intrinsic ARF
  • Structural injury in the kidney is the hallmark of intrinsic ARF, and the most common form is Acute Tubular Injury (ATN), either Ischemic or Cytotoxic.
  • Etiology :
    • Intrarenal vasoconstriction is the dominant mechanism for the reduced GFR in patients with ATN.
    • Urine backflow and intratubular obstruction (from sloughed cells and debris) are causes of reduced net ultrafiltration.
Failure to excrete concentrated urine, even in the presence of oliguria, is a helpful diagnostic clue to distinguish prerenal from intrinsic renal disease, in which urine osmolality is less than 300 mOsm/kg. In prerenal azotemia, urine osmolality is typically more than 500 mOsm/kg.

Postrenal ARF
  • Etiology :
    • Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or urethra.
    • Causes of obstruction include stone disease; stricture; and intraluminal, extraluminal, or intramural tumors.
  • Bilateral obstruction is usually a result of prostate enlargement or tumors in men and urologic or gynecologic tumors in women.
  • Patients who develop anuria typically have obstruction at the level of the bladder or downstream to it.
  • United States : About 1% of patients admitted to hospitals have ARF when admission
  • Approximately 95% of consultations with nephrologists are related to ARF.
  • Feest and colleagues calculated in their report that the appropriate nephrologist referral rate is approximately 70 cases per million population.
Mortality / Morbidity
  • Mortality Rate : Vary from 25-90%.
  • The in-hospital mortality rate is 40-50%. The in intensive care settings rate is 70-80%.
Increments of 0.3 mg/dL in serum creatinine have important prognostic significance.

  • No racial predilection is recognized.

The causes of AKI traditionally are divided into 3 main categories :

Prerenal ARF

  • Volume depletion,Renal losses (diuretics, polyuria),GI losses (vomiting, diarrhea)
  • Cutaneous losses (burns, Stevens-Johnson syndrome), Hemorrhage, Pancreatitis
  • Decreased cardiac output, Heart failure, Pulmonary embolus, Acute myocardial infarction
  • Severe valvular disease, Abdominal compartment syndrome (tense ascites)
  • Systemic vasodilation,Sepsis, Anaphylaxis, Anesthetics, Drug overdose
  • Afferent arteriolar vasoconstriction,Hypercalcemia
  • Drugs (NSAIDs, amphotericin B, calcineurin inhibitors, norepinephrine, radiocontrast agents), Hepatorenal syndrome,Efferent arteriolar vasodilation – ACEI or ARB
Intrinsic / Renal ARF
  • Vascular (large and small vessel)
    • Renal artery obstruction (thrombosis, emboli, dissection, vasculitis), Renal vein obstruction (thrombosis), Microangiopathy (TTP, hemolytic uremic syndrome [HUS], DIC, preeclampsia), Malignant hypertension,
    • Scleroderma renal crisis, Transplant rejection, Atheroembolic disease,
  • Glomerular
    • Anti–glomerular basement membrane (GBM) disease (Goodpasture syndrome)
    • Anti–neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-associated GN) (Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis)
    • Immune complex GN (lupus, postinfectious, cryoglobulinemia, primary membranoproliferative glomerulonephritis)
  • Tubular
    • Ischemi, Cytotoxic, Heme pigment (rhabdomyolysis, intravascular hemolysis)
    • Crystals (tumor lysis syndrome, seizures, ethylene glycol poisoning, megadose vitamin C, acyclovir, indinavir, methotrexate)
    • Drugs (aminoglycosides, lithium, amphotericin B, pentamidine, cisplatin, ifosfamide, radiocontrast agents)
  • Interstitial
    • Drugs (penicillins, cephalosporins, NSAIDs, proton-pump inhibitors, allopurinol, rifampin, indinavir, mesalamine, sulfonamides)
    • Infection (pyelonephritis, viral nephritides)
    • Systemic disease (Sjogren syndrome, sarcoid, lupus, lymphoma, leukemia, tubulonephritis, uveitis)
Postrenal AKI
  • Ureteric obstruction (stone disease, tumor, fibrosis, ligation during pelvic surgery),
  • Bladder neck obstruction (benign prostatic hypertrophy [BPH], cancer of the prostate [CA prostate or prostatic CA], neurogenic bladder, tricyclic antidepressants, ganglion blockers, bladder tumor, stone disease, hemorrhage/clot)
  • Urethral obstruction (strictures, tumor, phimosis)
Differential Diagnosis
  • Acute Tubular Necrosis
  • Azotemia
  • Chronic Renal Failure
  • Other consideration :
    • Obstructive uropathy, GI bleeding, Protein overloading, Steroid use

  • Detailed and Accurate history is crucial to aid in diagnosing the type of ARF
  • Distinguishing ARF from Chronic Renal Failure (CRF)
  • General History :
    • Hypotension,Volume contraction,Congestive heart failure (CHF)
    • Nephrotoxic drug ingestion
    • History of trauma or unaccustomed exertion
    • Blood loss or transfusions
    • Evidence of connective tissue disorders or autoimmune diseases
    • Exposure to toxic substances, such as ethyl alcohol or ethylene glycol
    • Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be encountered in welders and miners
    • Comorbid conditions (Higher Risk for ARF) :
      • Cardiac Failure, Diabetes, Multiple myeloma, Chronic infection, Myeloproliferative disorder
    • Urine output history can be useful. Oliguria generally favors AKI. Abrupt anuria suggests an acute obstruction, acute and severe glomerulonephritis, or an embolic event due to the renal artery occlusion. A gradually diminishing urine output may indicate a urethral stricture or bladder outlet obstruction due to prostate enlargement.
    • Because of a decrease in functioning nephrons, even a trivial nephrotoxic insult may cause AKI to be superimposed on chronic renal insufficiency.
Physical Examination

Obtaining a thorough physical examination is extremely important when collecting evidence about the etiology of AKI.
  • Skin
    • Petechiae, purpura, ecchymosis, and livedo reticularis provides clues to inflammation and vascular causes of AK
    • Infectious diseases, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), and embolic phenomena can present with typical cutaneous changes.
  • Eyes
    • Uveitis may indicate interstitial nephritis and necrotizing vasculitis.
    • Ocular palsy may indicate ethylene glycol poisoning or necrotizing vasculitis.
    • Findings suggestive of severe hypertension, atheroembolic disease, and endocarditis may be observed after a careful examination of the eyes.
  • Cardiovascular system
    • Include pulse rate and blood pressure recordings measured in both the supine position and the standing position
    • Close inspection of the jugular venous pulse;
    • Careful examination of the heart, lungs, skin turgor, and mucous membranes; and assessment for the presence of peripheral edema.
    • Hypovolemia leads to hypotension; however, hypotension may not necessarily indicate hypovolemia.
    • Severe congestive cardiac failure (CHF) may also cause hypotension. Although patients with CHF may have low blood pressure, volume expansion is present and effective renal perfusion is poor, which can result in AKI.
    • Severe hypertension with renal failure suggests renovascular disease, glomerulonephritis, vasculitis, or atheroembolic disease.
  • Abdomen
    • The presence of an epigastric bruit suggests renal vascular hypertension.
Lab Studies
  • These tests include complete blood cell count, serum biochemistries, urine analysis with microscopy, and urine electrolytes.
  • Blood urea nitrogen and serum creatinine
    • Although increased levels of BUN and creatinine are the hallmarks of renal failure, the rate of rise is dependent on the degree of renal insult as well as protein intake with respect to BUN.
  • The ratio of BUN to creatinine is an important finding because the ratio can exceed 20:1 in conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction) and suggests prerenal AKI.
  • BUN may be elevated in patients with GI or mucosal bleeding, steroid treatment, or protein loading.
  • Assuming no renal function, the rise in BUN over 24 hours can be roughly predicted using the following formula: 24-hour protein intake in milligrams X 0.16 divided by total body water in mg/dL added to the BUN value.
  • Assuming no renal function, the rise in creatinine can be predicted using the following formulas:
    • For males: weight in kilograms X [28 – 0.2(age)] divided by total body water in mg/dL added to the creatinine value
    • For females: weight in kilograms X [23.8 – 0.17(age)] divided by total body water added to the creatinine value
  • As a general rule, if serum creatinine increases to more than 1.5 mg/dL/d, rhabdomyolysis must be ruled out.
  • CBC, peripheral smear, and serology
    • These tests may be useful, and the peripheral smear results may show schistocytes in conditions such as HUS or TTP.
    • A finding of increased rouleaux formation suggests multiple myeloma, and the workup should be directed toward immunoelectrophoresis of serum and urine.
    • The presence of myoglobin or free hemoglobin, increased serum uric acid level, and other related findings may help further define the etiology of AKI.
  • Serologic tests for antinuclear antibody (ANA), ANCA, anti-GBM antibody, hepatitis, and antistreptolysin (ASO) and complement levels may help include and exclude glomerular disease. Although serologic tests can be informative, the costs can be prohibitive if not ordered judiciously.
  • Urinalysis
    • Findings of granular muddy-brown casts are suggestive of tubular necrosis. The presence of tubular cells or tubular cell casts also supports the diagnosis of ATN. Often, oxalate crystals are observed in cases of ATN.
    • Reddish brown or cola-colored urine suggests the presence of myoglobin or hemoglobin, especially in the setting of a positive dipstick for heme and no RBCs in the microscopic examination.
    • Dipstick assay findings may show the presence of significant proteinuria, which would suggest glomerular or interstitial disease.
    • The presence of RBCs in the urine is always pathologic. Eumorphic RBCs suggest bleeding along the collecting system. Dysmorphic RBCs or RBC casts indicate glomerular inflammation, suggesting glomerulonephritis is present.
    • The presence of WBCs or WBC casts suggests pyelonephritis or acute interstitial nephritis. The presence of urine eosinophils is helpful in establishing a diagnosis but is not necessary for allergic interstitial nephritis to be present.
    • The presence of eosinophils, as visualized with Wright stain or Hansel stain, suggests interstitial nephritis but can be seen in urinary tract infections, glomerulonephritis, and atheroembolic disease.
    • The presence of uric acid crystals may represent ATN associated with uric acid nephropathy.
    • Calcium oxalate crystals are usually present in cases of ethylene glycol poisoning.
  • Urine electrolytes
    • Urine electrolyte findings also can serve as valuable indicators of functioning renal tubules.
    • The fractional excretion of sodium (FENa) is the commonly used indicator. However, the interpretation of results from patients in nonoliguric states, those with glomerulonephritis, and those receiving or ingesting diuretics can lead to an erroneous diagnosis. FENa can be a valuable test for helping to detect extreme renal avidity for sodium in conditions such as hepatorenal syndrome. The formula for calculating the FENa is as follows:
Imaging Studies
  • Ultrasound
    • Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the urinary collecting system. The degree of hydronephrosis does not necessarily correlate with the degree of obstruction. Mild hydronephrosis may be observed with complete obstruction if found early.
    • Ultrasound scans or other imaging studies showing small kidneys suggest chronic renal failure.
  • Doppler scans
    • Doppler scans can be quite useful in the diagnosis of thromboembolic or renovascular disease.
  • Nuclear scans
    • Radionuclide imaging with a technetium Tc 99m diethylenetriamine pentaacetic acid (DTPA), 99m Tc-DTPA iodine I 131–hippuran scan can be used to assess renal blood flow and tubular functions.
Medical Care

  • Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary goals of treatment.
    • Furosemide can be used to correct volume overload when the patients are still responsive to it.
  • Correcting acidosis with Bicarbonate administration is important.
  • Therapeutic agents, such as dopamine, fenoldopam, and mannitol, are not indicated in the management of AKI and may be harmful for the patient.
  • Hyperkalemia, which can be life-threatening, should be treated by decreasing the intake of potassium, delaying the absorption of potassium, exchanging potassium across the gut lumen using potassium-binding resins, controlling intracellular shifts, and instituting dialysis.
  • Correcting hematologic abnormalities (eg, anemia, platelet dysfunction) warrants appropriate measures, including transfusions and administration of desmopressin or estrogens.
  • Drug Category
    • Diuretic : Furosemide (Lasix)
      • Although diuretics seem to have no effect on the outcome of established AKI, they appear useful in fluid homeostasis and are used extensively. The use of isotonic sodium chloride solution in conjunction with diuretics is debatable. The only therapeutic or preventive intervention that has an established beneficial effect in the management of AKI is administration of isotonic sodium chloride solution to keep the patient euvolemic or even hypervolemic.
    • Vasodilators : Dopamine (Intropin)
      • Dopamine in small doses (eg, 1-5 mcg/kg/min) causes selective dilatation of the renal vasculature, enhancing renal perfusion. Dopamine also reduces sodium absorption, thereby decreasing the energy requirement of the damaged tubules. This enhances urine flow, which, in turn, helps prevent tubular cast obstruction. Most clinical studies have failed to establish this beneficial role of renal-dose dopamine infusion.
    • Calcium channel blockers : Nifedipine (Adalat, Procardia)
      • Effective in animal models but efficacy not proven in humans. Effects are believed to be mediated through vasodilation, and calcium channel blockers increasingly are used to enhance the function of transplanted kidneys.
    • N-Acetylcysteine : N-acetylcysteine (Mucosil, Mucomyst)
      • Used for prevention of contrast toxicity in susceptible individuals such as those with diabetes mellitus.


  • Diet and fluid restriction become crucial in the management of oliguric renal failure,
  • Because potassium and phosphorous are not excreted optimally in patients with AKI, blood levels of these electrolytes tend to be high. Frequent measurements are mandatory to achieve acceptable blood levels by modification of the diet or by IV supplementation.
  • In the polyuric phase of AKI, potassium and phosphorous may be depleted and patients require dietary supplementation and intravenous fluids.
  • Calculation of the nitrogen balance can be challenging, especially in the presence of volume contraction, hypercatabolic states, gastrointestinal bleeding, and diarrheal disease.

  • The prognosis of patients with AKI is directly related to the cause of renal failure and, to a great extent, to the duration of renal failure prior to therapeutic intervention.
  • If AKI is defined by a sudden increment of serum creatinine of 0.5-1 mg/dL and is associated with a mild-to-moderate rise in creatinine, the prognosis tends to be worse.
  • However, even if renal failure is mild, the mortality rate is 30-60%. If these patients need dialytic therapy, the mortality rate is 50-90%.
  • The mortality rate is 31% in patients with normal urine sediment test results and is 74% in patients with abnormal urine sediment test results.
  • If using Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the survival rate is nearly 0% among patients with AKI who have a score higher than 40 and is 40% in patients with APACHE II scores of 10-19.
  • Other prognostic factors include the following:
    • Older age, Multiorgan failure (ie, the more organs that fail, the worse the prognosis)
    • Oliguria, Hypotension, Vasopressor support, Number of transfusions
    • Noncavitary surgery

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