ACUTE RENAL FAILURE
I. Definition
A sudden decrease in renal function resulting in the inability to excrete metabolic waste products such as urea nitrogen and creatinine and the inability to maintain proper fluid and electrolyte balance. The condition develops in 5% of hospitalized patients. Acute renal failure (ARF) is frequently defined as an acute increase in serum creatinine level from baseline (i.e., an increase of at least 0.5 mg/dl). Complete renal shutdown is present when serum creatinine level increases by at least 0.5 mg/dl per day and urine output is less than 400 ml per day (oliguria).
II. Classification/etiology
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A. Prerenal (60% to 70% of cases)
1. Characterized by diminished renal perfusion resulting from a decrease in blood supplying the kidneys. No nephron damage is present.
2. Causes:
a. Intravascular volume depletion (absolute decrease in blood volume)
i. Hemorrhage
ii. Gastrointestinal losses (e.g., diarrhea, vomiting, large amount of nasogastric tube aspirate)
iii. Urinary losses (e.g., diabetes insipidus, use of diuretics)
iv. Skin losses (third spacing, large surface area burns, and/or wounds)
b. Vasodilatory states (relative decrease in blood volume)
i. Sepsis
ii. Anaphylaxis
c. Decreased cardiac output (relative decrease in blood volume)
i. Congestive heart failure
ii. Myocardial infarction
iii. Cardiogenic shock
d. Arterial occlusion/vasoconstrictive states (catecholamines)
e. Uncontrolled hypertension/atherosclerosis
f. Liver disease
3. Results in increased tubular sodium and water reabsorption (in an attempt at reexpansion of circulating blood volume)
a. Oliguria
b. Decreased urine sodium (less than 20 mEq/L)
c. High urine osmolality (greater than 500 mOsm/L)
d. Urine specific gravity: increased (greater than 1.020)
4. Decreased distal tubular flow may cause increased urea absorption and decreased potassium secretion with marginal effect on creatinine.
5. BUN-to-creatinine ratio increased (20:1)
6. Ratio of urine-to-plasma (U/P) levels of creatinine greater than 40
7. Fractional excretion of sodium (FeNa+) less than 1%: the most sensitive differential test: less than 1 = prerenal; greater than 1 = renal
8. Increased renal “threshold” for plasma ions: increased bicarbonate (HCO3−) generation leads to contraction alkalosis.
9. Increased uric acid reabsorption: hyperuricemia
10. Increased antidiuretic hormone (ADH) secretion: increased water reabsorption; urinary osmolality greater than serum osmolality
11. Hyponatremia with free water loading until volume is restored
12. Urinary sediment: hyaline casts
B. Intrarenal (intrinsic) (25% to 40% of cases)
1. Abrupt decrease in glomerular filtration rate (GFR) due to tubular cell damage that results from renal ischemia or nephrotoxic injury
2. Acute tubular necrosis—accounts for most hospital-associated cases of intrinsic ARF around 50%
a. Ischemic
i. Decreased cardiac output
ii. Prolonged hypotension
iii. Volume depletion
iv. Catecholamines
v. Volume shift
vi. Liver disease (“hepatorenal syndrome”)
b. Nephrotoxic
i. Endogenous (e.g., hemoglobinuria [hemolysis], myoglobinuria [rhabdomyolysis], hyperuricemia, multiple myeloma)
ii. Exogenous (e.g., aminoglycosides, contrast media, ethylene glycol, amphotericin B, cyclosporine, antineoplastics such as cisplatin, heavy metals). Patients should be hydrated with 1 L of 0.45% saline over 12 hours before and after contrast administration (use cautiously in patients with preexisting cardiac dysfunction). Oral administration of N-acetylcysteine 600 mg 12 hours before and after contrast has produced a decrease in the incidence of dye-induced nephrotoxicity.
3. Acute tubulointerstitial nephritis accounts for 10% to 15% of cases of intrinsic renal failure. This is caused by the following:
a. Bacterial pylonephritis—Infectious causes may include streptococcal infection, leptospirosis, cytomegalovirus, histoplasmosis, and Rocky Mountain spotted fever.
b. More than 70% of cases are related to drug-induced hypersensitivity to the following:
i. Penicillins
ii. Cephalosporins
iii. Sulfonamides and sulfonamide-containing diuretics
iv. NSAIDs
v. Rifampin
vi. Phenytoin
vii. Allopurinol
c. Immunologic disorders—more commonly associated with glomerulonephritis, but systemic lupus erythematosus (SLE), Sjögren’s syndrome, sarcoidosis, and cryoglobulinemia may also be associated.
d. Idiopathic conditions
4. Urinalysis: urinary sediment, with the following:
a. Renal tubular epithelial cells
b. Cellular debris
c. Pigmented granular casts
d. Renal tubular cell casts
e. “Muddy brown” coarse granular casts (Table 42-1)
| ATN, Acute tubular necrosis; Cr, creatinine; RBC, red blood cell; RPGN, rapidly progressing glomerulonephritis; U/P, urine/plasma; WBC, white blood cell. | ||||
*Except NSAID-induced allergic interstitial nephritis with concomitant “nil disease.”  | ||||
| Prerenal | Postrenal (acute) | Intrinsic renal (acute) | Intrinsic renal (chronic) | |
|---|---|---|---|---|
| Urine volume | Decreased | Absent-to-wide fluctuation | Oliguric or nonoliguric | 1000 ml+ until end stage |
| Urinary creatinine | Increased (U/P Cr ± 40) | Decreased (U/P Cr ± 20) | Decreased (U/P Cr less than 20) | Decreased (U/P Cr less than 20) |
| Osmolarity | Increased (±400 mOsm/kg) | Less than 350 mOsm/kg | Less than 350 mOsm/kg | Less than 350 mOsm/kg |
| Degree of proteinuria | Minimum | Absent | Varies with cause of renal failure: modest with ATN; nephrotic range common with acute glomeru-lopathies, usually less than 2 g/24 hours with interstitial disease* | Varies with cause of renal disease (from 1 to 2 g/day to nephrotic range) |
| Urinary sediment | Negative, or occasional hyaline cast | Negative, or hematuria with stones or papillary necrosis; pyuria with infectious prostatic disease | ATN: muddy brown; interstitial nephritis: lymphocytes, eosinophils (in stained preparations), and WBC casts; RPGN: RBC casts; nephrosis oval fat bodies | Broad casts with variable renal “residual” acute findings |
5. Urine volume
a. Anuria: less than 100 ml/24 hours
b. Oliguria: 100-400 ml/24 hours
c. Nonoliguria: more than 400 ml/24 hours
d. Polyuria: more than 6 L/24 hours
6. Urine osmolality: isotonic (350 mOsm or less)
7. Urine specific gravity: fixed (1.0008 to 1.012)
9. FeNa+ greater than 1%
10. BUN-to-creatinine: less than 20:1
11. Low serum Na (less than 135 mEq)
12. Proteinuria may be seen, particularly in NSAID-induced interstitial nephritis, but is usually modest.
13. Other clinical findings may include fever (greater than 80%), rash (25% to 50%), arthralgias, and peripheral blood eosinophilia.
C. Postrenal (5% to 10% of cases)
1. Associated with conditions that cause obstruction of urinary flow and consequently a decrease in GFR
2. Mechanical
a. Calculi
b. Tumors (prostate cancer, cervical cancer)
c. Urethral strictures
d. Benign prostatic hyperplasia
e. Blood clots
f. Occluded Foley catheter
3. Functional
a. Neurogenic bladder
b. Diabetic neuropathy
c. Spinal cord disease
4. Urine volume may fluctuate between anuria and polyuria.
5. Urine osmolality: isotonic (less than 350 mOsm) (initially may be high)
6. Urine specific gravity: fixed (1.0008 to 1.012)
7. Urine Na: greater than 40 mEq/L (initially may be low—variable)
8. FeNa+: variable
9. Urinary sediment
a. Normal or red cells
b. White cells
c. Crystals
10. BUN-to-creatinine: greater than 20:1
11. In-and-out catheter may reveal increased postvoid residual volume, and renal ultrasound may demonstrate hydronephrosis.
12. Plain film x-ray (kidney, ureter, and bladder) of the abdomen will document the presence of two kidneys and will provide a check for kidney stones (Table 42-2).
| RTA, Renal tubular acidosis. | ||||
| *FeNa — UNa/PNa UCr/Pcr × 100. | ||||
| Prerenal | Postrenal (acute) | Intrinsic renal (acute) | Intrinsic renal (chronic) | |
|---|---|---|---|---|
| BUN | Increased 10:1 greater than Cr | Increased by 20 to 40/day | Increased by 20 to 40/day | Stable; increase varies with protein intake |
| Serum creatinine | Normal/moderate increase | Increased by 2 to 4/day | Increased by 2 to 4/day | Stable increase (production equals excretion) |
| Serum potassium | Normal/moderate increase | Increase varies with urinary volume | Large increase (particularly when patient is oliguric); even larger increase with rhabdomyolysis | Normal until end stage, unless tubular dysfunction (type 4 RTA) |
| Serum phosphorus | Normal/moderate increase | Moderate increase | Increased | Becomes significantly elevated when serum creatinine surpasses 3 mg/dl |
| Large increase with rhabdomyolysis | Poor correlation with duration of renal disease | |||
| Serum calcium | Normal | Normal/decreased with PO−43 | Decreased (poor correlation with duration of renal failure) | Usually decreased |
| Renal size by ultrasound FeNa* | Normal/increased by less than 1 | Increased and with dilated calyces less than 1 to greater than 1 | Normal/increased greater than 1 | Decreased and with increased echogenicity greater than 1 |
13. CT scan or MRI may also reveal obstruction.
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