FIGURE 9.1 Categorization of ARF.
■ Volume depletion versus dehydration. These are not the same; however, they frequently coexist.
■ Volume depletion is characterized by a reduction in the extracellular fluid (ECF) volume and hemodynamic changes, including tachycardia and orthostatic hypotension. Volume depletion indicates sodium and water depletion and is most commonly caused by hemorrhage, vomiting, diarrhea, or third-space sequestration.
■ Dehydration, on the other hand, is water depletion; this frequently leads to hypernatremia. Dehydration can lead to confusion, thirst, impaired sensorium, and coma or seizures.
Causes of Prerenal Failure
■ Hypovolemia
■ Blood loss
■ GI fluid loss
• Diuretics
• Diuretic phase of recovery from ARF
• Adrenal insufficiency
• Hypoaldosteronism (isolated)
• Renal tubular disorders (e.g., Bartter/Gitelman syndrome)
• Osmotic diuresis (e.g., hyperglycemia)
• Salt-wasting nephropathy (e.g., medullary cystic disease)
■ Sequestration of ECF that cannot be readily mobilized into the plasma (“third spacing”). Examples include the following:
• Pancreatitis
• Intestinal obstruction
• Peritonitis
• Crush injuries
• Bleeding into tissue compartments
■ Decreased cardiac output
■ Heart failure
■ Pericardial tamponade (impaired venous inflow into heart)
■ Massive pulmonary embolism (impaired pulmonary blood flow)
■ Systemic vasodilation
■ Sepsis (release of vasoactive mediators such as prostacyclin and nitric oxide produced by endothelial cells)
■ Cirrhosis (multifactorial, including endotoxin-induced stimulation of nitric oxide production)
■ Anaphylaxis (release of vasoactive mediators including histamine, bradykinin)
■ Autonomic insufficiency (decreased sympathetic tone)
■ Antihypertensive drugs (several mechanisms, including indirect effects such as decreased sympathetic tone or renin–angiotensin system (RAS) blockade and direct vasodilator effects)
■ Renal vasoconstriction
■ Sepsis (despite systemic vasodilation; complex and not well understood pathogenesis involving dysregulation of nitric oxide and other factors)
■ Cirrhosis (can lead to marked decrease in RBF and GFR, that is hepatorenal syndrome [HRS]; hemodynamically similar to sepsis)
■ Prostaglandin inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) (renal prostaglandins are vasodilatory and attempt to maintain RBF in the setting of renal vasoconstriction)
■ Calcineurin inhibitors (cyclosporine, tacrolimus) (impairment of endothelial cell function, leading to reduced production of vasodilators such as prostaglandins and nitric oxide and enhanced release of vasoconstrictors such as endothelin and thromboxane)
■ Vasoconstrictors (e.g., norepinephrine, phenylephrine)
■ Renal vascular disease
■ Decreased glomerular capillary pressure
■ RAS blockers (dilate efferent > afferent arterioles)
Pathophysiology of Prerenal Failure
■ Total body water (TBW) is about 60% of body weight in males and 50% in females. Although water distributes throughout all body compartments, sodium is excluded from the intracellular space. Consequently, total body sodium content determines the size of the ECF compartment (typically about 45% of TBW is extracellular and 55% is intracellular, but is affected by gender and obesity). Normally, 83% (5/6) of the ECF is in the interstitium and 17% (1/6) in the plasma. Thus, in a 70-kg male, TBW = 0.6 × 70 = 42 L, ECF is 0.45 × 42 L = 19 L, and plasma volume is 0.17 × 19 L = 3.2 L, or about 8% of TBW. Volume depletion occurs when salt loss results in a decrease in ECF.
■ With a decrease in either true or EABV (see above), compensatory changes occur to maintain hemodynamic stability. Baroreceptors in the carotid sinus and aortic arch sense volume depletion and cause an increase in sympathetic activity and increased catecholamine release (Kon et al., 1985). Heart rate and contractility increase and peripheral vascular resistance increases to maintain blood pressure. Blood is shunted from nonessential vascular beds such as skeletal muscle, skin, kidneys, and GI tract toward the coronary and cerebral circulation (Blantz, 1998).
■ The juxtaglomerular apparatus in the kidney senses decreased RBF and secretes renin to activate the RAS and increase reabsorption of sodium and water. Stimulation of antidiuretic hormone (ADH), also called arginine vasopressin, also increases water reabsorption. When compensatory mechanisms fail, as with loss of greater than 10% to 20% of blood volume, patients develop orthostatic hypotension, which can progress to supine hypotension and shock (impaired tissue perfusion) (Blantz, 1998).
Symptoms and Signs of Prerenal Failure
■ If renal hypoperfusion is due to hypovolemia, tachycardia, postural hypotension, flat neck veins, cool extremities with decreased capillary refill, and poor skin turgor are seen.
■ If renal hypoperfusion is due to decreased cardiac output, signs of CHF (distended neck veins, rales, and edema) may be present. Consider cardiac tamponade (check for pulsus paradoxus, which is an accentuated variability in BP with respiration).
■ If renal hypoperfusion is due to systemic vasodilation, warm extremities are expected; with liver disease, palmar erythema and spider angiomata are seen.
■ If renal hypoperfusion is due to renovascular disease, an abdominal or flank bruit and/or hypertension may be present.
■ Decreased urine output is seen in all cases unless prerenal failure is due to renal fluid losses (e.g., diuretics, uncontrolled diabetes).
Laboratory Evaluation in Prerenal Failure
■ Plasma sodium is usually normal in volume depletion (since salt and water are both depleted) but will be high in dehydration. Plasma sodium may be low in states of decreased EABV, primarily due to increased ADH release (see Chapter 5).
■ Hyperglycemia can cause osmotic diuresis, resulting in both volume depletion and dehydration (note, since hyperglycemia causes water movement from cells to ECF, the extent of dehydration can be underestimated; the “corrected” sodium concentration will be higher than the measured sodium concentration (see Chapter 5).
■ Hypokalemia may exist in patients with diarrhea, taking diuretics, or with renal tubular defects (see Chapter 6).
■ Hypercalcemia can cause polyuria and failure of the kidney to respond to ADH (nephrogenic diabetes insipidus), resulting in hypernatremia.
■ Acid/base—There can be non–anion gap metabolic acidosis or (rarely) metabolic alkalosis with diarrhea, metabolic alkalosis with vomiting, and lactic acidosis with shock.
■ Hemoglobin and hematocrit may be low in patients with blood loss or high with volume depletion or severe dehydration.
■ A blood urea nitrogen (BUN):creatinine ratio (BUN/Cr) >20:1 is usually caused by increased urea reabsorption and suggests prerenal azotemia. The plasma urea nitrogen is also high in GI bleeding (increased gut nitrogen absorption coupled with prerenal failure), hypercatabolic states or with glucocorticoid therapy (increased protein breakdown and urea generation).
■ A urine sodium or urine chloride <20 mmol per L suggests volume depletion. A fractional excretion of sodium (FENa) <1% suggests prerenal azotemia. A fractional excretion of urea (FEurea) <35% also suggests prerenal azotemia and can be used when a patient is on diuretics, as FENa may be elevated if diuretic-induced sodium losses are the causes of prerenal failure. ADH-mediated water retention increases urine osmolality (often to >450 mmol/kg). This response to hypertonicity (from either dehydration or dehydration with volume depletion) is incomplete if urinary concentrating ability is impaired.
Treatment of Prerenal Failure
■ Treatment is directed at the underlying etiology. Shock or severe intravascular volume depletion require large-volume IV fluid replacement. The choice of resuscitation fluid depends on the cause of the deficit.
■ In hemorrhage, typically both blood transfusion and fluid resuscitation are required. Loss of red blood cells (RBCs) diminishes O2-carrying capacity, which can only be improved with RBC transfusion.
■ In the absence of hemorrhage, crystalloid solutions (isotonic 0.9% saline or lactated Ringer’s solution) are typically used for intravascular volume replenishment. Isotonic fluid remains in the ECF whereas hypotonic fluid (e.g., 0.45% saline) and free water (e.g., D5W) will also distribute into the intracellular fluid and are not appropriate for initial volume resuscitation. Lactated Ringer’s solution will prevent dilutional acidosis from large-volume IV fluid replacement because lactate is a bicarbonate former. Alternatively, an isotonic solution containing bicarbonate can be used (e.g., 0.45% saline with 75 mEq per L sodium bicarbonate) if metabolic acidosis is present.
■ Colloid solutions (e.g., hydroxyethyl starch, albumin, dextrans) are also effective for volume replacement and, since they stay at least initially in the plasma space, result in a more rapid increased in blood volume as compared to saline. However, in comparison with isotonic saline, no survival differences have been proven. Albumin may have a negative inotropic effect, and dextrans and hydroxyethyl starch can adversely affect coagulation. However, albumin infusions have been shown to be beneficial in specific circumstances such as after large volume paracentesis or during spontaneous peritonitis of cirrhosis.
■ The best indicator that fluid resuscitation is working is a urine output of 0.5 to 1 mL/kg/h. Heart rate, mental status, and capillary refill are other parameters, but these may not be as useful depending on the underlying illness. Vasoconstriction may make mean arterial pressure less usable, especially if pressors are also used. Central venous pressure (CVP) is the mean pressure in the superior vena cava, reflecting preload. Normal CVP ranges from 2 to 7 mm Hg (3 to 9 cm H2O). A CVP <2 mm Hg suggests volume depletion. A CVP 12 to 15 mm Hg indicates that right-sided cardiac filling pressures are adequate and fluid administration may be risky. However, left-sided filling pressures may still be low despite high right-sided pressures in patients with pulmonary hypertension and right ventricular failure, and pulmonary artery catheterization should be considered for diagnosis and treatment/monitoring in such instances.
Hepatorenal Syndrome (HRS)
■ This is a type of prerenal failure that occurs only in patients with severe liver failure. Patients with HRS typically have jaundice and ascites. The pathogenesis is complex and poorly understood, but is characterized by profound systemic and splanchnic vasodilation leading to relative hypotension, increased cardiac output, but intense renal vasoconstriction. In its classic form, there is no kidney injury, and the syndrome is reversible with improvement of liver function or liver transplantation (Iwatsuki et al., 1973). HRS is characterized by activation of the RAS and the sympathetic nervous system (both of which decrease GFR), increased adenosine (which is a systemic vasodilator but a renal vasoconstrictor), and increased systemic but reduced renal nitric oxide and vasodilator prostaglandin generation (Ruiz-del-Arbol et al., 2005). Alternative theories entertain deficiency of a vasodilator factor or an enhanced hepatorenal reflex leading to renal vasoconstriction in HRS.
■ Types of HRS
■ Type 1 HRS—characterized by rapid development of renal failure often precipitated by spontaneous bacterial peritonitis or another infection. Without treatment, survival is less than 2 weeks, but selected patients can be supported and undergo successful liver transplantation.
■ Type 2 HRS—characterized by moderate, stable or slowly progressive reduction in GFR. Median survival is 3 to 6 months, but can often undergo successful liver transplantation.
■ Diagnosis of HRS
■ Major criteria:
• Decreased GFR (plasma Cr >1.5 mg/dL)
• Absence of shock, sepsis, fluid loss, nephrotoxic drugs
• No improvement in renal failure after diuretic withdrawal or fluid resuscitation (≥1.5 L)
• Proteinuria <500 mg per 24 hour; negative renal ultrasound
■ Minor criteria:
• Urine volume <500 mL per day
• Urine sodium <10 mmol per L
• Urine osmolality > Plasma osmolality
• Plasma sodium < 130 mmol per L
• Urine RBCs <50 per hpf
■ Treatment of HRS
■ Midodrine or norepinephrine (systemic vasoconstrictor) plus octreotide (splanchnic vasoconstrictor) plus albumin
■ Vasopressin
■ Telipressin plus albumin—not available in the US
■ N-acetylcysteine?
■ Liver transplantation is definitive treatment
Presentation and Pathogenesis
■ In postrenal failure, azotemia is caused by reduced RBF resulting from increased pressure within the renal collecting system and is characterized by dilatation of the collecting system on renal imaging (hydronephrosis). The site of obstruction can be intrarenal (pelvocalyceal system) or at the level of the ureters, bladder, or urethra. Upper tract (i.e., intrarenal or ureteral) obstruction can be unilateral or bilateral, whereas lower tract obstruction will affect both kidneys.
■ There may be no symptoms in chronic obstruction, though with lower tract obstruction there will usually be lower urinary tract symptoms, such as hesitancy, urinary dribbling, urgency, and urinary frequency. Acute obstruction of the ureter(s) typically leads to colicky pain starting in the flank(s) and radiating into the groin. In complete obstruction (either bilateral or unilateral in a solitary kidney), there will be anuria, though partial obstruction can be associated with no change in urine output or even polyuria (nephrogenic diabetes insipidus due to tubular damage).
■ Normal urine output is thus typical with partial obstruction and does not exclude the diagnosis. Thus, a renal ultrasound is recommended in virtually all cases of ARF.
Causes of Postrenal Failure
■ Lower urinary tract
■ Benign prostatic hyperplasia (BPH)
■ Cancer (prostate, bladder)
■ Neurogenic bladder
• Diabetes mellitus
• Multiple sclerosis
• Cerebrovascular accident/spinal cord injury
• Alpha-adrenergic blockers
■ Bladder stones/clots
■ Urethral stricture
■ Upper urinary tract
■ Cancer (prostate, ovarian, endometrial, cervical, colon, lymphoma)
■ Nephrolithiasis/intratubular crystal deposition (e.g., uric acid, acyclovir, methotrexate)
■ Anatomical abnormalities (e.g., ureteropelvic junction obstruction)
■ Retroperitoneal fibrosis
■ Endometriosis
■ Blood clots
■ Papillary necrosis
Prognosis of Postrenal Failure
■ Postrenal azotemia is characterized by hypertension, either due to volume expansion in bilateral obstruction or renin secretion in unilateral obstruction. Two to 8 days following relief of obstruction, postobstructive diuresis may ensue. This is due to an expanded extracellular volume, osmotic diuresis, and a concentrating defect.
■ The prognosis for renal functional recovery depends on the duration and extent of obstruction. Based on experimental studies and clinical observations, renal recovery after complete obstruction of the urinary tract in a previously normal kidney is as follows:
■ One week—normal function (Kerr, 1954)
■ Twelve weeks—minimal function (Better et al., 1973)
Laboratory Evaluation in Postrenal Failure
■ Urinalysis—hematuria (stone, tumor, clot), pyuria (urinary tract infection [UTI] associated with obstruction), crystals (amorphous—uric acid, tetragon—calcium oxalate, hexagon—cystine, see Chapter 1)
■ Abdominal X-ray of kidneys, ureter, in bladder without contrast (KUB)—most stones are radio opaque, except uric acid
■ Renal ultrasound—test of choice for hydronephrosis
■ Although hydronephrosis is the hallmark of urinary obstruction, there are a few settings where it may be absent: (1) recent onset (<3 days) of obstruction, in which there may be inadequate time for dilatation to occur (increased resistive index on duplex Doppler ultrasonography in the affected kidney may be present prior to hydronephrosis in unilateral obstruction); (2) when the collecting systems are encased by retroperitoneal tumor or fibrosis and cannot dilate (this is very rare)
■ CT abdomen without contrast (this has replaced KUB for acute nephrolithiasis)
■ Prostate-specific antigen (PSA) (elevated in prostate cancer)
■ Diuretic renogram—increase in urine flow should wash out the radioisotope during a renal scan; if this does not occur, obstruction may be present
■ Urodynamics—neurogenic bladder
■ Stone evaluation (see Chapter 17).
Treatment of Postrenal Failure
■ BPH—alpha blockers, finasteride, transurethral resection of the prostate (TURP) or laser prostatectomy
■ Prostate cancer—surgery versus radiation versus watchful waiting (especially in older patients)
■ Neurogenic bladder—cholinergic drugs, intermittent self-catheterization, chronic urinary drainage catheter (last resort)
■
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