Chapter 34. Acute Kidney Injury & Oliguria

Oliguria literally means “reduced” urine volume—less than that necessary to remove endogenous solute loads that are the end products of metabolism. If the patient concentrates urine in a normal fashion while consuming a regular Western diet, oliguria (for that person) is present at urine volumes <400 mL/day, or approximately 6 mL/kg body weight. If the kidney concentration is impaired and the patient can achieve a specific gravity of only 1.010, oliguria is present at urine volumes <1000–1500 mL/day.

In an attempt to standardize the diagnosis of acute renal failure, the new terminology acute kidney injury (AKI) was coined. New staging systems have been devised to compare severity of the damage sustained across different study groups and for prognostication.

AKI is a condition in which the glomerular filtration rate is abruptly reduced, causing a sudden retention of endogenous and exogenous metabolites (urea, potassium, phosphate, sulfate, creatinine, administered drugs) that are normally cleared by the kidneys. The urine volume is usually low (<400 mL/day). If renal concentrating mechanisms are impaired, the daily urine volume may be normal or even high (high-output or nonoliguric renal failure). In extreme cases, anuria occurs (urine output completely shuts down) in acute kidney injury.

The causes of AKI are listed in Table 34–1. Prerenal causes are usually reversible if treated promptly, but a delay in therapy may allow it to progress to a fixed intrinsic renal failure (eg, acute tubular necrosis). The other causes of AKI are classified on the basis of their involvement with vascular lesions, intrarenal disorders, or postrenal disorders.

The term prerenal denotes inadequate renal perfusion or lowered effective arterial circulation. The most common cause of this form of AKI is dehydration due to renal or extrarenal fluid losses from diarrhea, vomiting, excessive use of diuretics, and so on. Less common causes are septic shock, “third spacing” with extravascular fluid pooling (eg, pancreatitis), and excessive use of antihypertensive drugs. Heart failure with reduced cardiac output also can reduce effective renal blood flow. Careful clinical assessment may identify the primary condition responsible for the prerenal state, but many times several conditions can coexist. In the hospital setting, these circulatory abnormalities often are prolonged, leading to a more sustained injury (acute tubular necrosis).

Acute reductions in glomerular filtration rate may also be noted in patients with cirrhosis (hepatorenal syndrome) or in patients taking cyclosporine, tacrolimus, nonsteroidal anti-inflammatory drugs, or angiotensin-converting enzyme inhibitors. It is felt that these conditions represent significant intrarenal hemodynamic functional derangements. In these clinical circumstances, the urinary findings may mimic prerenal renal failure, but the patient's clinical assessment does not demonstrate the extrarenal findings seen in common prerenal conditions, as noted in the following section. Improvements in glomerular filtration rate are usually noted after drug discontinuance or, in cases of hepatorenal syndrome, with management of the liver disease or following liver transplantation.

Clinical Findings

Symptoms and Signs

Except for rare cases with associated cardiac or “pump” failure, patients usually complain of thirst or of dizziness in the upright posture (orthostatic dizziness). There may be a history of overt fluid loss. Weight losses reflect the degree of dehydration. Physical examination frequently reveals decreased skin turgor, collapsed neck veins, dry mucous membranes, and, most importantly, excessive orthostatic or postural changes in blood pressure (defined as a systolic drop >20 or a diastolic drop >10 mm Hg) and pulse.

Laboratory Findings

Urine

The urine volume is usually low. Accurate assessment may require bladder catheterization followed by hourly output measurements (which will also rule out lower urinary tract obstruction; see discussion following). High urine specific gravity (>1.025) and urine osmolality (>600 mOsm/kg) are also noted in this form of acute apparent renal failure. Routine urinalysis usually shows a bland sediment. However, as it progresses to acute tubular necrosis, sloughed off tubular cells and muddy brown casts may become apparent.

Urine and Blood Chemistries

The blood urea nitrogen–creatinine ratio, normally 10:1, is usually increased with prerenal renal failure. Other findings are set forth in Table 34–2. Because mannitol, radiocontrast dyes, and diuretics affect the delivery and tubular handling of urea, sodium, and creatinine, urine and blood chemistry tests performed after these agents have been given can be misleading.

Central Venous Pressure

A low central venous pressure indicates hypovolemia. If severe cardiac failure is the principal cause of prerenal renal failure (it is rarely the sole cause), reduced cardiac output and high central venous pressure are apparent.

Fluid Challenge

An increase in urine output in response to a carefully administered fluid challenge is both diagnostic and therapeutic in cases of prerenal renal failure. Rapid intravenous administration of 300–500 mL of physiologic saline is the usual initial treatment. Urine output is measured over the subsequent 1–3 hours. A urine volume increase of >50 mL/h is considered a favorable response that warrants continued intravenous infusion. If the urine volume does not increase, the physician should carefully review the results of blood and urine chemistry tests, reassess the patient's fluid status, and repeat the physical examination to determine whether an additional fluid challenge (with or without furosemide) might be worthwhile.

Treatment

In states of dehydration, fluid losses must be rapidly corrected to treat oliguria. Inadequate fluid management may cause further renal hemodynamic deterioration and eventual renal tubular ischemia (with fixed acute tubular necrosis; see discussion following). If oliguria and hypotension persists in a well-hydrated patient, vasopressor drugs are indicated in an effort to correct the hypotension associated with sepsis or cardiogenic shock. Pressor agents that restore systemic blood pressure while maintaining renal blood flow and renal function are most useful. However, the previously touted benefits of renally dosed dopamine (1–5 μg/kg/min) have not been proven. A more promising agent might be fenoldopam, a direct dopamine A-1 receptor agonist. However, this will have to be tested more rigorously in a randomized trial before it could be widely recommended. Discontinuance of antihypertensive medications or diuretics can, by itself, cure the apparent acute kidney injury resulting from prerenal conditions.

Common causes of acute kidney injury due to vascular disease include atheroembolic disease, dissecting arterial aneurysms, and malignant hypertension. Atheroembolic disease is rare before age 60 and precipitating events include vascular procedures, angiographic studies, and administration of heparin anticoagulation. Dissecting arterial aneurysms and malignant hypertension are usually clinically evident.

Rapid assessment of the arterial blood supply to the kidney requires arteriography or other noncontrasted blood flow studies (eg, magnetic resonance imaging or Doppler ultrasound). The cause of malignant hypertension may be identified on physical examination (eg, scleroderma). Primary management of the vascular process is necessary to affect the course of these forms of acute kidney injury.

Diseases in this category can be divided into specific and nonspecific parenchymal processes.

Specific Intrarenal Disease States

The most common causes of intrarenal acute kidney injury are acute or rapidly progressive glomerulonephritis, acute interstitial nephritis, toxic nephropathies, and hemolytic uremic syndrome.

Clinical Findings

Symptoms and Signs

Usually the history shows some salient data such as sore throat or upper respiratory infection, diarrheal illness, use of antibiotics, or intravenous use of drugs (often illicit types). Bilateral back pain, at times severe, is occasionally noted. Gross hematuria may be present. It is unusual for pyelonephritis to present as acute kidney injury unless there is associated sepsis, obstruction, or involvement of a solitary kidney. Systemic diseases in which acute kidney injury occurs include Henoch-Schönlein purpura, systemic lupus erythematosus, and scleroderma. Human immunodeficiency virus (HIV) infection may present with acute kidney injury from HIV-associated nephropathy.

Laboratory Findings

Urine

Urinalysis discloses variably active sediments: many red or white cells and multiple types of cellular and granular casts. Phase contrast microscopy usually reveals dysmorphic red cells in the urine. In allergic interstitial nephritis, eosinophils may be noted. The urine sodium concentration may range from 10 to 40 mEq/L.

Blood Test

Components of serum complement are often diminished (due to activation and consumption). In a few conditions, circulating immune complexes can be identified. Serologic tests may disclose systemic diseases such as lupus erythematosus (eg, anti-neutrophil antibody, anti-double-stranded DNA antibodies, anti-Smith antibodies). Thrombocytopenia and altered red cell morphologic structure are noted in peripheral blood smears in the hemolytic uremic syndrome. Rapidly progressive glomerulonephritis can be evaluated with tests for ANCA (antineutrophil cytoplasmic antibodies) and anti-GBM titers (anti-glomerular basement membrane antibodies).

Renal Biopsy

Light microscopic examination shows characteristic changes of glomerulonephritis (ie, crescents within Bowman's capsule, see Figure 34–1), acute interstitial nephritis, or glomerular capillary thrombi (in hemolytic uremic syndrome). Immunofluorescence microscopy showing immune deposits helps toward the diagnosis of rapidly progressive glomerulonephritis. The immune deposits can further be divided into subendothelial (lupus nephritis), subepithelial (postinfectious glomerulonephritis), or mesangial (IgA nephropathy).

X-Ray Findings

Dye studies should be avoided because of the risk of contrast-induced renal injury. For this reason, sonography is preferable to rule out obstruction.

Treatment

Therapy is directed toward removing the underlying injurious constituent, for example, eradication of infection, removal of antigen, elimination of toxic materials and drugs, suppression of autoimmune mechanisms, removal of autoimmune antibodies, or a reduction in effector-inflammatory responses. Immunotherapy may involve drugs (corticosteroids) or the temporary use of plasmapheresis. Initiation of supportive dialysis may be required (see discussion following).

Nonspecific Intrarenal States

Nonspecific intrarenal causes of acute kidney injury include acute tubular necrosis and acute cortical necrosis. The latter is associated with intrarenal intravascular coagulation and has a poorer prognosis than the former. These forms of acute kidney injury usually occur in hospital settings. Various morbid conditions leading to septic syndrome–like physiologic disturbances are often present.

Degenerative changes of the distal tubules (lower nephron nephrosis) are believed to be due to ischemia. With dialysis, most of these patients recover—usually completely—provided intrarenal intravascular coagulation and cortical necrosis does not occur.

Elderly patients, who are more prone to have this form of oliguric acute kidney injury, develop following hypotensive episodes. It appears that exposure to some drugs such as nonsteroidal anti-inflammatory agents may increase the risk of acute tubular necrosis. Although the classic picture of lower nephron nephrosis may not develop, a similar nonspecific acute kidney injury is noted in some cases of mercury (especially mercuric chloride) poisoning and following exposure to radiocontrast agents, especially in patients with preexisting renal impairment, diabetes mellitus, or myeloma.

Clinical Findings

Symptoms and Signs

Usually the clinical picture is that of the associated clinical state. Dehydration and shock may be present concurrently, but the urine output and acute kidney injury fail to improve following administration of intravenous fluids, in contrast to patients who have prerenal renal failure (see preceding discussion). On the other hand, there may be signs of excessive fluid retention in patients with acute kidney injury following radiocontrast exposure. Symptoms of uremia per se (eg, altered mentation or gastrointestinal symptoms) are unusual in acute kidney injury (in contrast to chronic kidney disease).

Laboratory Findings (Table 34–2)

Urine

The specific gravity is usually low or fixed in the 1.005–1.015 range. Urine osmolality is also low (<450 mOsm/kg and U/P osmolal ratio <1.5:1). Urinalysis often discloses tubular cells and granular casts; the urine may be muddy brown. If the urine is heme positive, but no red cells are seen on microscopy, one must be concerned about the presence of pigment nephropathy (myoglobinuria or hemoglobinuria). Tests for differentiating myoglobin pigment are available.

Central Venous Pressure

This is usually normal to slightly elevated.

Fluid Challenges

There is no increase in urine volume following intravenous administration of mannitol or physiologic saline. Occasionally, following the use of furosemide or “renal doses” of dopamine (1–5 μg/kg/min), a low urine output is converted to a high fixed urine output. Although, traditionally, it was thought that by converting patients with oliguric AKI into nonoliguric states by the above means translates into better prognosis, this does not appear to be evidence based. In fact, recent studies seem to suggest worse outcomes in those administered loop diuretics in the midst of AKI.

Treatment

If there is no response to the initial fluid or mannitol challenge, the volume of administered fluid must be sharply curtailed to noted losses. An assessment of serum creatinine and blood urea nitrogen and of the concentrations of electrolytes is necessary to predict the possible use of dialysis. With appropriate regulation of the volume of fluid administered, maintenance of nutritional intake to provide a caloric content of 30–35 kcal/kg is used to correct or reduce the severity of the catabolic state accompanying acute tubular necrosis.

Serum potassium must be closely monitored to ensure early recognition of hyperkalemia. This condition can be treated with (1) intravenous sodium bicarbonate administration; (2) Kayexalate, 25–50 g (with sorbitol) orally (enema preparations are less favored due to the risk of bowel ischemia); (3) intravenous glucose and insulin; and (4) intravenous calcium preparations to prevent cardiac irritability (usually given with electrocardiographic changes, eg, peaked T waves, widening of QRS complexes).

Strategies to prevent the development of contrast-induced nephropathy include administration of normal saline and sodium bicarbonate infusions, N-acetylcysteine and preemptive hemodialysis and hemodiafiltration. None has been definitively shown in randomized trials to confer protective effects, except for maybe volume expansion. The use of low-osmolar contrast dye has been adopted as standard, although no added benefits can be shown with iso-osmolar (iodixanol) contrast material.

Peritoneal dialysis or hemodialysis should be used as necessary to avoid or correct uremia, hyperkalemia, or fluid overload. Hemodialysis in patients with AKI can be either intermittent or continuous (with arteriovenous or venovenous hemofiltration techniques). Vascular access is obtained with percutaneous catheters. The continuous dialysis techniques allow for easier management in many hemodynamically unstable patients in intensive care units.

There remains no consensus over what the best modality of renal replacement therapy is amongst patients with AKI. Continuous venovenous hemofiltration/hemodialysis/hemodiafiltration did not confer a more favorable survival or renal recovery benefit compared with intermittent forms of dialysis. Earlier reports of more intensive dialysis prescriptions (6 days per week vs every other day dialysis) showing superior survival are not substantiated by more recent evidence. What has emerged, however, is the need for meticulous attention to the delivered dialysis dose with each session and to minimize interruptions in dialytic therapy because of poor vascular access.

Prognosis

Most cases are reversible within 7–14 days. Residual renal damage may be noted, particularly in elderly patients.

The conditions listed in Table 34–1 involve primarily the need for urologic diagnostic and therapeutic interventions. Following lower abdominal surgery, urethral or ureteral obstruction should be considered as a cause of AKI. The causes of bilateral ureteral obstruction are (1) peritoneal or retroperitoneal neoplastic involvement, with masses or nodes; (2) retroperitoneal fibrosis; (3) renal calculi; and (4) postsurgical or traumatic interruption. With a solitary kidney, ureteral stones can produce total urinary tract obstruction and acute kidney injury. Urethral or bladder neck obstruction is a frequent cause of renal failure, especially in elderly men (prostatic enlargement). Posttraumatic urethral tears are discussed in Chapter 17.

Clinical Findings

Symptoms and Signs

Pain and tenderness over the costovertebral angle often are present. If there has been an operative ureteral injury with associated urine extravasation, urine may leak through a wound. Edema from overhydration may be noted. Ileus is often present along with associated abdominal distention and vomiting.

Laboratory Findings

Urinalysis is usually not helpful. A large volume of urine obtained by catheterization may be both diagnostic and therapeutic for lower tract obstruction.

X-Ray Findings

Radionuclide renal scans may show a urine leak or, in cases of obstruction, retention of the isotope in the renal pelvis. Ultrasound examination often reveals a dilated upper collecting system with deformities characteristic of hydronephrosis.

Instrumental Examination

Cystoscopy and retrograde ureteral catheterization demonstrate ureteral obstruction.

Treatment

For further discussion of ureteral injuries, see Chapter 17.