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.
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.
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.
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).
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).
High power light micrograph showing an active hypercellular crescent containing fibrin, which has a bright red appearance (long arrow). Note that the severe inflammatory injury has led to fragmentation of the glomerular tuft (short arrow) and to creation of a rent in the capsule (double arrow). (Courtesy of Helmut Rennke, MD.)
Dye studies should be avoided because of the risk of contrast-induced renal injury. For this reason, sonography is preferable to rule out obstruction.
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.
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)
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.
This is usually normal to slightly elevated.
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.
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.
Most cases are reversible within 7–14 days. Residual renal damage may be noted, particularly in elderly patients.