Acute Kidney Injury (AKI)

Amount of urine output during acute kidney injury (AKI) does not clearly differentiate between prerenal, renal, or postrenal causes.

In acute tubular injury, urine output may have 3 phases:

Immediately reversible prerenal or postrenal causes of acute kidney injury must be excluded first. Extracellular fluid (ECF) volume depletion and obstruction are considered in all patients. The drug history must be accurately reviewed and all potentially renal toxic drugs stopped. Urinary diagnostic indices (see table ) are helpful in distinguishing prerenal AKI from acute tubular injury, which are the most common causes of AKI in hospitalized patients.

Prerenal causes are often apparent clinically. If so, correction of an underlying hemodynamic abnormality should be attempted. For example, in hypovolemia, volume infusion can be tried; in heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more (HF), diuretics and afterload-reducing drugs can be tried. Abatement of AKI confirms a prerenal cause.

Postrenal causes should be sought in most cases of AKI. Immediately after the patient voids, bedside ultrasonography Ultrasonography Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more of the bladder is done (or, alternatively, a urinary catheter Bladder Catheterization Bladder catheterization is used to do the following: Obtain urine for examination Measure residual urine volume Relieve urinary retention or incontinence Deliver radiopaque contrast agents or... read more is placed) to determine the residual urine in the bladder. A postvoid residual urine volume > 200 mL suggests bladder outlet obstruction, although detrusor muscle weakness and neurogenic bladder Neurogenic Bladder Neurogenic bladder is bladder dysfunction (flaccid or spastic) caused by neurologic damage. Symptoms can include overflow incontinence, frequency, urgency, urge incontinence, and retention.... read more may also cause residual volume of this amount. The catheter, if placed, may be kept in to accurately monitor urine output in response to therapies, but the catheter is removed in patients who are anuric (if bladder outlet obstruction is not present) to decrease the risk of infection.

Renal ultrasonography is then done to diagnose more proximal obstruction. However, sensitivity for obstruction is only 80 to 85% when ultrasonography is used because the collecting system is not always dilated, especially when the condition is acute, the ureter is encased (eg, in retroperitoneal fibrosis or neoplasm), or the patient has concomitant hypovolemia. If obstruction is strongly suspected, noncontrast CT Computed Tomography Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more can establish the site of obstruction and guide therapy.

The urinary sediment may provide etiologic clues. A normal urine sediment occurs in prerenal AKI and sometimes in obstructive uropathy Obstructive Uropathy Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more . With renal tubular injury, the sediment characteristically contains tubular cells, tubular cell casts, and many granular casts (often with brown pigmentation). Urinary eosinophils may indicate allergic tubulointerstitial nephritis Tubulointerstitial Nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more , but the diagnostic accuracy of this finding is limited. Red blood cell (RBC) casts and dysmorphic RBCs indicate glomerulonephritis or vasculitis but rarely may occur in acute tubular necrosis.

Renal causes are sometimes suggested by clinical findings. Patients with glomerulonephritis Overview of Glomerular Disorders The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day). Glomerular disorders are classified based on urine changes as those that manifest predominantly... read more often have edema, marked proteinuria (nephrotic syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more ), or signs of arteritis in the skin and retina, often without a history of intrinsic renal disease. Hemoptysis may result from granulomatosis with polyangiitis Granulomatosis with Polyangiitis (GPA) Granulomatosis with polyangiitis is characterized by necrotizing granulomatous inflammation, small- and medium-sized vessel vasculitis, and focal necrotizing glomerulonephritis, often with crescent... read more or anti-GBM disease Goodpasture Syndrome Goodpasture syndrome, a subtype of pulmonary-renal syndrome, is an autoimmune syndrome consisting of alveolar hemorrhage and glomerulonephritis caused by circulating anti-glomerular basement... read more (Goodpasture syndrome). Certain rashes (eg, erythema nodosum Erythema Nodosum Erythema nodosum is a specific form of panniculitis characterized by tender, red or violet, palpable, subcutaneous nodules on the shins and occasionally other locations. It often occurs with... read more , cutaneous vasculitis, discoid lupus) may indicate cryoglobulinemia Cryoglobulinemia Conditions that cause an abnormal protein content in the blood, typically in the form of immunoglobulins, can affect vascular fragility and lead to purpura. (See also Overview of Vascular Bleeding... read more , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more (SLE), or immunoglobulin A-associated vasculitis Immunoglobulin A–Associated Vasculitis (IgAV) Immunoglobulin A–associated vasculitis (formerly called Henoch-Schönlein purpura) is vasculitis that affects primarily small vessels. It occurs most often in children. Common manifestations... read more . Tubulointerstitial nephritis Tubulointerstitial Nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more , drug allergy, and possibly microscopic polyangiitis Microscopic Polyangiitis (MPA) Microscopic polyangiitis is a systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels. It may begin as a pulmonary-renal syndrome... read more are suggested by a history of drug ingestion and a maculopapular or purpuric rash.

To further differentiate renal causes, antistreptolysin-O and complement titers, antinuclear antibodies, and antineutrophil cytoplasmic antibodies are determined.

Renal biopsy may be done if the diagnosis remains elusive (see table ).

In addition to renal ultrasonography, other imaging tests are occasionally of use. In evaluating for ureteral obstruction, noncontrast CT Computed Tomography Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more is preferred over antegrade and retrograde urography. In addition to its ability to delineate soft-tissue structures and calcium-containing calculi, CT can detect nonradiopaque calculi.

Iodinated contrast agents should be avoided if possible. However, renal arteriography or venography may sometimes be indicated if macrovascular causes are suggested clinically. Magnetic resonance angiography was increasingly being used for diagnosing renal artery stenosis as well as thrombosis of both arteries and veins because MRI used gadolinium, which was thought to have a lower risk of AKI than the iodinated contrast agents used in angiography and contrast-enhanced CT. However, recent evidence suggests that gadolinium may be involved in the pathogenesis of nephrogenic systemic fibrosis, a serious complication that occurs in patients with AKI as well as chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more . Thus, gadolinium should be avoided if possible in patients with renal function below an estimated glomerular filtration rate (eGFR) of 30 mL/minute/1.73m². If clinically indicated, then group II gadolinium agents should be used preferentially due to lower risk of nephrogenic systemic fibrosis (2 Diagnosis references Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more ).

Kidney size, as determined with imaging tests, is helpful to know because, a normal or enlarged kidney favors reversibility, whereas a small kidney suggests chronic renal insufficiency. However, some chronic kidney diseases tend to present with enlarged kidneys, including the following:

Once the patient's volume status is optimized and genitourinary obstruction is excluded, AKI can be classified into 3 stages based on serum creatinine level or the amount of urine output (see table ).

Life-threatening complications are addressed, preferably in a critical care unit. Pulmonary edema Pulmonary Edema Pulmonary edema is acute, severe left ventricular failure with pulmonary venous hypertension and alveolar flooding. Findings are severe dyspnea, diaphoresis, wheezing, and sometimes blood-tinged... read more is treated with oxygen, IV vasodilators (eg, nitroglycerin), diuretics (often ineffective in AKI), or dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more .

Hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There... read more is treated as needed with IV infusion of 10 mL of 10% calcium gluconate, 50 g of dextrose, and 5 to 10 units of insulin. These drugs do not reduce total body potassium, so further (but slower-acting) treatment is needed (eg, sodium polystyrene sulfonate, diuretics, dialysis).

Although correction of an anion gap metabolic acidosis with sodium bicarbonate is controversial, correction of the nonanion gap portion of severe metabolic acidosis Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3⁻), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more (pH < 7.20) is often recommended and may be treated with IV sodium bicarbonate in the form of a slow infusion (≤ 150 mEq [or mmol] sodium bicarbonate in 1 L of 5% D/W at a rate of 50 to 100 mL/hour). Because variations in body buffer systems and the rate of acid production are hard to predict, calculating the amount of bicarbonate needed to achieve a full correction is usually not recommended. Instead, bicarbonate is given via continuous infusion and the anion gap is monitored serially.

Hemodialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more or hemofiltration Continuous Hemofiltration and Hemodialysis Continuous hemofiltration and hemodialysis procedures filter and dialyze blood without interruption. (See Overview of Renal Replacement Therapy for other renal replacement therapies.) The principal... read more is initiated when

Blood urea nitrogen (BUN) and creatinine levels are probably not the best guides for initiating dialysis in acute kidney injury (AKI). In asymptomatic patients who are not seriously ill, particularly those in whom return of renal function is considered likely, dialysis can be deferred until symptoms occur, thus avoiding placement of a central venous catheter with its attendant complications.

Nephrotoxic drugs are stopped, and all drugs excreted by the kidneys (eg, digoxin, some antibiotics) are adjusted; serum levels are useful.

Daily water intake is restricted to a volume equal to the previous day’s urine output plus measured extrarenal losses (eg, vomitus) plus 500 to 1000 mL/day for insensible loss. Water intake can be further restricted for hyponatremia or increased for hypernatremia. Although weight gain indicates excess fluid, water intake is not decreased if serum sodium remains normal; instead, dietary sodium is restricted.

Sodium and potassium intake is minimized except in patients with prior deficiencies or gastrointestinal losses. An adequate diet should be provided, including daily protein intake of about 0.8 g/kg. If oral or enteral nutrition is impossible, parenteral nutrition is used; however, in AKI, risks of fluid overload, hyperosmolality, and infection are increased by IV nutrition. Calcium salts (calcium carbonate, calcium acetate) or iron-based or synthetic phosphate binders before meals help maintain serum phosphate at < 5.5 mg/dL (< 1.8 mmol/L).

If needed to help maintain serum potassium at < 6 mmol/L in the absence of dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more (eg, if other therapies, such as diuretics, fail to lower potassium), a cation-exchange resin is prescribed when delayed onset of action of several hours is acceptable. Sodium polystyrene sulfonate is available in oral or rectal formulation; patiromer and sodium zirconium cyclosilicate are available via the oral route only.

An indwelling bladder catheter is rarely needed and should be used only when necessary because of an increased risk of urinary tract infection Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys ( pyelonephritis), and lower tract infections, which involve the bladder ( cystitis), urethra... read more and urosepsis.

In many patients, a brisk and even dramatic diuresis after relief of obstruction is a physiologic response to the expansion of extracellular fluid (ECF) during obstruction and does not compromise volume status. However, polyuria accompanied by the excretion of large amounts of sodium, potassium, magnesium, and other solutes may cause hypokalemia, hyponatremia, hypernatremia (if free water is not provided), hypomagnesemia, or marked contraction of ECF volume with peripheral vascular collapse. In this postoliguric phase, close attention to fluid and electrolyte balance is mandatory. Overzealous administration of salt and water after relief of obstruction can prolong diuresis. When postoliguric diuresis occurs, replacement of urine output with 0.45% saline at about 75% of urine output prevents volume depletion and the tendency for excessive free water loss while allowing the body to eliminate excessive volume if this is the cause of the polyuria.

1. National Institute of Diabetes and Digestive and Kidney Diseases. Acute Kidney Injury: Accessed February 23, 2023.