Which disorder contributes to a continued rise of nitrogenous wastes in a patient with acute kidney?

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 output. It often results from inadequate renal perfusion due to severe trauma, illness, or surgery but is sometimes caused by a rapidly progressive, intrinsic renal disease. Symptoms may include anorexia, nausea, and vomiting. Seizures and coma may occur if the condition is untreated. Fluid, electrolyte, and acid-base disorders develop quickly. Diagnosis is based on laboratory tests of renal function, including serum creatinine. Urinary indices, urinary sediment examination, and often imaging and other tests (including sometimes a kidney biopsy) are needed to determine the cause. Treatment is directed at the cause but also includes fluid and electrolyte management and sometimes dialysis.

In all cases of acute kidney injury (AKI), creatinine and urea build up in the blood over several days, and fluid and electrolyte disorders develop. The most serious of these disorders are 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 and fluid overload Volume Overload Volume overload generally refers to expansion of the extracellular fluid (ECF) volume. ECF volume expansion typically occurs in heart failure, kidney failure, nephrotic syndrome, and cirrhosis... read more (possibly causing pulmonary edema). Phosphate retention leads to hyperphosphatemia. Hypocalcemia is thought to occur because the impaired kidney no longer produces calcitriol (reducing calcium absorption from the gastrointestinal tract) and because hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more causes calcium phosphate precipitation in the tissues. Acidosis develops because hydrogen ions cannot be excreted. With significant uremia, coagulation may be impaired, and pericarditis Pericarditis Pericarditis is inflammation of the pericardium, often with fluid accumulation in the pericardial space. Pericarditis may be caused by many disorders (eg, infection, myocardial infarction, trauma... read more

• Prerenal

• Renal

• Postrenal

Prerenal AKI is due to inadequate renal perfusion. The main causes are

• Extracellular fluid volume depletion Volume Depletion Volume depletion, or extracellular fluid (ECF) volume contraction, occurs as a result of loss of total body sodium. Causes include vomiting, excessive sweating, diarrhea, burns, diuretic use... read more (eg, due to inadequate fluid intake, diarrheal illness, sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more )

• Decompensated liver disease

Prerenal conditions typically do not cause permanent kidney damage (and hence are potentially reversible) unless hypoperfusion is severe and/or prolonged. Hypoperfusion of an otherwise functioning kidney leads to enhanced reabsorption of sodium and water, resulting in oliguria (urine output < 500 mL/day) with high urine osmolality and low urine sodium.

Renal causes of AKI involve intrinsic kidney disease or damage. Disorders may involve the blood vessels, glomeruli, tubules, or interstitium. The most common causes are

Glomerular disease reduces glomerular filtration rate (GFR) and increases glomerular capillary permeability to proteins and red blood cells; it may be inflammatory (glomerulonephritis) or the result of vascular damage due to ischemia or vasculitis.

Tubules also may be damaged by ischemia and may become obstructed by cellular debris, protein or crystal deposition, and cellular or interstitial edema.

Obstructed ultrafiltrate, in tubules or more distally, increases pressure in the urinary space of the glomerulus, reducing GFR. Obstruction also affects renal blood flow, initially increasing the flow and pressure in the glomerular capillary by reducing afferent arteriolar resistance. However, within 3 to 4 hours, the renal blood flow is reduced, and by 24 hours, it has fallen to < 50% of normal because of increased resistance of the renal vasculature. Renovascular resistance may take up to a week to return to normal after relief of a 24-hour obstruction.

To produce significant AKI, obstruction at the level of the ureter requires involvement of both ureters unless the patient has only a single functioning kidney.

• Clinical evaluation, including review of prescription and over-the-counter drugs and exposure to iodinated IV contrast

• Serum creatinine

• Urinary sediment

• Urinary diagnostic indices

• Urinalysis and assessment of urine protein

Acute kidney injury (AKI) is suspected when urine output falls or serum blood urea nitrogen (BUN) and creatinine rise.

• Increase in the serum creatinine value of ≥ 0.3 mg/dL (26.52 micromol/L) in 48 hours

• Increase in serum creatinine of ≥ 1.5 times baseline within the prior 7 days

• Urine volume < 0.5 mL/kg/hour for 6 hours

A progressive daily rise in serum creatinine is diagnostic of AKI. Serum creatinine can increase by as much as 2 mg/dL/day (180 micromol/L/day), depending on the amount of creatinine produced (which varies with lean body mass) and total body water.

Urea nitrogen may increase by 10 to 20 mg/dL/day (3.6 to 7.1 mmol urea/L/day), but BUN may be misleading because it is frequently elevated in response to increased protein catabolism resulting from surgery, trauma, corticosteroids, burns, transfusion reactions, parenteral nutrition, or gastrointestinal or other internal bleeding.

When creatinine is rising, 24-hour urine collection for creatinine clearance and the various formulas used to calculate creatinine clearance from serum creatinine are inaccurate and should not be used in estimating the glomerular filtration rate (eGFR), because the rise in serum creatinine concentration is a delayed function of GFR decline.

Other laboratory findings are

• Progressive acidosis

• Anemia

Acidosis is ordinarily moderate, with a plasma bicarbonate content of 15 to 20 mmol/L; however, acidosis may be severe if there is underlying sepsis or tissue ischemia.

Rise in serum potassium concentration depends on overall metabolism, dietary intake, drugs, and potential tissue necrosis or cellular lysis.

Hyponatremia usually is moderate (serum sodium, 125 to 135 mmol/L) and correlates with a surplus of dietary or intravenous water intake.

Normochromic-normocytic anemia with a hematocrit of 25 to 30% is typical.

Hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more and hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more are common in AKI and may be profound in patients with rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more or tumor lysis syndrome Tumor Lysis and Cytokine Release Syndromes Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more . Profound hypocalcemia in rhabdomyolysis apparently results from the combined effects of calcium deposition in necrotic muscle, reduced calcitriol production, resistance of bone to parathyroid hormone (PTH), and hyperphosphatemia. During recovery from AKI following rhabdomyolysis-induced acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more

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 Urinary Diagnostic Indices in Prerenal AKI and Acute Tubular Injury Urinary Diagnostic Indices in Prerenal Acute Kidney Injury and Acute Tubular Injury

) are helpful in distinguishing prerenal AKI from acute tubular injury, which are the most common causes of AKI in hospitalized patients.

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 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.

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:

• Polycystic kidney disease

• Immediate treatment of pulmonary edema and hyperkalemia

• Dialysis as needed to control hyperkalemia, pulmonary edema, metabolic acidosis, and uremic symptoms

• Adjustment of drug regimen for degree of renal dysfunction

• Usually restriction of water, sodium, phosphate, and potassium intake, but provision of adequate protein

• Possibly phosphate binders (for hyperphosphatemia) and intestinal potassium binders (for hyperkalemia)

Acute kidney injury (AKI) can often be prevented by maintaining normal fluid balance, blood volume, and blood pressure in patients with trauma, burns, or severe hemorrhage and in those undergoing major surgery. Infusion of isotonic saline and blood may be helpful.

Use of iodinated contrast agents should be minimized, particularly in at-risk groups (eg, older patients and those with preexisting renal insufficiency, volume depletion, diabetes, or heart failure). If contrast agents are necessary, risk can be lowered by minimizing volume of the IV contrast agent, using nonionic and low osmolal or iso-osmolal contrast agents, avoiding nonsteroidal anti-inflammatory drugs, and pretreating with normal saline at 1 mL/kg/hour IV for 12 hours before the test. Infusion of isotonic sodium bicarbonate before and after contrast administration has also been used successfully instead of normal saline. N-acetylcysteine has been used to prevent contrast nephropathy in the past, but most recent studies did not find improved outcomes, and it is not currently recommended for this indication.

Before cytolytic therapy is initiated in patients with certain neoplastic diseases (eg, lymphoma, leukemia), treatment with rasburicase or allopurinol should be considered along with increasing urine flow by increasing oral or IV fluids to reduce urate crystalluria. Making the urine more alkaline (by giving oral or IV sodium bicarbonate or acetazolamide) has been recommended by some but is controversial because it may also induce urinary calcium phosphate precipitation and crystalluria, which may worsen AKI.

The renal vasculature is very sensitive to endothelin, a potent vasoconstrictor that reduces renal blood flow and glomerular filtration rate. Endothelin is implicated in progressive renal damage, and endothelin receptor antagonists have successfully slowed or even halted experimental renal disease. Antiendothelin antibodies and endothelin-receptor antagonists are being studied to protect the kidney against ischemic AKI.

• Causes of AKI can be prerenal (eg, kidney hypoperfusion), renal (eg, direct effects on the kidney), or postrenal (eg, urinary tract obstruction distal to the kidneys).

• With AKI, consider ECF volume depletion and nephrotoxins, obtain urinary diagnostic indices and measure bladder residual volume to identify obstruction.

• Avoid using iodinated IV contrast in imaging studies.

• Initiate hemodialysis or hemofiltration as needed for pulmonary edema, hyperkalemia, metabolic acidosis, or uremic symptoms unresponsive to other treatments.

• Minimize risk of AKI in patients at risk by maintaining normal fluid balance, avoiding nephrotoxins (including iodinated intravenous contrast agents) when possible, and taking precautions such as giving fluids or drugs when contrast or cytolytic therapy is necessary.

Which disorder is a Postrenal cause of acute kidney injury?

Which condition can cause rhabdomyolysis Eno?

Which clinical manifestation of acute kidney injury may cause changes in an electrocardiogram?

Which is the main electrolyte disturbance in rhabdomyolysis?