Two classification systems describe the stage of renal disease. The first, created by the Acute Dialysis Quality Initiative, is the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) classification system, which bases severity on the degree of change in serum creatinine or urine output from a baseline measurement (Table 114.1).² The second was created by AKIN. Although it is modeled on the RIFLE classification, it does not require the physician to know the patient’s baseline creatinine level. Its ease of use in the emergency department (ED) is improved by the fact that it does not use the glomerular filtration rate (GFR) as one of the criteria for staging kidney injury. The AKIN criteria are to be applied after adequate fluid resuscitation has taken place, and the authors of the criteria also recommend excluding easily reversible causes of kidney failure, such as urinary outflow obstruction (Table 114.2).¹

Table 114.1 RIFLE Classification System

	GFR CRITERIA	URINE OUTPUT CRITERIA
Risk	Increased Cr × 1.5	UO < 0.5 mL/kg/hr × 6 hr
	or
	GFR decreased >25%
Injury	Increased Cr × 2	UO < 0.5 mL/kg/hr × 12 hr
	or
	GFR decreased >50%
Failure	Increased Cr × 3	UO < 0.5 mL/kg/hr × 12 hr
	or	or
	GFR decreased >75%	anuria × 12 hr
Loss	Persistent ARF = complete loss of renal function for >4 wk	None
End-stage kidney disease	End-stage kidney disease > 4 mo	None

Cr, Creatinine; GFR, glomerular filtration rate; UO, urine output.

Table 114.2 AKIN Criteria for Staging Acute Kidney Injury

	CREATININE CRITERIA	URINE OUTPUT CRITERIA
Stage 1	Increased Cr × 1.5	UO < 0.5 mL/kg/hr > 6 hr
	or
	Increased ≥0.3 mg/dL
Stage 2	Increased Cr × 2	UO < 0.5 mL/kg/hr > 12 hr
Stage 3	Increased Cr × 3	UO < 0.5 mL/kg/hr > 24 hr or anuria for 12 hr
	or
	≥4 mg/dL with acute increase of 0.5 mg/dL
	or
	Patient receiving renal replacement therapy

AKIN, Acute Kidney Injury Network, Cr, creatinine; UO, urine output.

The National Kidney Foundation’s clinical practice guidelines define patients with chronic kidney disease as meeting one of the following criteria: (1) kidney damage for 3 or more months, defined as structural or functional abnormalities of the kidney, with or without an increased GFR, and demonstrated by either pathologic abnormalities or markers of kidney damage, including abnormalities in blood or urine or abnormal findings on imaging tests; or (2) a GFR lower than 60 mL/min/1.73 m² for 3 or more months, with or without kidney damage.³ The complicated definition of chronic kidney disease plus the need to monitor kidney function over an extended period means that it is unlikely that chronic kidney disease will be convincingly diagnosed in the ED. However, it is useful for the emergency physician (EP) to understand what it means when a patient has preexisting chronic kidney disease, as well as to be vigilant for suspected, but previously undiagnosed chronic kidney disease in a patient with the appropriate signs and symptoms.

Epidemiology

The prevalence and incidence of kidney failure in the United States are rising. The prevalence of chronic kidney disease is estimated to be greater than 10%.⁴ The annual incidence of acute kidney injury is 100 per 1 million population. The incidence of acute kidney injury in the community varies widely depending on the population, but hospital-acquired rates can be quite high, with as many as 30% of critical care patients in some studies developing acute kidney injury.⁵

Pathophysiology

The kidneys are located in the retroperitoneal space and are composed of three basic structures: vasculature, parenchyma, and the collecting system. The kidneys receive about a quarter of the body’s total cardiac output through the renal arterial system and an extensive network of arteries, arterioles, and capillaries that eventually drain into the renal vein. The renal parenchyma is composed of the medulla and cortex, which houses the functional unit of the kidney, the nephron. A single nephron consists of a glomerulus, proximal tubule, thin limbs of Henle, and a distal tubule. The connecting tubule joins the nephron to the collecting system, including the renal pelvis, minor and major calyces, and the ureter, bladder, and urethra (Fig. 114.1).

Fig. 114.1 Gross anatomy of the kidney.

The kidney is responsible for maintaining the volume and ionic composition of body fluids, excreting metabolic waste products such as urea, and eliminating exogenous drugs, hormones, and toxins. The kidneys also serve as a major endocrine organ through the production of renin, erythropoietin, 1,25-dihydroxycholecalciferol, prostaglandins, and kinins. Metabolic functions of the kidney include catabolism of small-molecular-weight proteins and anabolic roles in ammoniagenesis and gluconeogenesis.

In a person weighing 70 kg, the kidney forms approximately 180 L of glomerular filtrate each day. Cardiac output in combination with effective intravascular volume generates hydraulic pressure that drives fluid from the capillaries into the urinary space, which represents the main mechanism of urine formation. The final urinary filtrate is determined by a complex interaction between hydraulic and oncotic pressure, molecular size and charge, absorption, reabsorption, and secretion under hormonal control.

Renal failure can be the result of dysfunction in any part of this system. It is helpful to understand the pathophysiology of renal disease as a set of three etiologic categories: prerenal, intrinsic renal, and postrenal causes.

1. Prerenal failure results from the kidneys not receiving enough blood via a cause external to the kidneys themselves; it results in a reduced GFR, buildup of toxic waste products, and damage to the kidneys persisting after the underlying cause has been corrected. Causes of prerenal failure include hypovolemia, decreased cardiac output, and septic shock.

2. Renal failure may be caused by diseases intrinsic to the kidneys, including genetic syndromes such as polycystic kidney disease, infections, vascular diseases, and toxins or drugs.

3. Postrenal failure may result from obstruction to urinary flow external to the kidneys themselves. The obstruction causes increased fluid pressure within the nephron, which ultimately leads to loss of function. Ureteral stones, prostatic hypertrophy, tumors, and anticholinergic medications are some possible causes of postrenal kidney failure.

Renal failure can be divided into two categories: primary disturbances and secondary disturbances. Primary disturbances reflect a direct failure of the kidneys to perform critical functions, such as failure to excrete sodium (leading to volume overload) or a decrease in erythropoietin production (leading to anemia). Secondary disturbances result from an accumulation of metabolic products in other organ systems, as when hyperphosphatemia causes hyperparathyroidism or when nitrogenous waste products promote platelet dysfunction. The combination of primary and secondary disturbances disrupts the homeostatic balance of almost every organ system.

Primary Disturbances

When the kidney can no longer perform excretory functions, the result is volume overload, hyperkalemia, and hyperphosphatemia. As renal endocrine function declines, hypocalcemia and anemia develop. Renal failure can cause an increased circulating concentration of insulin and lower insulin requirements in diabetics. Loss of ammoniagenesis and the ability to excrete phosphate impairs clearance of the metabolic acid load by the kidneys and may lead to acidosis. Adverse drug reactions at normal dosages can occur when drugs that are metabolized or excreted by the kidneys are administered.

Secondary Disturbances

Accumulation of nitrogenous waste products, generically referred to as uremia, is a characteristic of not only renal excretory failure but also a host of metabolic and endocrine disease states. Derangements in protein, carbohydrate, and lipid metabolism will ensue and are associated with anemia, malnutrition, and metabolic bone disease. Loss of renal catabolism and an increase in endocrine secretion affect many hormones, including insulin, glucagon, luteinizing hormone, and prolactin. A normal platelet count may be maintained, although platelet function and bleeding time will probably become abnormal. Poorly understood immune system interactions can lead to immunosuppression, overwhelming infection, septic shock, and death.

Presenting Signs and Symptoms

Manifestations may vary greatly depending on the cause of the renal failure, but patients may describe a history of volume overload or decreased urine output. They may also have one or many of a long list of end-organ effects (Table 114.3). Renal failure is not a diagnosis that is necessarily obvious on initial encounter and is often made only after screening laboratory data are obtained.

Table 114.3 Organ System Effects of Renal Failure

ABNORMALITY CAUSED BY RENAL FAILURE	PHYSICAL FINDINGS, END-ORGAN EFFECT
Cardiovascular
Pulmonary edema	Crackles
Hypertension
Pericardial effusion
Metabolic
Hyperkalemia	Peaked T waves, arrhythmias, bradycardia, cardiac arrest
Hypocalcemia	Tetany, cardiac arrhythmias
Hypermagnesemia	Nausea and vomiting, arrhythmias
Neurologic
Uremia	Seizures
Acute and chronic neurologic changes	HyperreflexiaEncephalopathy, including asterixisSensory neuropathy
Hyponatremia or hypernatremia	Altered mental status, seizures
Dialysis-associated dementia	Loss of cognitive function
Immunologic
Immunosuppression	Recurrent infections
Pulmonary
Fluid overload: pleural effusions, pulmonary edema	Shortness of breath, hypoxia, crackles, dullness to percussion, peripheral edema
Gastrointestinal
Gastritis	Abdominal pain
Bleeding	Melena
Malnutrition	Cachexia, anemia
Endocrine
Glucose intolerance	Hyperglycemia
Renal osteodystrophy Myopathy Amyloid arthropathySecondary hyperparathyroidism	Bone and joint pain, myalgias
Skin
Uremia	Pruritus, uremic frost (urea crystals from sweat on skin)
Cardiovascular
Uremic pericarditis	Pericardial friction rub, chest pain worse with lying down, ECG changes: ST elevation and PR depression (only some or none of these may be seen)
Myocardial infarction	ST elevation in anatomic distribution or elevated enzymes
Acidosis	Hypotension
Hematologic
Uremic platelets	Bleeding
Musculoskeletal
Arthritis
Spontaneous tendon rupture
Carpal tunnel syndrome

ECG, Electrocardiographic.

Once the laboratory diagnosis of renal failure is made, the EP should go back through the patient’s history to look for signs and symptoms and findings on physical examination that suggest the cause of the renal failure, as well as signs of any complications that must be dealt with urgently. Pulmonary edema, cardiac arrhythmias, and altered mental status are particularly concerning findings.

Differential Diagnosis and Medical Decision Making

Although the classic teaching has been that fractional excretion of sodium and urea be used to determine the source of the renal dysfunction—prerenal, intrinsic renal, or postrenal—these calculated values are often unreliable indicators of the cause of renal failure, especially in the setting of diuretic use and underlying chronic renal disease. Their diagnostic value or usefulness in guiding therapy in the ED is questionable. Physical examination findings and the clinical history are more useful in determining the cause of the renal failure. Fractional excretion of sodium and urea can be used to support a conclusion or help eliminate alternative diagnoses.

Once a diagnosis of renal failure is made through creatinine screening or the presence oliguria or anuria (Box 114.1), a differential diagnosis of underlying conditions and complications should be generated by considering potential diseases of the vasculature, parenchyma, and collecting system, as well as conditions external to the kidneys that lead to decreased blood flow or obstruction to the flow of urine.

Box 114.1 Diagnostic Criteria for Acute Kidney Injury

An abrupt (within 48 hours) reduction in kidney function as defined by the following:

• An absolute increase in serum creatinine of 0.3 mg/dL or greater

• A 50% or greater increase in serum creatinine (1.5-fold higher than baseline)

• A reduction in urine output (documented oliguria of less than 0.5 mL/kg/hr for more than 6 hours)

Intrinsic Renal Failure: Vascular Causes

Vascular diseases of the kidney are manifested differently according to the size of the artery involved (Box 114.2). Sudden back or flank pain suggests large vessel aneurysm, dissection, embolism, or trauma. Poorly controlled hypertension and chronic renal insufficiency suggest renal artery stenosis. Systemic manifestations such as rash and fever suggest vasculitis in the smaller vessels of the kidney.

Intrinsic Renal Failure: Parenchymal Causes

The working unit of the kidney is the nephron, which is composed of a variety of cell types that are susceptible to many disease processes (Box 114.3). The medical history is invaluable in identifying the root cause within this category of kidney failure.

Obstructive Renal Failure

The collecting system of the kidneys is composed of the calyces, renal pelvis, ureter, bladder, and urethra—obstruction may occur at any level (Box 114.4). Obstruction to urinary flow is generally a reversible cause of renal failure. Alert patients may have symptoms of urinary retention or nephrolithiasis that are dramatic and obvious. Occult, potentially reversible renal obstruction should be considered in patients with altered mental status and acute renal failure.