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Introduction
One of the primary roles of the kidneys is to filter waste material from the blood. The inability of the kidneys to do this leads to renal failure. Acute renal insufficiency (ARI) is defined as the sudden onset (<48 h) of impaired kidney function. This is represented by a rise in the serum creatinine or a decrease in the urine output. The serum creatinine serves as a useful biomarker for measuring the flow rate of fluids through the kidneys, termed the glomerular filtration rate (GFR). As the clearance of creatinine and GFR decrease, the serum creatinine correspondingly increases signifying impaired renal function. The most common formula used to estimate GFR is the Cockcroft–Gault formula:
Classification
Initial classification systems simply divided ARI into two groups: oliguric or non-oliguric. Oliguric ARI is defined as having a urine output of less than 0.5 mL/kg/h or 5 mL/kg/day. While ARI with an elevated serum creatinine and near-normal urine output is called non-oliguric. Patients with non-oliguric ARI generally fair better and have a lower mortality rate than patients with oliguric ARI [1]. In an attempt to better differentiate the various stages of ARI, the Acute Dialysis Quality Initiative (ADQI) group developed the RIFLE criteria (Table 10.1) [2]. RIFLE stands for risk, injury, failure, loss, and end-stage renal disease, and represents progression of the disease. The staging is based on changes in the serum creatinine or urine output. Another similar classification system for acute renal failure also based on the serum creatinine and urine output is the Acute Kidney Injury Network (AKIN) criteria. While some studies have shown no difference between the two systems, others show that the RIFLE criteria are more robust and have an increased sensitivity of ARI detection during the first 48 hours in the intensive care unit (ICU) [3, 4].
Table 10.1
The RIFLE criteria
RIFLE criteria for ARI | ||
|---|---|---|
GFR criteria | Urine output criteria | |
Risk | 1.5× baseline serum creatinine or GFR decreased >25% | <0.5 mL/kg/h × 6 h |
Injury | 2× baseline serum creatinine or GFR decreased >50% | <0.5 mL/kg/h × 12 h |
Failure | 3× baseline serum creatinine or GFR decreased >75% or serum creatinine >4 mg/dL or acute rise of >0.5 mg/dL | <0.3 mL/kg/h × 24 h or anuria × 12 h |
Loss | Loss of kidney function × 4 weeks | |
ESRD | Loss of kidney function × 3 months | |
Epidemiology
Acute renal insufficiency usually presents as a complication of other disease processes and not as the primary disease. The reported incidence of ARI is 5–10% in all hospitalized patients and ∼30% in critically ill patients [3, 5]. Some identified risk factors for developing ARI include the following:
1.
Elderly (>65 years of age)
2.
Male gender
3.
Comorbid conditions (i.e., obesity, chronic obstructive pulmonary disease [COPD])
4.
Infection
5.
Major surgeries, especially cardiac surgery
6.
Cardiogenic shock
7.
Hypovolemia
8.
Nephrotoxic medications
9.
Cirrhosis
Since ARI is most commonly a secondary injury, its mortality rate varies widely, and therefore reflects the mortality rate of the underlying primary disease. In general, two organs failing have a 50% mortality rate, three organs—80%, and five organs—100% [6]. A large multicenter prospective study reported a 60% mortality rate in ICU patients who developed ARI [7]. Several studies have documented an association between the RIFLE classification of ARI and in-hospital mortality: 9–27% in the at risk group, 11–30% in the injury group, and 26–40% in the failure group [8, 9]. Some identified risk factors for mortality in ARI include the following:
1.
Elderly (>65 years of age)
2.
Male gender
3.
Comorbid conditions (i.e., obesity, chronic obstructive pulmonary disease [COPD])
4.
Oliguric ARI
5.
Sepsis
6.
Non-renal organ failure (heart, lungs, liver…)
7.
Mechanical ventilation
Etiology
The pathophysiology of ARI can be divided into three categories based on anatomy: prerenal, renal (parenchymal), and postrenal (obstructive). A combination of imaging and serum and urine studies can be utilized to differentiate between these categories. The urine sodium concentration and fractional excretion of sodium (FENa) are particularly useful in differentiating renal parenchymal injury from prerenal and postrenal pathologies, which is further discussed later in this chapter. The FENa formula is: where U Na = urine sodium, P Cr = plasma creatinine, U Cr = urine creatinine, and P Na = plasma sodium.
Prerenal Etiologies
Prerenal azotemia is caused by a decrease in renal perfusion and accounts for 30–60% of inpatient ARI [10]. There is no intrinsic renal disease but rather a systemic factor that decreases GFR. Most prerenal causes involve low flow states or shunting of the blood flow away from the kidneys (Table 10.2). A decrease in renal perfusion results in activation of the renin-angiotensin-aldosterone system. Angiotensin II increases glomerular filtration pressure by constricting the efferent arteriole, and also increases the proximal reabsorption of sodium, while aldosterone increases the distal reabsorption of sodium. Actions of these hormones not only preserve renal blood flow, but also help with the diagnosis since they decrease urine sodium concentration to less than 20 mmol/L and the FENa to less than 1%. Once pre-renal pathophysiology is established, clinical suspicion should guide the further differentiation between the numerous causes of prerenal ARI. Treatment includes reversing the underlying cause of renal hypoperfusion and is discussed later in this chapter.
Table 10.2
Acute renal insufficiency etiologies
Pre-renal | Parenchymal | Post-renal |
|---|---|---|
Hypovolemia | ATN | Prostatic disease |
Hypotension | AIN | Urethral stricture |
Decreased cardiac output | Glomerulonephritis | Pelvic or retroperitoneal mass |
Raised intra-abdominal pressure | Vasculitis | Nephrolithiasis (rare) |
Aortic stenosis | Nephrotoxins (aminoglycosides, amphotericin, cisplatin…) | Crystals (ethylene glycol, uric acid, light chain disease…) |
Mechanical ventilation | Sepsis | |
Medications (Ketorolac, ACEi, ARB…) | Trauma | |
Major surgery (AAA repair) | ||
Renal allograft rejection | ||
Contrast |
Renal (Parenchymal) Etiologies
Primary renal azotemia is caused by injury to the renal parenchyma either by ischemia or cytotoxic drugs and occurs in ∼50% of inpatient ARI [10]. Some of the causes of renal parenchymal injury are presented in Table 10.2. The most common cause of renal (parenchymal) disease is acute tubular necrosis (ATN), which is also the most common cause of ARI in general. As the name suggests, tubular function is impaired due to death and sloughing off of the renal tubular epithelial cells. The sloughed off cells obstruct the renal tubules reducing GFR, the process known as tubule-glomerular feedback. Tubular sodium reabsorption is also reduced, increasing the urine sodium concentration to greater than 40 mmol/L and the FENa to greater than 2%.
A urinalysis is most helpful in differentiation of renal azotemia from prerenal and postrenal causes of ARI. Tubular epithelial cells and casts in the urine are pathognomonic for ATN. Urine sediments with red cells and red cell casts are suggestive of glomerulonephritis or vasculitis. White cell casts are suggestive of acute interstitial nephritis (AIN) or infection. Finally, pigmented casts suggest myoglobinuria. Renal biopsy can be used to determine the cause of renal insufficiency, but due to its invasive nature should only be used if other methods are inconclusive and identification of a specific cause is necessary to direct treatment.
Postrenal (Obstructive) Etiologies
Postrenal (obstructive) azotemia is caused by the obstruction of urine flow distal to the renal tubules. Just like in prerenal azotemia, there is no intrinsic kidney disease, which leads to a similar urine sodium concentration and FENa as in prerenal disease. Postrenal azotemia accounts for ∼10% of inpatient ARI [10]. Obstruction can either be renal or extrarenal in origin (Table 10.2). Renal obstruction includes crystal formation from ethylene glycol poisoning, uric acid nephropathy from tumor lysis syndrome, and light chain diseases including multiple myeloma. Nephrolithiasis rarely causes obstructive azotemia unless there is only one functioning kidney. Extrarenal causes include prostatic disease, urethral stricture, and pelvic or retroperitoneal masses. Renal and pelvic ultrasound are the mainstay imaging studies for the diagnosis of postrenal azotemia. Consultation with a urologist may be warranted to discuss treatment options.
Diagnosis and Management
The initial diagnostic evaluation involves identifying prerenal and reversible causes of ARI. Commonly, ARI first presents as low urine output in a patient who recently had a significant systemic injury such as surgery, trauma, infection, or shock. Decreased urine output is not seen in patients with non-oliguric ARI and while they have better outcomes, they are also not detected as often. Clinical suspicion based on known risk factors should lead a clinician to follow the serum creatinine. An acute rise in serum creatinine (>0.5 mg/dL) suggests ARI and the need to investigate and treat the cause. A sudden onset of anuria in a patient with a urinary catheter suggests obstruction of the catheter. Flushing or changing the catheter may resolve the anuria. After a confirmed report of oliguria, the initial diagnostic tests that should be ordered include the following:
1.
Urinalysis
2.
Serum creatinine concentration
3.
Serum sodium concentration
4.
Urine creatinine concentration
5.
Urine sodium concentration
6.
Basic electrolytes
A FENa less than 1% signifies prerenal or postrenal disease, while a value greater than 2% signifies a renal cause, as previously mentioned. The exception is seen with myoglobinuria, where the FENa is less than 1%, while still being a renal parenchymal cause. Another caveat is that the recent use of loop diuretics (i.e., furosemide) makes the FENa calculation inaccurate. Microscopic analysis of urine sediments can help to further classify causes of renal azotemia. More specific testing can be done based on clinical suspicion.
Since early treatment is so important with ARI, the diagnosis and management often occur simultaneously. Fluid support is the first option for most causes of ARI. This typically involves a 500–1,000 mL crystalloid bolus or a 250–500 mL albumin containing bolus. This should occur while diagnostic testing is underway. The purpose of fluid support and resuscitation is to flush out toxins and prevent further renal injury. While a euvolemic state is preferred, if the fluid status of a patient is not known it may be better to be volume overloaded. This avoids end-organ hypoperfusion that may lead to irreversible ischemia. Volume overload does have its sequelae, including pulmonary edema and its associated risks. It is also relatively contraindicated in patients with critical aortic stenosis where additional volume may lead to heart failure.
A large variety of resuscitation fluids is available for use in the hypovolemic patient. Colloids may be more effective in keeping fluids in the intravascular space and therefore may be preferred. However, several studies have documented that some colloid solutions may be harmful to the kidneys. A meta-analysis evaluating nephrotoxicity of colloid solutions revealed that several hydroxyethyl starch (HES) containing solutions are nephrotoxic, while albumin containing colloids are not [11]. Furthermore, several subsequent meta-analyses have revealed that both starches and dextrans can exacerbate a renal insult [12, 13]. Therefore, crystalloids should be the first choice of resuscitation fluids until we gain a better understanding of colloid related renal injury.
Response to the fluid challenge needs to be assessed. If the patient responds with an appropriate increase in urine output but remains under-resuscitated, fluid boluses should be continued until the patient is euvolemic. If more invasive monitoring of the volume status is needed, central venous pressure (CVP) monitoring can be performed. In addition to patients with renal hypoperfusion, fluid resuscitation has also been shown beneficial in myoglobinuria, contrast-induced nephropathy, and in patients exposed to nephrotoxic drugs and drugs that cause tubular crystal precipitation [8]. If a patient is euvolemic but is hypotensive with a mean arterial pressure (MAP) of less than 65 mmHg, inotropes such as norepinephrine may be used to improve cardiac output and renal perfusion. Historically, low dose (“renal dose”) dopamine (2 μg/kg/min) was used to increase urine output by serving as a renal vasodilator. More recent evidence suggests that it is not effective, may actually be harmful, and thus should not be used [14, 15].
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