Acute Renal Failure

Acute Renal Failure
Objectives
By the end of this session you should be able to:
* List the three major etiologic categories of acute renal failure.
* List the major causes of each of the three major categories of acute renal failure.
* Be aware of the basic findings in the urine that suggests the etiology of a patient's renal compromise.
* Be aware of the information provided by urine electrolytes and urine osmolality.
* Be able to calculate FE Na and understand what the results of this calculation indicate.
* Cite the value, if any, of radiographic procedures such as intravenous pyelograms, ultrasound, and CT
scans.
* Cite the major causes of post-ischemic and nephrotoxic acute renal failure and be aware of the ways in
which it differs from pre-renal and post-renal causes of acute renal failure.
* Delineate the basic approach to managing patients with acute renal failure.
* Cite the most common complications that may need to be addressed in patients with acute renal failure.
* Diagnose the cause of a patient's renal failure and treat it appropriately depending on that etiology.
* List some of the more common medications that cause nephrotoxic acute renal failure.
* List the indications for dialysis in a patient in acute renal failure.

Outline
I. Introduction
II. Etiology of Acute Renal Failure
III. Pathophysiology of Acute Renal Failure
Pre-renal Acute Renal Failure
Intra-renal Acute Renal Failure
Glomerular Disease
Post-ischemic and Nephrotoxic Acute Renal Failure
Interstitial Disease
Post-renal Acute Renal Failure
IV. Diagnosis of Acute Renal Failure
History and Physical Findings
Laboratory Testing
Examination of the Urine
Dipstick findings
Microscopic findings
Serum and Urine Chemical Analysis
Creatinine and urea nitrogen
Urine osmolality
Urine sodium concentration
Other indicies
Radiographic Procedures
V. Specific Diseases Causing Acute Renal Failure
Pre-renal disease
Pre-renal azotemia caused by volume depletion
Pre-renal azotemia caused by advanced liver disease
Pre-renal azotemia caused by congestive heart failure
Post-ischemic and Nephrotoxic Acute Renal Failure
Initial phase
Maintenance phase
Recovery phase
Post-renal disease
VI. Complications of Acute Renal Failure
Cardiovascular system
Pulmonary system
Gastrointestinal system
Neurologic system
Infectious complications
Endocrine system
Electrolyte metabolism
VII. Treatment of Acute Renal Failure
Diuretics
Diet
Dialysis

I. INTRODUCTION
Acute renal failure (ARF) is the generic term used to define an abrupt decrease in renal function
sufficient to result in retention of nitrogenous waste (urea nitrogen and creatinine) in the body. The
hallmark of ARF is progressive azotemia caused by the accumulation of the nitrogenous end-products of
metabolism. This accumulation is accompanied by a wide range of other disturbances depending on the
severity and duration of the renal dysfunction. These include metabolic derangements such as metabolic
acidosis and hyperkalemia, disturbances of body fluid balance, and effects on many other organ systems.
Table 1
ARF - Incidence
• Community acquired
– 1% of hospital admissions
• pre-renal ARF (70%), intra-renal (11%), post-renal
(17%). Overall mortality 15%
• Hospital acquired
– 5% of hospitalized patients; 30% in ICU
• decreased renal perfusion, postoperative renal
insufficiency (60%), nephrotoxic agents (20%).
Overall mortality 45%; Mortality due to ARF 27%
ARF is commonly encountered in the
practice of medicine, and 5% of hospital
admissions to a general medical/surgical ward will
go on to develop ARF. This disorder is less
common in children than adults. Abrupt renal
decline and failure is a final common pathway for a
number of disease processes and is associated with
significant morbidity and mortality (Table 1).
II. ETIOLOGY OF ACUTE RENAL FAILURE
Table 2
ARF - Etiology
• Pre-renal ARF: ↓ renal blood flow
– Absolute volume depletion
– Functional volume depletion
• Intra-renal ARF: renal parenchymal disease
– Glomerular disease
– Tubulo -interstitial disease
• Post-renal ARF: Urinary obstruction
The various causes of ARF can be grouped into
three major categories (Table 2):
• those that decrease renal blood flow (prerenal)
• those that produce a renal parenchymal insult
(intra-renal)
• those that obstruct urine flow (post-renal or
obstructive).
Identification of either a pre-renal or post-renal cause of ARF makes the initiation of a specific therapy
possible. If, however, these two categories can be ruled out, then an intra-renal cause can be implicated.
The renal parenchymal causes of ARF are usually subdivided into those primarily affecting the glomeruli
or the renal interstitium. The term acute tubular necrosis denotes another broad category of intrinsic renal
failure characterized by renal tubular injury that cannot be attributed to glomerular, vascular, or interstitial
causes. The complete list of the most common causes of acute renal failure is noted in Table 3.

Table 3
Causes of Acute Renal Failure
Pre-renal Acute Renal Failure
Absolute volume depletion
Functional volume depletion
Advanced liver disease
Congestive heart failure
Pharmacologic agents
Angiotensin converting agents
Non-steroidal anti-inflammatory agents
Diseases of the Renal Vasculature
Renal Artery Occlusion
Thromboemboli
Thrombosis
Dissecting aortic aneurysm
Renal artery stenosis
Renal vein thrombosis
Dehydration (infants)
Diseases of the Renal Cortex
Bilateral Cortical Necrosis
Obstetrical accidents
Abruptio placentas
Placentas previa
Gram-negative septicemia
Ischemia
Hyperacute renal allograft rejection
Diseases of the Renal Medulla
Bilateral Papillary Necrosis
Analgesic abuse
Sickle cell disease
Diabetes mellitus
Acute Tubulointerstitial Diseases
Acute pyelonephritis
Acute allergic interstitial nephritis
Hypokalemic nephropathy
Hypercalcemia
Acute uric acid nephropathy
Multiple myeloma
Acute Glomerular Diseases
Acute Glomerulonephritis
Postinfectious glomerulonephritis
Bacterial endocarditis
Henoch-Schonlein Purpura
Hypersensitivity angiitis
Rapidly Progressive Glomerulonephritis
Systemic lupus erythematosis
Wegener’s Granulomatosis
Goodpasture’s syndrome
Thrombotic Microangiopathy
Hemolytic-uremic Syndrome
Thrombotic Thrombocytopenic Purpura
Scleroderma
Malignant Hypertension
Postischemic Acute Renal Failure
Nephrotoxic Acute Renal Failure
Urinary Obstruction
Intrarenal abnormalities
Ureteral obstruction
Diseases of bladder or urethra

III. PATHOPHYSIOLOGY OF ACUTE RENAL FAILURE
Table 4
Pre-Renal ARF
• Decrease in renal blood flow
• Glomerular filtration rate reduced
– Inability to excrete nitrogenous waste
• Kidney retains water and sodium
– Concentrated urine (500 mOsm/L)
– Oliguria (

Figure 1 shows the typical changes including
dilated tubules and interstitial edema.
Figure 1
Figure 1
Table 7
ARF: Interstitial Disease
• An inflammatory process is initiated in the renal
interstitium
• Etiology
–Drugs
–Toxic
– Infectious
– Infiltrative
c) Interstitial Disease (Table 7):
Interstitial nephritis is a complex collection of
disease processes with a poorly understood
pathophysiology. An inflammatory process is
initiated in the renal interstitium in response to a
wide variety of stimuli (toxic, metabolic,
infectious, immune, infiltrative), although drugs
are probably the most common causes.
Pathophysiology of Post-renal Acute Renal Failure:
Obstruction of the urinary tract leads to an
acute rise in intratubular pressure. As a result, there is
stimulation of the renin-angiotensin II system that results
in marked renal vasoconstriction. The vasoconstriction
then leads to a fall in the glomerular filtration rate and
acute renal failure (Figure 2).
Figure 2
Urinary Tract Obstruction
Intratubular pressure
Glomerular capillary pressure
Renal Vascular resistance
Glomerular filtration rate
3 Hours 24 Hours
Figure 3
Differential Diagnosis of Acute Renal Failure
Pre-Renal ARF ARF
Post-Ischemic ARF ARF
(50% of of cases)
Acute Renal Failure
Intrinsic ARF ARF
Post-Renal ARF ARF
Acute Glomerulonephritis
Acute
(5% (5% of of cases) Tubular Necrosis
Acute Interstitial Nephritis
(10% of of cases)
Nephrotoxic ARF ARF
(35% of of cases)
IV. DIAGNOSIS OF ACUTE RENAL
FAILURE
Obviously, there is a large range of medical
conditions that can result in ARF (Figure 3). Given
this broad range of conditions and their differing
therapeutic implications, it is important to rapidly
establish an accurate diagnosis.
A. History and physical exam
Evaluation of the medical history, physical exam findings, and the results of a few radiographic studies
are often necessary to determine the cause of acute renal failure. The initial history should include a review
of the patient’s outpatient record, or in the case of an inpatient, a review of the inpatient record. History
taking should always include certain questions or considerations:

• has nausea, vomiting, and/or diarrhea been present?
• has bleeding occurred?
• does the patient have a history of heart failure or recent symptoms of dyspnea?
• does the patient have a history of chronic liver disease, hepatitis, or jaundice?
• does the patient have a history of previous renal insufficiency?
• has edema, high blood pressure, or a change in urine color occurred?
• has the patient had any unusual rashes develop recently?
• what medications has the patient been placed on, in particular, are there any new medications?
• has the patient been ill enough to have prolonged episodes of hypotension?
• has the patient received any contrast dyes?
• does the patient have a history of renal stone disease or evidence or lower urinary tract obstruction?
Often, the history alone can suggest the cause as being pre-renal, renal, or post-renal. Physical exam is
usually most helpful in assessing the volume status of a patient. Both the total volume and the effective
circulating volume must be considered. Clues for the presence of a systemic disease (ex. vasculitis, CHF,
liver disease) should be sought. Despite a careful history and physical exam, the etiology of ARF often
remains unclear and additional tests must be done.
B. Laboratory testing to help with diagnosis
1. Examination of the Urine: Urinalysis is one of the first, and easiest, tests that can be done on the
patient with acute renal failure. It can provide both diagnostic information as well as prognostic
information about the patient. Hou et al. found that about one-half of 97 patients with ARF had an
abnormal microscopic urinalysis. This abnormal microscopic exam was associated with a "renal" cause of
ARF and a 35% mortality, while those with a normal urinalysis had a 15% mortality.
a. Dipstick Findings: A dipstick positive for protein (3+, 4+) suggests intrinsic renal disease with
glomerular damage. Pre-renal azotemia, obstruction, and acute tubular necrosis tend to be associated with
less proteinuria (trace-2+) than a glomerular lesion. If there is proteinuria present it should be quantified
using a 24-hour urine collection. If there is greater than 3 gm of protein, a glomerular, rather than a tubular
or interstitial, process is more likely. A dipstick positive for blood indicates the presence of RBC's (>
5/HPF). If no RBC's are present, then there may be either myoglobin or hemoglobin present in the urine.
b. Microscopic Examination Findings: In most cases the most significant amount of information is
obtained from the urinalysis comes from the examination of the sediment of a centrifuged urine sample.
This is prepared by placing 10 cc of urine in a conical tube and spinning at 2000 rpm for 5 minutes. The
supernatant is discarded. The sediment is then resuspended in the residual urine, and a drop is placed on a
slide and covered with a cover slip. The periphery of the slide, where casts tend to be concentrated, is
scanned using low power. The slide is then scanned under high power for red blood cells, white cells, renal
tubular epithelial cells, oval fat bodies, bacteria, and crystals.
Casts are formed from urinary Tamm-Horsfall protein, which is a product of the tubular epithelial cells.
This protein tends to gel in conditions of high concentration and when mixed with red cells, tubular cells,
or cellular debris. Thus, the composition of this cast reflects the contents of the tubule.
Hyaline casts (http://medstat.med.utah.edu/WebPath/jpeg2/URIN069.jpg) are those that are
devoid of contents, and are seen with dehydration, or after exercise.
Red cell casts (http://www.hsc.virginia.edu/med-ed/cell/resources/images/UrinaryFig7.jpg)
indicate glomerular hematuria, as seen with glomerulonephritis.
White cell casts (http://medlib.med.utah.edu/WebPath/jpeg2/URINE071.jpg)
imply the presence of renal parenchymal inflammation.

Granular casts are composed of cellular remnants and debris, and are generally a non-specific
indicator of renal parenchymal injury. Granular casts that are deeply pigmented, often referred to as
“muddy brown casts,” (http://www.udel.edu/medtech/mclane/ua11a.jpg), however, are a
fairly specific finding in acute tubular injury (nephrotoxic or ischemic “ATN”).
.
Fatty casts (http://www.lhsc.on.ca/lab/renal/images/slide10.jpg) are usually
associated with heavy proteinuria and the nephrotic syndrome (though they can be present in other
nonglomerular disease).
In patients with pre-renal azotemia, the sediment usually lacks cells, casts, and cellular debris. Similarly,
postrenal causes of ARF tend to be associated with a benign sediment. The presence of dysmorphic RBC's
and red cell casts is characteristic of a glomerular lesion. WBC's and white cell casts are seen in acute
interstitial nephritis. The finding of eosinophils in a Hansel’s-stained urine sediment has been suggested as
indicating a drug-induced acute interstitial nephritis (this is not a specific finding as eosinophils can be
present in other disease states).
2. Serum and Urine Chemical Analysis:
a. Creatinine and BUN: Creatinine is formed from the breakdown of muscle creatinine and is
proportional to the muscle mass. It should be stable from day to day. The creatinine concentration is a
function of the amount of creatinine entering the blood from muscle, its volume of distribution, and its rate
of excretion. Since the first two are usually constant, and changes in the serum creatinine level would
usually be a result of a change in the GFR. Abrupt cessation of glomerular filtration causes the serum
creatinine to rise by 1-2 mg/dL daily. The BUN also rises with renal dysfunction but is influenced by
extrarenal factors as well. Increased protein intake, catabolism, GI bleeding, and many other factor will
effect BUN.
The two important points to remember about elevations of serum creatinine and BUN are: First,
they are late signs of renal dysfunction because the GFR may need to be reduced by as much as 75% before
the BUN and creatinine rise to abnormal levels. Second, many non-renal variables affect both these levels.
Generally, a serum BUN to creatinine ratio of greater than 20 suggests pre-renal azotemia rather than ATN,
which is associated with a ratio of 10 to 1.
b. Urine Osmolality: Normally, the kidney can concentrate urine to levels of approximately 1,200
mOsm/kg. The ability to do this depends on an intact tubular system. Urine osmolality levels greater than
500 mOsm/kg suggest pre-renal azotemia (Table 8). By comparison, extensive tubular damage, such as that
seen in ATN, impairs the ability of the kidney to generate a concentrated urine. Typically, the urine
osmolality in ATN approximates that of the serum (300-350 mOsm/kg).
Table 8
Tests useful in the diagnosis of acute renal failure due to pre-renal
causes
Urine sodium less than 20 mEq/L
Urine osmolality greater than plasma osmolality
BUN-to-serum creatinine ratio greater than 20
Urine osmolality greater than 500 mOsm/kg
Fractional sodium excretion less than 1%
Diagnostic ultrasound shows normal sized
kidneys

Table 9
ATN versus Pre-renal Azotemia
Indices Prerenal ATN
UNa < 20 mEq/L > 40 mEq/L
FeNA < 1% > 4%
U/PCreat > 40 < 20
Uosm > 500 mOsm/kg 300-350 mOsm/kg
c. Urine Sodium Concentration: Urine sodium
excretion reflects how well the nephron retains the
filtered sodium load. With renal hypo-perfusion
due to either volume depletion or ineffective
circulating blood volume, the kidney will avidly
retain sodium as a result of increased proximal
and distal reabsorption. If the kidney is
responding appropriately to a decreased effective
intravascular volume, the urine sodium
concentration will usually be low (less than 20
mEq/L) and the fractional excretion of sodium
(FE Na ) will be < 1%. The average FE Na has been
reported to be > 4.0% in patients with
postischemic or nephrotoxic ARF (Table 9).
d. Other Indices: There are multiple other indices than can be measured when trying to evaluate renal
failure. These include Urine/Serum Creatinine Ratio, Renal Failure Index, Urine/Serum Urea Ratio,
creatinine clearance, and Free Water Clearance. None of these tests have advantages in diagnosis over the
FE Na .
Ischemic and
Nephrotoxic
Tubular Injury
Interstitial
Nephritis
Glomerulonephritis
Table 10
Urinary Findings in Intra-renal ARF
Protein
Mild to
moderate
Mild to
moderate
Moderate to
heavy
Urine sediment
“Muddy
brown”
granular casts
WBC casts
Eosinophiluria
RBC casts
Urine
Chemistries
Uosm 300-350
mOsm/kg
FENa+ > 4%
Uosm 300-350
mOsm/kg
FENa+ > 4%
Uosm > 500
mOsm/kg
FENa+ < 1 %
The urinary and serum indices help to
distinguish pre-renal from intrinsic causes of ARF
(Tables 10 &11). However, several points should
be remembered. In diseases that affect the renal
glomerulus primarily, such as acute
glomerulonephritis, the urinary and serum indices
will more closely resemble those of pre-renal
azotemia rather than intrinsic renal disease. Post
renal causes of ARF can also be associated with
indices similar to those of pre-renal azotemia early
in the course of obstruction. With continued
obstruction, tubular function becomes impaired
and the indices mimic those of intrinsic disease.
Table 11
Urinary Findings in Pre-renal and Post-renal ARF
Protein
Urine
Sediment
Urine
Chemistries
Pre-renal
None to trace
Normal or
hyaline casts
Uosm > 500
mOsm/kg
FENa+ < 1%
Post-renal
None to trace
Crystals, red or
white cell casts
Variable

3. Radiographic Procedures
a. Intravenous Pyelogram: IVP provides an anatomic picture of the kidney but does not help evaluate
kidney function. It also subjects the patient to a dye load. This can potentially be harmful to kidneys that
may have already had previous insult. At this time there is little indication for IVP in the patient with acute
renal failure.
b. Ultrasonography: Renal ultrasound is the most valuable diagnostic technique for the assessment of the
patient with ARF. It can be performed easily in the patient with impaired renal function and has no
associated morbidity. It is a sensitive test for obstruction (93-98%) and provides information about kidney
size (the kidney size can be helpful in judging the chronicity of the kidney disease).
c. Computed tomography (CT): This can be helpful in some patients. Hydronephrosis can be recognized
without contrast. The cause of obstruction (Ex. lymphoma, retroperitoneal fibrosis, etc) can often be
delineated. CT is the technique of choice for visualizing ureteral obstruction at the level of the bony pelvis.
d. Other Tests: Radionuclide scans can be used if there is a concern about vascular perfusion of the
kidneys. percutaneous nephrostomy combined with antegrade pyelography can be employed to diagnose
the precise level of obstruction in the urinary tract. Ultimately, if the diagnosis is still unclear, the patient
may need a renal biopsy.
Table 12
Diagnostic Evaluation of Renal Failure
• Assess volume status
• Exclude urinary tract obstruction
• Ascertain nephrotoxic exposures
• Examine the urine sediment
• Check urinary indices
So How do I Make the Diagnosis (Table 12)?
Start with the history and physical exam
as already discussed. The general strategy is to rule
out both pre-renal and postrenal causes before
considering the many intrinsic reasons. First,
sources of volume loss and causes of decreased
cardiac output should be sought in the history. The
patient should be questioned for bleeding sources,
GI losses, evidence of CHF, or history of liver
disease. In males, a history should be taken
searching for evidence of prostatic disease. A
documented history of anuria could imply highgrade
obstruction, but this can accompany severe
volume depletion, severe acute glomerulonephritis,
cortical necrosis, or bilateral vascular occlusion. Intermittent anuria is more suggestive of obstructive
disease.
The patient should further be questioned about the use of all medications as well as recent
exposure to contrast dyes. A history of recent pharyngitis, hypertension, rash, fever, or dark colored urine
may suggest glomerulonephritis associated with a multisystem process.
The physical exam should focus on signs of volume depletion or overload. An attempt to percuss
the bladder should be made. If the dome of the bladder is felt, this implies that there is 500cc of urine
present. Prostate exam in males and a pelvic exam in females are essential. The skin should be assessed for
the presence of a rash.

Laboratory evaluation should start with a dipstick of the urine and then microscopic analysis. An
attempt at quantification of urine output should be made. BUN, creatinine, urine electrolytes, and then
FENa levels should be determined. Next, a CBC, serum electrolytes, calcium, phosphorus, magnesium
should be done. A serum creatinine kinase should be obtained to evaluate for rhabdomyolysis when
suspected, such as following multiple trauma or crush injuries. An ECG and chest x-ray may aid in the
evaluation.
Pre-renal azotemia should be suspected in the setting of volume loss, volume redistribution, or
decreased effective renal perfusion. It is typically associated with a normal urinalysis, high BUN/Creat
ratio, increased urine osmolarity, urine sodium levels less than 20 mEq/L, and a FE Na less than 1%.
Urethral or bladder neck obstruction is documented by the finding of significant amounts of
residual urine in the bladder on catheterization after the patient attempts to void spontaneously. Urine
indices in obstruction may not be helpful, although the BUN/creat ratio may be elevated. Since obstruction
is a reversible cause of renal failure, an ultrasound should always be obtained early in the evaluation.
Finally, the presence of a renal parenchymal disorder can often be diagnosed by its manifestations
on microscopic urinalysis, by associated extrarenal manifestations, or by the clinical setting of recent
exposure to a new medication. In the absence of these clues, the failure to find evidence of pre-renal or
postrenal disease may be taken as presumptive evidence of an intrarenal parenchymal process. The
possibility of a vascular insult should always be kept in mind since timely intervention is critical to
preserving renal function.
V. SPECIFIC DISEASES CAUSING ACUTE RENAL FAILURE
1. Pre-renal Disease
A reduction in renal blood flow is the most common cause of acute renal failure. This can occur from
true volume depletion or from selective renal ischemia (as in bilateral renal artery stenosis or sepsis). The
usual causes of pre-renal azotemia are true volume depletion, or a decrease in the effective circulating
blood volume as occurs in sepsis, advanced liver disease, and congestive heart failure.
a. Pre-renal Azotemia Caused by True Volume Depletion: The cause of volume depletion is usually
evident from the history and exam. In severe cases the patient may be in hypovolemic shock. Oliguria is
present in most individuals and this is an appropriate response given the clinical situation. Normal or
increased urine output indicates that an osmotic agent or other diuretic agent is acting, or that there is
tubular dysfunction such as ATN.
b. Pre-renal Azotemia Caused by Sepsis: The mechanisms by which sepsis leads to decreased renal
perfusion are incompletely understood. Decreased renal blood flow independent from the effects of
systemic hypotension has been demonstrated. Factors that may contribute to such include altered
autonomic regulation of renal blood flow as well as cytokine-induced renal vasoconstriction.
c. Pre-renal Azotemia Caused by Advanced Liver Disease: Liver disease is associated with two major
changes in renal function: sodium retention, initially manifested as ascites, and a progressive decline in
GFR. Both humoral and hemodynamic factors play a primary role in the development of these problems.
The progressive decline in renal function that occurs in hepatic cirrhosis is thought to be hemodynamically
mediated because tubular function is intact (as evidenced by low urine sodium concentration and a normal
urinalysis) and the kidneys are histologically intact.
d. Pre-renal Azotemia Caused by Congestive Heart Failure: CHF is associated with two major
alterations in renal function: sodium retention early in the course of the disease and a decline in GFR as
cardiac function worsens. Neurohumoral factors and certain therapies may contribute to these problems.

2. Acute Tubular Necrosis:
The characteristic tubular injury in this disorder represents a nonspecific response that can be seen with a
variety of renal insults, including renal ischemia and exposure to exogenous or endogenous nephrotoxins
(see table 13). The net effect is a rapid decline in renal function that may require a period of dialysis before
spontaneous resolution occurs. There are two major histologic changes that take place in ATN: (1) tubular
necrosis with sloughing of the epithelial cells; and (2) occlusion of the tubular lumina by casts and by
cellular debris. These changes may be patchy and seem mild compared to the degree of the renal failure. In
addition of the tubular obstruction, two other factors appear to contribute to the development of renal
failure in ATN: backleak of filtrate across the damaged tubular epithelia and a primary reduction in
glomerular filtration. The decrease in glomerular filtration results both from arteriolar vasoconstriction and
from mesangial contraction. The decline in renal function in ATN has a variable onset. It typically begins
abruptly following a hypotensive episode, rhabdomyolysis, or the administration of a radiocontrast media.
In comparison, when aminoglycosides are the cause, the onset is more insidious, with the first rise in
creatinine being at seven or more days.

Table 13
Major Causes of Nephrotoxic Acute Renal Failure
Antibacterial Agents
• Aminoglycosides
• Beta Lactam Antibiotics
• Vancomycin
• Sulfonamides
Antiviral Agents
• Acyclovir
• Indinavir
• Foscarnet
Antifungal Agents
• Amphotericin
Antiprotozoal Agents
• Pentamidine
Chemotherapeutic Agents
Alkylating Agents
• Cisplatinum
Antimetabolites
• Methotrexate
Antitumor Antibiotics
• Mitomycin
Immunotherapeutic Agents
• Interleukin-2
• Interferon
Immunosuppressive Agents
• Cyclosporine
• Tacrolimus
Nonsteroidal Anti-inflammatory Drugs
Radiocontrast agents
Environmental and Occupational Agents
• Organic Solvents
• Ethylene Glycol
• Heavy Metals
• Mercury
• Pesticides, Insecticides, Herbicides and
Fungicides
• Chlordane, Paraquat
Biologicals
• Mycotoxins
• Ochratoxin A
• Venoms
• Mushrooms
Osmotic Agents
• Sucrose
• Mannitol
Heme Pigments
• Hemoglobin
• Myoglobin
Uric Acid
VI. COMPLICATIONS OF RENAL FAILURE
1. Cardiovascular System:
Complications of the cardiovascular system are common in ARF. In a study with 462 patients with ATN,
cardiovascular complications (congestive heart failure, myocardial infarction, and cardiac arrest) occurred
in 35% of cases. In the oliguric patient with ARF, volume overload with hypertension, edema, and
pulmonary congestion is an ever-present threat. Pericarditis may rarely complicate the course of ARF, and
may lead to pericardial tamponade and life-threatening cardiovascular compromise.
2. Pulmonary System Complications:
Pulmonary infiltrates due to edema from volume overload and/or infection are encountered frequently in
ARF. Remember that there are several disease processes that can cause simultaneous pulmonary and renal
involvement. These include glomerulonephritis, Goodpasture’s, SLE, Wegener's, polyarteritis, sarcoidosis,
renal vein thrombosis with pulmonary embolism, and several others. The development of pulmonary
complications in ARF is an adverse prognostic factor.

3. Gastrointestinal System Complications:
The most common GI manifestations of ARF are severe nausea, vomiting, and anorexia. Upper GI
bleeding is another significant complication. Stress ulcers and gastritis are common.
4. Neurologic System Complications:
CNS disorders are frequent accompaniments of ARF. Initially, lethargy, somnolence, lassitude, and
fatigue are present. These symptoms may progress to irritability, confusion, disorientation, decreased
memory, twitching, asterixis, and myoclonus. In advanced cases, generalized seizures may occur with
somnolence and coma. The encephalopathy of ARF has not yet been firmly identified as a complication of
a single specific identifiable toxin. Thus, the pathophysiology of neurologic complications of ARF remains
unclear. One thing to consider is whether the CNS disturbance may in fact be coming from the medications
the patient is on in the face of ARF.
5. Infectious Complications:
ARF and infections are commonly associated. Not only is septicemia frequently associated with the onset
of ARF, but also infections often complicate the course of ARF. Common foci include pulmonary, urinary,
and central venous catheter related bacteremia. These infectious complications can be a leading source of
morbidity and mortality.
6. Endocrine System Complications:
Several hormonal abnormalities have been described in ARF. For, example, ATN is often associated with
disturbances in divalent ion metabolism (hypocalcemia, hyperphosphatemia, and hypermagnesemia).
Altered PTH action and vitamin D metabolism may play a pathogenic role in the hypocalcemia and
hyperphosphatemia. Several studies have demonstrated high PTH levels in ATN, which may occur in
response to the low calcium levels. Thyroid function tests may show decreased levels of Total T4 and T3,
but the patients are usually euthyroid. High plasma renin activity and angiotensin II levels often occur in
the setting of ARF. Whether these factors contribute to the hypertension has yet to be determined.
7. Disorders of Electrolyte Metabolism:
Hyperkalemia, hyponatremia, metabolic acidosis, and hypocalcemia often occur in ARF. These
abnormalities should be expected and searched for so that the appropriate treatment can be initiated.
Certain other disease entities being present can significantly worsen these levels (such as rhabdomyolysis).
Hyperphosphatemia can also be expected, because of the decreased renal excretion of phosphate. In cases
of coexisting tissue damage this could be worse.
VII. TREATMENT OF ACUTE RENAL FAILURE
The patient with acute renal failure may present extremely ill and sometimes moribund. There is almost
no margin for error and the differential diagnosis can be extremely difficult. In spite of this, it is necessary
to take a strict logical approach to the patient. First, resuscitate, next search for the correct diagnosis and
treat accordingly, and finally prevent complications through the use of supportive measures and dialysis
(Table 14).
Resuscitation: The two most common causes of death early in the resuscitative phase are hyperkalemia and
pulmonary edema. Over hydration with resultant pulmonary edema is usually iatrogenic as a result of futile
attempts to restore urine output before the etiology of the renal failure has been established.

Post-renal Failure: In those with postrenal failure, a passage for the drainage of urine must be created. The
exact method that is used will depend entirely on the level of the obstruction and may be as simple as a
urinary catheter, or as complex as a percutaneous nephrostomy tube.
Pre-renal Failure: Treatment for True Volume Depletion: Therapy for this type of ARF is aimed at
restoration of the normal circulating blood volume. The major question that needs to be addressed is the
rate at which the fluid should be given. This usually depends on the clinical status of the patient. Initially
fluid boluses may be needed, and if indicated blood transfusion may be required. The patient must be
constantly reassessed to insure that the patient is not getting overhydrated. The adequacy of fluid repletion
can be assessed from physical exam and by monitoring renal function and urine output.
Pre-renal Failure: Treatment for ARF due to Advanced Liver Disease: Dietary sodium restriction and
periods of bed rest are the mainstays of nonmedical therapy in this disease entity. Medical therapies are as
follows. Diuretics therapy is often indicated and the preferred agent is spironolactone. Normally this is a
fairly weak diuretic, however in cases of liver failure it is very effective. Spironolactone is the only diuretic
that does not require secretion into the lumen of the kidney. Rather, it enters the collecting tubule cells
from the blood side and competes for the aldosterone receptor. The rate of diuresis needs to be slow and
steady. Paracentesis may be helpful in those patients with tense ascites. Albumin may be given at the same
time to help prevent the worsening of intravascular depletion. A peritoneovenous shunt, which drains into
the internal jugular vein and translocates the ascitic fluid into the vascular space may be helpful in cases of
severe portal hypertension and ascites, but is often complicated by worsening hepatic encephalopathy.
Pre-renal Failure: Treatment of ARF Caused by Congestive Heart Failure: The use of diuretics may be of
some help as this will increase the renal output and relieve pulmonary congestion. Another option is a trial
of inotropic agents to help increase cardiac output and thus increase renal perfusion. ACE inhibitors may
also be helpful to improve cardiac output, but must be used with caution in patients with acute renal failure
as they may cause a fall in GFR, particularly in patients with renal vascular disease.
Renal Causes of ARF: When pre-renal and renal causes of ARF have been ruled out, the challenge
becomes to identify the cause of the intrinsic renal failure, keeping in mind the multitude of known possible
causes.

Most commonly, the cause of the intrinsic renal failure will be from ATN. Therapy in established ATN,
other than correction of the underlying problem, is largely supportive. In particular, attention must be paid
to maintenance of the fluid and electrolyte balance and to proper nutrition. Despite management, some
patients will require dialysis. Indications for dialysis include:
• marked fluid overload
• severe hyperkalemia
• presence of uremic signs or symptoms (pericarditis, nausea and vomiting, confusion, bleeding with
coagulopathy present)
• severe metabolic acidosis (controversial)
• BUN levels greater than 100
Table 14
Summary of Therapy and Goals in the Initial Phase of Acute Renal Failure
Therapy
Volume expansion/hydration
Diuretics
Vasoactive agents
Dopamine
Atrial natriuretic peptide
Cytoprotective agents
Free radical scavengers
Xathine oxidase inhibitors
Calcium channel blockers
Prostaglandins
Goal
Prevention of injury
Management of volume overload
Restoration of renal perfusion
Preservation of cell integrity
The use of diuretics may be able to convert oliguric ATN into nonoliguric ATN. While nonoliguric ATN
has a better prognosis than oliguric ATN this is only the case when it occurs spontaneously. Conversion of
oliguric ARF to nonoliguric ARF by the use of diuretics does not improve the prognosis. Lasix is often
used in high doses either by rapid infusion or by a continuous drip to help manage volume overload.
Finally, dopamine may be an effective agent along with lasix in an effort to increase urine output but with
no documented improvement in outcome.