Back ground from acute glomerulonephritis

Acute glomerulonephritis (GN) firstly found in 1927. Acute poststreptococcal

glomerulonephritis (PSGN) is the archetype of acute GN. Acute nephritic syndrome is the
most serious and potentially devastating form of the various renal syndromes.
Acute GN comprises a specific set of renal diseases in which an immunologic mechanism
triggers inflammation and proliferation of glomerular tissue that can result in damage to
the basement membrane, mesangium, or capillary endothelium.
Acute GN is defined as the sudden onset of hematuria, proteinuria, and red blood cell
(RBC) casts. This clinical picture is often accompanied by hypertension, edema, azotemia
(ie, decreased glomerular filtration rate [GFR]), and renal salt and water retention. Acute
GN can be due to a primary renal disease or to a systemic disease. Most original research
focuses on acute PSGN.
Treatment of PSGN is mainly supportive, because there is no specific therapy for renal
disease. When acute GN is associated with chronic infections, the underlying infections
must be treated.

Pathophysiology
Glomerular lesions in acute GN are the result of glomerular deposition or in situ
formation of immune complexes. On gross appearance, the kidneys may be enlarged up
to 50%. Histopathologic changes include swelling of the glomerular tufts and infiltration
with polymorphonucleocytes (see Histologic Findings). Immunofluorescence reveals
deposition of immunoglobulins and complement.
Except in PSGN, the exact triggers for the formation of the immune complexes are
unclear. In PSGN, involvement of derivatives of streptococcal proteins has been reported.
A streptococcal neuraminidase may alter host immunoglobulin G (IgG). IgG combines
with host antibodies. IgG/anti-IgG immune complexes are formed and then collect in the
glomeruli. In addition, elevations of antibody titers to other antigens, such as
antistreptolysin O or antihyaluronidase, DNAase-B, and streptokinase, provide evidence
of a recent streptococcal infection.

Structural and functional changes

Acute GN involves both structural changes and functional changes.
Structurally, cellular proliferation leads to an increase in the number of cells in the
glomerular tuft because of the proliferation of endothelial, mesangial,[1] and epithelial
cells. The proliferation may be endocapillary (ie, within the confines of the glomerular
capillary tufts) or extracapillary (ie, in the Bowman space involving the epithelial cells).
In extracapillary proliferation, proliferation of parietal epithelial cells leads to the

formation of crescents, a feature characteristic of certain forms of rapidly progressive

GN.
Leukocyte proliferation is indicated by the presence of neutrophils and monocytes within
the glomerular capillary lumen and often accompanies cellular proliferation.
Glomerular basement membrane thickening appears as thickening of capillary walls on
light microscopy. On electron microscopy, this may appear as the result of thickening of
basement membrane proper (eg, diabetes) or deposition of electron-dense material, either
on the endothelial or epithelial side of the basement membrane. Electron-dense deposits
can be subendothelial, subepithelial, intramembranous, or mesangial, and they
correspond to an area of immune complex deposition.
Hyalinization or sclerosis indicates irreversible injury.
These structural changes can be focal, diffuse or segmental, or global.
Functional changes include proteinuria, hematuria, reduction in GFR (ie, oligoanuria),
and active urine sediment with RBCs and RBC casts. The decreased GFR and avid distal
nephron salt and water retention result in expansion of intravascular volume, edema, and,
frequently, systemic hypertension.

Poststreptococcal glomerulonephritis
Streptococcal M-protein was previously believed to be responsible for PSGN, but the
studies on which this belief was based have been discounted. Nephritis-associated
streptococcal cationic protease and its zymogen precursor (nephritis-associated protease
[NAPR]) have been identified as a glyceraldehyde-3-phosphate dehydrogenase that
functions as a plasmin(ogen) receptor. This binds to plasmin and activates complement
via an alternate pathway.
Antibody levels to NAPR are elevated in streptococcal infections (of group A, C, and G)
associated with GN but are not elevated in streptococcal infections without GN, whereas
anti-streptolysin-O titers are elevated in both circumstances. These antibodies to NAPR
persist for years and perhaps are protective against further episodes of PSGN. In a study
in adults, the 2 most frequently identified infectious agents were streptococci (27.9%) and
staphylococci (24.4%).[2]
http://emedicine.medscape.com/article/239278-overview#a0104
Etiology
The causal factors that underlie acute GN can be broadly divided into infectious and
noninfectious groups.
Infectious
The most common infectious cause of acute GN is infection by Streptococcus species (ie,
group A, beta-hemolytic). Two types have been described, involving different serotypes:

Serotype 12 - Poststreptococcal nephritis due to an upper respiratory infection, occurring

primarily in the winter months
Serotype 49 - Poststreptococcal nephritis due to a skin infection, usually observed in the
summer and fall and more prevalent in southern regions of the United States
PSGN usually develops 1-3 weeks after acute infection with specific nephritogenic
strains of group A beta-hemolytic streptococcus. The incidence of GN is approximately 510% in persons with pharyngitis and 25% in those with skin infections.
Nonstreptococcal postinfectious GN may also result from infection by other bacteria,
viruses, parasites, or fungi. Bacteria besides group A streptococci that can cause acute GN
include diplococci, other streptococci, staphylococci, and mycobacteria. Salmonella
typhosa, Brucella suis, Treponema pallidum, Corynebacterium bovis, and actinobacilli
have also been identified.
Cytomegalovirus (CMV), coxsackievirus, Epstein-Barr virus (EBV), hepatitis B virus
(HBV),[3] rubella, rickettsiae (as in scrub typhus), and mumps virus are accepted as viral
causes only if it can be documented that a recent group A beta-hemolytic streptococcal
infection did not occur. Acute GN has been documented as a rare complication of
hepatitis A.[4]
Attributing glomerulonephritis to a parasitic or fungal etiology requires the exclusion of a
streptococcal infection. Identified organisms include Coccidioides immitis and the
following parasites: Plasmodium malariae, Plasmodium falciparum, Schistosoma
mansoni, Toxoplasma gondii, filariasis, trichinosis, and trypanosomes.
Noninfectious
Noninfectious causes of acute GN may be divided into primary renal diseases, systemic
diseases, and miscellaneous conditions or agents.
Multisystem systemic diseases that can cause acute GN include the following:
Vasculitis (eg, Wegener granulomatosis) - This causes glomerulonephritis that combines
upper and lower granulomatous nephritides).
Collagen-vascular diseases (eg, systemic lupus erythematosus [SLE]) This causes
glomerulonephritis through renal deposition of immune complexes).
Hypersensitivity vasculitis This encompasses a heterogeneous group of disorders
featuring small vessel and skin disease.
Cryoglobulinemia This causes abnormal quantities of cryoglobulin in plasma that result
in repeated episodes of widespread purpura and cutaneous ulcerations upon
crystallization.
Polyarteritis nodosa - This causes nephritis from a vasculitis involving the renal arteries.
Henoch-Schnlein purpura This causes a generalized vasculitis resulting in
glomerulonephritis.
Goodpasture syndrome This causes circulating antibodies to type IV collagen and often
results in a rapidly progressive oliguric renal failure (weeks to months).
Primary renal diseases that can cause acute GN include the following:

Membranoproliferative glomerulonephritis (MPGN) - This is due to the expansion and

proliferation of mesangial cells as a consequence of the deposition of complements. Type
I refers to the granular deposition of C3; type II refers to an irregular process.
Berger disease (IgG-immunoglobulin A [IgA] nephropathy) - This causes GN as a result
of diffuse mesangial deposition of IgA and IgG.
Pure mesangial proliferative GN[1]
Idiopathic rapidly progressive glomerulonephritis - This form of GN is characterized by
the presence of glomerular crescents. Three types have been distinguished: Type I is an
antiglomerular basement membrane disease, type II is mediated by immune complexes,
and type III is identified by antineutrophil cytoplasmic antibody (ANCA).
Miscellaneous noninfectious causes of acute GN include the following:
Guillain-Barr syndrome
Irradiation of Wilms tumor
Diphtheria-pertussis-tetanus (DPT) vaccine
Serum sickness

Epidemiology
United States statistics
GN represents 10-15% of glomerular diseases. Variable incidence has been reported, in
part because of the subclinical nature of the disease in more than half the affected
population. Despite sporadic outbreaks, the incidence of PSGN has fallen over the past
few decades. Factors responsible for this decline may include better health care delivery
and improved socioeconomic conditions.
GN comprises 25-30% of all cases of end-stage renal disease (ESRD). About one fourth
of patients present with acute nephritic syndrome. Most cases that progress do so
relatively quickly, and end-stage renal failure may occur within weeks or months of the
onset of acute nephritic syndrome. Asymptomatic episodes of PSGN exceed symptomatic
episodes by a ratio of 3-4:1.

International statistics
Worldwide, Berger disease is the most common cause of GN.
With some exceptions, the incidence of PSGN has fallen in most Western countries.
PSGN remains much more common in regions such as Africa, the Caribbean, India,
Pakistan, Malaysia, Papua New Guinea, and South America. In Port Harcourt, Nigeria,
the incidence of acute GN in children aged 3-16 years was 15.5 cases per year, with a
male-to-female ratio of 1.1:1; the current incidence is not much different.[5]

Geographic and seasonal variations in the prevalence of PSGN are more marked for
pharyngeally associated GN than for cutaneously associated disease.[5, 6, 7]

Age-, sex-, and race-related demographics

Postinfectious GN can occur at any age but usually develops in children. Most cases
occur in patients aged 5-15 years; only 10% occur in patients older than 40 years.
Outbreaks of PSGN are common in children aged 6-10 years. Acute nephritis may occur
at any age, including infancy.
Acute GN predominantly affects males (2:1 male-to-female ratio). Postinfectious GN has
no predilection for any racial or ethnic group. A higher incidence (related to poor
hygiene) may be observed in some socioeconomic groups.

Prognosis
Most epidemic cases follow a course ending in complete patient recovery (as many as
100%). The mortality of acute GN in the most commonly affected age group, pediatric
patients, has been reported at 0-7%.
Sporadic cases of acute nephritis often progress to a chronic form. This progression
occurs in as many as 30% of adult patients and 10% of pediatric patients. GN is the most
common cause of chronic renal failure (25%).
In PSGN, the long-term prognosis generally is good. More than 98% of individuals are
asymptomatic after 5 years, with chronic renal failure reported 1-3% of the time.
Within a week or so of onset, most patients with PSGN begin to experience spontaneous
resolution of fluid retention and hypertension. C3 levels may normalize within 8 weeks
after the first sign of PSGN. Proteinuria may persist for 6 months and microscopic
hematuria for up to 1 year after onset of nephritis.
Eventually, all urinary abnormalities should disappear, hypertension should subside, and
renal function should return to normal. In adults with PSGN, full recovery of renal
function can be expected in just over half of patients, and prognosis is dismal in patients
with underlying diabetic glomerulosclerosis. Few patients with acute nephritis develop
rapidly progressive renal failure.
Approximately 15% of patients at 3 years and 2% of patients at 7-10 years may have
persistent mild proteinuria. Long-term prognosis is not necessarily benign. Some patients
may develop hypertension, proteinuria, and renal insufficiency as long as 10-40 years
after the initial illness. Immunity to type M protein is type-specific, long-lasting, and
protective. Repeated episodes of PSGN are therefore unusual.
The prognosis for nonstreptococcal postinfectious GN depends on the underlying agent,
which must be identified and addressed. Generally, the prognosis is worse in patients
with heavy proteinuria, severe hypertension, and significant elevations of creatinine level.

Nephritis associated with methicillin-resistant Staphylococcus aureus (MRSA) and

chronic infections usually resolves after treatment of the infection.
Other causes of acute GN have outcomes varying from complete recovery to complete
renal failure. The prognosis depends on the underlying disease and the overall health of
the patient. The occurrence of cardiopulmonary or neurologic complications worsens the
prognosis.

COMPLICATION

Complications
Progression to sclerosis is rare in the typical patient; however, in 0.5-2% of patients with
acute GN, the course progresses toward renal failure, resulting in kidney death in a short
period.
Abnormal urinalysis (ie, microhematuria) may persist for years. A marked decline in the
glomerular filtration rate (GFR) is rare.
Pulmonary edema and hypertension may develop. Generalized anasarca and
hypoalbuminemia may develop secondary to severe proteinuria.
A number of complications that result in relevant end-organ damage in the central
nervous system (CNS) or the cardiopulmonary system can develop in patients who
present with severe hypertension, encephalopathy, and pulmonary edema. Those
complications include the following:

Hypertensive retinopathy
Hypertensive encephalopathy
Rapidly progressive GN
Chronic renal failure
Nephrotic syndrome

Chronic renal failure

Background
Chronic kidney disease (CKD) is a worldwide public health problem and is now
recognized as a common condition that is associated with an increased risk of
cardiovascular disease and chronic renal failure (CRF).
The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney
Foundation (NKF) defines chronic kidney disease as either kidney damage or a decreased
kidney glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m2 for 3 or more
months. Whatever the underlying etiology, the destruction of renal mass with irreversible

sclerosis and loss of nephrons leads to a progressive decline in GFR. The different stages
of chronic kidney disease form a continuum in time; prior to February 2002, no uniform
classification of the stages of chronic kidney disease existed. At that time, K/DOQI
published a classification of the stages of chronic kidney disease, as follows:

Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m2)
Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2)
Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2)
Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2)
Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 or dialysis)

In stage 1 and stage 2 chronic kidney disease, GFR alone does not clinch the diagnosis.
Other markers of kidney damage, including abnormalities in the composition of blood or
urine or abnormalities in imaging tests, should also be present in establishing a diagnosis
of stage 1 and stage 2 chronic kidney disease.

Pathophysiology
Approximately 1 million nephrons are present in each kidney, each contributing to the
total GFR. Regardless of the etiology of renal injury, with progressive destruction of
nephrons, the kidney has an innate ability to maintain GFR by hyperfiltration and
compensatory hypertrophy of the remaining healthy nephrons. This nephron adaptability
allows for continued normal clearance of plasma solutes so that substances such as urea
and creatinine start to show significant increases in plasma levels only after total GFR has
decreased to 50%, when the renal reserve has been exhausted. The plasma creatinine
value will approximately double with a 50% reduction in GFR. A rise in plasma
creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still
within the reference range, actually represents a loss of 50% of functioning nephron
mass.
The residual nephron hyperfiltration and hypertrophy, although beneficial for the reasons
noted, has been hypothesized to represent a major cause of progressive renal dysfunction.
This is believed to occur because of increased glomerular capillary pressure, which
damages the capillaries and leads initially to focal and segmental glomerulosclerosis and
eventually to global glomerulosclerosis. This hypothesis has been based on studies of
five-sixths nephrectomized rats, which develop lesions that are identical to those
observed in humans with chronic kidney disease.
Factors other than the underlying disease process and glomerular hypertension that may
cause progressive renal injury include the following:

Systemic hypertension
Acute insults from nephrotoxins or decreased perfusion
Proteinuria
Increased renal ammoniagenesis with interstitial injury

Hyperlipidemia
Hyperphosphatemia with calcium phosphate deposition
Decreased levels of nitrous oxide
Smoking

http://emedicine.medscape.com/article/238798-overview#a0104

Epidemiology
Frequency

United States
In the United States, there is a rising incidence and prevalence of kidney failure, with
poor outcomes and high cost. Kidney disease is the ninth leading cause of death in the
United States. Data from the United States Renal Data System (USRDS) indicated that
there has been an increase of 104% in the prevalence of chronic renal failure (CRF)
between the years 1990-2001. There is an even higher prevalence of the earlier stages of
chronic kidney disease.
According to the Third National Health and Nutrition Examination Survey, it was
estimated that 6.2 million people (ie, 3% of total US population) older than 12 years had
a serum creatinine value above 1.5 mg/dL; 8 million people had a glomerular filtration
rate (GFR) of less than 60 mL/min, the majority of them being in the Medicare senior
population (5.9 million people). Therefore, for the first time, the US Surgeon General's
mandate for America's citizenry, Healthy People 2010, contains a chapter focused on
chronic kidney disease. The objectives of this chapter are to articulate goals and to
provide strategies to reduce the incidence, morbidity, mortality, and health costs of
chronic kidney disease in the United States. The burden of chronic kidney disease can be
assessed by multiple criteria, all of which underscore the need for improved detection,
treatment, and monitoring of clinical and fiscal outcomes. Reducing renal failure will
require additional public health efforts, including effective preventive strategies and early
detection and treatment of chronic kidney disease.
Because of the nonuniform definition of kidney disease prior to February 2002, among
other factors, most patients with earlier stages of chronic kidney disease have not been
recognized or adequately treated. The Third National Health and Examination Survey
(NHANES III) estimated that the prevalence of chronic kidney disease in adults in the
United States was 11% (19.2 million): 3.3% (5.9 million) had stage 1, 3% (5.3 million)
had stage 2, 4.3% (7.6 million) had stage 3, 0.2% (400,000) had stage 4, and 0.2%
(300,000) had stage 5.
Furthermore, the prevalence of chronic kidney disease stages 1-4 increased from 10% in
1988-1994 to 13.1% in 1999-2004. This increase is partially explained by the increase in
the prevalence of diabetes and hypertension, the two most common causes of chronic
kidney disease.

International
The incidence rates of end-stage renal disease (ESRD) have increased steadily
internationally since 1989. The United States has the highest incident rate of ESRD,
followed by Japan. Japan has the highest prevalence per million population, with the
United States taking second place.

Mortality/Morbidity
Chronic kidney disease is a major cause of morbidity and mortality, particularly at the
later stages. Although the diabetic population is at highest risk, in the United States, the
general hemodialysis and peritoneal dialysis populations have 2 hospital admissions per
patient per year; patients who have a renal transplant have an average of 1 hospital
admission per year. The 5-year survival rate for a patient undergoing chronic dialysis in
the United States is approximately 35%. This is approximately 25% in patients with
diabetes. The most common cause of death in the dialysis population is cardiovascular
disease.
Among patients with ESRD aged 65 years and older, the mortality rates are 6 times
higher than in the general population. In 2003, over 69,000 dialysis patients enrolled in
the ESRD program died (annual adjusted mortality rate of 210.7 per 1000 patient-years at
risk for the dialysis population, which represents a 14% decrease since peaking at 244.5
per 1000 patient-years in 1988). The highest mortality rate is within the first 6 months of
initiating dialysis, which then tends to improve over the next 6 months, before increasing
gradually over the next 4 years.
The mortality rates associated with hemodialysis are striking and indicate that the life
expectancy of patients entering into hemodialysis is markedly shortened. At every age,
patients with ESRD on dialysis have significantly increased mortality when compared
with nondialysis patients and individuals without kidney disease. At age 60 years, a
healthy person can expect to live for more than 20 years, whereas the life expectancy of a
60-year-old patient starting hemodialysis is closer to 4 years.

Race
Chronic kidney disease affects all races, but, in the United States, a significantly higher
incidence of ESRD exists in blacks as compared to whites; the incident rate for blacks is
nearly 4 times that for whites.
Choi et al found that rates of end-stage renal disease among black patients exceeded those
among white patients at all levels of baseline estimated glomerular filtration rate (eGFR).
[1]
Similarly, mortality rates among black patients were equal to or higher than those
among white patients at all levels of eGFR. Risk of end-stage renal disease among black
patients was highest at an eGFR of 45-59 mL/min/1.73 m2 (hazard ratio, 3.08), as was
the risk of mortality (hazard ratio, 1.32).

Sex

In NHANES III, the distribution of estimated GFRs for the chronic kidney disease stages
was similar in both sexes. Nonetheless, the USRDS 2004 Annual Data Report reveals that
the incident rate of ESRD cases is higher for males with 409 per million population in
2002 compared to 276 for females.

Age
Chronic kidney disease is found in persons of all ages. The normal annual mean decline
in the GFR with age from the peak GFR (approximately 120 mL/min/1.73 m2) attained
during the third decade of life is approximately 1 mL/min/y/1.73 m2, reaching a mean
value of 70 mL/min/1.73 m2 at age 70 years. Nonetheless, in the United States, the
highest incidence rate of ESRD occurs in patients older than 65 years. As per NHANES
III data, the prevalence of chronic kidney disease was 37.8% among patients older than
70 years. Besides diabetes mellitus and hypertension, age is an independent major
predictor of chronic kidney disease. The geriatric population is the most rapidly growing
kidney failure (chronic kidney disease stage 5) population in the United States.
The biologic process of aging initiates various structural and functional changes within
the kidney. Renal mass progressively declines with advancing age. Glomerulosclerosis
leads to a decrease in renal weight. Histologic examination is notable for a decrease in
glomerular number of as much as 30-50% by age 70 years.
Ischemic obsolescence of cortical glomeruli is predominant, with relative sparing of the
renal medulla. Juxtamedullary glomeruli see a shunting of blood from the afferent to
efferent arterioles, resulting in redistribution of blood flow favoring the renal medulla.
These anatomical and functional changes in renal vasculature appear to contribute to an
age-related decrease in renal blood flow. Renal hemodynamic measurements in aged
human and animals suggest that altered functional response of the renal vasculature may
be an underlying factor in diminished renal blood flow and increased filtration noted with
progressive renal aging. The vasodilatory response is blunted in the elderly when
compared to younger patients.
However, the vasoconstrictor response to intrarenal angiotensin is identical in both young
and older human subjects. A blunted vasodilatory capacity with appropriate
vasoconstrictor response may indicate that the aged kidney is in a state of vasodilatation
to compensate for the underlying sclerotic damage.
Given the histologic evidence for nephronal senescence with age, a decline in the GFR is
expected. However, a wide variation in the rate of decline in the GFR is reported because
of measurement methods, race, gender, genetic variance, and other risk factors for renal
dysfunction. Because of these anatomical and physiological changes, elderly patients
with chronic kidney disease may behave differently, in terms of progression and response
to pharmacological treatment, than younger patients.
Therefore, a serum creatinine value of 1.2 mg/dL in a 70-kg, 25-year-old man versus a
70-kg, 80-year-old man represents an eGFR of 74 mL/min/1.73m2 and 58
mL/min/1.73m2, respectively. What can appear as only mild renal impairment in a 70-kg,
80-year-old man with a pathologically elevated serum creatinine of 2 mg/dL actually

represents severe renal impairment when the eGFR is calculated to be 32 mL/min/1.73m2.

Therefore, an eGFR must be determined simply by using the Modification of Diet in
Renal Disease (MDRD) equation (see Other Tests) in elderly people so that appropriate
drug dosing adjustments can be made and nephrotoxins can be avoided in patients who
have more extensive chronic kidney disease than would be suggested by the serum
creatinine value alone.

Untuk bab IV buka

http://emedicine.medscape.com/article/777845overview
For acute renal failure
http://emedicine.medscape.com/article/243492overview
ACUTE REINAL FAILURE

Background
Acute renal failure (ARF), or acute kidney injury (AKI), as it is now referred to in the
literature, is defined as an abrupt or rapid decline in renal filtration function. This
condition is usually marked by a rise in serum creatinine concentration or by azotemia (a
rise in blood urea nitrogen [BUN] concentration).[1] (See Etiology and Prognosis.)
However, immediately after a kidney injury, BUN or creatinine levels may be normal,
and the only sign of a kidney injury may be decreased urine production. (See History.)
A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim)
that inhibit the kidneys tubular secretion. A rise in the BUN level can occur without renal
injury, resulting instead from such sources as GI or mucosal bleeding, steroid use, or
protein loading, so a careful inventory must be taken before determining if a kidney
injury is present.

Categories of AKI
AKI may be classified into 3 general categories, as follows:

Prerenal - as an adaptive response to severe volume depletion and hypotension,

with structurally intact nephrons

Intrinsic - in response to cytotoxic, ischemic, or inflammatory insults to the

kidney, with structural and functional damage
Postrenal - from obstruction to the passage of urine

While this classification is useful in establishing a differential diagnosis, many

pathophysiologic features are shared among the different categories. (See Etiology.)

Oliguric and nonoliguric patients with AKI

Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in
creatinine levels, and may have qualitative differences in urine solute concentrations and
cellular content. (Approximately 50-60% of all causes of AKI are nonoliguric.)
This lack of a uniform clinical presentation reflects the variable nature of the injury.
Classifying AKI as oliguric or nonoliguric based on daily urine excretion has prognostic
value. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse
prognosis, except in prerenal failure.
Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, suggests
bilateral obstruction or catastrophic injury to both kidneys. Stratification of renal failure
along these lines helps in decision-making (eg, timing of dialysis) and can be an
important criterion for patient response to therapy.

Etiology
The driving force for glomerular filtration is the pressure gradient from the glomerulus to
the Bowman space. Glomerular pressure is primarily dependent on renal blood flow
(RBF) and is controlled by combined resistances of renal afferent and efferent arterioles.
Regardless of the cause of acute kidney injury (AKI), reductions in RBF represent a
common pathologic pathway for decreasing GFR. The etiology of AKI consists of 3 main
mechanisms.

Prerenal failure - Defined by conditions with normal tubular and glomerular

function; GFR is depressed by compromised renal perfusion
Intrinsic renal failure - Includes diseases of the kidney itself, predominantly
affecting the glomerulus or tubule, which are associated with release of renal
afferent vasoconstrictors; ischemic renal injury is the most common cause of
intrinsic renal failure.
Postobstructive renal failure - Initially causes an increase in tubular pressure,
decreasing the filtration driving force; this pressure gradient soon equalizes, and
maintenance of a depressed GFR is then dependent on renal efferent
vasoconstriction

Patients with chronic renal failure may also present with superimposed AKI from any of
the aforementioned etiologies.

Depressed RBF eventually leads to ischemia and cell death. This may happen before
frank systemic hypotension is present and is referred to as normotensive ischemic AKI.
The initial ischemic insult triggers a cascade of events that includes production of oxygen
free radicals, cytokines and enzymes, endothelial activation and leukocyte adhesion,
activation of coagulation, and initiation of apoptosis. These events continue to cause cell
injury even after restoration of RBF.
Tubular cellular damage results in disruption of tight junctions between cells, allowing
back leak of glomerular filtrate and further depressing effective GFR. In addition, dying
cells slough off into the tubules, forming obstructing casts, which further decrease GFR
and lead to oliguria.
During this period of depressed RBF, the kidneys are particularly vulnerable to further
insults. This is when iatrogenic renal injury is most common. The following are common
iatrogenic combinations:

Preexisting renal disease (elderly, diabetic patients, jaundiced patients) with

radiocontrast agents, aminoglycosides, atheroembolism, or cardiovascular surgery
Angiotensin-converting enzyme (ACE) inhibitors with diuretics, small- or largevessel renal arterial disease
Nonsteroidal anti-inflammatory drugs (NSAIDs) with congestive heart failure
(CHF), hypertension (HTN), or renal artery stenosis
Hypovolemia with aminoglycosides, amphotericin, heme pigments, or radiologic
contrast agents

Restoration of renal blood flow and associated complications

Recovery from AKI is first dependent upon restoration of RBF. Early RBF normalization
predicts better prognosis for recovery of renal function. In prerenal failure, restoration of
circulating blood volume is usually sufficient. Rapid relief of urinary obstruction in
postrenal failure results in a prompt decrease of vasoconstriction. With intrinsic renal
failure, removal of tubular toxins and initiation of therapy for glomerular diseases
decreases renal afferent vasoconstriction.
Once RBF is restored, the remaining functional nephrons increase their filtration and
eventually hypertrophy. GFR recovery is dependent upon the size of this remnant
nephron pool. If the number of remaining nephrons is below some critical value,
continued hyperfiltration results in progressive glomerular sclerosis, eventually leading to
increased nephron loss. A vicious cycle ensues; continued nephron loss causes more
hyperfiltration until complete renal failure results. This has been termed the
hyperfiltration theory of renal failure and explains the scenario in which progressive renal
failure is frequently observed after apparent recovery from AKI.

Incidence in the United States

Approximately 1% of patients admitted to hospitals have acute kidney injury (AKI) at the
time of admission. The estimated incidence rate of AKI is 2-5% during hospitalization.

AKI develops within 30 days postoperatively in approximately 1% of general surgery

cases[3] ; it develops in up to 67% of intensive care unit (ICU) patients.[4] Approximately
95% of consultations with nephrologists are related to AKI.
Feest and colleagues calculated that the appropriate nephrologist referral rate is
approximately 70 cases per million population.[5]

History
A detailed and accurate history is crucial to the diagnosis of the type of acute kidney
injury (AKI) that a patient has and to determining the diseases subsequent treatment.
Distinguishing AKI from chronic renal failure is important, yet making the distinction
can be difficult. A history of chronic symptomsfatigue, weight loss, anorexia, nocturia,
and pruritussuggests chronic renal failure.
Take note of the following findings during the physical examination:

Hypotension
Volume contraction
Congestive heart failure
Nephrotoxic drug ingestion
History of trauma or unaccustomed exertion
Blood loss or transfusions
Evidence of connective tissue disorders or autoimmune diseases
Exposure to toxic substances, such as ethyl alcohol or ethylene glycol
Exposure to mercury vapors, lead, cadmium, or other heavy metals, which can be
encountered in welders and miners

People with the following comorbid conditions are at a higher risk for developing AKI:

Hypertension
Congestive cardiac failure
Diabetes
Multiple myeloma
Chronic infection
Myeloproliferative disorder

Urine output history can be useful. Oliguria generally favors AKI. Abrupt anuria suggests
acute urinary obstruction, acute and severe glomerulonephritis, or embolic renal artery
occlusion. A gradually diminishing urine output may indicate a urethral stricture or
bladder outlet obstruction due to prostate enlargement.
Because of a decrease in functioning nephrons, even a trivial nephrotoxic insult may
cause AKI to be superimposed on chronic renal insufficiency.

Acute kidney injury (AKI) has a long differential diagnosis. History can help classify the
pathophysiology of AKI as prerenal, intrinsic renal, or postrenal failure, and it may
suggest some specific etiologies.

Prerenal failure
Patients commonly present with symptoms related to hypovolemia, including thirst,
decreased urine output, dizziness, and orthostatic hypotension.
Elders with vague mental status change are commonly found to have prerenal or
normotensive ischemic AKI.
Ask about volume loss from vomiting, diarrhea, sweating, polyuria, or hemorrhage.
Patients with advanced cardiac failure leading to depressed renal perfusion may present
with orthopnea and paroxysmal nocturnal dyspnea.
Insensible fluid losses can result in severe hypovolemia in patients with restricted fluid
access and should be suspected in elderly patients and in comatose or sedated patients.

Intrinsic renal failure

Patients can be divided into those with glomerular etiologies and those with tubular
etiologies of AKI.
Nephritic syndrome of hematuria, edema, and HTN indicates a glomerular etiology of
AKI. Query about prior throat or skin infections.
ATN should be suspected in any patient presenting after a period of hypotension
secondary to cardiac arrest, hemorrhage, sepsis, drug overdose, or surgery.
A careful search for exposure to nephrotoxins should include a detailed list of all current
medications and any recent radiologic examinations (ie, exposure to radiologic contrast
agents).
Pigment-induced AKI should be suspected in patients with possible rhabdomyolysis
(muscular pain, recent coma, seizure, intoxication, excessive exercise, limb ischemia) or
hemolysis (recent blood transfusion).
Allergic interstitial nephritis should be suspected with fevers, rash, arthralgias, and
exposure to certain medications, including NSAIDs and antibiotics.

Postrenal failure
Postrenal failure usually occurs in older men with prostatic obstruction and symptoms of
urgency, frequency, and hesitancy. Patients may present with asymptomatic, high-grade
urinary obstruction because of the chronicity of their symptoms.

A history of prior gynecologic surgery or abdominopelvic malignancy often can be

helpful in providing clues to the level of obstruction.
Flank pain and hematuria should raise a concern about renal calculi or papillary necrosis
as the source of urinary obstruction.
Use of acyclovir, methotrexate, triamterene, indinavir, or sulfonamides implies the
possibility of tubular obstruction by crystals of these medications.