Post Graduate Studies Faculty – Master of Emergency Nursing

Course Name: Advanced Pathophysiology.

Acute Kidney Injury

Prerenal, Intrarenal and Postrenal causes of Renal Failure.

Designed By: Ashraf Z. Qotmosh

Instructor: Dr Ahmed Soboh.

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Overview ................................................................................................................ 3

Definition .............................................................................................................. 3

Background ........................................................................................................ 3-4

Epidemilogy ........................................................................................................... 5

Etiology ............................................................................................................. …5-6

Pathopysiology .................................................................................................... 6-7

Maifestations ......................................................................................................... 8

Risk Factors ........................................................................................................... 9

Diagnosis ........................................................................................................... 9-10

Managment&Treatment ................................................................................ 10-11

Prognosis ............................................................................................................. 11

Complication ....................................................................................................... 12

Preventions .................................................................................................... 12-13

References ..................................................................................................... 13-14

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Overview
Renal failure is a condition in which the kidneys fail to remove metabolic end products from the blood
and regulate the fluid, electrolyte, and pH balance of the extracellular fluids. The underlying cause may
be renal disease, systemic disease, or urologic defects of nonrenal origin.
Renal failure can occur as an acute or a chronic disorder. Acute renal injury is abrupt in onset and often
is reversible if recognized early and treated appropriately. In contrast, chronic kidney disease is the end
result of irreparable damage to the kidneys. It develops slowly, usually over the course of a number of
years. In fact, 80% of the nephrons need to be nonfunctioning before the symptoms of chronic kidney
disease are manifested. Approximately 26 million American adults, or 1 in 9 adults, have some form of
renal disease.[1]

Definition
Acute renal injury or also termed acute kidney injury (AKI) represents a rapid decline in kidney function
sufficient to increase blood levels of nitrogenous wastes and impair fluid and electrolyte balance.[1]
Unlike chronic kidney disease (CKD) and failure, acute renal injury is potentially reversible if the
precipitating factors can be corrected or removed before permanent kidney damage has occurred.
Acute renal injury is a common threat to seriously ill people in intensive care units, with a mortality rate
ranging from 40% to 90% [2,3]. Although treatment methods such as dialysis and renal replacement
therapies are effective in correcting life-threatening fluid and electrolyte disorders, the mortality rate
from acute renal failure has not improved substantially over the last few decades.[4] This probably is
because acute renal injury is seen more often in older adults than before, and because it frequently is
superimposed on other life-threatening conditions, such as trauma, shock, and sepsis and
comorbidities such as cardiovascular disease, diabetes, and respiratory disease.[4] The most common
indicator of AKI is azotemia, an accumulation of nitrogenous wastes (urea nitrogen, uric acid, and
creatinine) in the blood and a decrease in the glomerular filtration rate (GFR).

Background
Acute Kidney injury can be caused by several types of conditions, including a decrease in blood flow
without ischemic injury; ischemic, toxic, or obstructive tubular injury; and obstruction of urinary tract
outflow. The etiology of AKI consists of 3 main mechanisms: prerenal, intrinsic, and obstructive
(postrenal). [2] Collectively, prerenal and intrarenal causes account for 80% to 95% of acute renal failure
cases.[3]

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 I. Prerenal Failure
Prerenal failure, the most common form of acute renal failure, is characterized by a marked decrease in
renal blood flow. It is reversible if the cause of the decreased renal blood flow can be identified and
corrected before kidney damage occurs. Causes of prerenal failure include profound depletion of
vascular volume (e.g., hemorrhage, loss of extracellular fluid volume), impaired perfusion due to heart
failure and cardiogenic shock, and decreased vascular filling because of increased vascular capacity
(e.g., anaphylaxis or sepsis). Older adults are particularly at risk because of the predisposition to
hypovolemia and their high prevalence of renal vascular disorders.

II. Intrarenal Renal Failure (Acute Kidney Injury)

Intrarenal renal failure or acute kidney injury, as it is now more commonly known, results from
conditions that cause damage to structures within the kidney. The most frequent etiology of intrarenal
acute renal failure causes damage to the parenchyma in the glomeruli, vessels, tubules, or
interstitium.[6] The major causes of intrarenal failure are ischemia associated with prerenal failure, toxic
insult to the tubular structures of the nephron, and intratubular obstruction.
Acute glomerulonephritis and acute pyelonephritis also are intrarenal causes of acute renal failure. The
decreased glomerular filtration and epithelial injury are due to many causes such as intrarenal
vasoconstriction, decreased hydrostatic pressure in the glomeruli, changes in arterial tone by
tubuloglomerular feedback, decreased capillary permeability in the glomeruli, increased tubular
hydrostatic pressure secondary to obstruction, and backflow of glomerular filtrate into the
interstitium.[6] Injury to the tubular structures of the nephron is the most common cause and often is
ischemic or toxic in origin.

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III. Postrenal Failure
Postrenal failure results from obstruction of urine outflow from the kidneys.

Epidemiology
In the United States, approximately 1% of patients admitted to hospitals have AKI at the time of
admission. The estimated incidence rate of AKI during hospitalization is 2-5%. AKI develops within 30
days postoperatively in approximately 1% of general surgery cases and arises in more than 50% of
intensive care unit (ICU) patients. [10, 11] In recipients of solitary kidney transplants, 21% developed
AKI within the first 6 months after transplantation. [12]
Harding et al calculated that in the United States from 2000 to 2015, hospitalization rates for dialysis-
requiring AKI in adults increased considerably while mortality decreased. In adults with diabetes, rates
increased from 26.4 to 41.1 per 100,000 population, with relative increases greater in younger versus
older adults. In adults without diabetes, rates increased from 4.8 to 8.7 per 100,000 population
between 2000 and 2009, and then plateaued. Mortality declined significantly in patients both with and
without diabetes. [13]
In a prospective national cohort study in Wales that used an electronic AKI alert (a centralized
laboratory system that automatically compares measured creatinine values in an individual patient with
previous results to generate alerts), the incidence of AKI was 577 per 100,000 population. Community-
acquired AKI accounted for 49.3% of all incident episodes, and 42% occurred in the context of
preexisting chronic kidney disease. The 90-day mortality rate was 25.6%, and 23.7% of episodes
progressed to a higher AKI stage. [14]
In a Canadian study of severely ill children admitted to pediatric intensive care units, 30.3% developed
AKI and 12.2% developed severe AKI. The incidence rate for critical illness–associated AKI was 34 per
100,000 children-year, and the rate of severe AKI was 14 per 100,000 children-year. Severe AKI was
more common in boys (incidence rate ratio, 1.55) and in infants younger than 1 year old (incidence rate
ratio, 14.77). The AKI-associated mortality rate was 2.3 per 100,000 children-year. [15]
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. [16]

Etiology
I. Prerenal Failure Causes (Etiology)
Hypovolemia;
✓ Hemorrhage.
✓ Dehydration.
✓ Excessive loss of gastrointestinal tract fluids.
✓ Excessive loss of fluid due to burn injury.
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 Decreased vascular filling;
✓ Anaphylactic shock
✓ Septic shock
Heart failure and cardiogenic shock.
Decreased renal perfusion due to sepsis, vasoactive mediators, drugs, diagnostic agents.
II. Intrarenal Failure Causes (etiology)
Acute tubular necrosis/acute renal injury
✓ Prolonged renal ischemia.
✓ Exposure to nephrotoxic drugs, heavy metals, and organic solvents.
Intratubular obstruction resulting from hemoglobinuria, myoglobinuria, myeloma light
chains, or uric acid casts.
Acute renal disease (acute glomerulonephritis, pyelonephritis)

III. Causes of Postrenal Failure (etiology)

Bilateral ureteral obstruction.
Bladder outlet obstruction.

Pathophysiology
I. Prerenal Failure
Certain medications, vasoactive mediators, and testing methods can cause glomerular
hypoperfusion and prerenal failure by stimulating severe intrarenal vasoconstriction. Examples
include endotoxins, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine (an
immunosuppressive medication used to prevent transplant rejection), and radiocontrast agents
like those used for cardiac catheterization.[2] Furthermore, a number of widely prescribed
medication classes have the potential to impede renal adaptive mechanisms, thereby
transforming compensated renal hypoperfusion into prerenal failure.
Normally, the kidneys receive 20% to 25%% of the cardiac output.[5] This large blood supply is
required for the glomeruli to remove metabolic wastes and regulate body fluids and electrolytes.
Fortunately, the normal kidney can tolerate relatively large reductions in blood flow before renal
damage occurs. As renal blood flow is reduced, the GFR decreases, the amount of sodium and
other substances that are filtered by the glomeruli is reduced, and the need for energy-
dependent mechanisms to reabsorb these substances is reduced.[5]

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce
the effects of renin on renal blood flow; when combined with diuretics, they may cause prerenal
failure in persons with decreased blood flow due to large-vessel or small vessel kidney disease.
II. Intrarenal Failure
Intrarenal causes of AKI can be further subdivided into acute tubular necrosis (ATN) which is
the term used to designate AKI resulting from damage to the tubules. It is the most common

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 type of intrarenal kidney injury. AKI from glomerular damage occurs in severe cases of acute
glomerulonephritis (GN). AKI from vascular damage occurs because injury to intra-renal vessels
decreases renal perfusion and diminishes GFR and finally acute interstitial nephritis occurs due
to an allergic reaction to a variety medication or an infection.

This acute injury can be caused by a variety of conditions, including acute tubular damage due
to ischemia, sepsis, nephrotoxic effects of drugs, tubular obstruction, and toxins from a
massive infection.[2] Tubular epithelial cells are particularly sensitive to ischemia and also are
vulnerable to toxins. The tubular injury that occurs frequently is reversible.

o Ischemic ATN or acute tubular injury occurs most frequently in persons who have extensive
surgery, severe hypovolemia, or overwhelming sepsis, trauma, or burns. Sepsis produces
ischemia by provoking a combination of systemic vasodilation and intrarenal
hypoperfusion. In addition, sepsis results in the generation of toxins that sensitize renal
tubular cells to the damaging effects of ischemia. ATN complicating trauma and burns
frequently is multifactorial in origin, resulting from the combined effects of hypovolemia,
myoglobinuria, and other toxins released from damaged tissue.
o Nephrotoxic ATN or acute tubular injury complicates the administration of or exposure to
many structurally diverse drugs and other nephrotoxic agents. These agents cause tubular
injury by inducing varying combinations of renal vasoconstriction, direct tubular damage, or
intratubular obstruction.

Pharmacologic agents that are directly toxic to the renal tubule include antimicrobials such as
aminoglycosides (e.g., vancomycin, gentamicin), Radiocontrast media–induced nephrotoxicity is
thought to result from direct tubular toxicity and renal ischemia. The risk for renal damage caused
by radiocontrast media is greatest in older adults and those with preexisting kidney disease,
volume depletion, diabetes mellitus, and recent exposure to other nephrotoxic agents.[7]
The course of ATN or acute tubular injury can be divided into three phases:
I. Initiating phase
which lasts hours or days, is the time from the onset of the precipitating event (e.g., ischemic phase
of prerenal failure or toxin exposure) until tubular injury occurs.[9]
II. The Maintenance Phase
Characterized by a marked decrease in the GFR, causing sudden retention of endogenous metabolites,
such as urea, potassium, sulfate, and creatinine, that normally are cleared by the kidneys. The urine
output usually is lowest at this point. Fluid retention gives rise to edema, water intoxication, and
pulmonary congestion.

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 III. The Recovery Phase
The period during which repair of renal tissue takes place. Its onset usually is heralded by a gradual
increase in urine output and a fall in serum creatinine, indicating that the nephrons have recovered to
the point at which urine excretion is possible.

III. Postrenal Failure

The obstruction can occur in the ureter (i.e., calculi and strictures), bladder (i.e., tumors or
neurogenic bladder), or urethra (i.e., prostatic hyperplasia).
Due to the increased urine not being able to be excreted due to the obstruction, retrograde
pressure occurs throughout the tubules and nephrons, which ultimately damages the
nephrons.[2]
Prostatic hyperplasia is the most common underlying problem. Because both ureters must be
occluded to produce renal failure, obstruction of the bladder rarely causes acute renal failure
unless one of the kidneys already is damaged or a person has only one kidney.

Manifestations
Prerenal Failure
Prerenal failure is manifested by a sharp decrease in urine output and a disproportionate elevation of
blood urea nitrogen (BUN) in relation to serum creatinine levels. The kidney normally responds to a
decrease in the GFR with a decrease in urine output. Thus, an early sign of prerenal failure is a sharp
decrease in urine output.
A low fractional excretion of sodium (<1%) suggests that oliguria is due to decreased renal perfusion
and that the nephrons are responding appropriately by decreasing the excretion of filtered sodium in
an attempt to preserve vascular volume.[2]
BUN levels also depend on the GFR. A low GFR allows more time for small particles such as urea to be
reabsorbed into the blood. Creatinine, which is larger and non-diffusible, remains in the tubular fluid,
and the total amount of creatinine that is filtered, although small, is excreted in the urine.
Consequently, there also is a disproportionate elevation in the ratio of BUN to serum creatinine, from a
normal value of 10:1 to a ratio greater than 15:1 to 20:1. [2]
Intrarenal Failure
Patients can be divided into those with glomerular etiologies and those with tubular etiologies of AKI.
Nephritic syndrome of hematuria, edema, and hypertension indicates a glomerular etiology for AKI.
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.

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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. Flank pain and hematuria should raise concern about
renal calculi or papillary necrosis as the source of urinary obstruction. Use of acyclovir, methotrexate,
triamterene, indinavir, or sulfonamides implies the possibility that crystals of these medications have
caused tubular obstruction.

Risk Factors
People with the following comorbid conditions are at a high risk for developing AKI:
• Hypertension • Multiple myeloma
• Chronic heart failure • Chronic infection
• Diabetes • Myeloproliferative disorder
• Liver disease • Connective tissue disorders
• Obesity • Autoimmune diseases
Diagnosis
Given the high morbidity and mortality rates associated with acute renal failure, attention should be
focused on prevention and early diagnosis. For decades, the standard tests for assessing renal function
have been blood urea nitrogen (BUN), serum creatinine, GFR, and urine output measurement. But
recent research shows BUN and creatinine tests are inadequate and don’t reflect real-time kidney
function.
Careful observation of urine output is essential for people at risk for development of acute renal
failure.
Urine tests that measure urine osmolality, urinary sodium concentration, and fractional
excretion of sodium help differentiate prerenal azotemia. Further diagnostic information that can
be obtained from the urinalysis includes evidence of proteinuria, hemoglobinuria, and casts or
crystals in the urine.
Blood tests for BUN and creatinine provide information regarding the ability to remove
nitrogenous wastes from the blood.
GFR. This biomarker is reflected directly in urine output. Normal GFR depends on cardiac
output. Decreased cardiac output stemming from reduced blood volume or BP affects GFR
immediately, giving bedside clinicians more timely information on kidney perfusion. Also, GFR is
simple to monitor if the patient has an indwelling urinary catheter. It’s one of the best real-time
indicators of current kidney function.

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 Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the
urinary collecting system.
Doppler scans are useful for detecting the presence and nature of renal blood flow. Because
renal blood flow is reduced in prerenal and intrarenal AKI, findings are of little use in the
diagnosis of AKI.
A kidney biopsy can be useful in identifying intrarenal causes of AKI and can be justified if the
results may change management (eg, initiation of immunosuppressive medications).

New biomarkers for assessing AKI earlier than the conventional parameters:
Interleukin (IL)-18 is produced in the proximal tubule after AKI and is an inflammatory
cytokine.[4]
Neutrophil gelatinin– associated lipocalin (NGAL) is normally present in several organs including
the kidneys.[15] NGAL is measured in the blood and urine, and increased levels have been found
to be predictive of graft dysfunction in renal transplants.[17]
Cystatin C. Freely filtered and reabsorbed in the proximal tubule, cystatin C is detected in both
the urine and serum. Elevated serum levels have been found to be early AKI predictors. Cystatin
C also independently predicts increased mortality.
Tissue inhibitor metalloproteinase-2 (TIMP-2). This biomarker appears in the urine within 12
hours after renal tubular cells are injured from ischemia or sepsis. In one study, urinary TIMP-2
testing showed certain patients had seven times the risk of developing AKI

Management and Treatment

Maintenance of volume homeostasis and correction of biochemical abnormalities remain the
primary goals of treatment and may include the following measures:
• Correction of fluid overload with furosemide.
• Correction of severe acidosis with bicarbonate administration, which can be important as a
bridge to dialysis.
• Correction of hyperkalemia.
• Correction of hematologic abnormalities (eg, anemia, uremic platelet dysfunction) with
measures such as transfusions and administration of desmopressin or estrogens.
A major concern in the treatment of acute renal failure is identifying and correcting the cause
(e.g., improving renal perfusion, discontinuing nephrotoxic drugs).
Many cases overlap between prerenal and ATN types of AKI. [20,21] The best way to determine
if the AKI is prerenal or not is a fluid challenge. If there is no contraindication, all patients with
acute renal dysfunction should receive a fluid challenge. This requires close monitoring of urine
output and renal function. If the renal function improves with fluid, this indicates prerenal AKI.
Acute tubular necrosis and other intrarenal causes are often slow to recover and can take weeks
to months for complete recovery of renal function. Diuretics may be required during the oliguric

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 phase of ATN if significant volume overload develops. It is also important to avoid further kidney
insults, such as nephrotoxic drugs. In addition, many medications must be renally adjusted once
a patient develops AKI. Dietary ingestion of potassium and phosphorus should also be
monitored.If hyperkalemia develops, it needs to be managed expeditiously. Approaches to
lower potassium in the body.
Some AKI patients tend to develop volume overload, which should be corrected as early as possible to
avoid pulmonary and cardiac complications.
In some cases, short-term renal replacement therapy is needed for AKI until the kidney function
recovers. Some indications for RRT are severe and nonresponsive hyperkalemia, uremic pericarditis,
and pulmonary edema. This is seen especially in the oliguric phase of acute tubular necrosis, where the
patient is prone to develop multiple electrolyte and acid-base abnormalities as well as fluid
overload.[22] Dialysis in this setting is usually performed through a temporary venous catheter when
required. Continuous renal replacement therapy can also be utilized in patients who cannot tolerate
hemodialysis due to hypotension. It is a much slower, continuous type of dialysis. Correction of some of
the metabolic abnormalities, along with dialysis, may be required. Metabolic acidosis is one such
instance where systemic administration of citrate or bicarbonate is often required to maintain a
suitable blood pH. The requirement for renal replacement therapy should be reevaluated daily. Renal
replacement therapy is usually required for short periods, ranging from a few days to a few weeks;
however, some cases can take months to recover and may require intermittent RRT support.
Other treatments are directed at the etiology of the AKI. Examples include administering vasoactive
medications and colloids for the treatment of hepatorenal syndrome, cautious diuresis in cardiorenal
syndrome, immunosuppressive medication for various glomerulonephritis or vasculitis, or steroids for
AIN. Postrenal obstruction may need to be relieved operatively in certain situations. For example,
benign prostatic hypertrophy may require surgical intervention, and obstructive calculi may require
stenting and lithotripsy.

Prognosis
Most prerenal AKI cases recover completely with correction of the underlying insult if treated early;
however, the persistence of the underlying insult may lead to ATN, in which case the damage may not
be completely reversible. Another consideration is that although recovery from individual episodes may
be complete or partial, repeated AKI can lead to a cumulative worsening of renal function. Therefore, it
is essential to monitor these patients closely to normalize renal function or until a new baseline is
established. The in-hospital mortality rate for AKI is 40% to 50%, and the mortality for ICU patients is
more than 50%. Other prognostic factors include:
Older age Hypotension
Duration of illness Inotropic support
Fluid balance Multiorgan involvement
Diuretic use Sepsis
Oliguria Number of transfusions
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Over the long term, at least 12% to 15% of patients with AKI may require permanent dialysis. Mortality
is increased in patients with high APACHE III scores, advanced age, and persistent creatinine elevation.
[18, 19].

Complication
Several complications may associate AKI with mortality. Some of these complications are
directly associated with AKI and can easily be gauged (hyperkalemia, volume overload, metabolic
acidosis, hyponatremia); however, the effect of other complications on AKI-related mortality, such as
inflammation and infection, is more difficult to assess. The most common complications include
metabolic derangements such as:
1. Hyperkalemia can lead to arrhythmias and, if severe, is considered a medical emergency.
2. Metabolic acidosis may necessitate systemic administration of bicarbonate or citrate buffers.
3. Hyperphosphatemia can usually be prevented by decreasing dietary ingestion or using
phosphate binders.
4. Other adverse effects include pulmonary edema from volume overload and peripheral edema
from an inability to excrete body water. This is especially common in the oliguric phase of ATN.
It may necessitate the use of diuretics or renal replacement therapy.
The other organ-related complications include:
1. Cardiovascular: Heart failure secondary to fluid overload is attributable to oliguric AKI.
Arrhythmias can be secondary to acidosis and electrolyte abnormalities. Cardiac arrest can
result from metabolic derangements. Myocardial infarction and pericarditis are also rare
complications.
2. Gastrointestinal (GI): Nausea, vomiting, GI bleeding, and anorexia can be associated with
AKI. Amylase may be elevated with AKI, so the measurement of serum lipase should be used
to diagnose pancreatitis if clinical suspicion is present.
3. Neurologic: CNS-related signs of uremia include lethargy, somnolence, disturbed sleep-wake
cycle, and cognitive impairment.

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

Use of iodinated contrast agents should be minimized, particularly in at-risk groups (eg, older
patients and those with preexisting renal insufficiency, volume depletion, diabetes, or heart failure).

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If contrast agents are necessary, risk can be lowered by minimizing volume of the IV contrast agent,
using nonionic and low osmolal or iso-osmolal contrast agents, avoiding nonsteroidal anti-
inflammatory drugs, and pretreating with normal saline at 1 mL/kg/hour IV for 12 hours before the
test. Infusion of isotonic sodium bicarbonate before and after contrast administration has also been
used successfully instead of normal saline, especially in patients with concurrent metabolic acidosis.

N-acetylcysteine has been used to prevent contrast nephropathy in the past, but most recent studies
did not find improved outcomes, and it is not currently recommended for this indication.
Before cytolytic therapy is initiated in patients with certain neoplastic diseases (eg, lymphoma,
leukemia), treatment with allopurinol should be considered along with increasing urine flow by
increasing oral or IV fluids to reduce urate crystalluria. Making the urine more alkaline (by giving ora l
or IV sodium bicarbonate or acetazolamide) has been recommended by some but is controversial
because it may also induce urinary calcium phosphate precipitation and crystalluria, which may
worsen AKI.

References
[1] National Kidney Foundation. (2011). Chronic kidney disease. [Online]. Available:
http://www.kidney.org/kidneyDisease/. Retrieved July 21, 2011.
[2] Morton P. G., Fontaine D. (2009). Critical care nursing: A holistic approach (9th ed.). Philadelphia, PA:
Lippincott Williams & Wilkins.
[3] Ostermann M., Chang R. (2007). Acute kidney injury in the intensive care unit according to RIFLE.
Critical Care Medicine 35(8), 1837–1842
[4] Dirkes S. (2011). Acute kidney injury: Not just acute renal failure anymore? Critical Care Nurse 31(1),
37–49.
[5] Hall J. E. (2011). Guyton and Hall textbook of medical physiology (12th ed.). Philadelphia, PA:
Saunders.
[6] Rubin R., Strayer D. (2012). Rubin’s pathology: Clinicopathologic foundations of medicine (6th ed.).
Philadelphia, PA: Lippincott Williams & Wilkins.
[7] Tanagho E. A., McAninch J. W. (2008). Smith’s general urology (17th ed.). New York, NY: McGraw Hill.
[8] Linkermann A., Himmerkus N., Rolver L., et al. (2011). Renal tubular Fas ligand mediates fratricide in
cisplatin-induced acute kidney failure. Kidney International 79(2), 169–178.
[9] Yakin K. M. (2011). Acute kidney injury: An overview of pathophysiology and treatments. Nephrology
Nursing Journal 38(1), 13–19.

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[10] Kheterpal S et al, Development and validation of an acute kidney injury risk index for patients
undergoing general surgery: results from a national data set. The Journal of American Society of
Anesthesiologist. 2009 Mar;110(3):505-15.
[11] Ronco C, Bellomo R, Kellum JA , Acute Kidney Injury. 2019 Nov 23;394(10212):1949-1964.
[12] Jones A , Holmes J, Stephens M , Geen J, Williams J, Donovan K et al . Using electronic AKI alerts to
define the epidemiology of acute kidney injury in renal transplants. J Nephrol. 2021 Jun;34(3):829-838.
[13] Jessica L. Harding , Nilka R. Burrows, Meda E. Pavkov , Kai McKeever Bullard. US Trends in
Hospitalizations for Dialysis-Requiring Acute Kidney Injury in People With Versus Without Diabetes. Am
J Kidney Dis. 2020 Jun;75(6):897-907.
[14] Jennifer Holmes, Timothy Rainer, John Geen, Gethin Roberts, Kate May, Nick Wilson et al . Clin J Am
Soc Nephrol. 2016 Dec 7;11(12):2123-2131.
[15] Rashid Alobaidi, Catherine Morgan, Stuart L Goldstein, Sean M Bagshaw. Population-Based
Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Children. Pediatr Crit Care Med. 2020
Jan;21(1):82-91.
[16] T G Feest, C D Mistry, D S Grimes, N P Mallick. Incidence of advanced chronic renal failure and the
need for end stage renal replacement treatment. BMJ1990 Oct 20;301(6757):897-900.
[17] Parikh C. R., Devarjan P. New biomarkers for acute kidney injury. Critical Care Medicine 36(4
Suppl.), S159–S165.
[18] Huang ST, Ke TY, Chuang YW, Lin CL, Kao CH. Renal complications and subsequent mortality in acute
critically ill patients without pre-existing renal disease. CMAJ. 2018 Sep 10;190(36):E1070-E1080.
[19] Helgason D, Long TE, Helgadottir S, Palsson R, Sigurdsson GH, Gudbjartsson T, Indridason OS,
Gudmundsdottir IJ, Sigurdsson MI. Acute kidney injury following coronary angiography: a nationwide
study of incidence, risk factors and long-term outcomes. J Nephrol. 2018 Oct;31(5):721-730.
[20] Abdelsalam M, Elnagar SSE, Mohamed AH, Tawfik M, Sayed Ahmed N. Community Acquired Acute
Kidney Injury in Mansoura Nephrology Dialysis Unit: One Year Prospective Observational
Study. Nephron. 2018;140(3):185-193.
[21] Azzalini L, Vilca LM, Lombardo F, Poletti E, Laricchia A, Beneduce A, Maccagni D, Demir OM, Slavich
M, Giannini F, Carlino M, Margonato A, Cappelletti A, Colombo A. Incidence of contrast-induced acute
kidney injury in a large cohort of all-comers undergoing percutaneous coronary intervention:
Comparison of five contrast media. Int J Cardiol. 2018 Dec 15;273:69-73.
[22] Cahn A, Melzer-Cohen C, Pollack R, Chodick G, Shalev V. Acute renal outcomes with sodium-
glucose co-transporter-2 inhibitors: Real-world data analysis. Diabetes Obes Metab. 2019
Feb;21(2):340-348.

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