Acute kidney injury

Acute kidney injury (AKI), previously called acute renal failure (ARF),[1][2] is an abrupt loss of kidney function that develops within 7 days.[3]

Its causes are numerous. Generally it occurs because of damage to the kidney tissue caused by decreased kidney blood flow (kidney ischemia) from any cause (e.g., low blood pressure), exposure to substances harmful to the kidney, an inflammatory process in the kidney, or an obstruction of the urinary tract that impedes the flow of urine. AKI is diagnosed on the basis of characteristic laboratory findings, such as elevated blood urea nitrogen and creatinine, or inability of the kidneys to produce sufficient amounts of urine.

AKI may lead to a number of complications, including metabolic acidosis, high potassium levels, uremia, changes in body fluid balance, and effects on other organ systems, including death. People who have experienced AKI may have an increased risk of chronic kidney disease in the future. Management includes treatment of the underlying cause and supportive care, such as renal replacement therapy.

Acute kidney injury
SynonymsAcute renal failure (ARF)
Kidney – acute cortical necrosis
Pathologic kidney specimen showing marked pallor of the cortex, contrasting to the darker areas of surviving medullary tissue. The patient died with acute kidney injury.
SpecialtyNephrology, Urology

Signs and symptoms

The clinical picture is often dominated by the underlying cause.The symptoms of acute kidney injury result from the various disturbances of kidney function that are associated with the disease. Accumulation of urea and other nitrogen-containing substances in the bloodstream lead to a number of symptoms, such as fatigue, loss of appetite, headache, nausea and vomiting.[4] Marked increases in the potassium level can lead to abnormal heart rhythms, which can be severe and life-threatening.[5] Fluid balance is frequently affected, though blood pressure can be high, low or normal.[6]

Pain in the flanks may be encountered in some conditions (such as clotting of the kidneys' blood vessels or inflammation of the kidney); this is the result of stretching of the fibrous tissue capsule surrounding the kidney.[7] If the kidney injury is the result of dehydration, there may be thirst as well as evidence of fluid depletion on physical examination.[7] Physical examination may also provide other clues as to the underlying cause of the kidney problem, such as a rash in interstitial nephritis (or vasculitis) and a palpable bladder in obstructive nephropathy.[7]



Acute kidney injury is diagnosed on the basis of clinical history and laboratory data. A diagnosis is made when there is a rapid reduction in kidney function, as measured by serum creatinine, or based on a rapid reduction in urine output, termed oliguria (less than 400 mLs of urine per 24 hours).

Classic laboratory findings in AKI
Type UOsm UNa FeNa BUN/Cr
Prerenal >500 <10 <1% >20[8]
Intrinsic <350 >20 >2% <10-15[8]
Postrenal <350 >40 >4% >20[8]

AKI can be caused by systemic disease (such as a manifestation of an autoimmune disease, e.g. lupus nephritis), crush injury, contrast agents, some antibiotics, and more. AKI often occurs due to multiple processes. The most common cause is dehydration and sepsis combined with nephrotoxic drugs, especially following surgery or contrast agents.

The causes of acute kidney injury are commonly categorized into prerenal, intrinsic, and postrenal.

Acute kidney injury occurs in up to 30% of patients following cardiac surgery.[9]  Mortality increases by 60-80% in post-cardiopulmonary bypass patients who go on to require renal replacement therapy.  Preoperative creatinine greater than 1.2mg/dL, combined valve and bypass procedures, emergency surgery, and preoperative intraaortic balloon pump are risk factors most strongly correlated with post-cardiopulmonary bypass acute kidney injury.  Other well-known minor risk factors include: female gender, congestive heart failure, chronic obstructive pulmonary disease, insulin-requiring diabetes, and depressed left ventricular ejection fraction.[9]


Prerenal causes of AKI ("pre-renal azotemia") are those that decrease effective blood flow to the kidney and cause a decrease in the glomerular filtration rate (GFR). Both kidneys need to be affected as one kidney is still more than adequate for normal kidney function. Notable causes of prerenal AKI include low blood volume (e.g., dehydration), low blood pressure, heart failure (leading to cardiorenal syndrome), liver cirrhosis and local changes to the blood vessels supplying the kidney. The latter include renal artery stenosis, or the narrowing of the renal artery which supplies the kidney with blood, and renal vein thrombosis, which is the formation of a blood clot in the renal vein that drains blood from the kidney.


Intrinsic AKI refers to disease processes which directly damage the kidney itself. Intrinsic AKI can be due to one or more of the kidney's structures including the glomeruli, kidney tubules, or the interstitium. Common causes of each are glomerulonephritis, acute tubular necrosis (ATN), and acute interstitial nephritis (AIN), respectively. Other causes of intrinsic AKI are rhabdomyolysis and tumor lysis syndrome.[10] Certain medication classes such as calcineurin inhibitors (e.g., tacrolimus) can also directly damage the tubular cells of the kidney and result in a form of intrinsic AKI.


Postrenal AKI refers to acute kidney injury caused by disease states downstream of the kidney and most often occurs as a consequence of urinary tract obstruction. This may be related to benign prostatic hyperplasia, kidney stones, obstructed urinary catheter, bladder stones, or cancer of the bladder, ureters, or prostate.



Introduced by the KDIGO in 2012,[11] specific criteria exist for the diagnosis of AKI.

AKI can be diagnosed if any one of the following is present:

  • Increase in SCr by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or
  • Increase in SCr to ≥1.5 times baseline, which has occurred within the prior 7 days; or
  • Urine volume < 0.5 ml/kg/h for 6 hours.


The RIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in assessment of the severity of a person's acute kidney injury. The acronym RIFLE is used to define the spectrum of progressive kidney injury seen in AKI:[12][13]

Acute Renal Failure
Pathophysiology of acute kidney injury in the proximal renal tubule
  • Risk: 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours.
  • Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine output <0.5 mL/kg per hour for 12 hours
  • Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours
  • Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than four weeks
  • End-stage kidney disease: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than three months


The deterioration of kidney function may be signaled by a measurable decrease in urine output. Often, it is diagnosed on the basis of blood tests for substances normally eliminated by the kidney: urea and creatinine. Additionally, the ratio of BUN to creatinine is used to evaluate kidney injury. Both tests have their disadvantages. For instance, it takes about 24 hours for the creatinine level to rise, even if both kidneys have ceased to function. A number of alternative markers has been proposed (such as NGAL, KIM-1, IL18 and cystatin C), but none of them is currently established enough to replace creatinine as a marker of kidney function.[14]

Once the diagnosis of AKI is made, further testing is often required to determine the underlying cause. It is useful to perform a bladder scan or a post void residual to rule out urinary retention. In post void residual, a catheter is inserted into the urinary tract immediately after urinating to measure fluid still in the bladder. 50–100 ml suggests neurogenic bladder dysfunction.

These may include urine sediment analysis, renal ultrasound and/or kidney biopsy. Indications for kidney biopsy in the setting of AKI include the following:[15]

  1. Unexplained AKI, in a patient with two non-obstructed normal sized kidneys
  2. AKI in the presence of the nephritic syndrome
  3. Systemic disease associated with AKI
  4. Kidney transplant dysfunction

In medical imaging, the acute changes in the kidney are often examined with renal ultrasonography as the first-line modality, where CT scan and magnetic resonance imaging (MRI) are used for the follow-up examinations and when US fails to demonstrate abnormalities. In evaluation of the acute changes in the kidney, the echogenicity of the renal structures, the delineation of the kidney, the renal vascularity, kidney size and focal abnormalities are observed.[16] CT is preferred in renal traumas, but US is used for follow-up, especially in the patients suspected for the formation of urinomas. A CT scan of the abdomen will also demonstrate bladder distension or hydronephrosis. However, in AKI, the use of IV contrast is contraindicated as the contrast agent used is nephrotoxic.

Ultrasonography of acute pyelonephritis

Renal ultrasonograph of acute pyelonephritis with increased cortical echogenicity and blurred delineation of the upper pole.[16]

Ultrasonography of postoperative renal failure

Renal ultrasonograph in renal failure after surgery with increased cortical echogenicity and kidney size. Biopsy showed acute tubular necrosis.[16]

Ultrasonography of renal trauma with laceration

Renal ultrasonograph in renal trauma with laceration of the lower pole and subcapsular fluid collection below the kidney.[16]


The management of AKI hinges on identification and treatment of the underlying cause. The main objectives of initial management are to prevent cardiovascular collapse and death and to call for specialist advice from a nephrologist. In addition to treatment of the underlying disorder, management of AKI routinely includes the avoidance of substances that are toxic to the kidneys, called nephrotoxins. These include NSAIDs such as ibuprofen or naproxen, iodinated contrasts such as those used for CT scans, many antibiotics such as gentamicin, and a range of other substances.[17]

Monitoring of kidney function, by serial serum creatinine measurements and monitoring of urine output, is routinely performed. In the hospital, insertion of a urinary catheter helps monitor urine output and relieves possible bladder outlet obstruction, such as with an enlarged prostate.


In prerenal AKI without fluid overload, administration of intravenous fluids is typically the first step to improving kidney function. Volume status may be monitored with the use of a central venous catheter to avoid over- or under-replacement of fluid.

If low blood pressure persists despite providing a person with adequate amounts of intravenous fluid, medications that increase blood pressure (vasopressors) such as norepinephrine and in certain circumstances medications that improve the heart's ability to pump (known as inotropes) such as dobutamine may be given to improve blood flow to the kidney. While a useful vasopressor, there is no evidence to suggest that dopamine is of any specific benefit and may be harmful.[18]


The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to vasculitis or glomerulonephritis may respond to steroid medication, cyclophosphamide, and (in some cases) plasma exchange. Toxin-induced prerenal AKI often responds to discontinuation of the offending agent, such as ACE inhibitors, ARB antagonists, aminoglycosides, penicillins, NSAIDs, or paracetamol.[7]

The use of diuretics such as furosemide, is widespread and sometimes convenient in improving fluid overload. It is not associated with higher mortality (risk of death),[19] nor with any reduced mortality or length of intensive care unit or hospital stay.[20]


If the cause is obstruction of the urinary tract, relief of the obstruction (with a nephrostomy or urinary catheter) may be necessary.

Renal replacement therapy

Renal replacement therapy, such as with hemodialysis, may be instituted in some cases of AKI. Renal replacement therapy can be applied intermittently (IRRT) and continuously (CRRT). Study results regarding differences in outcomes between IRRT and CRRT are inconsistent. A systematic review of the literature in 2008 demonstrated no difference in outcomes between the use of intermittent hemodialysis and continuous venovenous hemofiltration (CVVH) (a type of continuous hemodialysis).[21] Among critically ill patients, intensive renal replacement therapy with CVVH does not appear to improve outcomes compared to less intensive intermittent hemodialysis.[17][22] However, other studies demonstrated that compared with IRRT, initiation of CRRT is associated with a lower likelihood of chronic dialysis.[23][24]


Metabolic acidosis, hyperkalemia, and pulmonary edema may require medical treatment with sodium bicarbonate, antihyperkalemic measures, and diuretics.

Lack of improvement with fluid resuscitation, therapy-resistant hyperkalemia, metabolic acidosis, or fluid overload may necessitate artificial support in the form of dialysis or hemofiltration.[5]



Mortality after AKI remains high. Overall it is 20%, 30% if the patient is referred to nephrology, 50% if dialyzed, and 70% if on ICU.

If AKI develops after major abdominal surgery (13.4% of all people who have undergone major abdominal surgery) the risk of death is markedly increased (over 12-fold).[25]

Kidney function

Depending on the cause, a proportion of patients (5–10%) will never regain full kidney function, thus entering end-stage kidney failure and requiring lifelong dialysis or a kidney transplant. Patients with AKI are more likely to die prematurely after being discharged from hospital, even if their kidney function has recovered.[2]

The risk of developing chronic kidney disease is increased (8.8-fold).[26]


New cases of AKI are unusual but not rare, affecting approximately 0.1% of the UK population per year (2000 ppm/year), 20x incidence of new ESKD. AKI requiring dialysis (10% of these) is rare (200 ppm/year), 2x incidence of new ESKD.[27]

There is an increased incidence of AKI in agricultural workers, particularly those paid by the piece. No other traditional risk factors, including age, BMI, diabetes, or hypertension, were associated with incident AKI. Agricultural workers are at increased risk for AKI because of occupational hazards such as dehydration and heat illness.[28]

Acute kidney injury is common among hospitalized patients. It affects some 3–7% of patients admitted to the hospital and approximately 25–30% of patients in the intensive care unit.[29]

Acute kidney injury was one of the most expensive conditions seen in U.S. hospitals in 2011, with an aggregated cost of nearly $4.7 billion for approximately 498,000 hospital stays.[30] This was a 346% increase in hospitalizations from 1997, when there were 98,000 acute kidney injury stays.[31] According to a review article of 2015, there has been an increase in cases of acute kidney injury in the last 20 years which cannot be explained solely by changes to the manner of reporting.[32]


Before the advancement of modern medicine, acute kidney injury was referred to as uremic poisoning while uremia was contamination of the blood with urine. Starting around 1847, uremia came to be used for reduced urine output, a condition now called oliguria, which was thought to be caused by the urine's mixing with the blood instead of being voided through the urethra.

Acute kidney injury due to acute tubular necrosis (ATN) was recognized in the 1940s in the United Kingdom, where crush injury victims during the London Blitz developed patchy necrosis of kidney tubules, leading to a sudden decrease in kidney function.[33] During the Korean and Vietnam wars, the incidence of AKI decreased due to better acute management and administration of intravenous fluids.[34]

See also


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  3. ^ Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007). "Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury". Critical Care (London, England). 11 (2): R31. doi:10.1186/cc5713. PMC 2206446. PMID 17331245. Archived from the original on 2010-10-30.
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  10. ^ Jim Cassidy; Donald Bissett; Roy A. J. Spence; Miranda Payne (1 January 2010). Oxford Handbook of Oncology. Oxford University Press. p. 706. ISBN 978-0-19-956313-5.
  11. ^ Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter.
  12. ^ Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004). "Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group". Crit Care. 8 (4): R204–12. doi:10.1186/cc2872. PMC 522841. PMID 15312219. Archived from the original on 2011-01-23.
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  16. ^ a b c d Content initially copied from: Hansen, Kristoffer; Nielsen, Michael; Ewertsen, Caroline (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics. 6 (1): 2. doi:10.3390/diagnostics6010002. ISSN 2075-4418. (CC-BY 4.0) Archived 2017-10-16 at the Wayback Machine
  17. ^ a b Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P (July 2008). "Intensity of renal support in critically ill patients with acute kidney injury". The New England Journal of Medicine. 359 (1): 7–20. doi:10.1056/NEJMoa0802639. PMC 2574780. PMID 18492867.
  18. ^ Holmes CL, Walley KR (2003). "Bad medicine: low-dose dopamine in the ICU". Chest. 123 (4): 1266–75. doi:10.1378/chest.123.4.1266. PMID 12684320.
  19. ^ Uchino S, Doig GS, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Nacedo E, Gibney N, Tolwani A, Ronco C, Kellum JA (2004). "Diuretics and mortality in acute renal failure". Crit. Care Med. 32 (8): 1669–77. doi:10.1097/01.CCM.0000132892.51063.2F. PMID 15286542.
  20. ^ Davis A, Gooch I (2006). "The use of loop diuretics in acute renal failure in critically ill patients to reduce mortality, maintain renal function, or avoid the requirements for renal support". Emergency Medicine Journal. 23 (7): 569–70. doi:10.1136/emj.2006.038513. PMC 2579558. PMID 16794108.
  21. ^ Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M (February 2008). "Renal replacement therapy in patients with acute renal failure: a systematic review". JAMA: the Journal of the American Medical Association. 299 (7): 793–805. doi:10.1001/jama.299.7.793. PMID 18285591.
  22. ^ Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S (October 2009). "Intensity of continuous renal-replacement therapy in critically ill patients". The New England Journal of Medicine. 361 (17): 1627–38. doi:10.1056/NEJMoa0902413. PMID 19846848.
  23. ^ Schoenfelder, T; Chen, X; Bless, HH (March 2017). "Effects of continuous and intermittent renal replacement therapies among adult patients with acute kidney injury". GMS Health Technol Assess. 13 (Doc01 (20170301)). Archived from the original on 8 August 2017. Retrieved 8 August 2017.
  24. ^ Schneider, AG; Bellomo, R; Bagshaw, SM; Glassford, NJ; Lo, S; Jun, M; Cass, A; Gallagher, M (June 2013). "Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis". Intensive care medicine. 39 (6): 987–97. doi:10.1007/s00134-013-2864-5. PMID 23443311.
  25. ^ O'Connor, M. E.; Kirwan, C. J.; Pearse, R. M.; Prowle, J. R. (24 November 2015). "Incidence and associations of acute kidney injury after major abdominal surgery". Intensive Care Medicine. 42 (4): 521–30. doi:10.1007/s00134-015-4157-7. PMID 26602784.
  26. ^ Coca, SG; Singanamala, S; Parikh, CR (March 2012). "Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis". Kidney International. 81 (5): 442–48. doi:10.1038/ki.2011.379. PMC 3788581. PMID 22113526.
  27. ^ "Renal Medicine: Acute Kidney Injury (AKI)". 2012-05-23. Archived from the original on 2013-08-08. Retrieved 2013-07-17.
  28. ^ Moyce, Sally, RN, BSN; Joseph, Jill, MD, PhD; Tancredi, Daniel, PhD; Mitchell, Diane, PhD; Schenker, Marc, MD, MPH (2016) "Cumulative Incidence of Acute Kidney Injury in California's Agricultural Workers" Journal of Environmental Medicine JOEM 58 Number 4, April 2016 391–97
  29. ^ Brenner and Rector's The Kidney. Philadelphia: Saunders. 2007. ISBN 1-4160-3110-3.
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  31. ^ Pfuntner A., Wier L.M., Stocks C. Most Frequent Conditions in U.S. Hospitals, 2011. HCUP Statistical Brief #162. September 2013. Agency for Healthcare Research and Quality, Rockville, MD. "Archived copy". Archived from the original on 2016-03-04. Retrieved 2016-02-09.CS1 maint: Archived copy as title (link)
  32. ^ Siew ED, Davenport A (2015). "The growth of acute kidney injury: a rising tide or just closer attention to detail?". Kidney International (Review). 87 (1): 46–61. doi:10.1038/ki.2014.293. PMC 4281297. PMID 25229340.
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External links

External resources
Acute tubular necrosis

Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI. Common causes of ATN include low blood pressure and use of nephrotoxic drugs. The presence of "muddy brown casts" of epithelial cells found in the urine during urinalysis is pathognomonic for ATN. Management relies on aggressive treatment of the factors that precipitated ATN (e.g. hydration and cessation of the offending drug). Because the tubular cells continually replace themselves, the overall prognosis for ATN is quite good if the underlying cause is corrected, and recovery is likely within 7 to 21 days.


Azotemia (azot, "nitrogen" + -emia, "blood condition") is a medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds) in the blood. It is largely related to insufficient or dysfunctional filtering of blood by the kidneys. It can lead to uremia and acute kidney injury (kidney failure) if not controlled.

BUN-to-creatinine ratio

In medicine, the BUN-to-creatinine ratio is the ratio of two serum laboratory values, the blood urea nitrogen (BUN) (mg/dL) and serum creatinine (Cr) (mg/dL). Outside the United States, particularly in Canada and Europe, the truncated term urea is used (though it is still the same blood chemical) and the units are different (mmol/L). The units of creatinine are also different (μmol/L), and this value is termed the urea-to-creatinine ratio. The ratio may be used to determine the cause of acute kidney injury or dehydration.

The principle behind this ratio is the fact that both urea (BUN) and creatinine are freely filtered by the glomerulus; however, urea reabsorbed by the tubules can be regulated (increased or decreased) whereas creatinine reabsorption remains the same (minimal reabsorption).

Contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is a form of kidney damage in which there has been recent exposure to medical imaging contrast material without another clear cause for the acute kidney injury. CIN is classically defined as a serum creatinine increase of at least 25% and/or an absolute increase in serum creatinine of 0.5 mg/dL after using iodine contrast agent without another clear cause for acute kidney injury, but other definitions have also been used.Despite extensive speculation, the actual occurrence of contrast-induced nephropathy has not been demonstrated in the literature. The mechanism of contrast-induced nephropathy is not entirely understood, but is thought to include direct damage from reactive oxygen species, contrast-induced increase in urine output, increased oxygen consumption, changes in dilation and narrowing of the blood vessels to the kidneys, and changes in urine viscosity.Analysis of observational studies has shown that radiocontrast use in CT scanning is not causally related to changes in kidney function. Given the increasing doubts about the contribution of radiocontrast to acute kidney injury, the American College of Radiology has proposed the name postcontrast acute kidney injury which does not imply a causal role, with CIN reserved for the rare cases where radiocontrast is likely to be causally related.

Creatine kinase

Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme (EC expressed by various tissues and cell types. CK catalyses the conversion of creatine and utilizes adenosine triphosphate (ATP) to create phosphocreatine (PCr) and adenosine diphosphate (ADP). This CK enzyme reaction is reversible and thus ATP can be generated from PCr and ADP.

In tissues and cells that consume ATP rapidly, especially skeletal muscle, but also brain, photoreceptor cells of the retina, hair cells of the inner ear, spermatozoa and smooth muscle, PCr serves as an energy reservoir for the rapid buffering and regeneration of ATP in situ, as well as for intracellular energy transport by the PCr shuttle or circuit. Thus creatine kinase is an important enzyme in such tissues.Clinically, creatine kinase is assayed in blood tests as a marker of damage of CK-rich tissue such as in myocardial infarction (heart attack), rhabdomyolysis (severe muscle breakdown), muscular dystrophy, autoimmune myositides, and acute kidney injury.

Crush injury

A crush injury is injury by an object that causes compression of the body. This form of injury is rare in normal civilian practice, but are common following a natural disaster. Other causes include industrial accidents, road traffic collisions, building collapse, accidents involving heavy plant, disaster relief or terrorist incidents.


In medicine, dialysis (from Greek διάλυσις, diàlysis, "dissolution"; from διά, dià, "through", and λύσις, lỳsis, "loosening or splitting") is the process of removing excess water, solutes, and toxins from the blood in people whose kidneys can no longer perform these functions naturally. This is referred to as renal replacement therapy.

Dialysis is used in patients with rapidly developing loss of kidney function, called acute kidney injury (previously called acute renal failure), or slowly worsening kidney function, called Stage 5 chronic kidney disease, (previously called chronic kidney failure and end-stage renal disease and end-stage kidney disease).

Dialysis is used as a temporary measure in either acute kidney injury or in those awaiting kidney transplant and as a permanent measure in those for whom a transplant is not indicated or not possible.In the United Kingdom and the United States, dialysis is paid for by the government for those who are eligible. The first successful dialysis was performed in 1943.

In research laboratories, dialysis technique can also be used to separate molecules based on their size. Additionally, it can be used to balance buffer between a sample and the solution "dialysis bath" or "dialysate" that the sample is in. For dialysis in a laboratory, a tubular semipermeable membrane made of cellulose acetate or nitrocellulose is used. Pore size is varied according to the size separation required with larger pore sizes allowing larger molecules to pass through the membrane. Solvents, ions and buffer can diffuse easily across the semipermeable membrane, but larger molecules are unable to pass through the pores. This can be used to purify proteins of interest from a complex mixture by removing smaller proteins and molecules.

Fluid replacement

Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous therapy, rectally such as with a Murphy drip, or by hypodermoclysis, the direct injection of fluid into the subcutaneous tissue. Fluids administered by the oral and hypodermic routes are absorbed more slowly than those given intravenously.

Grape and raisin toxicity in dogs

The consumption of grapes and raisins presents a potential health threat to dogs. Their toxicity to dogs can cause the animal to develop acute kidney injury (the sudden development of kidney failure) with anuria (a lack of urine production). The phenomenon was first identified by the Animal Poison Control Center (APCC), run by the American Society for the Prevention of Cruelty to Animals (ASPCA). Approximately 140 cases were seen by the APCC in the one year from April 2003 to April 2004, with 50 developing symptoms and seven dying.It is not clear that the observed cases of renal failure following ingestion are due to grapes only. Clinical findings suggest raisin and grape ingestion can be fatal, but the mechanism of toxicity is still considered unknown.


In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy which is used in the intensive care setting. It is usually used to treat acute kidney injury (AKI), but may be of benefit in multiple organ dysfunction syndrome or sepsis. During hemofiltration, a patient's blood is passed through a set of tubing (a filtration circuit) via a machine to a semipermeable membrane (the filter) where waste products and water (collectively called ultrafiltrate) are removed by convection. Replacement fluid is added and the blood is returned to the patient.

Inositol oxygenase

Inositol oxygenase, also commonly referred to as myo-inositol oxygenase (MIOX), is a non-heme di-iron enzyme that oxidizes myo-inositol to glucuronic acid. The enzyme employs a unique four-electron transfer at its Fe(II)/Fe(III) coordination sites and the reaction proceeds through the direct binding of myo-inositol followed by attack of the iron center by diatomic oxygen. This enzyme is part of the only known pathway for the catabolism of inositol in humans and is expressed primarily in the kidneys. Recent medical research regarding MIOX has focused on understanding its role in metabolic and kidney diseases such as diabetes, obesity and acute kidney injury. Industrially-focused engineering efforts are centered on improving MIOX activity in order to produce glucaric acid in heterologous hosts.

Ischemia-reperfusion injury of the appendicular musculoskeletal system

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Kidney disease

Kidney disease, or renal disease, also known as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

Chronic kidney disease causes the gradual loss of kidney function over time. Acute kidney disease is now termed acute kidney injury and is marked by the sudden reduction in kidney function over seven days. About one in eight Americans (as of 2007) suffer from chronic kidney disease.

Kidney failure

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys no longer function. It is divided into acute kidney failure (cases that develop rapidly) and chronic kidney failure (those that are long term). Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, or confusion. Complications of acute disease may include uremia, high blood potassium, or volume overload. Complications of chronic disease may include heart disease, high blood pressure, or anemia.Causes of acute kidney failure include low blood pressure, blockage of the urinary tract, certain medications, muscle breakdown, and hemolytic uremic syndrome. Causes of chronic kidney failure include diabetes, high blood pressure, nephrotic syndrome, and polycystic kidney disease. Diagnosis of acute disease is often based on a combination of factors such as decrease urine production or increased serum creatinine. Diagnosis of chronic disease is typically based on a glomerular filtration rate (GFR) of less than 15 or the need for renal replacement therapy. It is also equivalent to stage 5 chronic kidney disease.Treatment of acute disease typically depends on the underlying cause. Treatment of chronic disease may include hemodialysis, peritoneal dialysis, or a kidney transplant. Hemodialysis uses a machine to filter the blood outside the body. In peritoneal dialysis specific fluid is placed into the abdominal cavity and then drained, with this process being repeated multiple times per day. Kidney transplantation involves surgically placing a kidney from someone else and then taking immunosuppressant medication to prevent rejection. Other recommended measures from chronic disease include staying active and specific dietary changes.In the United States acute disease affects about 3 per 1,000 people a year. Chronic disease affects about 1 in 1,000 people with 3 per 10,000 people newly develop the condition each year. Acute disease is often reversible while chronic disease often is not. With appropriate treatment many with chronic disease can continue working.


Modimelanotide (INN) (code names AP-214, ABT-719, ZP-1480) is a melanocortinergic peptide drug derived from α-melanocyte-stimulating hormone (α-MSH) which was under development by, at different times, Action Pharma, Abbott Laboratories, AbbVie, and Zealand for the treatment of acute kidney injury. It acts as a non-selective melanocortin receptor agonist, with IC50 values of 2.9 nM, 1.9 nM, 3.7 nM, and 110 nM at the MC1, MC3, MC4, and MC5 receptors. Modimelanotide failed clinical trials for acute kidney injury despite showing efficacy in animal models, and development was not further pursued.


NephroCheck is a test that tries to determine the risk of some who is seriously sick developing acute kidney injury. Whether or not the test improves outcomes, however, is unclear as of 2016.NephroCheck tests for the presence of insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2) in the urine, which are associated with acute kidney injury. The laboratory test was developed by Astute Medical, in San Diego, California.


Onconephrology (from the Ancient Greek onkos (ὄγκος) meaning bulk, mass, or tumor, nephros (νεφρός) meaning kidney, and the suffix -logy (-λογία), meaning "study of") is a burgeoning new specialty in nephrology that deals with the study of kidney diseases in cancer patients.

A nephrologist who takes care of patients with cancer is called an Onconephrologist. This branch of nephrology encompasses both the hematologic and oncology based cancers and their treatment related complications that deal with the kidney. Unlike general nephrology, there are several aspects of onconephrology that are unique. Kidney failure from break down of cancer cells, usually after chemotherapy, is unique to onconephrology. The Syndrome of Inappropriate Anti Diuretic Hormone (SIADH) that causes low serum sodium concentration and first described in lung cancer patients is common in cancer patients. Kidney diseases that are unique to bone marrow transplant (aka Stem Cell Transplant or SCT) are frequently seen in cancer patients. Fluid, electrolytes and acid base disturbances are much more common and often severe in cancer patients, especially in those who receive chemotherapy. Several chemotherapeutic agents – for example cisplatin – are associated with acute and chronic kidney injuries. Newer agents such as anti Vascular Endothelial Growth Factor (anti VEGF) are also associated with similar injuries, as well as proteinuria, hypertension and thrombotic microangiopathy.The most common form of kidney disease in cancer patients is acute kidney injury (AKI) which can usually be due to volume depletion from vomiting and diarrhea that occur following chemotherapy or occasionally due to kidney toxicities of chemotherapeutic agents. Less frequently AKI can occur due to obstruction to urine flow from tumor or lymph node enlargement. Also, cancer cells by infiltrating the kidney or myeloma proteins by precipitating with in the tubules of the kidney can cause kidney injury.Cancer management has become comprehensive and multidisciplinary, and often an onconephrologist is included in major centers to address and advice on kidney problems in cancer patients.

Topics that are usually of interest to onco-nephrologists are:

1. Electrolyte disorders of malignancy

2. Secondary Glomerular diseases of malignancy

3. Cancer related renal complications

4. Chemotherapy related renal complications

5. Myeloma Nephrology

6. Amyloidosis Nephrology

7. Thrombotic Microangiopathy and all its causes and treatment strategies( HUS/TTP)

8. Bone marrow transplant related kidney diseases

9. Radiation Nephropathy

10. Tumor Lysis Syndrome

11. Acute Kidney injury in the hospitalized cancer patient.

12. The ethics of dialysis in the dying cancer patient

13. Dialysis and chemotherapy agents

14. Tumor invasion of the kidney

15. Obstructive renal disease

16. Chronic Kidney disease after chemotherapy induced AKI

17. Renal cell cancer

18. CKD following nephrectomy

Centers in the United States and other countries have started forming onconephrology-related patient approach. At Brigham and Women's hospital( Harvard University), the Urology, Nephrology and oncology teams that are involved in the care of the renal cell cancer patient have developed a center of onco-nephrology expertise. A similar approach as been taken at the Northwell Cancer institute kidney cancer section.

Two textbooks have been written on this topic. Onconephrology: cancer, chemotherapy and the kidney by Jhaveri and Salahudeen by Springer [1] and Cancer and the Kidney by Cohen by Oxford Univ Press [2]

In addition, the American Society of Nephrology formed the first ever Onconephrology Forum (ONF) under the leadership of Salahudeen and Bonventre focusing on onconephrology at national levels.The cancer and kidney international network( CKIN)[3] was created to allow for research collaboration in onconephrology and promote better patient care. In addition, there is now an official journal for CKIN called the Journal of Onconephrology(JON)[4]

Renal angina

Renal angina is a clinical methodology to risk stratify patients for the development of persistent and severe acute kidney injury (AKI). The composite of risk factors and early signs of injury for AKI, renal angina is used as a clinical adjunct to help optimize the use of novel AKI biomarker testing. The term angina from Latin (“infection of the throat”) and from the Greek ẚnkhone (“strangling”) are utilized in the context of AKI to denote the development of injury and the choking off of kidney function.

Unlike angina pectoris, commonly caused due to ischemia of the heart muscle secondary to coronary artery occlusion or vasospasm, renal angina carries no obvious physical symptomatology (i.e., flank tenderness, suprapubic tenderness, pain with voiding or micturition). Renal angina was derived as a conceptual framework to identify evolving AKI. Like acute coronary syndrome which precedes or is a sign of a heart attack, renal angina is used as a herald sign for a kidney attack.

Detection of renal angina is performed by calculating the renal angina index.

Renal replacement therapy

Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called renal failure and includes acute kidney injury and chronic kidney disease. Renal replacement therapy includes dialysis (hemodialysis or peritoneal dialysis), hemofiltration, and hemodiafiltration, which are various ways of filtration of blood with or without machines. Renal replacement therapy also includes kidney transplantation, which is the ultimate form of replacement in that the old kidney is replaced by a donor kidney.

These treatments are not truly cures for kidney disease. In the context of chronic kidney disease, they are more accurately viewed as life-extending treatments, although if chronic kidney disease is managed well with dialysis and a compatible graft is found early and is successfully transplanted, the clinical course can be quite favorable, with life expectancy of many years. Likewise, in certain acute illnesses or trauma resulting in acute kidney injury, a person could very well survive for many years, with relatively good kidney function, before needing intervention again, as long as they had good response to dialysis, they got a kidney transplant fairly quickly if needed, their body did not reject the transplanted kidney, and they had no other significant health problems. Early dialysis (and, if indicated, early renal transplant) in acute renal failure usually brings more favorable outcomes.

Hemodialysis, hemofiltration, and hemodiafiltration can be continuous or intermittent and can use an arteriovenous route (in which blood leaves from an artery and returns via a vein) or a venovenous route (in which blood leaves from a vein and returns via a vein). This results in various types of RRT, as follows:

continuous renal replacement therapy (CRRT)

continuous hemodialysis (CHD)

continuous arteriovenous hemodialysis (CAVHD)

continuous venovenous hemodialysis (CVVHD)

continuous hemofiltration (CHF)

continuous arteriovenous hemofiltration (CAVH or CAVHF)

continuous venovenous hemofiltration (CVVH or CVVHF)

continuous hemodiafiltration (CHDF)

continuous arteriovenous hemodiafiltration (CAVHDF)

continuous venovenous hemodiafiltration (CVVHDF)

intermittent renal replacement therapy (IRRT)

intermittent hemodialysis (IHD)

intermittent venovenous hemodialysis (IVVHD)

intermittent hemofiltration (IHF)

intermittent venovenous hemofiltration (IVVH or IVVHF)

intermittent hemodiafiltration (IHDF)

intermittent venovenous hemodiafiltration (IVVHDF)

Diseases of the urinary system (N00–N39, 580–599)
Kidney disease
Urinary tract

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