Acute kidney injury: Difference between revisions
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At the level of the efferent arteriole, an increase in resistance is crucial for appropriate maintenance of glomerular hydrostatic pressure. This is achieved by an increase in the production of angiotensin II (via the Renin-Angiotensin System) which acts preferentially on the efferent arteriole leading to vasoconstriction.<ref name="pmid9892156">{{cite journal| author=Arendshorst WJ, Brännström K, Ruan X| title=Actions of angiotensin II on the renal microvasculature. | journal=J Am Soc Nephrol | year= 1999 | volume= 10 Suppl 11 | issue= | pages= S149-61 | pmid=9892156 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9892156 }} </ref> Important medications that target angiotensin II production and action are ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) which may be responsible for renal decompensation in patients dependent on the action of angiotensin II to maintain glomerular perfusion pressure. Such is the case in chronic kidney disease patients, whose autoregulatory mechanisms are typically operating at maximum capacity.<ref name="pmid17715412">{{cite journal| author=Abuelo JG| title=Normotensive ischemic acute renal failure. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 8 | pages= 797-805 | pmid=17715412 | doi=10.1056/NEJMra064398 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17715412 }} </ref> | At the level of the efferent arteriole, an increase in resistance is crucial for appropriate maintenance of glomerular hydrostatic pressure. This is achieved by an increase in the production of angiotensin II (via the Renin-Angiotensin System) which acts preferentially on the efferent arteriole leading to vasoconstriction.<ref name="pmid9892156">{{cite journal| author=Arendshorst WJ, Brännström K, Ruan X| title=Actions of angiotensin II on the renal microvasculature. | journal=J Am Soc Nephrol | year= 1999 | volume= 10 Suppl 11 | issue= | pages= S149-61 | pmid=9892156 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9892156 }} </ref> Important medications that target angiotensin II production and action are ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) which may be responsible for renal decompensation in patients dependent on the action of angiotensin II to maintain glomerular perfusion pressure. Such is the case in chronic kidney disease patients, whose autoregulatory mechanisms are typically operating at maximum capacity.<ref name="pmid17715412">{{cite journal| author=Abuelo JG| title=Normotensive ischemic acute renal failure. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 8 | pages= 797-805 | pmid=17715412 | doi=10.1056/NEJMra064398 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17715412 }} </ref> | ||
As such, the pathophysiology of prerenal azotemia entails a drop in renal plasma flow beyond the capacity of autoregulation, a blunted or inadequate renal compensation for an otherwise tolerable change in perfusion, or a combination of both. | As such, the pathophysiology of prerenal azotemia entails a drop in renal plasma flow beyond the capacity of autoregulation, a blunted or inadequate renal compensation for an otherwise tolerable change in perfusion, or a combination of both. This eventually leads to ischemic renal injury particularly to the medulla which is maintained in hypoxic conditions at baseline. As prerenal AKI progresses, it transforms into acute tubular necrosis (ATN) crossing into the realm of intrinsic AKI. | ||
[[Image:PrerenalAKI.jpg|center|border]] | [[Image:PrerenalAKI.jpg|center|border]] | ||
Revision as of 06:11, 19 October 2013
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Acute kidney failure; acute renal failure; acute uremia; AKI; ARF
Overview
Acute kidney injury (AKI), formerly known as acute renal failure, is characterized by an abrupt loss of kidney function resulting in a failure to excrete nitrogenous waste products (among others), and a disruption of fluid and electrolyte homeostasis. AKI defines a spectrum of disease with common clinical features including an increase in the serum creatinine and BUN levels, often associated with a reduction in urine volume. AKI can be caused by a multitude of factors broadly categorized into pre-renal (usually ischemic), intrinsic renal (usually toxic), and post-renal (usually obstructive) injuries. Generally, treatment is supportive until renal function is restored especially in light of the fluid overload, electrolyte imbalances, and uremic toxin accumulation. Still, renal replacement modalities are sometimes indicated.
Definition
Over 30 different definitions of AKI have been used in the literature since it was first described, which prompted the need for a uniform definition. In 2002, The Acute Dialysis Quality Initiative (ADQI) proposed the first consensus definition known as the RIFLE criteria. The acronym combines a classification of 3 levels of renal dysfunction (Risk, Injury, Failure) with 2 clinical outcomes (Loss, ESRD). This unified classification was proposed to enable a viable comparison in trials of prevention and therapy and to observe clinical outcomes of the defined stages of AKI.[1]
| Classification | GFR criteria | Urine output criteria |
| Risk | 1.5x increase in SCr or GFR decrease >25% | <0.5 mL/kg/h for 6 hours |
| Injury | 2x increase in SCr or GFR decrease >50% | <0.5 mL/kg/h for 12 hours |
| Failure | 3x increase in SCr or GFR decrease >75% | <0.3 mL/kg/h for 24 hours or anuria for 12 hours |
| Loss | Complete loss of renal function >4 weeks | |
| End-stage Renal Disease | Complete loss of renal function >3 months | |
In 2007, the Acute Kidney Injury Network (AKIN) proposed a modified diagnostic criteria based on the RIFLE criteria. The initiative separated the definition and staging into 2 separate entities previously combined in the RIFLE criteria. This made the definition more clinically applicable. AKI was defined as either one of the following:[2]
|
In March 2012, the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Acute Kidney Injury retained the AKIN definition while implementing modifications to the staging criteria of AKI. [3]
Historical Perspective
It is really unclear when acute kidney injury or acute renal failure came to light as a separate disease entity. The first documented report of abrupt loss of renal function came from Beall et al in 1941 who described a man admitted to St. Thomas's Hospital after a crush injury to the leg in a bombing incident. They describe a course of rapidly progressive renal insufficiency with dark urine, edema, elevated potassium levels, and disorientation. [4]
The earliest definition came from Lucké in 1946 who described the histologic pathology we now know as acute tubular necrosis. The term lower nephron nephrosis was introduced and was later used to refer to abrupt renal failure secondary to excessive vomiting, thermal burns, crush injuries, hemolysis, and obstructive prostate disease.[5][6] The term slowly drifted to become acute renal failure to depict a clinical syndrome rather than a pathologic finding. Acute renal failure was then replaced by acute kidney injury in 2006 following a consensus that even minor changes in serum creatinine not necessarily overt failure can lead to significant changes in outcome.
Staging
Initially, the staging of AKI was a part of the proposed definition by the ADQI initiative and the RIFLE criteria. In 2007, AKIN proposed separated the 2 and created a new staging scheme modified from the RIFLE criteria. Prior to the 2012, RIFLE and AKIN criteria were used interchangeably to stage patients with renal injury.[1][2] Although certain concerns about the differences between the 2 classification schemes, it was shown that the differences do not carry through to mortality and outcome measures.[7]
| Classification | GFR criteria | Urine output criteria |
| Stage 1 | Increase in SCr ≥0.3 mg/dL or 1.5x to 2x increase from baseline | <0.5 mL/kg/h for 6 hours |
| Stage 2 | 2x to 3x increase in SCr from baseline | <0.5 mL/kg/h for 12 hours |
| Stage 3 | >3x increase in SCr or SCr≥ 4.0 mg/dL with acute increase >0.5 md/dL | <0.3 mL/kg/h for 24 hours or anuria for 12 hours |
In 2012, the KDIGO AKI guidelines proposed a combined staging scheme that takes into account both criteria and clinical outcome. [3] The rationale behind AKI staging is the needed to determine overall outcome as higher stags of AKI carry a greater risk of all cause and cardiovascular mortality, renal replacement, as well as chronic kidney disease even after AKI resolution.[8][9][10][11]
| Staging | GFR criteria | Urine output criteria |
| Stage 1 | 1.5 - 1.9 times baseline or ≥ 0.3 mg/dl increase | <0.5 ml/kg/h for 6 - 12 hours |
| Stage 2 | 2.0 - 2.9 times baseline | <0.5 ml/kg/h for ≥ 12 hours |
| Stage 3 | 3.0 times baseline or increase in serum creatinine to 4.0 mg/dL or initiation of renal replacement therapy or decrease in eGFR to <35 ml/min per 1.73 m2 (in patients <18 years) |
<0.3 mL/kg/h for 24 hours or anuria for 12 hours |
The guidelines also advocated that in case of discordance between urine output and serum creatinine patients should be classified to the highest applicable AKI stage. Also, new emphasis on the differences seen in the pediatric population gave rise to revised definition of Stage 3 AKI in patients less than 18 years of age.[3]
Pathophysiology & Etiologies
Etiologies of AKI can be divided based on pathophysiologic mechanisms into 3 broad categories: prerenal, intrinsic renal, and postrenal causes.
Prerenal AKI
Prerenal AKI, known as prerenal azotemia, is by far the most common cause of AKI representing 30-50% of all cases. It is provoked by inadequate renal blood flow commonly due to decreased effective circulating blood flow. This causes a decrease in the intraglomerular hydrostatic pressure required to achieve proper glomerular filtration.
Blood flow to the kidneys can vary with systemic changes; however, glomerular perfusion pressure and GFR are maintained relatively constant by the kidney itself. Under physiologic conditions, minor drops in blood flow to the renal circulation are counteracted by changes in the resistances across the afferent and efferent arterioles of individual glomerular capillary beds.[12] The afferent arteriole vasodilates via 2 mechanisms. The myogenic reflex, mediating medial smooth muscle relaxation in states of decrease perfusion pressure, vasodilates the afferent arteriole leading to increased blood flow.[13] Additionally, intrarenal synthesis of vasodilatory prostaglandins such as prostacyclin and prostaglandin E2 causes further dilation of the afferent arteriole.[14] The mechanism explains why the intake of NSAIDs leads to acute kidney injury by inhibiting this autoregulatory mechanism.[15]
At the level of the efferent arteriole, an increase in resistance is crucial for appropriate maintenance of glomerular hydrostatic pressure. This is achieved by an increase in the production of angiotensin II (via the Renin-Angiotensin System) which acts preferentially on the efferent arteriole leading to vasoconstriction.[16] Important medications that target angiotensin II production and action are ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) which may be responsible for renal decompensation in patients dependent on the action of angiotensin II to maintain glomerular perfusion pressure. Such is the case in chronic kidney disease patients, whose autoregulatory mechanisms are typically operating at maximum capacity.[17]
As such, the pathophysiology of prerenal azotemia entails a drop in renal plasma flow beyond the capacity of autoregulation, a blunted or inadequate renal compensation for an otherwise tolerable change in perfusion, or a combination of both. This eventually leads to ischemic renal injury particularly to the medulla which is maintained in hypoxic conditions at baseline. As prerenal AKI progresses, it transforms into acute tubular necrosis (ATN) crossing into the realm of intrinsic AKI.
Causes
AKI can be caused by disease, crush injury, contrast agents, some antibiotics, and more.
The causes of acute kidney injury are commonly categorized into prerenal, intrinsic, and postrenal.
| Type | UOsm | UNa | FeNa | BUN/Cr |
|---|---|---|---|---|
| Prerenal | >500 | <10 | <1% | >20 |
| Intrinsic | <350 | >20 | >2% | <15[citation needed] |
| Postrenal | <350 | >40 | >4% | >15 |
Prerenal
Prerenal causes of AKI ("pre-renal azotemia") are those that decrease effective blood flow to the kidney. These include systemic causes, such as low blood volume, low blood pressure, heart failure, 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.
Renal ischaemia ultimately results in functional disorder, depression of GFR, or both. These causes stem from the inadequate cardiac output and hypovolemia or vascular diseases causing reduced perfusion of both kidneys. Both kidneys need to be affected as one kidney is still more than adequate for normal kidney function.
Intrinsic
Sources of damage to the kidney itself are dubbed intrinsic. Intrinsic AKI can be due to damage to the glomeruli, renal tubules, or interstitium. Common causes of each are glomerulonephritis, acute tubular necrosis (ATN), and acute interstitial nephritis (AIN), respectively. A cause of intrinsic acute renal failure is tumor lysis syndrome.[18]
Postrenal
Postrenal AKI is a consequence of urinary tract obstruction. This may be related to benign prostatic hyperplasia, kidney stones, obstructed urinary catheter, bladder stone, bladder, ureteral or renal malignancy. 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 immediately after urinating to measure fluid still in the bladder. 50-100ml suggests neurogenic bladder. A renal ultrasound will demonstrate hydronephrosis if present. A CT scan of the abdomen will also demonstrate bladder distension or hydronephrosis, however, in case of acute renal failure, the use of IV contrast is contraindicated. On the basic metabolic panel, the ratio of BUN to creatinine may indicate post renal failure.
Epidemiology
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 ESRD. AKI requiring dialysis (10% of these) is rare (200 ppm/year), 2x incidence of new ESRD.[19]
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.[20]
Risk Factors
Natural History
Complications
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.[21]
Prognosis
Depending on the cause, a proportion of patients will never regain full renal function, thus entering end-stage renal failure and requiring lifelong dialysis or a kidney transplant. Patients with AKI are more likely to die prematurely after they were discharged from hospital even if their kidney function has recovered.[22]
Diagnosis
Signs and symptoms
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.[23] Marked increases in the potassium level can lead to irregularities in the heartbeat, which can be severe and life-threatening.[21] Fluid balance is frequently affected, though hypertension is rare.[24]
Pain in the flanks may be encountered in some conditions (such as thrombosis of the renal blood vessels or inflammation of the kidney); this is the result of stretching of the fibrous tissue capsule surrounding the kidney.[25] If the kidney injury is the result of dehydration, there may be thirst as well as evidence of fluid depletion on physical examination.[25] Physical examination may also provide other clues as to the underlying cause of the kidney problem, such as a rash in interstitial nephritis and a palpable bladder.[25]
Inability to excrete sufficient fluid from the body can cause accumulation of fluid in the limbs (peripheral edema) and the lungs (pulmonary edema),[23] as well as cardiac tamponade as a result of fluid effusions.[24]
Detection
The deterioration of renal function may be discovered by a measured decrease in urine output. Often, it is diagnosed on the basis of blood tests for substances normally eliminated by the kidney: urea and creatinine. 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 are currently established enough to replace creatinine as a marker of renal function.[citation needed][when?]
Sodium and potassium, two electrolytes that are commonly deranged in people with acute kidney injury, are typically measured together with urea and creatinine.[citation needed]
Further testing
Once the diagnosis of AKI is made, further testing is often required to determine the underlying cause. These may include urine sediment analysis, renal ultrasound and/or kidney biopsy. Indications for renal biopsy in the setting of AKI include:[26]
- Unexplained AKI
- AKI in the presence of the nephritic syndrome
- Systemic disease associated with AKI
Treatment
The management of AKI hinges on identification and treatment of the underlying cause. 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, iodinated contrasts such as those used for CT scans, many antibiotics such as gentamicin, and a range of other substances.[27]
Monitoring of renal 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.
Specific therapies
In prerenal AKI without fluid overload, administration of intravenous fluids is typically the first step to improve renal function. Volume status may be monitored with the use of a central venous catheter to avoid over- or under-replacement of fluid.
Should low blood pressure prove a persistent problem in the fluid-replete patient, inotropes such as norepinephrine and dobutamine may be given to improve cardiac output and hence renal perfusion. While a useful pressor, there is no evidence to suggest that dopamine is of any specific benefit,[28] and may be harmful.
The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to Wegener's granulomatosis may respond to steroid medication. Toxin-induced prerenal AKI often responds to discontinuation of the offending agent, such as aminoglycoside, penicillin, NSAIDs, or paracetamol.[25]
If the cause is obstruction of the urinary tract, relief of the obstruction (with a nephrostomy or urinary catheter) may be necessary.
Diuretic agents
The use of diuretics such as furosemide, is widespread and sometimes convenient in ameliorating fluid overload, and is not associated with higher mortality (risk of death).[29]
Renal replacement therapy
Renal replacement therapy, such as with hemodialysis, may be instituted in some cases of AKI. A systematic review of the literature in 2008 demonstrated no difference in outcomes between the use of intermittent hemodialysis and continuous venovenous hemofiltration (CVVH).[30] Among critically ill patients, intensive renal replacement therapy with CVVH does not appear to improve outcomes compared to less intensive intermittent hemodialysis.[27][31]
See also
- BUN-to-creatinine ratio
- Chronic kidney disease
- Dialysis
- Renal failure
- Rhabdomyolysis
- Contrast-induced nephropathy
Related Chapters
References
- ↑ 1.0 1.1 Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup (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.
- ↑ 2.0 2.1 Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG; et al. (2007). "Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury". Crit Care. 11 (2): R31. doi:10.1186/cc5713. PMC 2206446. PMID 17331245.
- ↑ 3.0 3.1 3.2 Kidney Disease Improving Global Outcomes Work Group (2012). "2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury". Kidey Int Supp. 2: 69–88. doi:10.1038/kisup.2011.34.
- ↑ Beall D, Bywaters EG, Belsey RH, Miles JA (1941). "Crush Injury with Renal Failure". Br Med J. 1 (4185): 432–4. PMC 2161708. PMID 20783578 Check
|pmid=value (help). - ↑ LUCKE B (1946). "Lower nephron nephrosis; the renal lesions of the crush syndrome, of burns, transfusions, and other conditions affecting the lower segments of the nephrons". Mil Surg. 99 (5): 371–96. PMID 20276793.
- ↑ STRAUSS MB (1948). "Acute renal insufficiency due to lower-nephron nephrosis". N Engl J Med. 239 (19): 693–700. doi:10.1056/NEJM194811042391901. PMID 18892579.
- ↑ Bagshaw SM, George C, Bellomo R, ANZICS Database Management Committe (2008). "A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients". Nephrol Dial Transplant. 23 (5): 1569–74. doi:10.1093/ndt/gfn009. PMID 18281319.
- ↑ Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C (2006). "An assessment of the RIFLE criteria for acute renal failure in hospitalized patients". Crit Care Med. 34 (7): 1913–7. doi:10.1097/01.CCM.0000224227.70642.4F. PMID 16715038.
- ↑ Bagshaw SM, George C, Dinu I, Bellomo R (2008). "A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients". Nephrol Dial Transplant. 23 (4): 1203–10. doi:10.1093/ndt/gfm744. PMID 17962378.
- ↑ Ricci Z, Cruz D, Ronco C (2008). "The RIFLE criteria and mortality in acute kidney injury: A systematic review". Kidney Int. 73 (5): 538–46. doi:10.1038/sj.ki.5002743. PMID 18160961.
- ↑ Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W; et al. (2007). "Incidence and outcomes in acute kidney injury: a comprehensive population-based study". J Am Soc Nephrol. 18 (4): 1292–8. doi:10.1681/ASN.2006070756. PMID 17314324.
- ↑ Loutzenhiser R, Griffin K, Williamson G, Bidani A (2006). "Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms". Am J Physiol Regul Integr Comp Physiol. 290 (5): R1153–67. doi:10.1152/ajpregu.00402.2005. PMC 1578723. PMID 16603656.
- ↑ Cupples WA, Braam B (2007). "Assessment of renal autoregulation". Am J Physiol Renal Physiol. 292 (4): F1105–23. doi:10.1152/ajprenal.00194.2006. PMID 17229679.
- ↑ Herbaczynska-Cedro K, Vane JR (1973). "Contribution of intrarenal generation of prostaglandin to autoregulation of renal blood flow in the dog". Circ Res. 33 (4): 428–36. PMID 4355037.
- ↑ Winkelmayer WC, Waikar SS, Mogun H, Solomon DH (2008). "Nonselective and cyclooxygenase-2-selective NSAIDs and acute kidney injury". Am J Med. 121 (12): 1092–8. doi:10.1016/j.amjmed.2008.06.035. PMID 19028206.
- ↑ Arendshorst WJ, Brännström K, Ruan X (1999). "Actions of angiotensin II on the renal microvasculature". J Am Soc Nephrol. 10 Suppl 11: S149–61. PMID 9892156.
- ↑ Abuelo JG (2007). "Normotensive ischemic acute renal failure". N Engl J Med. 357 (8): 797–805. doi:10.1056/NEJMra064398. PMID 17715412.
- ↑ Jim Cassidy, Donald Bissett, Roy A. J. Spence, Miranda Payne (1 January 2010). Oxford Handbook of Oncology. Oxford University Press. p. 706.
- ↑ "Renal Medicine: Acute Kidney Injury (AKI)". Renalmed.co.uk. 2012-05-23. Retrieved 2013-07-17.
- ↑ Brenner and Rector's The Kidney. Philadelphia: Saunders. 2007. ISBN 1-4160-3110-3.
- ↑ 21.0 21.1 Weisberg LS (2008). "Management of severe hyperkalemia". Crit. Care Med. 36 (12): 3246–51. doi:10.1097/CCM.0b013e31818f222b. PMID 18936701. Unknown parameter
|month=ignored (help) - ↑
- ↑ 23.0 23.1 Skorecki K, Green J, Brenner BM (2005). "Chronic renal failure". In Kasper DL, Braunwald E, Fauci AS; et al. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1653–63. ISBN 0-07-139140-1.
- ↑ 24.0 24.1 Tierney, Lawrence M. (2004). "22". CURRENT Medical Diagnosis and Treatment 2005 (44 ed.). McGraw-Hill. p. 871. ISBN 0-07-143692-8. Unknown parameter
|coauthors=ignored (help);|access-date=requires|url=(help) - ↑ 25.0 25.1 25.2 25.3 Brady HR, Brenner BM (2005). "Chronic renal failure". In Kasper DL, Braunwald E, Fauci AS; et al. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1644–53. ISBN 0-07-139140-1.
- ↑ Papadakis MA, McPhee SJ (2008). Current Medical Diagnosis and Treatment. McGraw-Hill Professional. ISBN 0-07-159124-9.
- ↑ 27.0 27.1 Palevsky PM, Zhang JH, O'Connor TZ; et al. (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. Unknown parameter
|month=ignored (help) - ↑ 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.
- ↑ Uchino S, Doig GS, Bellomo R; et al. (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.
- ↑ Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M (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. Unknown parameter
|month=ignored (help) - ↑ Bellomo R, Cass A, Cole L; et al. (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. Unknown parameter
|month=ignored (help)
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