Renal failure
Classification and external resources
ICD-10 | N 17-N 19
ICD-9 | 584-585
DiseasesDB | 26060
MeSH | Failure&field=entry#TreeC12.777.419.780.500 C12.777.419.780.500

A hemodialysis machine, used to physiologically aid or replace the kidneys in renal failure

Renal failure or kidney failure (formerly called renal insufficiency) is a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood. The two forms are acute (acute kidney injury) and chronic (chronic kidney disease); a number of other diseases or health problems may cause either form of renal failure to occur.

Renal failure is described as a decrease in glomerular filtration rate. Biochemically, renal failure is typically detected by an elevated serum creatinine level. Problems frequently encountered in kidney malfunction include abnormal fluid levels in the body, increased acid levels, abnormal levels of potassium, calcium, phosphate, and (in the longer term) anemia as well as delayed healing in broken bones. Depending on the cause, hematuria (blood loss in the urine) and proteinuria (protein loss in the urine) may occur. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.

## Classification[edit]

Renal failure can be divided into two categories: acute kidney injury or chronic kidney disease. The type of renal failure is determined by the trend in the serum creatinine. Other factors that may help differentiate acute kidney injury from chronic kidney disease include anemia and the kidney size on ultrasound. Chronic kidney disease generally leads to anemia and small kidney size.

### Acute kidney injury[edit]

Main article: Acute kidney injury

Acute kidney injury (AKI), previously called acute renal failure (ARF), is a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults,[1] less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); and fluid and electrolyte imbalance. AKI can result from a variety of causes, generally classified as prerenal, intrinsic, and postrenal. An underlying cause must be identified and treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes.

### Chronic kidney disease[edit]

Main article: Chronic kidney disease

Chronic kidney disease (CKD) can develop slowly and, initially, show few symptoms. CKD can be the long term consequence of irreversible acute disease or part of a disease progression.

### Acute-on-chronic renal failure[edit]

Acute kidney injuries can be present on top of chronic kidney disease, a condition called acute-on-chronic renal failure (AoCRF). The acute part of AoCRF may be reversible, and the goal of treatment, as with AKI, is to return the patient to baseline renal function, typically measured by serum creatinine. Like AKI, AoCRF can be difficult to distinguish from chronic kidney disease if the patient has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.

## Symptoms[edit]

Symptoms can vary from person to person. Someone in early stage kidney disease may not feel sick or notice symptoms as they occur. When kidneys fail to filter properly, waste accumulates in the blood and the body, a condition called azotemia. Very low levels of azotaemia may produce few, if any, symptoms. If the disease progresses, symptoms become noticeable (if the failure is of sufficient degree to cause symptoms). Renal failure accompanied by noticeable symptoms is termed uraemia.[2]

Symptoms of kidney failure include:[2][3][4][5]

- High levels of urea in the blood, which can result in:
  - Vomiting and/or diarrhea, which may lead to dehydration
  - Nausea
  - Weight loss
  - Nocturnal urination
  - More frequent urination, or in greater amounts than usual, with pale urine
  - Less frequent urination, or in smaller amounts than usual, with dark coloured urine
  - Blood in the urine
  - Pressure, or difficulty urinating
  - Unusual amounts of urination, usually in large quantities
- A build up of phosphates in the blood that diseased kidneys cannot filter out may cause:
  - Itching
  - Bone damage
  - Nonunion in broken bones
  - Muscle cramps (caused by low levels of calcium which can be associated with hyperphosphatemia)
- A build up of potassium in the blood that diseased kidneys cannot filter out (called hyperkalemia) may cause:
  - Abnormal heart rhythms
  - Muscle paralysis[6]
- Failure of kidneys to remove excess fluid may cause:
  - Swelling of the legs, ankles, feet, face and/or hands
  - Shortness of breath due to extra fluid on the lungs (may also be caused by anemia)
- Polycystic kidney disease, which causes large, fluid-filled cysts on the kidneys and sometimes the liver, can cause:
  - Pain in the back or side
- Healthy kidneys produce the hormone erythropoietin that stimulates the bone marrow to make oxygen-carrying red blood cells. As the kidneys fail, they produce less erythropoietin, resulting in decreased production of red blood cells to replace the natural breakdown of old red blood cells. As a result, the blood carries less hemoglobin, a condition known as anemia. This can result in:
  - Feeling tired and/or weak
  - Memory problems
  - Difficulty concentrating
  - Dizziness
  - Low blood pressure
- Proteins are usually too big to pass through the kidneys, but they can pass through when the glomeruli are damaged. This does not cause symptoms until extensive kidney damage has occurred,[7] after which symptoms include:
  - Foamy or bubbly urine
  - Swelling in the hands, feet, abdomen, or face
- Other symptoms include:
  - Appetite loss, a bad taste in the mouth
  - Difficulty sleeping
  - Darkening of the skin
  - Excess protein in the blood
  - With high dose penicillin, renal failure patients may experience seizures[8]

## Causes[edit]

### Acute renal failure[edit]

Acute kidney failure usually occurs when the blood supply to the kidneys is suddenly interrupted or when the kidneys become overloaded with toxins. Causes of acute failure include accidents, injuries, or complications from surgeries in which the kidneys are deprived of normal blood flow for extended periods of time. Heart-bypass surgery is an example of one such procedure.

Drug overdoses, accidental or from chemical overloads of drugs such as antibiotics or chemotherapy, may also cause the onset of acute kidney failure. Unlike chronic kidney disease, however, the kidneys can often recover from acute failure, allowing the patient to resume a normal life. People suffering from acute failure require supportive treatment until their kidneys recover function, and they often remain at increased risk of developing future kidney failure.[9]

Among the accidental causes of renal failure is the crush syndrome, when large amounts of toxins are suddenly released in the blood circulation after a long compressed limb is suddenly relieved from the pressure obstructing the blood flow through its tissues, causing ischemia. The resulting overload can lead to the clogging and the destruction of the kidneys. It is a reperfusion injury that appears after the release of the crushing pressure. The mechanism is believed to be the release into the bloodstream of muscle breakdown products ? notably myoglobin, potassium, and phosphorus ? that are the products of rhabdomyolysis (the breakdown of skeletal muscle damaged by ischemic conditions). The specific action on the kidneys is not fully understood, but may be due in part to nephrotoxic metabolites of myoglobin.

### Chronic kidney disease[edit]

CKD has numerous causes. The most common is diabetes mellitus. The second most common is long-standing, uncontrolled hypertension, or high blood pressure. Polycystic kidney disease is another well-known cause of CKD. The majority of people afflicted with polycystic kidney disease have a family history of the disease. Other genetic illnesses affect kidney function, as well.

Overuse of common drugs such as aspirin, ibuprofen, and acetaminophen (paracetamol) can also cause chronic kidney damage.[10]

Some infectious diseases, such as hantavirus, can attack the kidneys, causing kidney failure.

### Genetic predisposition[edit]

The APOL1 gene has been proposed as a major genetic risk locus for a spectrum of nondiabetic renal failure in individuals of African origin, these include HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies.[11] Two western African variants in APOL1 have been shown to be associated with end stage kidney disease in African Americans and Hispanic Americans.[12][13]

## Diagnostic approach[edit]

### Measurement for CKD[edit]

Stages of kidney failure

Chronic kidney failure is measured in five stages, which are calculated using a patient?s GFR, or glomerular filtration rate. Stage 1 CKD is mildly diminished renal function, with few overt symptoms. Stages 2 and 3 need increasing levels of supportive care from their medical providers to slow and treat their renal dysfunction. Patients in stages 4 and 5 usually require preparation of the patient towards active treatment in order to survive.Stage 5 CKD is considered a severe illness and requires some form of renal replacement therapy (dialysis) or kidney transplant whenever feasible.

Glomerular filtration rate

A normal GFR varies according to many factors, including sex, age, body size and ethnicity. Renal professionals consider the glomerular filtration rate (GFR) to be the best overall index of kidney function.[14] The National Kidney Foundation offers an easy to use on-line GFR calculator[15] for anyone who is interested in knowing their glomerular filtration rate. (A serum creatinine level, a simple blood test, is needed to use the calculator).

### Use of the term uremia[edit]

Before the advancement of modern medicine, renal failure was often referred to as uremic poisoning. Uremia was the term for the contamination of the blood with urine. Starting around 1847, this included reduced urine output, which was thought to be caused by the urine mixing with the blood instead of being voided through the urethra.[citation needed] The term uremia is now used for the illness accompanying kidney failure.[16]

## References[edit]

1. ^ Klahr S, Miller S (1998). "Acute oliguria". N Engl J Med 338 (10): 671?5. doi:10.1056/NEJM199803053381007. PMID 9486997.
2. ^ a b Dr Per Grinsted (2005-03-02). "Kidney failure (renal failure with uremia, or azotaemia)". Retrieved 2009-05-26.
3. ^ Dr Andy Stein (2007-07-01). Understanding Treatment Options For Renal Therapy. Deerfield, Illinois: Baxter International Inc. p. 6. ISBN 1-85959-070-5.
4. ^ The PD Companion. Deerfield, Illinois: Baxter International Inc. 2008-05-01. pp. 14?15. 08/1046R.
5. ^ Amgen Inc. (2009). "10 Symptoms of Kidney Disease". Retrieved 2009-05-26.
6. ^ MedicineNet, Inc. (2008-07-03). "Hyperkalemia". Retrieved 2009-05-26.
7. ^ Lee A. Hebert, M.D., Jeanne Charleston, R.N. and Edgar Miller, M.D. (2009). "Proteinuria". Retrieved 2011-03-24.
8. ^ Katzung, Bertram G. (2007). Basic and Clinical Pharmacology, 10th Edition. New York, NY: McGraw Hill Medical. p. 733. ISBN 978-0-07-145153-6.
9. ^ Your Kidneys and How They Work- How do kidneys fail? National Kidney and Urologic Diseases Information Clearing House. NIDDK. NIH Publication No. 07?3195.August 2007. * Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. http://kidney.niddk.nih.gov/Kudiseases/pubs/yourkidneys/#7.
10. ^ Perneger TV, Whelton PK, Klag MJ (December 1994). "Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs". N. Engl. J. Med. 331 (25): 1675?9. doi:10.1056/NEJM199412223312502. PMID 7969358.
11. ^ Bostrom MA, Freedman BI. (2010). "The spectrum of MYH9-associated nephropathy.". Clin J Am Soc Nephrol 5 (6): 1107?13. doi:10.2215/CJN.08721209. PMID 20299374.
12. ^ Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR. (Jul 2010). "Association of Trypanolytic ApoL1 Variants with Kidney Disease in African-Americans". Science 329 (5993): 841?5. doi:10.1126/science.1193032. PMC 2980843. PMID 20647424.
13. ^ Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A, Bekele E, Bradman N, Wasser WG, Behar DM, Skorecki K. (Jul 2010). "Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.". Human Genetics 128 (3): 345?50. doi:10.1007/s00439-010-0861-0. PMC 2921485. PMID 20635188.
14. ^ Fadem, Stephen Z., M.D., FACP, FASN. Calculators for HealthCare Professionals. National Kidney Foundation. 13 Oct 2008
15. ^ "GFR calculator". Kidney.org. Retrieved 2011-09-25.
16. ^ Meyer TW and Hostetter, TH (2007). "Uremia". N Engl J Med 357 (13): 1316. doi:10.1056/NEJMra071313. PMID 17898101.

## External links[edit]

- Connecting dialysis community around the World (US)
- National Kidney Foundation (US)
- The Kidney Foundation of Canada(CA)

Urinary system · Pathology · Urologic disease / Uropathy (N00–N39, 580–599)
Abdominal |
Nephropathy/ (nephritis+ nephrosis) |
Glomerulopathy/ glomerulitis/ (glomerulonephritis+ glomerulonephrosis) |
Primarily nephrotic |
Non-proliferative | Minimal change · Focal segmental · Membranous
Proliferative | Mesangial proliferative · Endocapillary proliferative · Membranoproliferative/mesangiocapillary
By condition | Diabetic · Amyloidosis
Primarily nephritic, RPG |
Type I RPG/Type II hypersensitivity | Goodpasture's syndrome
Type II RPG/Type III hypersensitivity | Post-streptococcal · Lupus (DPN) · IgA/Berger's
Type III RPG/Pauci-immune | Granulomatosis with polyangiitis (Wegener's) · Microscopic polyangiitis · Churg-Strauss Syndrome
Tubulopathy/ tubulitis |
Proximal | RTA (RTA 2) · Fanconi syndrome
Thick ascending | Bartter syndrome
Distal convoluted | Gitelman syndrome
Collecting duct | Liddle's syndrome · RTA (RTA 1) · Diabetes insipidus (Nephrogenic)
Renal papilla | Renal papillary necrosis
Major calyx/pelvis | Hydronephrosis · Pyonephrosis · Reflux nephropathy
Any/all | Acute tubular necrosis
Interstitium | Interstitial nephritis (Pyelonephritis, Danubian endemic familial nephropathy)
Any/all |
General syndromes | Renal failure (Acute renal failure, Chronic renal failure) · Uremic pericarditis · Uremia
Vascular | Renal artery stenosis · Renal Ischemia · Hypertensive nephropathy · Renovascular hypertension · Renal Cortical Necrosis
Other | Analgesic nephropathy · Renal osteodystrophy · Nephroptosis · Abderhalden-Kaufmann-Lignac syndrome
Ureter | Ureteritis · Ureterocele · Megaureter
Pelvic |
Bladder | Cystitis (Interstitial cystitis, Hunner's ulcer, Trigonitis, Hemorrhagic cystitis) · Neurogenic bladder · Bladder sphincter dyssynergia · Vesicointestinal fistula · Vesicoureteral reflux
Urethra | Urethritis (Non-gonococcal urethritis) · Urethral syndrome · Urethral stricture/Meatal stenosis · Urethral caruncle
Any/all | Obstructive uropathy · Urinary tract infection · Retroperitoneal fibrosis · Urolithiasis (Bladder stone, Kidney stone, Renal colic) · Malacoplakia · Urinary incontinence (Stress, Urge, Overflow)
M: URI | anat/phys/devp/cell | noco/acba/cong/tumr, sysi/epon, urte | proc/itvp, drug (G4B), blte, urte

Organ failure
General | Heart failure Respiratory failure Liver failure Acute liver failure Chronic liver failure Renal failure Acute renal failure Chronic renal failure
Multiple | Multiple organ dysfunction syndrome