Chronic kidney disease
|Chronic kidney disease|
|Classification and external resources|
|ICD-9||585.9 585.1-585.5 403|
Chronic kidney disease (CKD), also known as chronic renal disease (CRD), is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months.
Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis (testing of a urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging, blood tests and often renal biopsy (removing a small sample of kidney tissue) are employed to find out if there is a reversible cause for the kidney malfunction. Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is often called end stage renal disease (ESRD), end stage renal failure (ESRF), or end-stage kidney disease (ESKD) and is synonymous with the now outdated terms chronic kidney failure (CKF) or chronic renal failure (CRF).
There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis, this may be treated directly to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease. Severe CKD requires renal replacement therapy, which may involve a form of dialysis, but ideally constitutes a kidney transplant.
Signs and symptoms
- Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the RAS (renin-angiotensin system), increasing one's risk of developing hypertension and/or suffering from congestive heart failure
- Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Urea is excreted by sweating and crystallizes on skin ("uremic frost").
- Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias)
- Erythropoietin synthesis is decreased
- Fluid volume overload — symptoms may range from mild edema to life-threatening pulmonary edema
- Hyperphosphatemia — due to reduced phosphate excretion
- Hypocalcemia — due to 1,25 dihydroxyvitamin D3 deficiency. The 1,25 dihydroxyvitamin D3 deficiency is due to stimulation of fibroblast growth factor-23.
- Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered enzyme activity by excess acid acting on enzymes and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia)
- Iron deficiency anemia, which increases in prevalence as kidney function decreases, and is especially prevalent in those requiring haemodialysis. It is multifactoral in cause but includes increased inflammation, reduction in Erythropoietin, hyperuricemia leading to bone marrow suppression.
People with chronic kidney disease suffer from accelerated atherosclerosis and are more likely to develop cardiovascular disease than the general population. Patients afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.
Sexual dysfunction is very common in both men and women with chronic kidney disease. A majority of men have a reduced sex drive, difficulty obtaining an erection and reaching orgasm, and the problems get worse with age. A majority of women have trouble with sexual arousal, and painful periods and problems with performing and enjoying sex are common.
Historically, kidney disease has been classified according to the part of the renal anatomy that is involved.
- Vascular, includes large vessel disease such as bilateral renal artery stenosis and small vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome and vasculitis
- Glomerular, comprising a diverse group and subclassified into
- Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathy
- Obstructive such as with bilateral kidney stones and diseases of the prostate
- On rare cases, pin worms infecting the kidney can also cause nephropathy.
- non traditional causes of CKD are denoted if the common causes of CKD are not present, e.g. in El Salvador, Nicaragua, ... in rural communities with agriculture.
In many CKD patients, previous renal disease or other underlying diseases are already known. A small number present with CKD of unknown cause. In these patients, a cause is occasionally identified retrospectively.
It is important to differentiate CKD from acute renal failure (ARF) because ARF can be reversible. Abdominal ultrasound, in which the size of the kidneys is measured, is commonly performed. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys, with notable exceptions such as in diabetic nephropathy and polycystic kidney disease. Another diagnostic clue that helps differentiate CKD from ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests), it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.
Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA scans are also used in renal imaging; with both MAG3 and DMSA being used chelated with the radioactive element Technetium-99.
In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today.
|CKD Stage||GFR level (mL/min/1.73 m2)|
|Stage 1||≥ 90|
|Stage 2||60 – 89|
|Stage 3||30 – 59|
|Stage 4||15 – 29|
|Stage 5||< 15|
All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications.
All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR > 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.
The loss of protein in the urine is regarded as an independent marker for worsening of renal function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if there is significant protein loss.
- Stage 1
Slightly diminished function; kidney damage with normal or relatively high GFR (≥90 mL/min/1.73 m2). Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
- Stage 2
Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
- Stage 3
- Stage 4
Severe reduction in GFR (15–29 mL/min/1.73 m2) Preparation for renal replacement therapy
- Stage 5
Established kidney failure (GFR <15 mL/min/1.73 m2, permanent renal replacement therapy (RRT), or end stage renal disease (ESRD)
NDD-CKD vs. ESRD
The term non-dialysis dependent CKD, also abbreviated as NDD-CKD, is a designation used to encompass the status of those persons with an established CKD who do not yet require the life-supporting treatments for renal failure known as renal replacement therapy (including maintenance dialysis or renal transplantation). The condition of individuals with CKD, who require either of the 2 types of renal replacement therapy (dialysis or transplantation), is referred to as the end-stage renal disease (ESRD). Hence, the start of the ESRD is practically the irreversible conclusion of the NDD-CKD. Even though the non-dialysis dependent status refers to the status of persons with earlier stages of CKD (stages 1 to 4), patients with advanced stage of CKD (Stage 5), who have not yet started renal replacement therapy are also referred to as NDD-CKD.
Screening those who neither have symptoms or risk factors for chronic kidney disease is not recommended. Those who should be screened include: those with hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60 years, subjects with indigenous racial origin, those with a history of renal disease in the past, as well as subjects who have relatives who had kidney disease requiring dialysis. Screening should include calculation of estimated GFR/1.73 m2 from the serum creatinine level, and measurement of urine-to-albumin creatinine ratio in a first-morning urine specimen as well as dipstick screen for hematuria. Guidelines for nephrologist referral vary among different countries. Nephrology referral is useful when eGFR/1.73m2 is less than 30 or decreasing by more than 3 mL/min/year, when urine albumin-to-creatinine ratio is more than 30 mg/g, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. Other benefits of early nephrology referral include proper patient education regarding options for renal replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those patients opting for future hemodialysis.
The presence of chronic kidney disease confers a markedly increased risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such as hyperlipidemia. The most common cause of death in people with CKD is therefore cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.
Apart from controlling other risk factors, the goal of therapy is to slow down or halt the progression of CKD to stage 5. Control of blood pressure and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to stage 5. Although the use of ACE inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT and RENAAL studies, which reported a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional methods.
Replacement of erythropoietin and calcitriol, two hormones processed by the kidney, is often necessary in people with advanced disease. Guidelines recommend treatment with parenteral iron prior to treatment with erythropoietin. A target hemoglobin level of 9-12 g/dL is recommended. Phosphate binders are also used to control the serum phosphate levels, which are usually elevated in advanced chronic kidney disease. Zerenex(TM), a very promising new drug developed by Keryx Biopharma will have the ability to treat both elevated serum phosphate levels and anemia in CKD patients likely reducing or eliminating the need for other drugs i.e. IV iron and ESA's.
The normalization of hemoglobin has not been found to be of any benefit to the CKD but does significantly improve the patient's quality of life in reducing symptoms such as fatigue and can improve other co-morbidities that might be present, such as chronic heart failure (CHF). Although the evidence for them is limited, phosphodiesterase-5 inhibitors and zinc show potential for helping men with sexual dysfunction.
The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney function decreases. The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.
While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected. Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic options; however, it is associated with an increased short-term mortality due to complications of the surgery. Transplantation aside, high intensity home hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three times a week hemodialysis and peritoneal dialysis.
Patients with end-stage renal disease are at increased overall risk for cancer. This risk is particularly high in younger patients and gradually diminishes with age. Medical specialty professional organizations recommend that physicians not perform routine cancer screening in patients with limited life expectancies due to ESRD because evidence does not show that such tests lead to improved patient outcomes.
Chronic kidney disease globally resulted in 735,000 deaths in 2010 up from 400,000 deaths in 1990.
In Canada 1.9 to 2.3 million people have chronic kidney disease. In the US, the Centers for Disease Control and Prevention found that CKD affected an estimated 16.8% of adults aged 20 years and older, during 1999 to 2004. UK estimates suggest that 8.8% of the population of Great Britain and Northern Ireland have symptomatic CKD.
Chronic kidney disease (CKD) is a major concern in African Americans, mostly due to increased prevalence of hypertension. As an example, 37% of end-stage renal disease cases in African Americans can be attributed to high blood pressure, compared with 19% among caucasians. Treatment efficacy also differs between racial groups. Administration of anti-hypertensive drugs generally halts disease progression in white populations, but has little effect in slowing renal disease among blacks, and additional treatment such as bicarbonate therapy is often required. While lower socioeconomic status contributes to prevalence of CKD, there are still significant differences in CKD prevalence between African Americans and whites when controlling for environmental factors. Studies have shown that there is a true association between history of chronic renal failure in first or second-degree relatives, and risk of disease. In addition, African Americans may have higher serum levels of human leukocyte antigens (HLA). High HLA concentrations can contribute to increased systemic inflammation, which indirectly may lead to heightened susceptibility for developing kidney disease. Lack of nocturnal reduction in blood pressure among groups of African Americans is also offered as an explanation, which lends further credence to a genetic etiology of CKD racial disparities.
A high and so-far unexplained incidence of chronic kidney disease, referred to as the Mesoamerican nephropathy, has been noted among male workers in Central America, mainly in sugar cane fields in the low-lands of El Salvador and Nicaragua. Heat stress from long hours of piece-rate work at high average temperatures (in the range of 96°F) is suspected as are agricultural chemicals and other factors.
In the USA, the National Kidney Foundation is a national organization representing patients and professionals who treat kidney diseases. The American Kidney Fund (AKF) is a national non-profit organization providing treatment-related financial assistance to 1 out of every 5 dialysis patients each year. The Renal Support Network (RSN) is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by CKD. The American Association of Kidney Patients (AAKP) is a non-profit, patient-centric group focused on improving the health and well-being of CKD and dialysis patients. The Renal Physicians Association (RPA) is an association representing nephrology professionals.
In the United Kingdom, the UK National Kidney Federation represents patients, and the Renal Association represents renal physicians and works closely with the National Service Framework for kidney disease.
Kidney Health Australia serves that country.
The International Society of Nephrology is an international body representing specialists in kidney diseases.
- National Kidney Foundation (2002). "K/DOQI clinical practice guidelines for chronic kidney disease". Retrieved 2008-06-29.
- Bacchetta J, Sea JL, Chun RF, Lisse TS (August 2012). "FGF23 inhibits extra-renal synthesis of 1,25-dihydroxyvitamin D in human monocytes". J Bone Miner Res. 28 (1): 46–55. doi:10.1002/jbmr.1740. PMC 3511915. PMID 22886720.
- Adrogué HJ, Madias NE (September 1981). "Changes in plasma potassium concentration during acute acid-base disturbances". Am. J. Med. 71 (3): 456–67. doi:10.1016/0002-9343(81)90182-0. PMID 7025622.
- Vecchio, M.; Navaneethan, SD.; Johnson, DW.; Lucisano, G.; Graziano, G.; Saglimbene, V.; Ruospo, M.; Querques, M.; Jannini, EA. (2010). "Interventions for treating sexual dysfunction in patients with chronic kidney disease.". Cochrane Database Syst Rev (12): CD007747. doi:10.1002/14651858.CD007747.pub2. PMID 21154382.
- National Institute for Health and Clinical Excellence. Clinical guideline 73: Chronic kidney disease. London, 2008.
- Qaseem, A; Hopkins, RH; Sweet, DE; Starkey, M; Shekelle, P (2013 Oct 22). "Screening, Monitoring, and Treatment of Stage 1 to 3 Chronic Kidney Disease: A Clinical Practice Guideline From the Clinical Guidelines Committee of the American College of Physicians.". Annals of internal medicine. PMID 24145991.
- Johnson, David (2011-05-02). "Chapter 4: CKD Screening and Management: Overview". In Daugirdas, John. Handbook of Chronic Kidney Disease Management. Lippincott Williams and Wilkins. pp. 32–43. ISBN 1-58255-893-0.
- Chauhan V, Vaid M (November 2009). "Dyslipidemia in chronic kidney disease: managing a high-risk combination". Postgrad Med 121 (6): 54–61. doi:10.3810/pgm.2009.11.2077. PMID 19940417.
- Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G (October 1998). "Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy". Lancet 352 (9136): 1252–6. doi:10.1016/S0140-6736(98)04433-X. PMID 9788454.
- Ruggenenti P, Perna A, Gherardi G et al. (July 1999). "Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria". Lancet 354 (9176): 359–64. doi:10.1016/S0140-6736(98)10363-X. PMID 10437863.
- Lewis EJ, Hunsicker LG, Clarke WR et al. (2001). "Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes". N Engl J Med 345 (12): 851–60. doi:10.1056/NEJMoa011303. PMID 11565517.
- Brenner BM, Cooper ME, de ZD et al. (2001). "Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy". N Engl J Med 345 (12): 861–9. doi:10.1056/NEJMoa011161. PMID 11565518.
- Roehr, Bob (April 6, 2009). "NKF 2009: Bardoxolone May Improve Renal Function Through Inflammatory Pathways". Medscape Medical News.
- "Avosentan May Slow Progression Of Diabetic Kidney Disease". Medical News Today. 14 February 2009.
- NICE: Anaemia management in people with chronic kidney disease (CG114)
- Locatelli, F; Aljama, P; Canaud, B; Covic, A; De Francisco, A; Macdougall, IC; Wiecek, A; Vanholder, R; Anaemia Working Group of European Renal Best Practice, (ERBP) (2010 Sep). "Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study". Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 25 (9): 2846–50. doi:10.1093/ndt/gfq336. PMID 20591813.
- Clement, FM; Klarenbach, S; Tonelli, M; Johnson, JA; Manns, BJ (2009 Jun 22). "The impact of selecting a high hemoglobin target level on health-related quality of life for patients with chronic kidney disease: a systematic review and meta-analysis". Archives of Internal Medicine 169 (12): 1104–12. doi:10.1001/archinternmed.2009.112. PMID 19546410.
- Levin A, Hemmelgarn B, Culleton B et al. (November 2008). "Guidelines for the management of chronic kidney disease". CMAJ 179 (11): 1154–62. doi:10.1503/cmaj.080351. PMC 2582781. PMID 19015566.
- Perazella MA, Khan S (March 2006). "Increased mortality in chronic kidney disease: a call to action". Am. J. Med. Sci. 331 (3): 150–3. doi:10.1097/00000441-200603000-00007. PMID 16538076.
- Sarnak MJ, Levey AS, Schoolwerth AC et al. (October 2003). "Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention". Circulation 108 (17): 2154–69. doi:10.1161/01.CIR.0000095676.90936.80. PMID 14581387.
- Tonelli M, Wiebe N, Culleton B et al. (July 2006). "Chronic kidney disease and mortality risk: a systematic review". J. Am. Soc. Nephrol. 17 (7): 2034–47. doi:10.1681/ASN.2005101085. PMID 16738019.
- Heidenheim AP, Kooistra MP, Lindsay RM (2004). "Quality of life". Contrib Nephrol. Contributions to Nephrology 145: 99–105. doi:10.1159/000081673. ISBN 3-8055-7808-3. PMID 15496796.
- de Francisco AL, Piñera C (January 2006). "Challenges and future of renal replacement therapy". Hemodial Int 10 (Suppl 1): S19–23. doi:10.1111/j.1542-4758.2006.01185.x. PMID 16441862.
- Groothoff JW (July 2005). "Long-term outcomes of children with end-stage renal disease". Pediatr. Nephrol. 20 (7): 849–53. doi:10.1007/s00467-005-1878-9. PMID 15834618.
- Giri M (2004). "Choice of renal replacement therapy in patients with diabetic end stage renal disease". Edtna Erca J 30 (3): 138–42. PMID 15715116.
- Pierratos A, McFarlane P, Chan CT (March 2005). "Quotidian dialysis--update 2005". Curr. Opin. Nephrol. Hypertens. 14 (2): 119–24. doi:10.1097/00041552-200503000-00006. PMID 15687837.
- Maisonneuve, P.; Agodoa, L.; Gellert, R.; Stewart, J. H.; Buccianti, G.; Lowenfels, A. B.; Wolfe, R. A.; Jones, E.; Disney, A. P.; Briggs, D.; McCredie, M.; Boyle, P. (1999). "Cancer in patients on dialysis for end-stage renal disease: An international collaborative study". Lancet 354 (9173): 93–99. doi:10.1016/S0140-6736(99)06154-1. PMID 10408483.
- American Society of Nephrology. "Five Things Physicians and Patients Should Question". Choosing Wisely: an initiative of the ABIM Foundation (American Society of Nephrology). Retrieved August 17, 2012
- Chertow, G. M.; Paltiel, A. D.; Owen, W. F.; Lazarus, J. M. (1996). "Cost-effectiveness of Cancer Screening in End-Stage Renal Disease". Archives of Internal Medicine 156 (12): 1345–1350. doi:10.1001/archinte.1996.00440110117016. PMID 8651845.
- Lozano, R (2012 Dec 15). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.". Lancet 380 (9859): 2095–128. PMID 23245604.
- Centers for Disease Control and Prevention (CDC) (March 2007). "Prevalence of chronic kidney disease and associated risk factors—United States, 1999–2004". MMWR Morb. Mortal. Wkly. Rep. 56 (8): 161–5. PMID 17332726.
- The Association of Public Health Observatories – Chronic Kidney Disease Prevalence Estimates. 2007 [cited 1/3/2010]; Available from: http://www.apho.org.uk/resource/item.aspx?RID=63798.
- Appel LJ, Wright JT, Greene T, et al. (April 2008). "Long-term effects of renin-angiotensin system-blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans". Arch. Intern. Med. 168 (8): 832–9. doi:10.1001/archinte.168.8.832. PMID 18443258.
- Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J (1997). "End-stage renal disease in African-American and white men. 16-year MRFIT findings". JAMA 277 (16): 1293–8. doi:10.1001/jama.1997.03540400043029. PMID 9109467.
- Wesseling C, Crowe J, Hogstedt C, Jakobsson K, Lucas R, Wegman DH. The Epidemic of Chronic Kidney Disease of Unknown Etiology in Mesoamerica: A Call for Interdisciplinary Research and Action. Am J Public Health. 2013 Sep 12. [Epub ahead of print]
- Johnson RJ, Sánchez-Lozada LG. Chronic kidney disease: Mesoamerican nephropathy-new clues to the cause. Nat Rev Nephrol. 2013 Oct;9(10):560-1. doi: 10.1038/nrneph.2013.174. [Epub ahead of print]
- Sasha Chavkin; Ronnie Greene (December 12, 2011). "Thousands of sugar cane workers die as wealthy nations stall on solutions". International Consortium of Investigative Journalists. Retrieved November 26, 2012.
- Orantes, Carlos M.; Raúl Herrera, Miguel Almaguer, Elsy G. Brizuela, Carlos E. Hernández, Héctor Bayarre, Juan C. Amaya, Denis J. Calero, Patricia Orellana, Rosa M. Colindres, María E. Velázquez, Sonia G. Núñez, Verónica Mabel Contreras, Bertha E. Castro (October 2011). "Chronic Kidney Disease and Associated Risk Factors in the Bajo Lempa Region of El Salvador: Nefrolempa Study, 2009". MEDICC Review 13 (4). Retrieved November 26, 2012.
|Find more about Chronic kidney disease at Wikipedia's sister projects|
|Definitions and translations from Wiktionary|
|Media from Commons|
|Learning resources from Wikiversity|
|Quotations from Wikiquote|
|Source texts from Wikisource|
|Textbooks from Wikibooks|
- National Kidney Foundation
- Dialysis Complications of Chronic Renal Failure at eMedicine
- The Kidney Foundation of Canada