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Encyclopedia > Renal tubular acidosis
Renal tubular acidosis
Classification & external resources
Nephrocalcinosis on xray as seen in dRTA
ICD-10 N25.8
OMIM 179800
DiseasesDB 11687 11673 11705
MeSH D000141

Renal tubular acidosis, or RTA, is a medical condition in which the kidneys fail to dispose of a normal amount of acid into the urine, which may lead to acidosis (where the blood becomes too acidic). Image File history File links No higher resolution available. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... // N00-N39 - Diseases of the genitourinary system: urinary system (N00-N08) Glomerular diseases Prefixes: .2 Diffuse membranous glomerulonephritis (N00) Acute nephritic syndrome (N01) Rapidly progressive nephritic syndrome (N02) Recurrent and persistent haematuria (N03) Chronic nephritic syndrome (N04) Nephrotic syndrome Lipoid nephrosis (N05) Unspecified nephritic syndrome (N06) Isolated proteinuria with specified... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... A disease is any abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person affected or those in contact with the person. ... Acidity redirects here. ... Acidosis is an increased acidity (i. ...


This is due to the renal tubules failing to acidify the urine, rather than acid accumulating in the body due to kidney failure. As such it is a cause of a normal anion gap acidosis. The kidney tubule, also renal tubule, is the portion of the kidney containing the fluid filtered through the glomerulus. ... This article or section is in need of attention from an expert on the subject. ... Acidity redirects here. ... Renal failure is when the kidneys fail to function properly. ... In renal physiology, normal anion gap acidosis, and less precisely non-anion gap acidosis, is an acidosis that is not accompanied by an anion gap. ...


In RTA, the renal tubules either fail to appropriately reclaim bicarbonate (in the proximal tubule) or excrete hydrogen ions (in the distal tubule). In inorganic chemistry, a bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. ... Hydronium is the common name for the cation H3O+. Nomenclature According to IUPAC ion nomenclature, it should be referred to as oxonium. ...

Contents

Types

There are several different types of RTA (which are different syndromes with different causes).


The different subtypes:

  • Distal or type 1 RTA
  • Proximal or type 2 RTA
  • Type 3 RTA (very rare)
  • Hypoaldosteronism or type 4 RTA

In medicine (endocrinology), hypoaldosteronism refers to decreased levels of the hormone aldosterone. ...

Distal RTA (Type I)

Distal RTA (dRTA) is the most common and also the classical form of RTA, being the first described. It has a number of causes which cause a common underlying problem, which is a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This leads to a failure acidify the urine to a pH of less than 5.3 even if the blood is too acidic (ie there is systemic acidemia), and consequently there is a tendency towards acidemia. This leads to the clinical features of dRTA;[1] Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ... The collecting duct system of the kidney consists of a series of tubules and ducts that connect the nephrons to the ureter. ... In zootomy, several terms are used to describe the location of organs and other structures in the body of bilateral animals. ... A nephron is the basic structural and functional unit of the kidney. ... The correct title of this article is . ... Acidosis is an increased acidity (i. ...

The acidosis is variable, and one may have dRTA with alpha intercalated cell failure without necessarily being acidemic, this is termed incomplete dRTA. The diagnosis of dRTA can be made by the observation of a urinary pH of greater than 5.3 in the face of a systemic acidemia (usually taken to be a serum bicarbonate of 20 mmol/l or less). In the case of an incomplete dRTA, failure to acidify the urine following an oral acid loading challenge is often used as a test. The test usually performed is the short ammonium chloride test,[2] in which ammonium chloride capsules are used as the acid load. In medicine, metabolic acidosis is a state in which the blood pH is low (under 7. ... Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. ... Bladder stone redirects here. ... Nephrocalcinosis, also known as Albrights calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Atomic mass 40. ... Grays Anatomy illustration of a human femur. ... It has been suggested that Osteomalacia be merged into this article or section. ... To meet Wikipedias quality standards, this article may require cleanup. ... The correct title of this article is . ... The mole (symbol: mol) is one of the seven SI base units and is commonly used in chemistry. ... The litre or liter (U.S. spelling, see spelling differences) is a unit of volume. ... Ammonium chloride or Sal Ammoniac (chemically ammonium chloride (NH4Cl); also nushadir salt, zalmiak, sal armagnac, sal armoniac, salmiakki, salmiak and salt armoniack) is, in its pure form, a clear white water-soluble crystalline salt with a biting taste. ...


The symptoms and sequelae of dRTA are variable and ranging from being completely asymptomatic, through loin pain and hematuria from kidney stones to failure to thrive and severe rickets in childhood forms as well as possible renal failure and even death. In medicine, a disease is asymptomatic when it is at a stage where the patient does not experience symptoms. ... A loincloth is one-piece garment, sometimes kept in place by a belt, that is used: in societies where there is no more advanced clothing as an undergarment to express soberness Mohandas Gandhi wore a dhoti, a Hindu loincloth, as a way of identifying with the poorest Indians, even though... In medicine, hematuria (or haematuria) is the presence of blood in the urine. ... Kidney stones are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. ... Failure to thrive is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in infancy. ... It has been suggested that Osteomalacia be merged into this article or section. ... Renal failure is the condition in which the kidneys fail to function properly. ... This article or section does not adequately cite its references or sources. ...


Causes

Cartoon of the alpha intercalated cell, showing the apical proton pump and the basolateral band 3 (kAE1)
Cartoon of the alpha intercalated cell, showing the apical proton pump and the basolateral band 3 (kAE1)

Image File history File links Size of this preview: 771 × 599 pixel Image in higher resolution (777 × 604 pixel, file size: 45 KB, MIME type: image/jpeg) Self made cartoon I, the creator of this work, hereby release it into the public domain. ... Image File history File links Size of this preview: 771 × 599 pixel Image in higher resolution (777 × 604 pixel, file size: 45 KB, MIME type: image/jpeg) Self made cartoon I, the creator of this work, hereby release it into the public domain. ... Anion Exchanger 1 (AE1) or Band 3 is a phylogenetically preserved transport protein responsible for catalysing the electroneutral exchange of chloride (Cl-) for bicarbonate (HCO3-) across a plasma membrane. ... It has been suggested that this article or section be merged into Dominance relationship. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Alpha intercalated cell The apical membrane of a polarized cell is the part of the plasma membrane that forms its lumenal surface, distinct from the basolateral membrane. ... A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment, thereby creating a difference or gradient in both pH and electrical charge (ignoring differences in buffer capacity) and tending to establish an electrochemical potential. ... This article discusses the way the word deaf is used and how deafness is perceived by hearing and Deaf communities. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Sjögrens syndrome is an autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. ... Rheumatoid arthritis (RA) is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... Gamma globulins, or Igs, are a class of proteins in the blood, identified by their position after serum protein electrophoresis. ... The collecting duct system of the kidney consists of a series of tubules and ducts that connect the nephrons to the ureter. ... Ifosfamide (Mitoxana®) Ifosfamide (pronounced i fos fa mide) is chemotherapy that is given as a treatment for many different types of cancer. ... Toluene, also known as methylbenzene or phenylmethane is a clear, water-insoluble liquid with the typical smell of paint thinners, redolent of the sweet smell of the related compound benzene. ... Lithium carbonate (Li2CO3) is a chemical compound of lithium and carbonate that is used as a mood stabilizer in psychiatric treatment of manic states and bipolar disorder. ... Amphotericin B (Fungilin®, Fungizone®, Abelcet®, AmBisome®, Fungisome®, Amphocil®, Amphotec®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. ... Urinary retention also known as ischuria is a lack of ability to urinate. ... Kidney transplantation or renal transplantation is the organ transplant of a kidney in a patient with chronic renal failure. ... Sickle-shaped red blood cells Sickle cell anemia (American English), sickle cell anaemia (British English) or sickle cell disease is a genetic disease in which red blood cells may change shape under certain circumstances. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ...

Treatment

This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate or sodium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalema and urinary stone formation and nephrocalcinosis can be treated with potassium citrate tablets which not only replace potassium but won't increase calcium excretion and thus exacerbate stone disease as sodium bicarbonate or citrate may do.[12] Sodium bicarbonate is the chemical compound with the formula NaHCO3. ... Sodium citrate is the sodium salt of citric acid with the chemical formula of Na3C6H5O7. ... Potassium Citrate may be used to control Uric acid kidney stones. ...


Proximal RTA

Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to resorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalised dysfunction of the proximal tubular cells called Fanconi's syndrome where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria. The principle feature of Fanconi's syndrome is bone demineralisation due to phosphate wasting. Correction with oral bicarbonate may exacerbate urinary potassium losses and precipitate hypokalemia. The proximal tubule is the portion of the duct system of the nephron leading from Bowmans capsule to the loop of Henle. ... Fanconi syndrome is a disorder in which the proximal tubular function of the kidney is impaired. ... Hypophosphatemia is an electrolyte disturbance in which there is an abnormally depleted level of phosphate in the blood. ... Proteinuria (from protein and urine) means the presence of an excess of serum proteins in the urine. ... In inorganic chemistry, a bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. ... Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. ...


Causes

Familial disorders

Acquired disorders Cystinosis is a hereditary disorder of the renal tubules characterized by the presence of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium ions and phosphates. ... Wilsons disease or hepatolenticular degeneration is an autosomal recessive hereditary disease, with an incidence of about 1 in 30,000 in most parts of the world and a male preponderance. ... Galactosemia is a rare genetic metabolic disorder which affects an individuals ability to properly digest the sugar galactose. ... Tyrosinemia (or Tyrosinaemia) is an error of metabolism, usually inborn, in which the body can not effectively break down the amino acid tyrosine, found in most animal and plant proteins. ... Fructose intolerance is a hereditary condition due to a deficiency of liver enzymes that metabolise fructose. ...

Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahlers disease after Otto Kahler) is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. ... The term antiretroviral drugs is used to describe drugs used against HIV infection (HIV is an RNA retrovirus). ... Ifosfamide (Mitoxana®) Ifosfamide (pronounced i fos fa mide) is chemotherapy that is given as a treatment for many different types of cancer. ... For PB or pb as an abbreviation, see PB. General Name, Symbol, Number lead, Pb, 82 Chemical series poor metals Group, Period, Block 14, 6, p Appearance bluish gray Atomic mass 207. ... General Name, Symbol, Number cadmium, Cd, 48 Chemical series transition metals Group, Period, Block 12, 5, d Appearance silvery gray metallic Atomic mass 112. ...

Treatment

Again this depends on oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate diuresis. The amount of bicarbonate given may have to be very large, to stay ahead of the urinary losses. As with dRTA, reversal of the chronic acidosis should reverse bone demineralisation.[14] Diuresis is the production of urine by the kidney. ...


Type 3 RTA

This was previously used to designate a rare and transient mixed dRTA and pRTA of uncertain aetiology. Now it is used to describe a genetic defect in type 2 carbonic anhydrase (CA2), which is found in both the proximal and distal tubular cells, as well in bone. As a result it causes; Etiology (alternately aetiology, aitiology) is the study of Greek words aitia = cause and logos = word/speech) is used in philosophy, physics and biology in reference to the causes of various phenomena. ... Carbonic anhydrase (carbonate dehydratase) is a family of metalloenzymes (enzymes that contain one or more metal atoms as a functional component of the enzyme) that catalyze the rapid interconversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. ...

It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb region of North Africa, possibly due to the high prevalence of consanguinity there.[15] The kidney problems are treated as described above, there is no treatment for the osteopetrosis or cerebral calcification, unfortunately. Osteopetrosis is an extremely rare inherited disorder whereby the bones harden, becoming denser. ... Dystrophic calcification is the mineralization of soft tissue without a systemic mineral imbalance. ... This page is a candidate for speedy deletion. ... Marrakech, Morocco, in front of Atlas mountains in Maghreb The Maghreb (المغرب العربي ; sometimes also rendered Moghreb), meaning western in Arabic, is the region of the continent of Africa north of the Sahara desert and west of the Nile — specifically, the modern countries of Morocco, Western Sahara (annexed and occupied by Morocco...  Northern Africa (UN subregion)  geographic, including above North Africa or Northern Africa is the northernmost region of the African continent, generally divided by the formidable barrier of the Sahara from Sub-Saharan Africa. ... Consanguinity, literally meaning common blood, describes how close a person is related to another in the sense of a family. ...


Type 4 RTA (Hypoaldosteronism)

Type 4 RTA is not actually a tubular disorder at all, and nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in distal tubular ammonium excretion, which is secondary to hypoaldosteronism. It's cardinal feature is hyperkalemia, and measured urinary acidification is normal. In medicine (endocrinology), hypoaldosteronism refers to decreased levels of the hormone aldosterone. ... A ball-and-stick model of the ammonium cation Fumes from hydrochloric acid and ammonia forming a white cloud of ammonium chloride Ammonium is also an old name for the Siwa Oasis in western Egypt. ... In medicine (endocrinology), hypoaldosteronism refers to decreased levels of the hormone aldosterone. ... Hyperkalemia is an elevated blood level (above 5. ...


Causes;

  1. Primary adrenal insufficiency
  2. Congenital adrenal hyperplasia
  3. Aldosterone synthase deficiency
  4. Potassium sparing diuretics
  • Hyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction[16])
  1. Renal dysfunction-most commonly diabetic nephropathy
  2. HIV infection
  3. ACE inhibitors
  4. NSAIDs
  5. Ciclosporin
  • Aldosterone resistance
  1. Drugs (Amiloride, Spironolactone,Trimethoprim, Pentamidine)
  2. Pseudohypoaldosteronism

Aldosterone is a steroid hormone synthesized from cholesterol by the enzyme aldosterone synthase. ... In medicine, adrenal insufficiency (or hypocortisolism) is the inability of the adrenal gland to produce adequate amounts of cortisol in response to stress. ... Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. ... Aldosterone synthase (or 18-hydroxylase) is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone. ... Photomicrography of nodular glomerulosclerosis in Kimmelstein-Wilson syndrome. ... Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. ... ACE inhibitors, or inhibitors of Angiotensin_Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. ... Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ... Ciclosporin (INN), cyclosporine or cyclosporin (former BAN), is an immunosuppressant drug. ... Amiloride is an antihypertensive, a potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. ... Spironolactone (marketed as Aldactone®, Novo-Spiroton®, Spiractin®, Spirotone®, or Berlactone®) is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics, used primarily to treat ascites in patients with liver disease, low-renin hypertension, hypokalemia, and Conns syndrome. ... Trimethoprim is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections (cystitis). ... Pentamidine isethionate is a drug primarily given for prevention and treatment of Pneumocystis carinii pneumonia (PCP), a type of pneumonia often seen in people with HIV infection. ... Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and in an increase in plasma chloride concentration. ...

Treatment

Mineralocorticoids is a class of steroids characterised by their similarity to aldosterone and their influence on salt and water metabolism. ... Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. ... Cortisol is a corticosteroid hormone produced by the adrenal cortex that is involved in the response to stress; it increases blood pressure, blood sugar levels, may cause infertility in women, and suppresses the immune system. ... Fludrocortisone acetate is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. ... For other forms of hypertension, see Hypertension (disambiguation). ... Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ... A diuretic (colloquially called a water pill) is any drug or herb that elevates the rate of bodily urine excretion (diuresis). ... Thiazides are a class of drug that promote water loss from the body ((diuretics)). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. ... Bendroflumethiazide, (formerly known as bendrofluazide), is a thiazide diuretic, used to treat hypertension. ... Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. ... Furosemide (INN) or frusemide (former BAN) is a loop diuretic used in the treatment of congestive heart failure and edema. ... Hyperkalemia is an elevated blood level (above 5. ...

Trivia

dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.[19][20] Tiny Tim is a fictional character in the classic story A Christmas Carol by Charles Dickens. ... A Christmas Carol (full title: A Christmas Carol in Prose, Being a Ghost Story of Christmas) is Charles Dickens little Christmas Book first published on December 19,[1] 1843 and illustrated by John Leech. ...


See also

Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and in increase in plasma chloride concentration. ... Hypokalemia is a potentially fatal condition in which the body fails to retain sufficient potassium to maintain health. ... Bladder stone redirects here. ...

References

  1. ^ Laing, C M (Jun 2005). "Renal tubular acidosis: developments in our understanding of the molecular basis.". Int J Biochem Cell Biol 37 (6): 1151-61. 
  2. ^ Wrong, O; Davies HEF (1959). "The Excretion of Acid in Renal Disease". QJM 28: 259-313. 
  3. ^ Bruce, L J (1997). "Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene". J Clin Invest 100: 1693-1707. 
  4. ^ Bruce, L J (2000). "Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells". Biochem J 350: 41-51. 
  5. ^ Karet, F E (May 1998). "Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis". PNAS 95 (11): 6337-6342. 
  6. ^ Karet, F E (1999). "Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness". Nature Genetics 21: 81-90. 
  7. ^ Wrong, OM (1993). "Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis". QJM 86 (8): 513-542. 
  8. ^ Skinner, R (Aug 1996). "Risk factors for ifosfamide nephrotoxicity in children". Lancet 348(9027): 578-80. 
  9. ^ Battle, DC (1988). "On the mechanism of toluene-induced renal tubular acidosis". Nephron 49 (3): 210-8. 
  10. ^ Boton, R (Nov 1987). "Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy". Am J Kidney Dis 10 (5): 329-45. 
  11. ^ McCurdy, DK (Jan 1968). "Renal tubular acidosis due to amphotericin B". NEJM 278 (3): 124-30. 
  12. ^ Morris, R C (2002). "Alkali Therapy In Renal Tubular Acidosis: Who Needs It?". J Am Soc Nephrol 13: 2186–2188. 
  13. ^ Skinner, R (July 2003). "Chronic ifosfamide nephrotoxicity in children". Medical and Pediatric Oncology 41 (3): 190-197. 
  14. ^ McSherry, E (1981). "Renal tubular acidosis in childhood". Kidney International 20: 799. 
  15. ^ Fathallah, D. M. (1997). "Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for founder effect and genomic recombination at the CA II locus". Human Genetics (99): 634-637. 10.1007/s004390050419. 
  16. ^ DeFronzo, RA (1980). "Hyperkalemia in hyporeninemic hypoaldosteronism". Kidney International (17): 118.. 
  17. ^ DeFronzo, RA (1980). "Hyperkalemia in hyporeninemic hypoaldosteronism". Kidney International (17): 118.. 
  18. ^ Sebastian, A (1984). "Amelioration of hyperchloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal tubular acidosis". Am J Nephrol 4 (5): 287-300. 
  19. ^ Lewis D (1992). "What was wrong with Tiny Tim?". Am J Dis Child 146 (12): 1403-7. PMID 1340779. 
  20. ^ http://www.time.com/time/magazine/article/0,9171,977391,00.html

 
 

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