Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the

distal tubule The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...

and

cortical collecting duct The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in ele ...

of the distal

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...

. This failure of acid secretion may be due to a number of causes. It leads to relatively alkaline urine, due to the kidney's inability to acidify the urine to a pH of less than 5.3.

Symptoms and signs

Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards

acidemia Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes t ...

. This leads to the clinical features of dRTA: * Normal

anion gap The anion gap (AG or AGAP) is a value calculated from the results of multiple individual medical lab tests. It may be reported with the results of an electrolyte panel, which is often performed as part of a comprehensive metabolic panel. The an ...

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...

/acidemia *

Hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

Urinary stone A bladder stone is a stone found in the urinary bladder. Signs and symptoms Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is d ...

formation (related to alkaline urine,

hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels ...

, and low urinary citrate). *

Nephrocalcinosis Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the d ...

(deposition of

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

in the substance of the kidney) *

Bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

demineralisation (causing

rickets Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications ma ...

in children and

osteomalacia Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bon ...

in adults) The symptoms and sequelae of dRTA are variable and range from being completely asymptomatic, to

loin The loins, or lumbus, are the sides between the lower ribs and pelvis, and the lower part of the back. The term is used to describe the anatomy of humans and quadrupeds, such as horses, pigs, or cattle. The anatomical reference also applies to pa ...

pain and

hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...

from

kidney stones Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a calculus (medicine), solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the ...

, to

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

and severe

in childhood forms as well as possible

renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

and even death. dRTA commonly leads to sodium loss and volume contraction, which causes a compensatory increase in blood levels of aldosterone. Aldosterone causes increased resorption of sodium and loss of potassium in the collecting duct of the kidney, so these increased aldosterone levels cause the hypokalemia which is a common symptom of dRTA.

Causes

* Autoimmune disease. Classically Sjögren's syndrome, but it is also associated with systemic lupus erythematosus,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

and even

hypergammaglobulinemia Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin. It is a type of immunoproliferative disorder. Types Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunogl ...

. Hypokalaemia is often severe in these cases. * Hereditary causes include mutations of

Band 3 Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the gene in humans. Band 3 anion transport protein is a phylogenetically-preserved ...

the basolateral bicarbonate transporter of the intercalated cell, which may be transmitted in an autosomal dominant fashion in western European cases, or in an autosomal recessive fashion in South East Asian cases. The South East Asian cases are associated with more severe hypokalemia. Other hereditary causes include mutations of subunits of the

apical Apical means "pertaining to an apex". It may refer to: *Apical ancestor, refers to the last common ancestor of an entire group, such as a species (biology) or a clan (anthropology) *Apical (anatomy), an anatomical term of location for features loc ...

proton pump A proton pump is an integral membrane protein pump that builds up a proton gradient across a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell f ...

vH⁺-ATPase, which are transmitted in an autosomal recessive fashion, and may be associated with sensorineural

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

. * Liver

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

. *

. While it is a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the

. *

Renal transplantation Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantat ...

. *

Sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...

. * Toxins, including

ifosfamide Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, ...

(more commonly causing pRTA than dRTA), lithium carbonate and

amphotericin B Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...

. * Chronic

urinary tract obstruction Urinary tract obstruction is a urologic disease consisting of a decrease in the free passage of urine through one or both ureters and/or the urethra. It is a cause of urinary retention. Complete obstruction of the urinary tract requires prompt tre ...

. *

Toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) a ...

causes a non-anion gap metabolic acidosis with hypokalemia and a positive urinary anion gap that looks a lot like distal RTA but there is no hydrogen secretion defect and the acidosis is due to acid production during the metabolism of toluene.

Diagnosis

The pH of patient's blood is highly variable, and acidemia is not necessarily characteristic of people with dRTA at any given time. One may have dRTA caused by alpha intercalated cell failure without necessarily being acidemic; termed ''incomplete dRTA,'' which is characterized by an inability to acidify urine, without affecting blood pH or plasma bicarbonate levels. The diagnosis of dRTA can be made by the observation of a relatively alkaline urinary pH of greater than 5.3 in the face of a systemic acidemia (usually taken to be a serum bicarbonate of 20

mmol The mole, symbol mol, is the unit of amount of substance in the International System of Units (SI). The quantity amount of substance is a measure of how many elementary entities of a given substance are in an object or sample. The mole is define ...

/ 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'', in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by m ...

and

fludrocortisone Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydroc ...

has been described. dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.

Treatment

This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate,

sodium citrate Sodium citrate may refer to any of the sodium salts of citric acid (though most commonly the third): * Monosodium citrate * Disodium citrate * Trisodium citrate The three forms of salt are collectively known by the E number E331. Applications ...

potassium citrate Potassium citrate (also known as tripotassium citrate) is a potassium salt of citric acid with the molecular formula K3C6H5O7. It is a white, hygroscopic crystalline powder. It is odorless with a saline taste. It contains 38.28% potassium by mass ...

. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with

tablets which not only replace potassium but also inhibit calcium excretion and thus do not exacerbate stone disease as sodium bicarbonate or citrate may do.

References

External links