Renal tubular acidosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Kidneys serve as a buffering system to maintain acid-base balance. Kidneys reabsorb the filtered bicarbonate and excrete acid to maintain acid-base balance. HCO3 reabsorption is facilitated by Na-H and proton pumps. Collecting tubules serve the function of excretion of acid. When ever there is disruption in the normal physiological mechanisms of tubular system of kidneys acidosis sets in. . Potassium is the most common electrolyte abnormality that can be noticed with renal tubular acidosis. It can be either hypokalemic renal tubular acidosis or hyperkalemic renal tubular acidosis. Renal tubular acidosis can be classified into type 1 (distal), type 2 (proximal), type 4 (hypoaldosteronism) and voltage-dependent RTA. Genetic mutations are the most common etiology for renal tubular acidosis. If left untreated renal tubular acidosis leads to growth failure and chronic kidney failure. Urine pH is the gold standard test for the diagnosis of renal tubular acidosis. Alkalization of the urine along with correction of electrolyte abnormalities is the mainstay of treatment in patients diagnosed by renal tubular acidosis. Sodium bicarbonate with potassium replacement are the medications recommended along with correction of underlying cause.

Renal tubular acidosis was first described as separate entity by Dr. Lightwood in 1935. Later Dr.Butler in 1936 described the pathophysiology and genetic inheritance of renal tubular acidosis in the children.

Based on underlying defect in concentration of urine process in renal tubule, renal tubular acidosis can be classified into type 1 (distal), type 2 (proximal), type 4 (hypoaldosteronism) and voltage-dependent RTA.

Kidneys reabsorb the filtered bicarbonate and excrete acid to maintain acid-base balance. HCO3 reabsorption is facilitated by Na-H and proton pumps. Collecting tubules serve the function of excretion of acid. Renal tubular acidosis is described as any one of a number of disorders, in which either of above buffering mechanism is impaired. Potassium is the most common electrolyte abnormality that can be noticed with renal tubular acidosis. It can be either hypokalemic renal tubular acidosis or hyperkalemic renal tubular acidosis. Mode of inheritance can autosomal dominant or recessive depending upon type of disease abnormality, Common genes involved include ATP6V1B1, ATP6V0A4, SLC4A1.

Primary causes of renal tubular acidosis include genetic mutations causing defects in the kidney anion exchanger [kAE1] in distal tubule intercalated cells and congenital adrenal hyperplasia. Secondary causes include medications and autoimmune diseases.

Renal tubular acidosis must be differentiated form other diseases as most of them have a similar presentation of acidosis on ABG, dehydration (nausea and vomiting) and specific history pertaining to underlying etiology.

The estimated annual incidence of distal renal tubular acidosis is 10 in 100,000 population. Renal tubular acidosis is more common in infants than other group of population. There is racial predilection for renal tubular acidosis.

Common risk factors in the development of renal tubular acidosis include childhoodurinary tract obstruction, diabetes mellitus, primary biliary cirrhosis, nephrocalcinosis, nephrolithiasis, Amphotericin-B therapy, cisplatinum, Untreated adrenal insufficiency.

Screening for renal tubular acidosis is usually not recommended for asymptomatic patients. Screening is only recommended for patients with increased risk of having proximal RTA or metabolic disorders associated with the development of Fanconi syndrome.

If left untreated renal tubular acidosis leads to growth failure and chronic kidney failure. Common complications associated with renal tubular acidosis include volume depletion, electrolyte disturbances, nephrocalcinosis, osteoporosis, growth retardation, renal rickets. Prognosis of renal tubular acidosis is generally good with appropriate therapy.

Urine pH is the gold standard test for the diagnosis of renal tubular acidosis.

Patients with renal tubular acidosis can present with acute or chronic onset of symptoms. Patients usually doesn’t have a typical history or symptoms. Common symptoms of renal tubular acidosis include vomiting, dehydration and electrolyte abnormalities with acidosis.

Patients with acute onset of renal tubular acidosis appear confused and stupor where as with chronic acidosis usually appear tired.

The diagnosis of renal tubular acidosis should be considered in any patient presenting with metabolic acidosis.The first step in diagnosing metabolic acidosis includes measuring the blood pH. The next steps includes measurement of urine pH and estimation of urinary ammonium excretion.

Electrocardiogram findings associated with renal tubular acidosis include changes due to potassium levels. Peaked T waves are the earliest sign of hyperkalemia. where as hypokalemia presents with ST segment depression, decreased T wave amplitude, and prominent U waves.

Electrocardiogram findings associated with renal tubular acidosis include changes due to potassium levels. Peaked T waves are the earliest sign of hyperkalemia. where as hypokalemia presents with ST segment depression, decreased T wave amplitude, and prominent U waves.

There are no echocardiography/ultrasound findings associated with renal tubular acidosis.

There are no CT scan findings associated with renal tubular acidosis.

There are no MRI findings associated with renal tubular acidosis.

There are no specific imaging findings associated with renal tubular acidosis. However, imaging modalities can be helpful in diagnosing underlying complications of renal disease.

There are no other diagnostic studies associated with renal tubular acidosis.

Alkalization of the urine along with correction of electrolyte abnormalities is the mainstay of treatment in patients diagnosed by renal tubular acidosis. Sodium bicarbonate with potassium replacement are the medications recommended along with correction of underlying cause.

Surgical intervention is not recommended for the management of renal tubular acidosis.

There are no effective primary preventive measures for renal tubular acidosis. However, preventive approaches can be helpful in the case of Fanconi syndrome secondary to toxin exposure which includes regulation of the use of medications responsible in high-risk groups with caution.

Secondary preventive measures of renal tubular acidosis are similar to primary prevention.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Renal tubular acidosis was first described as separate entity by Dr. Lightwood in 1935. Later Dr.Butler in 1936 described the pathophysiology and genetic inheritance of renal tubular acidosis in the children.

• In 1935, Lightwood was the first to discover and describe renal tubular acidosis in detail.^[1]
• In 1936, Butler was the first to describe in detail about the patho-physiology and inheritance of renal tubular acidosis in children.^[2]
• In 1945, Baines was the first describe renal tubular acidosis it in adults.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Syed Ahsan Hussain, M.D.[3] Jogeet Singh Sekhon, M.D. [4]

Based on underlying defect in concentration of urine process in renal tubule, renal tubular acidosis can be classified into type 1 (distal), type 2 (proximal), type 4 (hypoaldosteronism) and voltage-dependent RTA.

Renal tubular acidosis can be classified into 4 types. Renal tubular acidosis type 1( distal), renal tubular acidosis type 2 ( proximal), hypoaldosteronism (type 4) and voltage-dependent RTA. Potassium is the most common electrolyte abnormality associated renal tubular acidosis. Hypokalemia is seen in RTA type 1 and type 2 while type 4 and voltage-dependent RTA are hyperkalemic.^[1][2][3]

Type of RTA	Primary defect	Plasma HCO3 mEq/L	Urine pH	Plasma potassium	Urine anion gap	Urine calcium/creatinine ratio	Risk for nephrolithiasis
RTA type 1	Impaired distal acidification	< 10	>5.3	Hypokalemic	Positive	↑	↑
RTA type 2	Reduced proximal HCO3 reabsorption.	12 to 20	<5.3	Hypokalemic	Negative	Normal	–
RTA type 3	Mixed (distal+ proximal RTA)	Variable	Variable	Variable	Variable	Variable	Variable
RTA type 4	Decreased aldosterone secretion  Aldosterone resistance	>17	Variable	Hyperkalemia	Positive	Normal	–
Voltage-dependent RTA	Reduced sodium reabsorption	>17	Variable	Hyperkalemia	Positive	Normal	–

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Syed Ahsan Hussain, M.D.[3] Jogeet Singh Sekhon, M.D. [4]

Kidneys reabsorb the filtered bicarbonate and excrete acid to maintain acid-base balance. HCO3 reabsorption is facilitated by Na-H and proton pumps. Collecting tubules serve the function of excretion of acid. Renal tubular acidosis is described as any one of a number of disorders, in which either of above buffering mechanism is impaired. Potassium is the most common electrolyte abnormality that can be noticed with renal tubular acidosis. It can be either hypokalemic renal tubular acidosis or hyperkalemic renal tubular acidosis. Mode of inheritance can autosomal dominant or recessive depending upon type of disease abnormality, Common genes involved include ATP6V1B1, ATP6V0A4, SLC4A1.

• Normally kidneys reabsorb the filtered bicarbonate and excrete acid to maintain acid-base balance.^[1][2]
• HCO3 reabsorption is facilitated by Na-H and proton pumps.
  • Na-H reabsorbs about 80-90% of the filtered HCO₃ at the proximal tubule.
  • Proton pumps (H-ATPase and H-K ATPase) in the distal nephron reabsorbs remaining 10 percent of HCO₃.
  • There is no HCO₃ in the final urine.
• Collecting tubules serve the function of excretion of acid.^[3][4]
  • Hydrogen ions need a buffer to get excreted.
  • The principal buffers in the urine are ammonia and phosphate.
    • Acidosis stimulates ammonia production in renal tubules.
    • While ammonia can freely diffuse across membranes, ammonium cannot.
    • The secretion of hydrogen ions into the tubular lumen trap ammonia as ammonium which can easily flush out along with .
    • Increased production of ammonium is required in cases of acidosis to maintain near-normal balance.

• Potassium is the most common electrolyte abnormality that can be noticed with renal tubular acidosis.^[5][6]
• It can be either hypokalemic renal tubular acidosis or hyperkalemic renal tubular acidosis.
• Almost all of the filtered potassium is reabsorbed passively in the proximal tubule and loop of Henle.
• The potassium excreted in the urine is derived from secretion into the tubular lumen by cells in the distal nephron.
• Distal potassium secretion is primarily influenced by two factors, both promote sodium reabsorption:
• Depending upon the site of the defect and the mechanism responsible for the various forms of renal tubular acidosis, can result in hypokalemia or hyperkalemia:
• Hypokalemia frequently develops in patients with distal renal tubular acidosis.
  • Usually improves with alkali therapy in contrast to to hypokalemia in proximal renal tubular acidosis which is exacerbated by alkali therapy.
• Hyperkalemia occurs frequently with hypoaldosteronism (type 4 ) and in patients with other defects in distal nephron sodium reabsorption (voltage-dependent renal tubular acidosis).

• Hypokalemic renal tubular acidosis
  • Type 1 renal tubular acidosis
  • Type 2 renal tubular acidosis
• Hyperkalemic renal tubular acidosis
  • Type 4 renal tubular acidosis
  • Voltage-dependent renal tubular acidosis

• Type 1 renal tubular acidosis is characterized by impaired hydrogen ion secretion in the distal nephron.
• If left untreated, it results in progressive hydrogen ion retention leading to normal anion gap metabolic acidosis.
• Type 1 renal tubular acidosis results in hypokalemia.
• Impaired hydrogen ion secretion in patients with distal renal tubular acidosis can be caused by several defects:
  • Decreased net activity of the proton pump.
  • Increased hydrogen ion permeability of the luminal membrane.

• Incomplete distal renal tubular acidosis is a variant in which patients cannot acidify their urine, resulting in a urine pH that is persistently 5.5 or higher.
• The low rate of citrate excretion and relatively high rate of ammonium excretion are believed to the inciting factor for a reduced intracellular pH within the cells of the proximal tubule .
• Persistent hypo-citraturia is a consistent feature of incomplete renal tubular acidosis.

• Proximal renal tubular acidosis is characterized by a decrease in re-absorption of bicarbonate in the proximal tubule.
• Within proximal tubule cells, hydrogen ions and bicarbonate are generated from carbonic acid.
• Na-K-ATPase pump facilitates the movement of sodium down the electrochemical concentration gradient from the lumen into the cells.
• This concentration gradient drives hydrogen ions in the opposite direction which is counter balanced by bicarbonate ions via a sodium-bicarbonate cotransporter.
• The net effect of this process is that, for every hydrogen ion molecule secreted into the lumen, a bicarbonate molecule enters the peritubular capillary.
• Abnormalities of one or more of these proximal tubule transporters, pumps, or enzymes can impair sodium bicarbonate reabsorption and cause the bicarbonate wasting found in proximal renal tubular acidosis.

Most common causes of hyperkalemic renal tubular acidosis include:

• Voltage-dependent renal tubular acidosis

• Hypoaldosteronism.

• Voltage-dependent renal tubular acidosis occurs with markedly reduced distal sodium delivery
• Inherited or acquired defects in sodium reabsorption by the principal cells.
• Most common etiology include
  • Hypovolemia
  • UTI
  • Lupus nephritis
  • Sickle cell disease
  • Medications

• Aldosterone deficiency or resistance produces a hyperkalemic renal tubular acidosis.^[7]
• Type 4 renal tubular acidosis is associated with milder
• The acidification defect is primarily due to a reduced rate of proton secretion.
• Thus, when very little buffer (ammonia [NH3] and/or phosphate) is present in the renal tubule lumen, the pH can be appropriately reduced below pH 5.5 (but the quantity of excreted acid is relatively low).
• By contrast, when greater amounts of buffer are present in the distal tubule, the impaired rate of hydrogen ion secretion produces a faster rise in the urine pH above 5.5 than is seen in normal subjects.
• In either case, the reduction in net acid excretion results in metabolic acidosis.

Patients with hyperkalemia usually have lower urine ammonia levels and, therefore, a more acidic urine. The defect produced by the various forms of voltage-dependent distal RTA discussed above is similar but generally more severe. In that disorder, the urine pH often cannot be reduced below 5.5 but can also vary with the rate of urine ammonia excretion.

Type of RTA	Primary defect	Plasma HCO3 mEq/L	Urine pH	Plasma potassium	Urine anion gap	Urine calcium/creatinine ratio	Risk for nephrolithiasis
RTA type 1	Impaired distal acidification	< 10	>5.3	Hypokalemic	Positive	↑	↑
RTA Type 2	Reduced proximal HCO3 reabsorption.	12 to 20	<5.3	Hypokalemic	Negative	Normal	–
RTA type 4	Decreased aldosterone secretion  Aldosterone resistance	>17	Variable	Hyperkalemia	Positive	Normal	–
Voltage-dependent RTA	Reduced sodium reabsorption	>17	Variable	Hyperkalemia	Positive	Normal	–

Common conditions associated with renal tubular acidosis include:

• Congenital hypoaldosteronism
• Primary adrenal insufficiency
• Wilson disease
• Sarcoidosis
• Autoimmune disorders

• DRTA may be inherited as an autosomal dominant or recessive trait.^[8]
  • Autosomal recessive DRTA often presents in infancy
  • Autosomal dominant DRTA may not present until adolescence or young adulthood.
  • Mutations in the genes encoding carbonic anhydrase II, kidney anion exchanger 1 (kAE1), and subunits of the renal proton pump (H+‐ATPase) have been identified in patients with DRTA.
• Genetically transmitted PRTAs include autosomal dominant and recessive forms.
  • PRTA (with ocular abnormalities) may be caused by inactivating mutations in the Na/HCO3 cotransporter gene (SLC4A4).
  • PRTA may also be associated with other genetically transmitted disorders, such as osteopetrosis with carbonic anhydrase II deficiency.
• Inherited defects leading to Type 4 RTA are due to aldosterone deficiency or resistance.
  • Congenital adrenal hyperplasia with salt wasting
  • Isolated hypoaldosteronism
  • Pseudohypoaldosteronism (defect at the aldosterone receptor level)

Type of RTA		Gene	Gene location	Protein
Type 1 (distal) RTA	Autosomal recessive with deafness	ATP6V1B1	2p13	B1 subunit of H-ATPase
	Autosomal recessive without deafness	ATP6V0A4	7q33-q34	a4 subunit of H-ATPase
	Autosomal dominant	SLC4A1	17q21-q22	Chloride-bicarbonate exchanger
Type 2 (proximal) RTA	Autosomal recessive	SLC4A4	4q21	Sodium bicarbonate cotransporter
Type 3 (mixed) RTA	Autosomal recessive	Carbonic anhydrase II	8q22	Carbonic anhydrase II

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2] Jogeet Singh Sekhon, M.D. [3] Syed Ahsan Hussain, M.D.[4]

Primary causes of renal tubular acidosis include genetic mutations causing defects in the kidney anion exchanger [kAE1] in distal tubule intercalated cells and congenital adrenal hyperplasia. Secondary causes include medications and autoimmune diseases.

The following table summarizes the common primary and secondary causes of renal tubular acidosis.^[1][2][3]

	Primary Causes	Secondary Causes
Type 1	Idiopathic Familial Autosomal dominant Mainly due to mutations causing defects in the kidney anion exchanger [kAE1] in distal tubule intercalated cells. Autosomal recessive Mainly due to mutations causing defects in V-ATPase in distal tubule intercalated cells.	Autoimmune disorders Medications Ifosfamide Amphotericin B Lithium carbonate Ibuprofen Hypercalciuric conditions Hyperparathyroidism Vitamin D intoxication Sarcoidosis Idiopathic hypercalciuria Others
Type 2	Recessive  Proximal tubule cell sodium bicarbonate co-transporter (NBCe1) defect Carbonic anhydrase type 2 deficiency Cystinosis Tyrosinemia Hereditary fructose intolerance Galactosemia Glycogen storage disease (type I) Lowe syndrome	M-protein disorders Amyloidosis Multiple myeloma Medications Ifosfamide Tenofovir Acetazolamide Topiramate Aminoglycosides Heavy metals Lead Cadmium Mercury Copper Other Medullary sponge kidney Obstructive uropathy Renal transplant rejection Wilson disease
Type 4	Congenital hypoaldosteronism 21-hydroxylase deficiency Isolated hypoaldosteronism Pseudohypoaldosteronism type 2 Primary adrenal insufficiency Pseudohypoaldosteronism type 1	Angiotensin inhibitors, such as ACE inhibitors Angiotensin II receptor blockers Direct renin inhibitors Antibiotics, trimethoprim, and pentamidine Potassium-sparing diuretics Spironolactone Eplerenone Amiloride Triamterene

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Renal tubular acidosis must be differentiated form other diseases as most of them have a similar presentation of acidosis on ABG, dehydration (nausea and vomiting) and specific history pertaining to underlying etiology.

Renal tubular acidosis must be differentiated form other diseases as most of them have a similar presentation of acidosis on ABG, dehydration (nausea and vomiting) and specific history pertaining to underlying etiology.

Category	Disease		Mechanism			Clinical								Paraclinical																		Gold standard diagnosis	Other findings
						Symptoms				Signs				Lab data
														ABG			CBC		Chemistry								Renal		U/A
			↑ acid production	Loss of bicarbonate	↓ renal acid excretion	Fever	N/V	Diarrhea	Dyspnea	Toxic/ill	BP	Dehydration	Level of consciousness	HCO3−	paCO2	O2	WBC	Hb	BS	Cl−	K+	Na+	Ketones	Lactic acid	Serum AG[1]	Osmolar gap[2]	Bun	Cr	Urine pH	Urine AG	Urine ketone
Ketoacidosis	Diabetic ketoacidosis[3]		+	−	−	+	+	+	+	+	↓	+	↓	↓	↓	Nl to ↓	↑	Nl to ↑	↑↑	Nl	↑	↓	↑	↑	↑	↑	Nl to ↑	Nl	↓	+	+	Clinical + hyperglycemia + ketosis	Labs might show elevated K+ even in K+ depletion due to extravasation of intracellular K+ in exchanged with extracellular H+
	Starvation[4]		+	−	−	−	+	−	−	+	↓	+	↓	↓	↓	Nl	Nl	Nl	Nl to ↓	Nl	↓	↓	↑	Nl	↑	Nl	Nl	Nl	Nl	+	−	Clinical manifestation	Refeeding syndrome may occur during or after treatment
	Alcoholic ketoacidosis (Ethanol)[5]		+	−	−	−	+	±	−	+	↓ ↑	+	Agitated	↓	↓	↓	Nl to ↑	Nl to ↑	↓ Nl ↑	Nl	↓	↓	↑↑	↑	↑	↑↑	↑	Nl	↓	+	+	Clinical manifestation + ketosis	Chronic alcohol abuse Zero or low alcohol level
Systemic	Sepsis[6]		+	−	−	+	+	−	+	+	↓ ↑	+	↓	↓	↓	Nl to ↓	↑	Nl	Nl	Nl	↑	↓	Nl	Nl to ↑	Nl	Nl	↑	↑	Nl	−	−	Clinical manifestation and lab finding	Not applicable
	Ischemia[7]		+	−	−	−	+	−	+	+	↓	+	−	↓	↓ ↑	Nl to ↓	Nl to ↑	Nl	Nl	Nl	↑	↓	Nl	Nl to ↑	Nl	Nl	Nl to ↑	Nl to ↑	Nl	−	−	Clinical manifestation and lab finding	Not applicable
	Lactic acidosis[8]		+	−	−	±	+	−	−	+	↓ ↑	±	Agitated	↓	↓	↓	Nl to ↑	↓	Nl	Nl	Nl	Nl	Nl	↑	↑	↑	Nl or ↑	Nl	↓	−	−	Clinical manifestation and lab finding	Not applicable
Renal	Uremia[9]		−	−	+	+	+	−	−	+	↓ ↑	±	↓	↓	↓	Nl to ↓	↑	↓	Nl	Nl	↑	↑	Nl	Nl	↑	↑	↑	↑	↓	+	−	Clinical manifestation and lab finding	May lead to pericarditis
	Renal failure[10]		−	−	+	−	+	−	−	+	↓	+	↓	↓	↓	Nl to ↓	↑	↓	Nl	↑	↑	↓	Nl	Nl	↑	↑	↑	↑	↓	−	−	Renal function test	Not applicable
	Renal tubular acidosis[11]	Type I[12]	−	−	+	±	±	−	−	−	↓ ↑	−	−	↓	↓	Nl	Nl	Nl	Nl	↑	↓	↓	Nl	Nl	Nl	Nl	↑	↑	↑	+	−	Clinical manifestation and lab finding	Associated with autoimmune diseases Growth retardation in children
		Type II	−	+	−	±	±	−	−	−	↓ ↑	−	−	↓	↓	Nl	Nl	Nl	Nl	↑	↓	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	−	−	Clinical manifestation and lab finding	Not applicable
		Type IV	−	−	+	±	±	±	−	−	↓	−	−	↓	↓	Nl	Nl	Nl	Nl	↑	↑	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	+	−	Clinical manifestation and lab finding	Hypoaldosteronism
Heart	Heart failure[13]		+	+	−	−	±	−	+	+	↓ ↑	+	−	↓	↓ ↑	↓	Nl	Nl	Nl	Nl	↓	↓	Nl	Nl	Nl	Nl	Nl to ↑	Nl to ↑	Nl	−	−	Clinical manifestation+ echocardiogram	Hypoalbuminemia Elevated serum natriuretic peptide
	Myocardial infarction[14]		+	−	−	−	+	−	+	+	↓ ↑	−	↓	↓	↓ ↑	Nl to ↓	Nl to ↑	Nl	Nl	Nl	↑	↓	Nl	↑	Nl	Nl	Nl to ↑	Nl to ↑	Nl	−	−	Clinical manifestation + ECG	Not applicable
GI	Diarrhea[15]		−	+	−	±	+	+	−	+	↓	+	May be lethargic	↓	↓	Nl	Nl	↓	↓	↑	↑	Nl	Nl	Nl	Nl	Nl	↑	Nl	Nl	−	−	Stool exam	Not applicable
	Hyperalimentation[16]		+	+	−	−	−	+	−	−	Nl	−	−	↓	↓	Nl	Nl	↓	Nl	↑	↑	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	−	−	Clinical manifestation	Not applicable
	Liver failure[17]		−	+	−	−	+	+	−	+	↓	+	Confused	↓	↓	Nl	Nl	↓	↓ ↑	↑	↓	↓	Nl	Nl	Nl	Nl	Nl	Nl	Nl	−	−	Liver biopsy	Not applicable
Endocrine	Hyperparathyroidism[18]		−	+	+	−	+	−	−	−	Nl	+	Confused	↓	↓	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl to ↑	Nl	Nl	−	−	PTH level	Not applicable
	Addison’s disease[19]		−	+	−	−	+	+	−	−	↓	+	Irritable	↓	↓	Nl	Nl	Nl	↓	Nl	↑	↓	Nl	Nl	Nl	Nl	Nl	Nl	Nl	−	−	Hormone level	Weakness Hyperpigmentation Adrenal Crisis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The estimated annual incidence of distal renal tubular acidosis is 10 in 100,000 population. Renal tubular acidosis is more common in infants than other group of population. There is a racial predilection for renal tubular acidosis.

• The estimated annual incidence of distal renal tubular acidosis is 10 in 100,000 population.
• Proximal renal tubular acidosis is less common than distal renal tubular acidosis.

• Renal tubular acidosis is more common in infants than the other group of population.^[1]

• Distal renal tubular acidosis affects men and women equally.
• However, proximal renal tubular acidosis is more common in males than females.

• There is racial predilection for renal tubular acidosis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Common risk factors in the development of renal tubular acidosis include urinary tract obstruction, diabetes mellitus, primary biliary cirrhosis, nephrocalcinosis, nephrolithiasis, Amphotericin-B therapy, cisplatinum, Untreated adrenal insufficiency.

Common risk factors in the development of renal tubular acidosis include:^[1][2][3][4]

• Urinary tract obstruction
• Diabetes mellitus
• Primary biliary cirrhosis
• Nephrocalcinosis
• Nephrolithiasis
• Amphotericin-B therapy
• Cisplatinum
• Untreated adrenal insufficiency
• Family history
  • RTA without deafness
  • RTA with deafness
• Hereditary fructose intolerance
• Wilson disease
• Galactosemia
• Disorders of mitochondrial metabolism
• Glycogen storage diseases
• Tyrosinemia
• Lowe syndrome
• Cadmium
• Ifosfamide therapy
• Cystinosis
• Antiviral therapy (cidofovir, adefovir, or tenofovir)

Less common risk factors in the development of renal tubular acidosis include:

• Cyclosporine therapy
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blocking drugs
• Heparin therapy
• Medications interfering with sodium transport
• Use of carbonic anhydrase inhibitors
• Abnormalities of filtered immunoglobulins
• Interstitial nephritis
• Hyperparathyroidism
• Thai or southeast Asian ancestry
• Outdated tetracycline
• Balkan heritage

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Screening for renal tubular acidosis is usually not recommended for asymptomatic patients. Screening is only recommended for patients with increased risk of having proximal RTA or metabolic disorders associated with the development of Fanconi syndrome.

• Screening for renal tubular acidosis is usually not recommended for asymptomatic patients.^[1][2]
• Screening is only recommended for patients with increased risk of having proximal RTA or metabolic disorders associated with the development of Fanconi syndrome.
• Screening evaluation include measurement of :
  • Serum phosphate
  • Urinary glucose
  • Urinary amino acids
  • Urinary phosphate excretion

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

If left untreated renal tubular acidosis leads to growth failure and chronic kidney failure. Common complications associated with renal tubular acidosis include volume depletion, electrolyte disturbances, nephrocalcinosis, osteoporosis, growth retardation, renal rickets. Prognosis of renal tubular acidosis is generally good with appropriate therapy.

If left untreated renal tubular acidosis leads to growth failure and chronic kidney failure leading to electrolyte disturbances, bone abnormalities, cranial nerve compression and in severe cases it may lead to heart failure and death.^[1]

Common complications associated with renal tubular acidosis include:^[2][3]

• Volume depletion
• Electrolyte disturbances
• Nephrocalcinosis
• Osteoporosis
• Growth retardation
• Renal rickets
• Fludrocortisone-associated hypertension and edema or pulmonary edema
• Osteopetrosis

• Prognosis of renal tubular acidosis is generally good with appropriate therapy.^[4][5]
• Alkali therapy seems effective in prevention of renal stones and nephro-calcinosis in patients with incomplete distal renal tubular acidosis.
• Aggressive correction of acidosis has been shown to restore growth in children with renal tubular acidosis.
• Effective treatment proved no effect on already occurred damage such as blindness and deafness due to nerve compression.
• The prognosis of Fanconi syndrome depend on etiology.
  • In inherited metabolic disease, it is of poor prognosis .
  • When it is secondary due to drugs or toxin exposure, prognosis is generally good as it regresses on with drawl of the offending agent.