Primary tubular proximal acidosis

Primary Tubular Proximal Acidosis

Primary tubular proximal acidosis, also known as proximal renal tubular acidosis (pRTA), is a disorder characterized by the inability of the proximal tubules of the kidneys to reabsorb bicarbonate (HCO₃⁻) efficiently. This condition leads to a decrease in blood bicarbonate levels, resulting in metabolic acidosis. It is a type of renal tubular acidosis (RTA), which is a group of disorders that affect the renal tubules' ability to maintain acid-base balance.

Pathophysiology

The proximal tubules are responsible for reabsorbing approximately 85% of the filtered bicarbonate in the kidneys. In primary tubular proximal acidosis, there is a defect in this reabsorption process, leading to bicarbonate wasting in the urine. This defect can be due to genetic mutations affecting the transporters involved in bicarbonate reabsorption, such as the sodium-bicarbonate cotransporter (NBCe1) or carbonic anhydrase enzymes.

The resulting bicarbonate loss leads to a decrease in blood pH (acidemia) and a compensatory increase in chloride reabsorption, causing hyperchloremic metabolic acidosis. Unlike distal renal tubular acidosis, proximal RTA is often associated with other tubular dysfunctions, such as glycosuria, aminoaciduria, and phosphaturia, due to generalized proximal tubular dysfunction, also known as Fanconi syndrome.

Clinical Presentation

Patients with primary tubular proximal acidosis may present with:

- Growth retardation in children - Polyuria and polydipsia - Muscle weakness - Bone pain or osteomalacia due to phosphate wasting - Rickets in children

The condition can be isolated or part of a syndrome, such as Fanconi syndrome, which includes additional symptoms due to the generalized dysfunction of the proximal tubule.

Diagnosis

Diagnosis of primary tubular proximal acidosis involves:

- Blood tests: Showing low bicarbonate levels and normal anion gap metabolic acidosis. - Urine tests: Demonstrating bicarbonate wasting, especially after bicarbonate loading tests. - Genetic testing: May be performed to identify mutations in genes associated with proximal RTA.

Treatment

The primary treatment for proximal RTA involves:

- Alkali therapy: Oral bicarbonate or citrate supplements to correct acidosis. - Phosphate supplements: In cases with phosphate wasting. - Vitamin D: To manage bone disease.

Management of underlying conditions, such as Fanconi syndrome, is also crucial.

Prognosis

With appropriate treatment, patients can lead normal lives, although growth and bone development in children need careful monitoring.

Also see

- Renal Tubular Acidosis - Fanconi Syndrome - Metabolic Acidosis - Bicarbonate Reabsorption