Proximal renal tubular acidosis, also known as type 2 renal tubular acidosis, is distinguished by the impaired absorption of bicarbonate in the proximal tubule of the nephron. Wasting of bicarbonate, as well as other electrolytes, proteins and glucose in the proximal tubule lead to symptoms. Urinalysis is needed to make the diagnosis.
Although several compensatory mechanisms are employed in the setting of proximal tubule defects (increased bicarbonate reabsorption occurs in the thick ascending limb of the loop of Henle and in the distal parts of the nephron), their capacity is not able to overcome proximal tubule loss, leading to the appearance of symptoms . Proximal renal tubular acidosis (RTA) is most frequently encountered as a constitutive feature of Fanconi's syndrome, a disorder characterized by proximal tubule dysfunction due to mutations in the sodium-phosphate cotransporter (NaPi-II), in which loss of bicarbonate is accompanied by loss of glucose, amino acids, phosphate, uric acid and other electrolytes . In addition, several genetic and acquired etiologies may cause proximal RTA, such as cystinosis, multiple myeloma, wilson disease, sjögren syndrome, primary hyperparathyroidism, drug-induced (gentamicin, ifosfamide, sodium valproate, antiretroviral drugs, and cisplatin are known inducers), cadmium poisoning and several variants of inherited RTA - autosomal dominant and two autosomal recessive forms that presumably occur due to carbonic anhydrase (CA) deficiency and mutations in several other gene families    . Nevertheless, the clinical features, because of the extensive nutrient loss, are similar and include growth retardation and short stature in childhood, osteomalacia due to the inability of vitamin D to convert into its active form in the proximal tubule, as well as hypothyroidism, hyperparathyroidism, dental defects and ocular abnormalities (cataracts, glaucoma, keratopathies)    . Muscle and generalized weakness, reduced deep tendon reflexes and other signs of hypokalemia may be seen, whereas osteopetrosis and cerebral calcifications are characteristic for certain inherited forms .
Signs and symptoms of proximal renal tubular acidosis are non-specific, but with a high dose of clinical suspicion, a presumptive diagnosis of electrolyte imbalance can be made. Moreover, a detailed physical examination and a thoroughly obtained patient history may reveal key information, such as recent use of drugs that are known inducers of proximal RTA, the presence of similar symptoms in siblings, parents or close relatives, or confirmed underlying disorders that can predispose to electrolyte imbalance. Laboratory evaluation and urinalysis, however, are the mainstay during workup. Assessment of sodium, potassium, bicarbonate, calcium and phosphorus in serum is detrimental to make the diagnosis and proximal RTA manifests as a normal anion gap metabolic acidosis   . A low urine pH (< 5.5) and a very low bicarbonate in serum strongly suggests defects of the proximal tubule, and probes such as administration of sodium bicarbonate (NaHCO3) can be performed to solidify the diagnosis . When NaHCO3 is administered, urine pH markedly increases (pH > 7.5) due to the inability of the proximal tubule to absorb bicarbonate (HCO3), and a fractional excretion of HCO3 of more than 15% is considered diagnostic for proximal RTA  . The test must be done cautiously and with potassium supplementation, as severe hypokalemia can occur and cause severe cardiac and skeletal abnormalities. Additional findings from urinalysis include glycosuria, hyperphosphaturia, and proteinuria . If the underlying cause is not disclosed, a full laboratory workup, comprised of thyroid and parathyroid hormones, vitamin D levels, renal and hepatic function tests, arterial blood gasses (ABGs), and a complete blood count (CBC), should be performed.