Renal tubular acidosis

Distal (type 1) and proximal (type 2) renal tubular acidosis (RTA) are rare renal disorders. They mostly occur in adults. Renal tubular acidosis is classified into distal RTA, proximal RTA, mixed RTA, and Hyperkalemic RTA. This article is aimed at discussing the aetiology and diagnosis of proximal and distal RTA.


Aetiology of distal (type 1) and proximal (type 2) renal tubular acidosis


Type 1 Distal RTA Aetiology


  • The most common causes of distal renal tubular acidosis in adults are autoimmune diseases such as SLE or systemic lupus erythematosus, Rheumatoid arthritis, Sjogren syndrome, Hepatitis, Thyroiditis, and Systemic sclerosis. 


  • It can occur secondary to genetic syndromes like Ehler Danlos syndrome, Marfan syndrome, and Sickle cell disease. 


  • Chronic hypercalcemia; tubulointerstitial diseases such as chronic interstitial nephritis, chronic pyelonephritis, and obstructive uropathy; and conditions with increased gamma globulin like multiple myeloma, amyloidosis, and cryoglobulinemia can also lead to distal renal tubular acidosis. 


  • Certain drugs like amphotericin B, lithium, lead, NSAIDs, and antivirals can give rise to this disease. Other miscellaneous causes are hypercalciuria and glue sniffing. Glue sniffing is the act of inhaling toluene as recreational drug abuse. 


Type 2 Proximal RTA Aetiology


  • The most common causes of proximal renal tubular acidosis are conditions with increased gamma globulin such as multiple myeloma, light chain monoclonal gammopathy, and amyloidosis. 


  • It can occur secondary to autoimmune diseases like Systemic lupus erythematosus and Sjogren syndrome.


  • Certain drugs such as carbonic anhydrase inhibitors (topiramate, acetazolamide), some tetracyclines, valproate, aminoglycosides, tenofovir, and mercury can lead to proximal RTA. 


  • Miscellaneous causes of proximal renal tubular acidosis include Fanconi syndrome, interstitial nephritis, vitamin D deficiency, chronic hepatitis, and secondary hyperparathyroidism. 


Diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis

  • Serum electrolytes and acid-base balance status: 


  • Most cases of renal tubular acidosis have a defective acid-base buffering system in the kidney. This leads to non-anion gap metabolic acidosis. In renal tubular acidosis, the performance of the kidney is satisfactory. The main problem lies with the faulty acid-base mechanisms.


  • The acid-base imbalance in renal tubular acidosis is due to the faulty NH4+ transport. Also, there is an abnormal distribution of potassium in the kidney. 


  • Glomerular filtration rate or GFR in renal tubular acidosis (in the absence of other renal pathologies) is normal or slightly decreased. 


  • Distal (type 1) and proximal (type 2) RTA patients have hypokalemia or decreased serum potassium levels. As the name suggests, hyperkalemic RTA has hyperkalemia.


  • Some proximal renal tubular acidosis patients may be findings consistent with Fanconi syndrome. These findings include nutritional deficiencies like hyponatremia, hypophosphatemia, hypoproteinemia, or hypoglycemia.

  • Urine examination and biochemical evaluation:


  • A urine examination is essential for RTA diagnosis. The pH of normal urine is 5-6.9. If a patient has alkaline urine (pH >5.5) along with hyperchloremic metabolic acidosis, it is strongly suggestive of renal tubular acidosis.


  • Urinary pH alone is not a reliable tool to conclude a diagnosis of renal tubular acidosis. This is because intravascular volume depletion and urinary tract infection also lead to an increase in urinary pH. The appearance of renal tubular acidosis is mimicked, and, therefore, there is a chance of having a false diagnosis with urinary pH alone. 


  • In distal and hyperkalemic renal tubular acidosis, urinary pH is often <5.5. Here urinary calcium levels are increased. This explains why there is an increased risk of kidney stones in these patients. 

  • Confirmatory test: 


  • It is complex to confirm the diagnosis of renal tubular acidosis. Indices of acid and bicarbonate secretion in urine need to be measured.


  • Distal renal tubular acidosis patients have a defect on the distal end of the tubule, leading to the inability to excrete hydrogen. Proximal renal tubular acidosis patients have a defect on the proximal tubular end, and the problem is with bicarbonate reabsorption. This results in a decrease in bicarbonate and pH. 


  • Hyperkalemic renal tubular acidosis shows features of hypoaldosteronism or decreased aldosterone activity. It occurs when hypoaldosteronism is severe enough to cause derangement in the acid-base balance. A normal anion gap metabolic acidosis is seen in this case. 


  • Hyperkalemic RTA, distal RTA, and proximal RTA can be easily differentiated. Hyperkalemia and serum aldosterone level measurements lead to a diagnosis of hyperkalemic RTA. Proximal RTA is confirmed by a bicarbonate loading test, while distal RTA is confirmed by an NH4+ loading test. 
Back to Top