Metabolic acidosis is classified as either high anion gap (caused by increased production or ingestion of acid and impaired renal acid excretion) or normal anion gap (caused by the loss of bicarbonate from the kidney or gastrointestinal tract).
Nonanion gap metabolic acidosis associated with a positive urine anion gap suggested that the metabolic acidosis was most likely the result of a renal tubular defect rather than a consequence of diarrhea. A distal acidification defect was strongly suspected because although the patient had a nonacute proximal renal tubular acidosis, she still had a urine pH of 8. carbonic anhydrase inhibitors can also interfere with H+ secretion by the distal tubule . In addition to its multiple antiepileptic activities, topiramate inhibits isoenzymes of carbonic anhydrase in proximal renal tubules. Reduction in carbonic anhydrase activity impairs the exchange of H+ for Na+ in the proximal tubule, as well as the reabsorption of bicarbonate (HCO3−), and may result in nephrolithiasis, paresthesia, somnolence, and metabolic acidosis.chronic topiramate use may result in a distal tubular acidification defect, which in turn may lead to a higher risk of calcium phosphate nephrolithiasis.
There are several reports in the literature of an association between TMP and hyperchloremic normal anion gap metabolic acidosis with an alkaline urine and positive urine anion gap (due to increased urine HCO3–)
Renal tubular acidosis caused by TMP can lead to decreased urine citrate concentration; hypocitraturia combined with decreased urine acidification in the distal convoluted tubules can contribute to the formation of calcium phosphate stones [16, 17]. The risk of the renal stone formation increases to 10 folds with the use of TMP.
Treatment with an alkali such as sodium bicarbonate or potassium citrate and citric acid can be used to restore normal serum HCO3– in patients with RTA. This can also decrease urinary calcium excretion and increase urinary citrate excretion which can prevent renal stone formation and improve bone disease in adults
proximal RTA (the way you like it), the defect is a decreased capacity to reclaim filtered bicarbonate in the proximal tubule. The renal bicarbonate losses continue until steady state is reached where the serum bicarbonate—and thus the filtered bicarbonate load—has decreased so much that it is able to be completely reabsorbed. When proximal RTA is in steady state or not treated, and the problem is isolated to bicarbonate reabsorption in the proximal tubule, then there will be no problems with NH4+ production in proximal tubule, so therefore the urine anion gap will be negative. Also, there will be no problems with the H+ pumps in the distal nephron, so the urine pH should be less than 5.5
Her fractional excretion of bicarbonate was 17%.
So this patient demonstrates the inability to acidify her urine also in steady state conditions. In the face of severe acidemia one would expect her urine to be maximally acidified, and yet this young patient with otherwise normal renal function is unable to get the urine pH lower than 5.5.Henle A problem with distal acidification. So you’re thinking about a distal RTA also?Nephron Exactly. In fact, a mixed proximal and distal nephrogenic tubular acidosis caused by topiramate
patient who presented with a hyperchloremic metabolic acidosis, symptomatic for 1 week, with bicarbonate initially of 12. The history and urine studies suggested a nephrogenic cause of the acidosis. Potassium was normal. Her urine was consistent with a distal acidification defect, but she also demonstrated increased FE bicarbonate after receiving bicarbonate supplementation. And all of these findings are consistent with adverse effects related to topiramate
