Renal tubular acidosis aka RTA deconstructed by @Kidney_Boy, Joel Topf MD, Chief of Nephrology at Kashlak Memorial Hospital. We review the three buckets of non gap metabolic acidosis, normal renal physiology & acid base handling, points of failure in RTA, complications and treatment of RTA. Check out Dr Topf’s awesome slides on renal tubular acidosis at http://thecurbsiders.com/podcast . You may want to go back and check out episode #88 Acid Base, Boy Bands and Grandfather Clocks with Joel Topf MD if you haven’t heard it yet.
Written by: Matthew Watto MD and Joel Topf MD
Slides and figures by: Joel Topf MD
Produced by: Matthew Watto MD
Hosts: Matthew Watto MD, Stuart Brigham MD, Paul Williams MD
Guest: Joel Topf MD
Non gap metabolic acidosis (NAGMA)
Split non-gap metabolic acidosis into three buckets (see figure below):
Bucket 1: GI losses – diarrhea, surgical drains, ureteral diversion to bowel, cholestyramine
Bucket 2: Chloride intoxication – normal saline (common), HCl or chloride gas intoxication (rare)
Bucket 3: Renal losses – Renal tubular acidosis types 1, 2, 4
Normal renal acid base handling involves:
Failure of the kidney to complete these processes results in renal tubular acidosis.
The goal is to mitigate the negative effects of chronic metabolic acidosis (e.g. osteoporosis from bone buffering), but comes with the downside of increase calcium phosphate stone formation since the resulting bicarbonaturia leads to HPO42- binding calcium instead of hydrogen causing calcium phosphate stone formation.
Sodium bicarbonate 650 mg tab = 8 mmol bicarbonate
Sodium bicarbonate 325 mg tab = 4 mmol bicarbonate
Baking soda, one teaspoon = 60 mmol bicarbonate
Urine anion gap
(Urine Na+ + K+) – Urine Cl– = Urine anion gap
Urine cations aka positive charges = sodium Na+, potassium K+, ammonium NH4+
Urine anions aka negative charges = chloride Cl–
A negative (“neg-GUT-ive”) anion gap implies the presence of ammonium (NH4+), which means renal acid secretion remains intact. A positive urinary anion gap (when the sum of Na+ plus K+ is greater than Cl-) implies impaired renal acid secretion aka absence of ammonium. The combination of a positive urine anion gap plus metabolic acidosis is suggestive of a renal tubular acidosis.
Proximal RTA (Type 2)
Hallmark – bone loss; low serum bicarbonate despite aggressive repletion
Pathophysiology – Damage to proximal tubule → failure to reabsorb all filtered bicarbonate in the proximal tubule. New set point for bicarbonate drops from 28 to mid-teens (e.g. HCO3 = 15). See figure 3.
Causes – Acetazolamide, topiramate, tenofovir; Multiple myeloma
Treatment – Very challenging to treat due to fixed bicarbonate reabsorption capacity. Attempts to raise serum bicarbonate above the new set point lead to bicarbonaturia, which causes hypokalemia and calcium phosphate stone formation. Patients often require both sodium bicarbonate and potassium salt supplementation. (Treatment Type 1 & 2 RTA. UpToDate 2018).
Distal RTA (Type 1)
Hallmark – alkalotic urine, calcium phosphate stones and bone loss from buffering
Pathophysiology – Normal renal hydrogen ion [H+] secretion involves:
Step 1) reabsorption of sodium to create a negative gradient in the tubular lumen
Step 2) excretion of [H+] by ATPase
Step 3) a specialized epithelium to prevent [H+] ions from diffusing back out of the tubular lumen.
Failure at any step results in an RTA: Failure of step one causes impaired H+ and K+ secretion into the tubular lumen with resultant hyperkalemic metabolic acidosis. The “classic distal RTA” occurs when the H+ ATPase (step 2) fails causing a lack of competition between H+ and K+ for negative charge in the tubular lumen with resultant hypokalemic metabolic acidosis. The specialized epithelium (step 3) can be damaged by amphotericin B leading to back diffusion of [H+] and hypokalemic metabolic acidosis.
Treatment – Replace bicarbonate. Much more achievable than in proximal RTA since distal tubule only needs to handle 1 mmol/kg body wt/day (see figure below). Exacerbation of stone formation can occur as a side effect of bicarbonate replacement due to bicarbonaturia. -Dr Topf
Type 4 RTA (Hyporenin, Hypoaldosteronism)
Check out this great post by our Chair of Medicine, Robert Centor MD, aka @medrants http://www.medrants.com/archives/8897.
Hallmark – hyperkalemia and mild metabolic acidosis (e.g. HCO3 = 22) in setting of long standing diabetes or culprit medication (e.g. ACE inhibitor, angiotensin receptor blocker)
Pathophysiology – Normally, ammonia combines with H+ ions in the distal nephron to buffer the daily acid load and becomes ammonium (NH4+). This process is the kidneys most adaptable response to an increased daily acid load since the kidney cannot drop the urine pH below 4.5 and titratable acid (HPO42-) cannot be increased. Chronic hyperkalemia of any cause leads to impaired ammoniagenesis (NH3 production), hampering the kidney’s ability to respond to the daily acid load by “stowing” H+ in ammonium (NH4+). Note: Aldosterone induced secretion of H+ in the distal nephron is NOT the driving force of metabolic acidosis in type 4 RTA. It’s the impaired ammoniagenesis!
Complications – hyperkalemia; mild acidosis (usually HCO3 in the low 20s).
Treatment – Stop any culprit medications. Treat the hyperkalemia!
Goal: Listeners will be familiar with the physiology, pathogenesis, clinical manifestations and treatment of renal tubular acidosis and non anion gap metabolic acidosis
After listening to this episode listeners will…
Disclosures: Dr Topf reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
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