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.
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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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Great review. Btw, I’m an ed doc and lots of us are using LR after a liter or two of NS and we are aware and believe the new evidence. I’m having trouble finding a pdf of show notes for this and other epusodes
I should have stipulated that the ED at Kashlak is not yet on the LR bandwagon. I'm glad to hear using LR is more en vogue elsewhere. Thanks for your comments!
Regarding the PDF - do you subscribe to our newsletter? If not, you can sign up here: http://thecurbsiders.com/knowledgefood Once you are signed up, you can access PDFs here:https://us15.campaign-archive.com/home/?u=de162490a18f8c8c1ddfe91d7&id=c471d75855
Another great episode - surprised and pleased that you cited my blog post! Couple of comments: bicarbonate replacement - the hospitals where I work have 1300 mg bicarbonate tabs (approximately 15 mEq) some patients prefer a liquid - sodium citrate (Shohl's solution or bicitra) - 1 mEq/cc Add the normal gap acidosis of progressive CKD (usually stage 3b or 4) - recent data on treating the acidosis to slow progression of CKD Finally, worthwhile to discuss the conundrum of the diabetic renal patient with significant proteinuria and who develops type IV RTA on an ACE-I or ARB. Do you add one of the expensive potassium lowering meds to continue the ACE-I/ARB? The same problem occurs with some diabetic renal disease patients who have systolic dysfunction. Thanks for this podcast!
These are great insights. I too see a lot of patients on Shohl's solution. The dosing there can be titrated similarly to the tablets. We didn't get to it on are, but it'd be a good follow up question for kidney boy on twitter about whether or not he commonly treats NAGMA in CKD 3-4 to prevent progression.
This was a great podcast that I will listen to again as part of a spaced repetition strategy. I recent began commuting a couple of hours to work each day and I have gone back and listened to many of your earlier podcasts. I found the evolution of your style and format interesting. I think you're doing this right. On a side note, I got an email message from a 41 year-old female (ambulatory, well-nourished) patient this morning asking "What does anion gap being at a low value mean?" This was on a BMP obtained to check blood sugar (yes, shame on me for not just ordering a FBS). Na 137 - Cl 106 - CO2 29 = AG 2. Her K is 4.1 and Ca 9.1. Previous AGs were 7 and 13. I didn't have a reason to get an albumin but it has been normal in the past. In reviewing causes of low AG, I came across this old study: The Myth of the Low Anion Gap Robert J. Goldstein, MD; Norman S. Lichtenstein, MD; Daniel Souder, MD JAMA. 1980;243(17):1737-1738 Sixty-seven thousand seven hundred forty consecutive sets of electrolyte levels measured at the Massachusetts General Hospital were reviewed, and their anion gaps were calculated. A low anion gap (less than 8 mEq/L) was found in 304 patients (0.8%). Repeatedly low anion gaps were found in only 19 patients. Eight patients were hypoalbuminemic, and eight were hyponatremic. For the entire population, there was a positive correlation between sodium concentration and anion gap. The average anion gap was 16.25 mEq/L. The most common cause of a low anion gap was presumptive laboratory error. I suspect that in my patient, the low gap probably comes from a low normal sodium and high normal Cl and CO2. My inclination is to rinse and repeat. Jorge J. Scheirer, MD, FACP, MBI