RTA

Renal Tubular Acidosis (RTA): A Simple Framework​

Note: There are a number of processes and nuances that are not discussed here; this is intended to be a "primer" and give a fundamental understanding of renal handling of acidosis and how things can go wrong.  If you want a slightly deeper yet digestible dive, see the suggested readings at the end of this post.

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Big Picture

​The kidney maintains acid–base balance by doing two essential jobs:

1. Reabsorbing filtered bicarbonate (HCO₃⁻). ~80+% is reabsorbed in the proximal tubule

2. Generating new bicarbonate to match daily acid production (from consumption of nonvolatile acids (i.e. cannot be converted to CO2 and exhaled, therefore must be eliminated in the kidneys.  e.g. sulfur and methionine, which are present in various proteins) 

 

RTA occurs when one or both of these processes fail.

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1: Reabsorbing Filtered Bicarbonate

• Large amounts of bicarbonate are filtered daily at the glomerulus.

• Nearly all must be reabsorbed, or base is lost in urine.

• This process occurs primarily in the proximal tubule.

• However, this process only maintains the current serum bicarbonate level.

 

Failure to reabsorb bicarb → bicarbonate wasting → metabolic acidosis.

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2: Generating New Bicarbonate

​         As stated above, reabsorption alone is not enough. The body produces acid daily, so the kidney must create new bicarbonate.

            Key principles

                               Glutamine Metabolism (Proximal Tubule)

                                 - Glutamine is metabolized inside proximal tubule cell

                                        - Each molecule of glutamine produces:             

 

                                                                          

                 

 

               

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Failure to excrete acid (i.e. failure to excrete NH4+) + inability to generate new Bicarb-> metabolic acidosis

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What Is Renal Tubular Acidosis?​

RTA = normal anion gap metabolic acidosis caused by impaired renal acid handling

The kidney fails to:

• Reabsorb bicarbonate

• Excrete acid as ammonium

• Or both

Diagnosing RTA​

1. Identify normal anion gap metabolic acidosis (serum pH <7.35, HCO3- low. Tip: pH MUST be low!!)

2. Exclude obvious gastrointestinal bicarbonate loss (e.g., diarrhea)

3. Assess renal acid excretion:

   • Urine pH

   • Urine Na+, K+, Cl- to determine the urine anion gap (UAG)

   • Urine ammonium is not measured as it is difficult to measure. (*see suggested readings)

Types of RTA

 Type 1 – Distal RTA

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Type 2 – Proximal RTA

Mnemonic: “Type TWO → Too much BI (i.e. 2)-carbonate loss” NOTE: Isolate RTA with no other electrolyte derangements is rare. Typically, the proximal tubule as a whole is affected, so you see glucosuria in the setting of normal serum glucose, phosphate wasting, et.c)

• Defect: impaired proximal bicarbonate reabsorption due to lowered threshold (i.e. the proximal tubule can only absorb ~15-18 mEq/L of bicarb instead of the normal 24-28 mEq/L). Often due to medications decreasing CA activity or gene defects. 

• If bicarb intake is high the bicarb load overwhelms the distal tubule (typically reabsorbs ~10% of filtered bicarb) and there is  bicarbonate wasting, resulting in alkaline urine and serum bicarb of only ~15-18mEqL. If intake drops/bicarb is at new steady state, the distal nephron compensates so urine can acidify, i.e. a low urine pH.

• Causes (see simplified image): Genetic (NBCE1, Wilson's, Cystinosis (MC genetic cause of Proximal RTA).

• Medications

  • (e.g. Ifosfamide, Valproate, Acetazolamide)

• Features:

  • Variable urine pH (depends on intake, as above)

  • Often part of Fanconi syndrome.

  • Hypokalemia

  • (isolated proximal RTA is rare).   

  • Urine anion gap may be variable

                  - (intact NH4+ excretion)

           

Typical "Boards" patient is child receiving chemo etc with MULTIPLE electrolyte abnormalities or blond haired young child who has been squinting or weak with MULTIPLE electrolyte abnormalities (Cytinosis- NOT Cystinuria, which is a kidney stone disease).

 

 

 

 

Type 4 – Hyperkalemic RTA

Think- hypoaldosteronism (Low Na+, High K+, Low HCO3-)

• Defect: hypoaldosteronism or aldosterone resistance

• Causes: Genetic (aldosterone synthase deficienncy), Chronic kidney disease, obstructive uropathy, medications (e.g. Tacrolimus, TMP/SMX, ,Cyclosporine, ACE-I/ARB

• Consequences:

  • Decreased ammonium production

  • Impaired acid excretion

• Features:

  • Hyperkalemia

  • Mild metabolic acidosis

  • Urine pH often < 5.5​

 

Urine Anion Gap (UAG)

Used to estimate urinary ammonium excretion. When considering/thinking how the UAG differs between diarrhea and RTA, using distal RTA as the paradigm is ideal since, as noted, proximal RTA may be variable.

Formula:
UAG = Urine Na + Urine K − Urine Cl. Urine ammonium(NH4+)  is unmeasured.

• NH₄⁺ is excreted with Cl⁻ to maintain electroneutrality

• If kidney acidification is intact, acidosis-> more NH₄⁺ → more urine Cl⁻ → more negative UAG​ (not great test, see suggested readings)

• ​Urine osmolar gap (indirect measure of NH4+ excretion- if high, renal acidification is intact- see suggested readings)

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Diarrhea vs RTA: Why UAG Differs​

Diarrhea (Extrarenal Acidosis)

• Kidney response is appropriate

• NH₄⁺ excretion increases

• Urine chloride increases

• UAG is negative (neGUTive)

RTA (Renal Acidosis)

• Kidney fails to excrete NH₄⁺

• Urine chloride is low

• UAG is positive

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