Renal Tubular Acidosis B&B

Question 1

what occurs in a Type I renal tubular acidosis?

Answer 1

Type I (distal) RTA: distal nephron can’t excrete H+ or resorb K+ —> acidemia and hypokalemia

very low HCO3- (recall H+ secretion is needed for HCO3- reabsorption) and urine pH is high (>5.5)

diagnosis made if urine is alkaline despite a metabolic acidosis

Question 2

what symptoms are caused by a Type I rental tubule acidosis?

Answer 2

Type I (distal) RTA: distal nephron can’t acidify urine, high urine pH

—> chronic kidney stones because alkaline urine precipitates stones (can be bilateral)
—> Rickets because acidosis increases Ca2+ resorption from bone and suppresses Ca2+ resorption in kidney

Question 3

which 2 autoimmune diseases are classically associated with Type I renal tubule acidosis?

Answer 3

Type I (distal) RTA: distal nephron can’t acidify urine, high urine pH

1. Sjögren’s syndrome
2. Rheumatoid arthritis

Question 4

what does the urine anion gap represent?

Answer 4

urine anion gap: Na + K - Cl

surrogate of NH4 excretion (main method of removing H+), which leaves with Cl

UAG is negative when acid (H+) is being excreted

Question 5

how will the urine anion gap be altered by diarrhea vs distal renal tubule acidosis?

Answer 5

urine anion gap (Na + K - Cl) is surrogate for NH4 (H+) excretion

diarrhea (GI metabolic acidosis): UAG becomes negative because NH4 excretion increases (and Cl follows) - urine [Cl] increases

Type I/distal RTA: UAG is positive because kidneys can’t excrete H+ (no increase in NH4 or Cl)

Question 6

what is the purpose of an NH4Cl challenge for patients with a suspected metabolic acidosis?

Answer 6

NH4Cl challenge: given acid load and urine pH should drop

if patient has Type I/distal renal tubule acidosis, urine pH will remain >5.3 because kidneys can’t excrete H+, and urine anion gap (UAG) will be positive

if patient has GI metabolic acidosis (diarrhea), UAG will be negative (urine will acidify)

Question 7

Pt is a 25yoF with PMH of Sjorgren’s disease presenting with bilateral kidney stones. Blood work shows a very low bicarb (<10), hypokalemia, high urine pH (>5.5), and the urine anion gap is positive. What is going on and what treatment can you give them?

Answer 7

Type I (distal) RTA: distal nephron can’t acidify urine (secrete H+ / resorb K+), high urine pH

associated with Sjorgren’s (and Rheumatoid arthritis), alkaline urine produces stones

treatment: sodium bicarbonate

Question 8

what occurs in Type II renal tubule acidosis?

Answer 8

Type II (proximal) RTA: defect in proximal HCO3- reabsorption

—> initially high urine pH (due to HCO3- excretion), which corrects as distal tubule excretes H+
—> hypokalemia because loss of HCO3- reabsorption causes diuresis and volume contraction, which stimulates aldosterone (which increases K+ excretion)

• milder than Type I/distal RTA because the distal intercalated cells are functionally normally and can secrete H+ to compensate (no kidney stones)

Question 9

which type of renal tubule acidosis can be seen with Fanconi syndrome?

Answer 9

Fanconi syndrome: generalized failure of proximal tubule —> urine loss of phosphate, glucose, amino acids, urate, protein

can cause Type II (proximal) RTA: defect in proximal tubule HCO3- reabsorption

Question 10

Patient is a 35yo M presenting at their annual wellness visit. Routine blood work reveals hypokalemia, mildly reduced HCO3- (10-20), and a low urine pH (<5.3). What is likely going on and how can you treat them?

Answer 10

Type II (proximal) renal tubule acidosis: defect in proximal HCO3- reabsorption

milder than type I/distal RTA because distal intercalated cells can secrete H+ to compensate (—> low urine pH)

treat with sodium bicarbonate

Question 11

what occurs in a Type IV renal tubule acidosis?

Answer 11

Type IV RTA: distal tubule fails to respond to aldosterone (deficiency or resistance)

—> HYPERkalemia (due to less excretion)
—> impaired ammonium (NH4+) excretion causes acidosis
—> urine pH remains low (<5.4)

Question 12

what are some causes of decreased aldosterone vs aldosterone resistance that can result in a Type IV renal tubule acidosis?

Answer 12

Type IV RTA: distal tubule fails to respond to aldosterone (deficiency or resistance)

deficiency: diabetic renal disease, ACE inhibitors or ARBs, NSAIDs, adrenal insufficiency

resistance: K+ sparing diuretics, TMP/SMX (antibiotic)

Question 13

Patient is a 37yo M with PMH of diabetes and renal insufficiency. Routine lab work shows unexplained hyperkalemia. What is likely going on and what treatment can you give them?

Answer 13

Type IV renal tubule acidosis: distal tubule fails to respond to aldosterone (deficiency or resistance)

in case of renal insufficiency, cause is aldosterone deficiency —> treat with fludrocortisone (mineralocorticoid)

Question 14

what is the cause of Type I vs Type II vs Type IV renal tubule acidosis?

Answer 14

Type I: distal failure to excrete H+ —> high urine pH, very low HCO3-, kidney stones

Type II: proximal failure to resorb HCO3- —> mild acidosis, seen in Fanconi’s

Type IV: lack of distal aldosterone activity —> hyperkalemia, seen in diabetes and renal failure

Question 15

for Type I vs Type II vs Type IV renal tubule acidosis, provide the following:
a. what channel is affected
b. how is plasma K+ affected
c. what will urine pH be

Answer 15

Type I: distal H+/K+ exchangers —> low [K+] (<3.5), high urine pH (>5.4)

Type II: proximal HCO3- channels —> low plasma [K+] (<3.5), low urine pH (<5.4)

Type IV: aldosterone channels —> high plasma K+ [>5], low urine pH (<5.4)