Renal tubular acidosis — formative SAQs

SAQ 1 (10)

A 7-month-old infant presents with failure to thrive, vomiting, polyuria, and muscle weakness. Bloods show sodium 138, potassium 2.6, chloride 118, and bicarbonate 12 mmol per litre. The anion gap is normal. The urine pH is 6.8, and a renal ultrasound shows bilateral nephrocalcinosis. [1][8]

1. Define renal tubular acidosis and explain why the anion gap is normal in this condition. (2) [9][2]
2. Identify the type of RTA, giving three supporting features from the stem, and explain the mechanism of the nephrocalcinosis. (4) [3][8]
3. Outline the immediate and definitive management, naming the drug, dose, route and rationale, and state two dangers of over-rapid bicarbonate correction. (4) [2][9]

Model answer

Definition and the normal anion gap. Renal tubular acidosis is a metabolic acidosis with a normal anion gap (hyperchloraemic) caused by a defect in renal acid-base handling rather than by kidney failure or unmeasured acid accumulation. The anion gap is calculated as sodium minus the sum of chloride and bicarbonate. In RTA the kidney loses bicarbonate, and chloride rises to preserve electroneutrality, so the gap stays normal (8 to 12, up to 16 mmol per litre). A high anion gap acidosis (DKA, lactic acidosis, renal failure, toxins) is never RTA. [9][2]

Type identification and nephrocalcinosis mechanism. This is type 1 (distal) RTA. Three supporting features: the urine pH is 6.8, persistently above 5.5 despite systemic acidosis, showing the alpha-intercalated cell cannot secrete hydrogen via the H-ATPase; the potassium is low at 2.6 mmol per litre from distal potassium wasting; and nephrocalcinosis is present. The nephrocalcinosis arises because chronic acidosis buffers calcium out of bone, producing hypercalciuria; intracellular acidosis increases proximal citrate reabsorption, so urinary citrate falls; and the alkaline urine favours calcium phosphate precipitation. Hypocitraturia plus hypercalciuria plus alkaline urine equals nephrocalcinosis. [3][8]

Management. Immediate management for severe symptomatic acidosis is cautious intravenous sodium bicarbonate to raise the bicarbonate only partially, to around 12 mmol per litre, with potassium replaced first because correction will shift potassium into cells. Definitive management is oral alkali (sodium or potassium citrate, or bicarbonate) at 1 to 4 mEq per kg per day, because in distal RTA the bicarbonate threshold is normal and little is wasted once the plasma level is restored; children need the higher end to restore growth. Identify the cause with genetics (ATP6V1B1, ATP6V0A4) and a hearing assessment. Two dangers of over-rapid correction: hypokalaemia from potassium shifting into cells, and hypocalcaemic tetany or seizures as ionised calcium falls (a third is hypernatraemia and fluid overload). [2][9]

SAQ 2 (10)

A 3-year-old child presents with chronic diarrhoea and is found to have a normal anion gap metabolic acidosis. The urine anion gap (sodium plus potassium minus chloride) is negative. Separately, you are asked to counsel the family of a child newly diagnosed with proximal RTA due to cystinosis. [9][10]

1. Explain how the urine anion gap separates a renal cause from a gastrointestinal cause of a normal anion gap acidosis, and interpret this child's result. (4) [10][9]
2. Explain why the oral alkali dose for proximal RTA (10 to 20 mEq per kg per day) is so much higher than for distal RTA (1 to 4 mEq per kg per day). (3) [6][2]
3. Outline the management of proximal RTA in cystinosis, including the role of cysteamine, and two monitoring priorities. (3) [6][2]

Model answer

Urine anion gap interpretation. The urine anion gap, calculated as the sum of urine sodium and potassium minus urine chloride, is a surrogate for urinary ammonium excretion, because ammonium is excreted mainly with chloride. A negative gap indicates high ammonium excretion, meaning the kidney is responding appropriately to the acidosis and the cause is gastrointestinal bicarbonate loss (diarrhoea). A positive gap indicates low ammonium excretion, meaning the kidney is failing and the cause is renal tubular acidosis or renal failure. This child has a negative gap with chronic diarrhoea, so the cause is gastrointestinal and the kidney is compensating appropriately. The gap is unreliable when urine sodium is below 25 mmol per litre or when unmeasured urinary anions (ketoacids, hippurate) are present. [10][9]

The alkali dose difference. The dose reflects the bicarbonate threshold. In proximal RTA the proximal tubule's threshold for bicarbonate reabsorption is lowered, so the kidney continues to spill bicarbonate into the urine above that threshold no matter how much is replaced, requiring 10 to 20 mEq per kg per day. In distal RTA the threshold is normal, so once the plasma bicarbonate is restored the kidney reabsorbs it and only a modest maintenance dose (1 to 4 mEq per kg per day) is lost. Under-dosing proximal RTA leaves the child acidotic and growth-impaired. [6][2]

Cystinosis management and monitoring. Management combines high-dose alkali (10 to 20 mEq per kg per day in divided doses) with potassium supplementation (because distal bicarbonate delivery drives potassium wasting), phosphate and vitamin D for the rickets, and cysteamine, which depletes lysosomal cystine and dramatically slows the progression to renal failure. Two monitoring priorities are growth (weight, height, and recovery of the centiles as a marker of adequate therapy) and renal function (serum bicarbonate, potassium, phosphate and creatinine, and surveillance for progression). Leukocyte cystine levels guide the cysteamine dose. [6][2]