Diabetes insipidus and polyuria-polydipsia — formative SAQs

SAQ 1 (10)

A 4-month-old boy is admitted for the third time with fever, vomiting, and poor feeding. He is irritable and dehydrated, and his weight has fallen across two centile lines. Serum sodium is 158 mmol/L, glucose is normal, and the urine is dilute (osmolality 120 mmol/kg) despite the dehydration. A maternal uncle had "kidney trouble as a baby." [3][9]

1. Give the most likely diagnosis, the pattern of inheritance, and the pathophysiological basis. (3) [9]
2. Outline how you would confirm the diagnosis and exclude the main alternatives. (3) [5][9]
3. Describe the long-term management and explain why early diagnosis matters. (4) [9][3]

Model answer

Diagnosis, inheritance, and pathophysiology. This is congenital nephrogenic diabetes insipidus (arginine vasopressin resistance). The picture — a young boy with recurrent fevers, vomiting, faltering growth, and hypernatraemia with inappropriately dilute urine, plus a maternally related affected male — points to the X-linked form from an AVPR2 mutation, which accounts for about 90 per cent of inherited cases. The V2 receptor on the collecting duct cannot respond to vasopressin, so aquaporin-2 is not inserted into the apical membrane, the kidney cannot concentrate urine, and free water is lost despite a high circulating vasopressin. [9]

Confirmation and alternatives. First exclude osmotic diuresis with the (normal) glucose. Confirm the water diuresis with paired serum and urine osmolality and a serum sodium — a high serum osmolality/sodium with a low urine osmolality is diagnostic of a concentrating defect. Distinguish nephrogenic from central disease by the response to desmopressin: in nephrogenic disease the urine does not concentrate, whereas central disease does. A high copeptin supports nephrogenic disease because vasopressin is present but ignored. Check calcium and potassium to exclude acquired nephrogenic causes, and take a family history for the X-linked pattern. Genetic testing (AVPR2, then AQP2) confirms the subtype. [5][9]

Long-term management and why early diagnosis matters. Desmopressin does not work in nephrogenic disease, so treatment reduces the solute the kidney must excrete and removes reversible factors. Provide a low-solute (low-sodium) diet with age-appropriate protein and free access to water, and use a thiazide diuretic with amiloride, adding indometacin to potentiate concentration. Early diagnosis matters because repeated hypernatraemic dehydration in infancy causes neurodevelopmental harm; recognising the pattern rather than repeatedly treating "sepsis" or "gastroenteritis" protects the developing brain and allows growth to be maintained. [9][3]