The child with polyuria and polydipsia

1. The child with polyuria and polydipsia Detlef Bockenhauer

2. Objectives • To provide an overview of polyuria/polydipsia by giving case scenarios • Aetiology • Assessment • management

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4. Case 1: History A 6-month old boy is referred because of failure-to-thrive and vomiting No other significant past or family history, born at 37 weeks gestation, normal pregnancy

5. Case 1: examination Unremarkable examination: weight: 5.54 kg (<0.4th 5ile), height: 62.5 cm (>0.4th), OCF: 42.5 cm (<9th %ile) BP: 94 mmHg systolic Normal renal US

6. Diagnosis? • Diabetes insipidus (central or nephrogenic)

7. Further investigations • Admission for iv DDAVP test • Max urine osm: 83 mosm/kg

8. Diagnosis? • Nephrogenic diabetes insipidus

9. NDI: management • Dietetic advice: restricting solute load to 15 mosm/kg/d but providing appropriate calories and RDA for protein • Each gram protein is metabolised to appr. 4 mmol of urea • Each gram of salt constitutes appr. 18 mosm (9 each for sodium and chloride) • Lipids and carbohydrates do not generate solute load (hence maxijul fortified milk)

10. NDI: medications • Indometacin: enhances (?) proximal tubular sodium uptake. NOT by chemical nephrectomy • Thiazide: enhances proximal tubular sodium uptake • As PT is permeable for water, enhanced sodium uptake results in enhanced water reabsoprtion, thus less water is transported to CD, where it cannot be reabsorbed. • Medications can often be discontinued with increasing age

11. Case 2: History A 3-year old boy is referred because of long-standing polyuria/polydipsia (since age 10 months) He drinks about 2.5 to 3 litres of fluid per day He gets up once or twice at night to drink Local assessment: normal growth and biochemistries Water deprivation test (age 18 m): unable (screams constantly for water) After DDAVP: generalised convulsion with Na of 125 mmol/l. Max urine osm: 482 msom/kg No significant past or family history

12. Case 2: examination Unremarkable examination: weight, height, OCF: all around 9th %ile BP: 100/52 mmHg Normal renal US

13. Diagnosis? • (partial) Diabetes insipidus (central or nephrogenic) based on max Uosm of 482 • Habitual polydipsia

14. Further investigations • Admission for water deprivation /iv DDAVP test • Max urine osm: 630 mosm/kg (normal plasma Na throughout), 639 mosm/kg after DDAVP

15. Diagnosis? • ?(partial) Diabetes insipidus (central or nephrogenic) • Habitual polydipsia

16. Case 2: discussion • not documented normal urine concentrating capacity (>800 mosm/kg) ?washout • Urine osmolality on spot samples always well below (<100 mosm/kg) documented concentrating capacity (>600 mosm/kg) • Assuming an osmol load of 20 mosm/kg, urine output with urine of 600 mosm/kg in a 20 kg child would be 0.67 litres/day • Polyuria thus likely secondary to polydipsia • Hyponatraemic seizure during DDAVP highly suspicious of habitual polydipsia

17. Case 3 • An 8-month old boy with excess polyuria and polydipsia from newborn period (1200 ml/d) • Normal growth, normal feeding • DDAVP test at age 11-month (1 mcg IM injection): Urine Osmolality baseline 101 maximum 254

18. Diagnosis? • Nephrogenic diabetes insipidus • Treated with Indometacin and thiazide • “Presentation is unusually mild”

19. Family history of polyuria & polydipsia I1 II1 II8 II4 III1 III10 III13 Mother,III13: insulin dependent diabetes mellitus Grandmother,II8: “cranial” DI Maternal uncle,III1: nephrogenic DI Maternal uncle,III10: nephrogenic DI Maternal g’aunt II1: nephrogenic DI Maternal g’aunt II4: nephrogenic DI Maternal g’grandfather I1: history of severe polyuria Nephron Physiol 114(1), p1-p10

20. Case 3 continued • Aged 5y, remained very well • Treated with Indometacin and bendroflumethiazide • Excellent growth Ht 75th, Wt 25th centiles • Normal plasma biochemistry • Never admitted

21. IV1: repeat DDAVP test: 2mcg IM

22. Mutation analysis All tested carry a mutation in AVPR2 : V88M

23. Diagnosis? • Partial NDI • Now treated with desmopressin at night

24. Case 4: Bartter • A 4-months old ex-26 wk premie is referred because of persistent polyuria (up to 12 ml/kg/h) and intermittent hypernatraemia

25. History • Parents are first cousins, mother 24 y old primigravida • History of maternal polyhydramnion and s/p 2 amnioreductions

26. Diagnosis?

27. Bartter Syndrome

28. Treatment of Bartter Syndrome • COX-inhibitors • Salt and potassium supplementation

29. Indomethacin (1 mg/kg/d) was started Chemistries the next day as follows: Na 150 mmol/l K 4.8 mmol/l Cl 119 mmol/l HCO3 21 mmol/l Osmolality: 311 mosm/kg Urine Na: <5 mmol/l Urine osmolality: 76 mosm/kg Surprise!

30. A case of Diabetes Insipidus? DDAVP 0.05 mcg im was given. Chemistries 4 hours later: Na 140 mmol/l Osmolality 290 mosm/kg Urine Na 7 mmol/l Urine osmolality 63 mosm/kg

31. Off Indomethacin - Bartter Na 159 K 2.9 HCO3 24 Urine Na 82 Urine osmolality 253 Back on Indomethacin - DI Na 142 K 4.8 HCO3 20 Osmolality 299 Urine Na 5 Urine osmolality 76 Bartter? or DI?

32. Discussion case 4 • Bartter syndrome classically associated with isosthenuria • About 20% of cases (Bartter 1 and 2) have hyposthenuria (NDI) • Mechanism unclear (hypercalciuria?) • Treatment quandary: to give or not to give salt

33. Polyuria: causes Non-renal • Excess water intake • Increased solute load (DKA, mannitol) Renal • Impaired water reabsorption in CD (NDI) • Impaired concentration gradient (Bartter, NPHP, TIN)

34. conclusions • Polyuria can be water (NDI, polydipsia) or solute driven (Bartter, DKA, Mannitol etc.) • Urine osmolality can help in assessment: (Uosm<Posm in water diuresis; Uosm≥Posm in solute diuresis) • Clear distinction not always possible (e.g. secondary NDI in Bartter) • Maximal Uosm can be impaired in Habitual polydipsia (“medullary washout”) • Careful observation mandatory during DDAVP test