The child with polyuria and polydipsia

Detlef Bockenhauer

Objectives

• To provide an overview of polyuria/polydipsia by giving case scenarios

• Aetiology

• Assessment

• management

?

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

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

biochemistries Plasma Urine unit

Sodium 157 <5 mmol/l

creatinine 0.03 1.1 mmol/l

osmolality 319 83 mosmol/kg

Diagnosis?

• Diabetes insipidus (central or nephrogenic)

Further investigations

• Admission for iv DDAVP test• Max urine osm: 83 mosm/kg

Diagnosis?

• Nephrogenic diabetes insipidus

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)

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

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

Case 2: examination

• Unremarkable examination: weight, height, OCF: all around 9th %ile

• BP: 100/52 mmHg• Normal renal US

biochemistries Plasma Urine unit

Sodium 141 15 mmol/l

creatinine 0.03 2.5 mmol/l

osmolality 288 55 mosmol/kg

Diagnosis?

• (partial) Diabetes insipidus (central or nephrogenic) based on max Uosm of 482

• Habitual polydipsia

Further investigations

• Admission for water deprivation /iv DDAVP test

• Max urine osm: 630 mosm/kg (normal plasma Na throughout), 639 mosm/kg after DDAVP

Diagnosis?

• ?(partial) Diabetes insipidus (central or nephrogenic)

• Habitual polydipsia

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

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

biochemistries Plasma Urine unit

Sodium 141 15 mmol/l

creatinine 0.03 2.5 mmol/l

osmolality 288 55 mosmol/kg

Diagnosis?

• Nephrogenic diabetes insipidus• Treated with Indometacin and thiazide

• “Presentation is unusually mild”

Family history of polyuria & polydipsia

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

III13

III10III1

II1 II4II8

I1

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

IV1: repeat DDAVP test: 2mcg IM

Blood Baseline 20mins 2 h 3 h 4 h 5 h

Na 142 141

Osm 291 289

Urine

Na 14 38 62 76 61 43

Osm 117 232 370 416 570 280

Mutation analysis

tested x x

All tested carry a mutation in AVPR2 : V88M

Diagnosis?

• Partial NDI

• Now treated with desmopressin at night

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

History

• Parents are first cousins, mother 24 y old primigravida

• History of maternal polyhydramnion and s/p 2 amnioreductions

biochemistries Plasma Urine unit

Sodium 157 45 mmol/l

creatinine 0.047 0.9 mmol/l

osmolality 318 197 mosmol/kg

Diagnosis?

Bartter Syndrome

Treatment of Bartter Syndrome

• COX-inhibitors

• Salt and potassium supplementation

Surprise!

Indomethacin (1 mg/kg/d) was startedChemistries the next day as follows:

Na 150 mmol/lK 4.8 mmol/lCl 119 mmol/lHCO3 21 mmol/lOsmolality: 311 mosm/kg

Urine Na: <5 mmol/lUrine osmolality: 76 mosm/kg

A case of Diabetes Insipidus?

DDAVP 0.05 mcg im was given. Chemistries 4 hours later:Na 140 mmol/lOsmolality 290 mosm/kg

Urine Na 7 mmol/lUrine osmolality 63 mosm/kg

Bartter? or DI?

Off Indomethacin - Bartter

Na 159

K 2.9

HCO3 24

Urine Na 82

Urine osmolality253

Back on Indomethacin - DI

Na 142

K 4.8

HCO3 20

Osmolality299

Urine Na 5Urine osmolality76

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

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)

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