Transcript Διερεύνηση παιδιού με πολυουρία

The polyuric child
When we worry?
Andromachi Mitsioni
Departement of Pediatric Nephrology
”P. & A. Kyriakou” Children’s Hospital
Athens - GREECE
ESPN, Lyon-Sept.2008
POLYURIA is defined as an increase in
total daily outpout of urine
Urine outpout > 40 ml/kg/24h
or > 2000 ml/m2/24h
preschool children >1l/24h
school children
>2l/24h
adults
>3l/24h
Polyuria
 Distinguish from:
frequent micturition
nocturia
enuresis
 Are not associated with an increase in
the total urine output
Polyuria
The volume of urine depends upon:
1.The amount of solute (solute load) and
water ingested or produced by
metabolism in excess of needs
2.The ability to concetrate or dilute the
urine
The ability to concetrate the urine depends on:
 the presence of antidiuretic hormone
(ADH) and
 A hyperosmolar medullary interstitium
with an intact countercurrent multiplier
system
1. Active sodium chloride
transport in the thick ascending
limb of loop of Henle (TΑL)
TΑL
3. Water permeable
segment in the thin
descending limb of
loop of Henle
5. In the presence
of ADH, collecting
tubule highly
permeant to water
4. Urea reabsorption
in the collecting
tubule
2. Passive reabsorption of sodium in the thin ascending
limb of loop of Henle
POLYURIA
 Water diuresis
(urine osmolality
<250mOsm/kg)
 Solute diuresis (urine osmolality
>250 mOsm/kg)
 More than one abnormality may be present in any
form of polyuria
Water diuresis may be due to:
 PRIMARY POLYDIPSIA
 DIABETES INSIPIDUS
Neurogenic (failure of neurohypophysis
to synthesize or secrete ADH)
Nephrogenic (failure of the kidney to
respond appropriately to ADH)
 partial to complete
Primary polydipsia
 Compulsive water drinking
(rare in children,most commonly in adolescents
with a psychological distiburbance)
 Treatment with large quantities of
water
(treatment of nephrolithiasis , or with drugs as CP)
 Defect in the thirst center (in the
hypothalamus of CNS)
Excessive fluid intake will supress vasopressin secretion and induce
polyuria (normoNa patients with normal or reduced plasma osmolality)
DIABETES INSIPIDUS
 Neurogenic (central) DI
Primary
Secondary
 Nephrogenic DI
Congenital (hereditary)
Acquired(Secondary)
NEUROGENIC (CENTRAL)DIABETES INSIPIDUS
PRIMARY
 Idiopathic (30-50% in children)
autoimmune process
+/-presence of cytoplasmic antibodies against VS
 Familial (5% )
autosomal dominant disease caused by mutations
in the arginine-vasopressin gene(chromosome 20)
 DIDMOAD (Wolfran syndrome)
Neurogenic DI,Diabetes Mellitus,Optic Atrophy
Deafness.
autosomal recessive trait
NEUROGENIC(CENTRAL)DIABETES INSIPIDUS
SECONDARY
Neurosurgery
Trauma (head injury)
Infection(meningitis,encephalitis,CNS abscess,congenital infection.)
Tumor(craniopharyngioma,glioma ,germinoma,metastasis)
CNS granulomatous disease(sarcoidosis, histiocytosis X)
Hypoxia
Intracranial hemorrhage(aneurysm,thrombosis,embolus)
Drugs (phenyntoin,clonidine,alcohol)
,
NEPHROGENIC DIABETES INSIPIDUS
HEREDITARY(CONGENITAL)
 a PURE type characterized by loss of
water only
 a COMPLEX type characterized by loss of
water and ions(Na+,Cl-,Ca++,K+,Mg+)
Peter Agre and Roderick McKinnon,
(the 2003 Nobel Prize in Chemistry) answered 2 questions
 How does a cell let one type of ion through
the lipid membrane to the exclusion of others?
 How does water permeate the cell without
ion?
These 2 problems are relevant to the molecular
understanding of 2 types of hereditary
nephrogenic DI
Vasopressin makes the cortical and medullary
collecting ducts permeable to water
Mechanisms for blocking proton
permeation by aquaporin
 The water channels let
water go through but not
protons. Protons are
jumping from one water
molecule to another, but
due to the special
arrangement of these
two asparagines ,there is
a link and the protons
cannot jump to the next
water molecule.
PURE Gongenital Nephrogenic DI
 X-linked(90-95%)
mutation of V2 receptor gene (AVPR2)
chromosome region Xq28
 Autosomal dominant or autosomal recessive
5-10% of patients
mutation of aquaporin 2 gene (AQP2)
chromosome region 12q13
183 AVPR2 mutations
X-linked
Aquaporin-2: 26 mutations responsible for
autosomal dominant and autosomal recessive
forms of NDI
COMPLEXE Nephrogenic diabetes insipidus
Separation of salt and water in thick ascending
limb (TAL) of loop of Henle
ABNORMALITIES IN ANY OF THESE PROTEINS
OF THE TAL CAN LEAD TO SALT –LOSING
NEPHROPATHY
As a result of these different molecular alterations:
 NaCl is lost into the lumen
 positive voltage is abolished
 Ca++,Mg++ ,K+,NH4+ cannot be reabsorbed in
the paracelullar space
COMPLEX POLYURIC DISORDERS
NEPRHOGENIC DIABETES INSIPIDUS
SECONDARY
 Acquired metabolic aberrations
hypokaliemia, hypercalcemia
 Drugs
lithium,αmphotericin Β,diphenylhydantoin,foscarnet,
cidofovir
 Medullary damage
chronic pyelonephritis ,cystinosis, sickle cell disease
chronic renal failure, obstructive nephropathy,
infiltrative disease (leukemia,lymphoma,amyloidosis)
SOLUTE DIURESIS
(accumulation of organic or inorganic
solutes in urine)
Organic
 Glycose (diabetes mellitus,
renal glycosuria)
 Urea
(large protein intake
increased catabolism
relief of obstruction)
 Mannitol
Inorganic
 Sodium chloride(diuretics,
mineralocorticoid deficiency
salt-losing renal diseases)
CLINICAL EVALUATION
 Larger quantities of urine± dehydration
infancy - excessively heavy diapers
children -
irritability, seizures
unexplained fever
constipation, vomiting
failure to thrive,mental retardation
polydipsia
enuresis, nocturia
 non obstructive hydronephrosis ,hydroureter and megacystis
by the large urinary volumes
DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
 Onset of polyuria
Hereditary nephrogenic DI first week of life
Familial central DI
after the first year of life
ADULTS Central DI
abrupt onset
Aquired nephrogenic DI
gradual onset
Primary polydipsia
gradual onset
Onset of nocturia is often the first clue to DI
Relationship with CNS injury
 Family history
 Plasma sodium concentration
 Presence of polyhydramnios
Laboratory Investigations
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24hour urine collection
Serum glycose,urea and creatinine
Κ, Ca, Na,biccarbonates
Urine(first morning) osmolality , urinalysis
Serum osmolality
Water restriction test
Test of dDAVP
Plasma ADH measurement
Genetic studies
Osmoregulation of ADH
The normal physiologic response is based upon
the following observations:
 Raising the plasma osmolality leads to a progressive
elevation in ADH release and an increase in urine
osmolality in normals
 Once the plasma osmolality reaches 295 to 300
mOsmol/kg ,the effect of endogenous ADH on the
kidney is maximal. At this point administering ADH
will no further elevate the urine osmolality unless
endogenous ADH release is impaired (central DI)
WATER RESTRICTION TEST
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Is not performed in newborns or very young infants
Is not performed when plasma Na>145 mEq/l
It should be performed in the hospital under medical supervision
The test is terminated when one of the end points are attained:
 Urine SG> 1020 or Urine osmolality > 600mOsm/kg
( infant ) 1015
>500
 Plasma osmolality >295 mOsm/kg or plasma Na >147mEq/l
 Loss of 5% of body weight or signs of volume depletion
 Period of water restriction
6hours in infants < 6months of age
8 hours
6 months -2 years
12 hours
>2 years
TEST dDAVP

Children who continue to have impaired urinary concentration
despite reaching a plasma osmolality 295mosmol/kg or sodium of
150meq/L
5-10μg desmopressin by nasal insufflation (20μg/m2)
or 2,5-5U aqueous vasopressin subcutaneously
 Accurate interpretation requires that exogenous ADH not given
before the plasma osmolality has reached 295 mosm/kg
 If
urine osmol. >100%
15-50%
<10%
complete central DI
partial central DI
partial nephrogenic DI
complete nephrogenic DI
Polyuria- Laboratory Investigations
Plasma ADH measurement before and after water
restriction test
 NEPHROGENIC DI is excluded if there is an appropriate
relationship between the rise in urine osmolality and
plasma ADH
 CENTRAL DI is excluded if there is an appropriate rise
in plasma ADH with the rise in plasma sodium or plasma
osmolality
Polyuria-Laboratory Investigations
 Patients with central DI
 MRI scans of pituitary gland, hypothalamus
and surrounding structures (serial)
 Investigation of anterior pituitary hormone
deficits (GH,TSH,ACTH,FSH,LH)
 Patients with nephrogenic DI
 Renal ultrasound
 Bladder function tests