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The polyuric child When we worry? Andromachi Mitsioni Departement of Pediatric Nephrology P. & A. Kyriakou Childrens Hospital Athens - GREECE ESPN, Lyon-Sept.2008.

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Presentation on theme: "The polyuric child When we worry? Andromachi Mitsioni Departement of Pediatric Nephrology P. & A. Kyriakou Childrens Hospital Athens - GREECE ESPN, Lyon-Sept.2008."— Presentation transcript:

1 The polyuric child When we worry? Andromachi Mitsioni Departement of Pediatric Nephrology P. & A. Kyriakou Childrens Hospital Athens - GREECE ESPN, Lyon-Sept.2008

2 POLYURIA is defined as an increase in total daily outpout of urine Urine outpout > 40 ml/kg/24h or > 2000 ml/m 2 /24h preschool children >1l/24h school children >2l/24h adults >3l/24h

3 Polyuria Distinguish from: frequent micturition nocturia enuresis Are not associated with an increase in the total urine output

4 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

5 the presence of antidiuretic hormone (ADH) and A hyperosmolar medullary interstitium with an intact countercurrent multiplier system The ability to concetrate the urine depends on:

6 TΑLTΑL 1. Active sodium chloride transport in the thick ascending limb of loop of Henle (TΑL) 2. Passive reabsorption of sodium in the thin ascending limb of loop of Henle 3. Water permeable segment in the thin descending limb of loop of Henle 4. Urea reabsorption in the collecting tubule 5. In the presence of ADH, collecting tubule highly permeant to water

7 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 More than one abnormality may be present in any form of polyuria

8 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

9 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)

10 DIABETES INSIPIDUS Neurogenic (central) DI Primary Secondary Nephrogenic DI Congenital (hereditary) Acquired(Secondary)

11 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

12 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)

13 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+)

14 Peter Agre and Roderick McKinnon, (the 2003 Nobel Prize in Chemistry) answered 2 questions How does a cell let one type of ion through How does a cell let one type of ion through the lipid membrane to the exclusion of others? the lipid membrane to the exclusion of others? How does water permeate the cell without ion? How does water permeate the cell without ion? These 2 problems are relevant to the molecular understanding of 2 types of hereditary nephrogenic DI

15 Vasopressin makes the cortical and medullary collecting ducts permeable to water

16 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. 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.

17 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

18 183 AVPR2 mutations X-linked

19 Aquaporin-2: 26 mutations responsible for autosomal dominant and autosomal recessive forms of NDI

20 COMPLEXE Nephrogenic diabetes insipidus Separation of salt and water in thick ascending limb (TAL) of loop of Henle

21 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+,NH 4 + cannot be reabsorbed in the paracelullar space COMPLEX POLYURIC DISORDERS

22 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)

23 SOLUTE DIURESIS 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)

24 CLINICAL EVALUATION Larger quantities of urine± dehydration infancy - excessively heavy diapers irritability, seizures unexplained fever constipation, vomiting failure to thrive,mental retardation children - polydipsia enuresis, nocturia non obstructive hydronephrosis,hydroureter and megacystis by the large urinary volumes

25 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

26 Laboratory Investigations 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

27 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 )

28 WATER RESTRICTION TEST 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

29 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% complete central DI 15-50% partial central DI partial nephrogenic DI <10% complete nephrogenic DI

30 Polyuria- Laboratory Investigations Plasma ADH measurement before and after water restriction test 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

31 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


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