In nocturnal enuresis

Transcription

1 The role of the kidney In nocturnal enuresis Kostas Kamperis MD PhD Dept of Pediatrics, Section of Nephrology Aarhus University Hospital, Aarhus, Denmark

2 Enuresis prototypes Nocturnal polyuria Bladder issues Uvol Uvol

3 Glomerular filtration rate Regulated by nephrons Autoregulation (intrinsic) Hormones Blood pressure, renal perfusion Local autacoids (prostaglandins) Autonomic nervous system Circadian clock

4 Renal Tubular Reabsorption Organic solutes: Glucose Phosphate Amino acids Low MW proteins Secretion: Prox: organic anions/cations Distal: NH4 +, H +, K + Na + : Prox (Na/K-ATPase): 67% Henle (NKCC2): 20% Distal (NCCT): 7% Coll.duct (ENaC): 5% Ca + : Prox : 70% Henle: 20% Distal: 7% Coll.duct: 2% K + : Reabs: app. 100% Distal: secretion HCO3 - : Prox: 80-90% Distal: 10-15%

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6 Antidiuretic hormone (AVP) The basics Peptide synthetized in hypothalamus (SON PVN) Stored in posterior pituitary Half life min

7 Regulation of AVP secretion Stimuli Osmoreceptors (hypothalamus) Baroreceptors (atrium, veins, carotis) Emesis/nausea Secretion modifiers? alcohol ANG II ANP

8 Site of AVP action Diuresis : <100ml->25Lt Gross reabsorption in proximal tubule Fine-adjustment in CD AQP2 the dedicated channel Build-up of hypertonicity in inner medulla

9 AQP2. It is all about preserving water Short term regulation/shuttling (minutes) Long term regulation (days) Food intake -> up-regulation Ca 2+ -> down-regulation Clinical settings pregnancy heart failure cirrhosis

10 Urine Osmolality (mosm/kg) The clinical effect: Concentration of urine On- Off effect? Plasma AVP (pg/ml)

11 Enuresis an AVP issue? Rittig et al, 1989

12 Urine Osmolality (mosm/kg) Factors influencing antidiuresis Hypertonicity of renal medulla (Na and urea AVP dependent) Stimulation -> overexpression (shortterm - longterm) Osmotic diuresis (sodium, glucose, other) Plasma AVP (pg/ml) Antagonists (Ca +2, prostaglandins, sympaticus) Sensitivity of the AVPR2-AQP2 (Sex?)

13 Hypercalciuria modulator of urine concentration its role in enuresis still unclear Procino et al, 2012

14 Renal prostaglandins and enuresis 0.5 U-PGE2 (ngr/h/kg) Vasoactive properties, regulate renal perfusion 0.4 P < 0.05 Counteract the concentrating properties of AVP 0.3 Natriuretic properties 0.2 PG inhibition leads to anti-natriuresis and antidiuresis controls non-polyurics polyurics

15 Sodium and Enuresis Abnormal circadian sodium and potassium excretion rhythms in juvenile enuretics with apparent nocturnal polyuria Diurnal variation of plasma natriuretic peptide in normals and patients with enuresis nocturna. Rittig et al 1991 Scand J Clin Lab invest A physiological analysis of kidney ion-regulating function in children with enuresis Kuznetsova et al 1996 Fiziol Zh Im I M Sechenova Sodium and potassium excretion higher in enuretic patients and the circadian variation is abolished Hypernatriuria and kaliuresis in enuretic children and the diurnal variation. Vurgun et al 1998 J Urol

16 Simple loop keeping BP stable Excretion of sodium load BP Pressure natriuresis Volume expansion Cardiac Output BP Tissue overperfusion Vasoconstriction

17 Sodium rabsorption accross the nephron 25 mol Na + filtered mmol Na/lt in urine

18 Renin Angiotensin Aldosterone - ANP

19 Excess natriuresis in refractory enuresis U-flow (ml/h/kg) E-Na (mmol/h/kg) NS NS NS NS NS NS NS NS P< P< bed night bed night controls non-polyurics polyurics dry night Kamperis et al 2006

20 Increased urea and osmotic excretion 0.6 E-urea (mmol/h/kg) 1.50 E-osm (mmol/h/kg) 2.5 TcH2O (ml/min) 0.5 P< P< NS controls non-polyurics polyurics dry night Kamperis et al 2006

21 ..osmotic load and the kidney a more important role for nutritional and fluid intake than accepted Vande Walle et al 2007

22 Autonomic nervous system and the kidney Adrenergic stimulation Renin release Sodium retention Renal vasoconstriction GFR changes Antidiuresis Direct effects in renal environment Indirect through blood flow changes

23 Blood pressure and nocturnal polyuria Figure 2b Enuresis RTX MAP (mmhg) TX1 Controls Kruse et al, J Urol, 2009 Time Alstrup et al, Transpl Proc, 2010 Nocturia BPH Graugaard-Jensen et al, J Urol, 2006 Matthiesen et al, J Urol, 1996

24 Circadian GFR rhythm in polyurics and non-polyurics Dossche et al 2015

25 A study in enuresis. Polyurics vs non-polyurics Temp Galvanic Skin Response Energy Mets

26 Bladder signals/oab Intrinsic circadian clock Disturbed sleep Autonomic nervous system Autonomic nervous system PLMS Increased arousal Autonomic nervous system AVP Blood pressure Urine concentration AgII Hormones Renal factors Tubular reabsorption Aldo ANP Integrative physiology Nocturnal polyuria GFR

27 How many pieces of the puzzle do we miss?