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Pathophysiological aspects of nocturnal polyuria in monosymptomatic enuresis nocturna

Konstantinos Kamperis

Summary

The excretion of large amounts of urine at night defined as nocturnal polyuria is a major etiological factor in nocturnal enuresis. An abnormal diurnal rhythm in AVP synthesis that is easily corrected with dDAVP has been identified in enuretics with nocturnal polyuria. However, a subgroup of enuretics present with dDAVP resistant nocturnal polyuria. In the present Ph.D. thesis we evaluate the normal circadian variations in urine production and urinary composition in healthy children and the physiological mechanisms responsible for the dDAVP resistant nocturnal polyuria seen in a subgroup of enuretics. Furthermore, we assess the effect of dDAVP and indomethacin on renal water and solute handling in enuretics with nocturnal polyuria and controls.  
    This thesis consists of 3 studies. In study I we report that circadian variations in urine output, electrolyte, and solute excretion are evident in healthy children between the ages of 3 and 14 years. The reductions in the amount of urine and solutes excreted during night correlate with analogous reductions in the amount of PGE2 excreted. The previously established diurnal rhythm in plasma AVP levels could not be confirmed when using the urinary excretion of the hormone as a marker.  
    In study II we show that enuretic children with dDAVP resistant nocturnal polyuria lack the normal nycthemeral rhythm in urine output and excrete larger amounts of urine at night than non-polyurics and controls. In these patients the nocturnal polyuria seems mainly to be secondary to increased sodium and urea excretion. Sodium regulating hormones of the RAAS and ANP do not seem to be responsible for the enuresis related natriuresis which instead can be attributable to an increased nocturnal PGE2 excretion.   
    Children with MNE and nocturnal polyuria showing non-optimal response to dDAVP at home respond well to the agent when given during hospitalization and under standardized conditions. DDAVP markedly reduces not only free water excretion but also the amount of sodium and urea excreted. This is most likely a direct effect of dDAVP on renal tubules as neither sodium regulating hormones nor renal prostaglandins are influenced by the agent. 
    Indomethacin being a potent cyclooxygenase inhibitor has antinatriuretic properties in both enuretics with nocturnal polyuria and controls. Despite this, the agent does not seem to reduce the nocturnal urine output in children with nocturnal polyuria to the same extent as dDAVP.