Therapeutic window for desmopressin in noctunal enuresis

Title: THERAPEUTIC WINDOW FOR DESMOPRESSIN IN NOCTUNAL ENURESIS Authors: Sevasti Karamaria1,2, Lien Dossche1,2, Ann Raes 1,2, Evelien Snauwaert1, Johan Vande Walle1,2 1Department of Pediatric Nephrology, UZ Gent, Ghent, 2Ghent University Background Nocturnal enuresis is caused by nocturnal urine production and functional bladder capacity mismatch. ICCS suggests patient classification into MNE and NMNE, where MNE is likely to respond to desmopressin and/or alarm. This led to the misconception that NMNE could not benefit from desmopressin. With the recent ICCS standardization, most patients are now labeled NMNE. Desmopressin’s anti-diuretic effect and renal concentrating response have no direct correlation with bladder dysfunction and should be evaluated independently. Many patients have LUTS and nocturnal polyuria and could benefit from desmopressin in combination therapy. Methods Aim: identify patients in a tertiary center who might benefit from desmopressin (defined as urinary osmolality (Uosmol)<850 mOsm/l) and study the timing overnight. Methods: retrospective analysis of 398 enuretic children who performed a 24h-urine concentration profile at home (4 daytime (D1-D4), 4 nighttime urine collections (N1-N4)). Results 212 children (>50%) had Uosmol850mOsm/l over 24h, suggesting lower maximal renal concentration capacity of the normal spectrum or high 24h fluid intake. Conclusion: Classification into MNE and NMNE is mainly bladder/LUTS driven and is widely accepted to predict the anti-enuretic effect of therapy, thus an indication for desmopressin. However, many patients have a combination of LUTS and abnormal circadian diuresis pattern. Desmopressin’s anti-diuretic effect may be expected in most patients with high diuresis and low Uosmol overnight. >50% of patients have a low Uosmol early the night, hence a therapeutic window for desmopressin. In 1/3 patients, Uosmol remains longer low, needing longer-acting V2-stimulation, without risk of too prolonged action. It is evident that desmopressin’s PK/PD characteristics do not fulfill these promises