Desmopressin resistant nocturnal polyuria may benefit from furosemide therapy administered in the morning.
OBJECTIVE
There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response.


METHODS
We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group.


RESULTS
Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis.


CONCLUSIONS
This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime.
De Guchtenaere
A
A
Pediatric Uro-Nephrological Center, University Hospital Ghent, Ghent, Belgium.
Vande Walle
C
C
Van Sintjan
P
P
Donckerwolcke
R
R
Raes
A
A
Dehoorne
J
J
Van Laecke
E
E
Hoebeke
P
P
Vande Walle
J
J
D002648:Child; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage*; D004231:Diuresis / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D053206:Nocturnal Enuresis / Q000175:diagnosis / Q000188:drug therapy; D010865:Pilot Projects; D011141:Polyuria / Q000175:diagnosis* / Q000188:drug therapy*; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014563:Urodynamics
D005665:Furosemide; D003894:Deamino Arginine Vasopressin