Pituitary adenylate cyclase-activating polypeptide deficiency associated with increased platelet count and aggregability in nephrotic syndrome.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) was recently identified as an inhibitor of megakaryopoiesis and platelet aggregability. OBJECTIVE: We studied PACAP levels in children with nephrotic syndrome (NS), which is associated with thrombocytosis, platelet hyperaggregability, and an increased risk of thrombosis. PATIENTS/METHODS: In four children with congenital NS (CNS) and 24 children with idiopathic NS (INS), plasma and urine levels of PACAP and ceruloplasmin were measured, as were platelet counts and platelet aggregation responses to collagen. In CNS patients, in vitro megakaryopoiesis and nuclear factor-κB expression in platelet lysates were also measured. All tests were performed during the nephrotic state and the non-nephrotic state. RESULTS: Urinary losses of PACAP and ceruloplasmin were observed during the nephrotic state, and disappeared during the non-nephrotic state. Plasma PACAP deficiency was more pronounced in CNS patients than in INS patients. Thrombocytosis was observed in all CNS patients and in 11 of 29 INS patients during the nephrotic state. During the PACAP-deficient state, in vitro megakaryopoiesis was increased for CNS patients, and this effect could be reversed by the addition of recombinant PACAP. Platelet hyperaggregability was observed during the nephrotic state in both CNS and INS patients. In INS patients, the addition of recombinant PACAP to patients' platelets was studied, and resulted in decreased aggregation during the nephrotic state. Platelet aggregation correlated inversely with plasma PACAP levels, but not with serum albumin levels. CONCLUSIONS: We demonstrate urinary losses of PACAP and plasma PACAP deficiency in children with NS, associated with thrombocytosis and platelet hyperaggregability.

Nocturnal polyuria is related to 24-hour diuresis and osmotic excretion in an enuresis population referred to a tertiary center.

PURPOSE: Primary nocturnal enuresis is a heterogeneous disorder, causing a mismatch between overnight diuresis volume and functional bladder capacity. Despite increasing insights in pathogenesis, lack of efficacy of the available treatments is a major problem. We evaluated characteristics of bladder volume and diuresis rate in patients with nocturnal enuresis referred to a tertiary enuresis center. MATERIALS AND METHODS: Noninvasive screening including maximal voided volume, 24-hour circadian rhythm of diuresis and osmotic excretion from 1,000 consecutive patients. RESULTS: Of the patients referred as having monosymptomatic nocturnal enuresis 32% were subsequently classified as having nonmonosymptomatic nocturnal enuresis. Differences in bladder volume and nocturnal diuresis characteristics between the monosymptomatic nocturnal enuresis and nonmonosymptomatic nocturnal enuresis groups were minimal. CONCLUSIONS: The most common observation is a nocturnal diuresis volume greater than maximal voided volume, which in both groups can be caused by nocturnal polyuria or small bladder volume for patient age. The most striking observation is that the positive correlation between nocturnal diuresis volume rate and nocturnal osmotic excretion and 24-hour fluid intake is significantly higher than with the inversed urinary osmolality overnight, which is not only unexpected based on the theory of the primary suppression of vasopressin levels overnight, but also points to a more important role for nutritional and fluid intake than accepted, if not in the primary pathogenesis, then at least in therapy resistance.