Estimating risk of rapid disease progression in pediatric patients with autosomal dominant polycystic kidney disease: a randomized trial of tolvaptan.

BACKGROUND: Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5-17 years). However, progression risk was not part of study eligibility criteria due to lack of validated criteria for risk assessment in children. As risk estimation is important to guide clinical management, baseline characteristics of the study participants were retrospectively evaluated to determine whether risk of rapid disease progression in pediatric ADPKD can be assessed and to identify parameters relevant for risk estimation. METHODS: Four academic pediatric nephrologists reviewed baseline data and rated participant risk from 1 (lowest) to 5 (highest) based on clinical judgement and the literature. Three primary reviewers independently scored all cases, with each case reviewed by two primary reviewers. For cases with discordant ratings (≥ 2-point difference), the fourth reviewer provided a secondary rating blinded to the primary evaluations. Study participants with discordant ratings and/or for whom data were lacking were later discussed to clarify parameters relevant to risk estimation. RESULTS: Of 90 evaluable subjects, primary reviews of 69 (77%) were concordant. The proportion considered at risk of rapid progression (final mean rating ≥ 3.5) by age group was: 15-17 years, 27/34 (79%); 12- < 15, 9/32 (28%); 4- < 12, 8/24 (33%). The panelists agreed on characteristics important for risk determination: age, kidney imaging, kidney function, blood pressure, urine protein, and genetics. CONCLUSIONS: High ratings concordance and agreement among reviewers on relevant clinical characteristics support the feasibility of pediatric risk assessment.

Uterine contraction frequency during treatment of pyelonephritis in pregnancy and subsequent risk of preterm birth.

AIMS: To assess ceftriaxones effect on uterine contraction frequency and determine risk factors for subsequent preterm birth in women with pyelonephritis. METHODS: Seventy-one women with pyelonephritis at greater than 24 weeks' gestation with continuous external tocodynamometry after antibiotic administration were studied. Patients received 2 doses of ceftriaxone 1 gram intramuscularly at 24-hour intervals. Temperatures, timing of antibiotic administration, and gestational age at delivery were recorded. RESULTS: Uterine contraction frequency was measured for the hour prior to antibiotic administration, as well as the six hours after. Uterine activity steadily and significantly decreased from a mean of 5.1 +/- 7.3 at presentation to 2.0 +/- 2.9 uterine contractions per hour (P = .04, student t-test) six hours after ceftriaxone administration. The maximal number of contractions per hour each woman experienced did not correlate with temperature (r = .02, linear regression analysis). Uterine contractility and recurrent urinary tract infection were both associated with subsequent preterm birth (P = .004 and .016 respectively using nominal logistic regression analysis). CONCLUSIONS: (1) A significant decrease in uterine activity from baseline occurs after ceftriaxone administration for acute pyelonephritis in pregnancy. (2) Temperature elevations are not associated with increased uterine activity. (3) Patients with significant uterine activity or recurrent urinary tract infection are at risk for preterm birth.