Background/Methods: We have examined the hypothesis that cyst formation is key in the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK) model of autosomal-recessive polycystic kidney disease (ARPKD), by determining the relationship between cyst development and indices of renal function and cardiovascular disease. Results: In the LPK (n = 35), cysts appear at week 3 (1.1 ± 0.1 mm) increasing to week 24 (2.8 ± 2 mm). Immunostaining for nephron-specific segments indicate cysts develop predominantly from the collecting duct. Cyst formation preceded hypertension (160 ± 22 vs. Lewis control 105 ± 20 mm Hg systolic blood pressure (BP), n = 12) at week 6, elevated creatinine (109 ± 63 vs. 59 ± 6 µmol/l, n = 16) and cardiac mass (0.7 vs. 0.4% bodyweight, n = 15) at week 12, and left ventricular hypertrophy (2,898 ± 207 vs. 1,808 ± 192 µm, n = 14) at week 24 (all p ≤ 0.05). Plasma-renin activity and angiotensin II were reduced in 10- to 12-week LPK (2.2 ± 2.9 vs. Lewis 11.9 ± 4.9 ng/ml/h, and 25.0 ± 19.1 vs. 94.9 ± 64.4 pg/ml, respectively, n = 26, p ≤ 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced mean BP in the LPK (52 vs. Lewis 4%, n = 9, p ≤ 0.05). Conclusion: Cyst formation is a key event in the genesis of hypertension while the sympathetic nervous system is important in the maintenance of hypertension in this model of ARPKD.

No abstract

Rationale: Historical studies suggest that airway infection in cystic fibrosis (CF) initiates with Staphylococcus aureus and Haemophilus influenzae with later emergence of Pseudomonas aeruginosa. Aspergillus species are regarded as relatively infrequent, late occurring infections. Objectives: To assess the prevalence and change in prevalence of early lower airway infections in a modern cohort of children with CF. Methods: All infants diagnosed with CF after newborn screening, participating in the AREST-CF cohort study between 2000-2018, were included. Participants prospectively underwent bronchoalveolar lavage (BAL) at 3-6 months,1 year and annually up to 6 years of age. Lower airway infection prevalence was described. Changes in prevalence patterns were assessed longitudinally using generalized estimating equations controlling for age and repeated visits. Measurements and Main Results: A total of 380 infants underwent 1,759 BALs. The overall prevalence and median age of first acquisition of the most common infections were: S. aureus 11%, 2.5yrs, P. aeruginosa 8%, 2.4yrs, Aspergillus species 11%, 3.2yrs, H. influenzae 9%, 3.1yrs. During the study, a significant decrease in prevalence of P. aeruginosa (p<0.001) and S. aureus (p<0.001) was observed with significant change towards more aggressive treatment. Prevalence of Aspergillus infections did not significantly change (p=0.669). Conclusion: Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy. The decrease in prevalence of P. aeruginosa and S. aureus since 2000, coinciding with more aggressive therapeutic approach, has resulted in Aspergillus becoming the most commonly isolated pathogen in young children. Further research is warranted to understand the implication of these findings.