Progression of autosomal-dominant polycystic kidney disease in children1

Progression of autosomal-dominant polycystic kidney disease in children.BackgroundAlthough many case reports describe manifestations of autosomal-dominant polycystic kidney disease (ADPKD) in children, no longitudinal studies have examined the natural progression or risk factors for more rapid progression in a large number of children from ADPKD families.MethodsSince 1985, we have studied 312 children from 131 families with a history, a physical examination, blood and urine chemistries, an abdominal ultrasonography, and gene linkage analysis. One hundred fifteen of 185 affected children were studied multiple times for up to 15 years. Renal volumes were determined by ultrasound imaging. Graphs of mean renal volumes according to age were compared between affected and unaffected children, ADPKD children with and without early severe disease, and children with and without high blood pressure.ResultsAffected children had faster renal growth than unaffected children. ADPKD children with severe renal enlargement at a young age continued to experience faster renal growth than those with mild enlargement or normal kidney size for their age, and affected children with high blood pressure had faster renal growth than those with lower blood pressure. Glomerular filtration rate did not decrease in any children except for two with unusually severe early onset disease.ConclusionsThe progression of ADPKD clearly occurs in childhood and manifests as an increase in cyst number and renal size. This study identifies children at risk for rapid renal enlargement who may benefit the most from future therapeutic interventions

Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease

Introduction: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. Methods: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin−angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR) > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI) measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. Results: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both). Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively). Conclusion: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI. Keywords: autosomal dominant polycystic kidney disease, hypertension, left ventricular hypertrophy, left ventricular mass inde