Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and has important clinical manifestations in childhood. Numerous studies have documented the superiority of magnetic resonance imaging (MRI) for serial monitoring of kidney and cyst volume in this condition in adults. However, no studies have examined the utility of MRI for serial assessment of kidney and cyst volume in children with ADPKD.
Subjects 4 to 21 years of age with ADPKD underwent abdominal MRI on an annual basis for 5 years. Subjects were grouped according to BP as hypertensive (HBP; BP≥95th percentile for age, height, and gender) or as normotensive (NBP; BP<95th percentile). Total kidney volume (TKV), cyst volume, and cyst number were assessed by stereology.
MRI studies (n=302) were obtained in 77 children with ADPKD. TKV and cyst volume were significantly increased in HBP versus NBP subjects. HBP subjects demonstrated a greater increase in fractional cyst volume over time versus NBP subjects. Cyst number increased more rapidly in HBP ADPKD children.
This is the first large-scale clinical study examining the utility of MRI for serial assessment of TKV, cyst volume, and cyst number in children with ADPKD. These results demonstrate that MRI is an acceptable means to follow these parameters in children with ADPKD. Because of the embryonic occurrence of cysts, interventional trials are needed in ADPKD children and MRI may be the preferred renal imaging approach.
[Show abstract][Hide abstract] ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney condition and is associated with important renal and cardiovascular manifestations in childhood. Renal cystic disease can be documented in some cases as early as in utero. Early intervention is critical if the long-term complications of this condition, including end-stage renal disease, are to be ameliorated. Here we describe our ongoing randomized double-blind placebo-controlled phase III clinical trial to assess the effect of pravastatin treatment on renal and cardiovascular disease progression in 107 children and young adults age 8-22 years with ADPKD who are receiving the angiotensin converting enzyme inhibitor lisinopril. Baseline demographic and laboratory data are provided. Results of this study could markedly impact the standard of care for evaluation and treatment of ADPKD in this population.
[Show abstract][Hide abstract] ABSTRACT: The weight of evidence gathered from studies in humans with hereditary polycystic kidney disease (PKD)1 and PKD2 disorders, as well as from experimental animal models, indicates that cysts are primarily responsible for the decline in glomerular filtration rate that occurs fairly late in the course of the disease. The processes underlying this decline include anatomic disruption of glomerular filtration and urinary concentration mechanisms on a massive scale, coupled with compression and obstruction by cysts of adjacent nephrons in the cortex, medulla and papilla. Cysts prevent the drainage of urine from upstream tributaries, which leads to tubule atrophy and loss of functioning kidney parenchyma by mechanisms similar to those found in ureteral obstruction. Cyst-derived chemokines, cytokines and growth factors result in a progression to fibrosis that is comparable with the development of other progressive end-stage renal diseases. Treatment of renal cystic disorders early enough to prevent or reduce cyst formation or slow cyst growth, before the secondary changes become widespread, is a reasonable strategy to prolong the useful function of kidneys in patients with autosomal dominant polycystic kidney disease.
[Show abstract][Hide abstract] ABSTRACT: Orskov and colleagues demonstrate the impact of birth weight on the mean age of end-stage renal disease (ESRD) in a large Danish ADPKD cohort. Each kilogram of birth weight extended the mean age of ESRD onset by 1.7 years. Placental insufficiency, activation of the renin-angiotensin-aldosterone system, increased fetal vasopressin levels, compensatory increases in insulin like growth factor-I, and a reduction in total nephron number may all contribute to this observation. Collectively, these changes result in an accelerated pace of cyst formation and expansion, and an inability to maintain glomerular hyperfiltration during kidney expansion which results in a more rapid progression to ESRD. Therefore the intrauterine environment may play a critical role in disease severity in ADPKD.
Kidney International 05/2012; 81(9):814-5. DOI:10.1038/ki.2012.8 · 8.56 Impact Factor
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