Key Points
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In autosomal dominant polycystic kidney disease (ADPKD), renal cyst formation begins in utero and continues throughout life
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Renal cysts originate in tubules and contribute to the development of renal insufficiency
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Individual renal cysts progressively expand at a constant rate that can differ widely from the growth rate of neighbouring cysts
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Cysts disrupt the renal ultrastructure in the early stages of ADPKD and cause renin-dependent hypertension, albuminuria, interstitial inflammation, fibrosis, and the destruction of functioning nephrons.
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Evidence indicates that the annual rate of kidney growth in ADPKD is inversely linked to the decline in glomerular filtration rate so can be used to predict future decline in glomerular function
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Longitudinal studies in thousands of patients have provided evidence to validate the use of total kidney volume as a prognostic marker and as a potential indicator of treatment efficacy in ADPKD
Abstract
The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue.
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J.J.G and V.E.T contributed equally to researching data for the article, discussion of the content, and revising or editing the manuscript before submission.
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J.J.G and V.E.T have consulted for and received research grants from Otsuka Pharmaceutical Development and Commercialization, Inc.
Glossary
- Planar cell polarity
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Planar polarization refers to the spatial orientation of a group of cells, whereby the cells and their structures are orientated within the same plane.
- Desmopressin
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A synthetic and highly specific vasopressin V2 agonist.
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Grantham, J., Torres, V. The importance of total kidney volume in evaluating progression of polycystic kidney disease. Nat Rev Nephrol 12, 667–677 (2016). https://doi.org/10.1038/nrneph.2016.135
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DOI: https://doi.org/10.1038/nrneph.2016.135
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