The importance of total kidney volume in evaluating progression of polycystic kidney disease

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.

Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD

“…Autosomal dominant polycystic kidney disease (ADPKD) is the most common of a group of inherited kidney disorders characterized by progressive cyst development and various extrarenal manifestations (1,2). Cystogenesis in the human kidneys can progressively occupy the normal parenchyma of the kidney and lead to renal failure, which usually occurs in mid-to-late adulthood.…”

“…Several studies have reported that many promising drugs showed potential therapeutic effects for ADP-KD in a large number of preclinical and clinical trials (1,7,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). However, some of those in clinical trials -these promising drugs included mTOR inhibitors (55,56), somatostatin analogs (57,58), ACEI/ ARB (59,60), and tyrosine kinase inhibitor (61) -did not prevent the decline of EGFR in ADPKD patients.…”

Automatic Segmentation of Kidneys using Deep Learning for Total Kidney Volume Quantification in Autosomal Dominant Polycystic Kidney Disease

“…The annual increase in TKV has been estimated to be around 5% 7, 10 per year, suggesting that TKV measurement should be accurate to capture small changes over time. The most commonly used methods for kidney volume computation such as manual delineation and stereology 13 are simple but time consuming and subject to intra/inter-observer variability.…”

A Review of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression

“…Recent studies have used changes in TKV as a primary endpoint [9,12]. The role of TKV in evaluating ADPKD progression and its possible role as a surrogate endpoint in randomized clinical trials has also been reviewed [18]. However, some studies have indicated a lack of correlation between TKV growth rate and decline in renal function [19,20], leading to discussions regarding the use of TKV as a secondary endpoint.…”