Dataset Information

Limited Performance of Estimated Total Kidney Volume for Follow-up of ADPKD.

ABSTRACT:

Introduction

Total kidney volume (TKV) is a qualified biomarker for disease progression in autosomal dominant polycystic kidney disease (ADPKD). Recent studies suggest that TKV estimated using ellipsoid formula correlates well with TKV measured by manual planimetry (gold standard). We investigated whether the ellipsoid formula could replace manual planimetry for follow-up of ADPKD patients.

Methods

Abdominal magnetic resonance images of patients with ADPKD performed between January 1, 2013, and June 31, 2019, in Saint-Luc Hospital, Brussels, were used. Two radiologists independently performed manual TKV (mTKV) measures and kidney axial measures necessary for estimating TKV (eTKV) using ellipsoid equation. Repeatability and reproducibility of axial measures, mTKV and eTKV, and agreement between mTKV and eTKV were assessed (Bland-Altman). Intraclass correlation coefficient (ICC) was used to assess agreement on Mayo Clinic Imaging Classification (MCIC) scores.

Results

140 patients were included with mean age 45±13 years, estimated glomerular filtration rate (eGFR) 71±31 ml/min per 1.73 m², and mTKV 1697±1538 ml. Repeatability and reproducibility were superior for mTKV versus eTKV (repeatability coefficient 2.4% vs. 14% in senior reader, and reproducibility coefficient 6.7% vs. 15%). Intertechnique reproducibility coefficient (95% confidence interval [CI]) was 19% (17%, 21%) in senior reader. Intertechnique agreement on derived MCIC scores was very good (ICC = 0.924 [0.884, 0.949]).

Conclusion

TKV estimated using ellipsoid equation demonstrates poor repeatability and reproducibility compared with that of mTKV. Intertechnique agreement is also limited, even when measurements are performed by an experienced radiologist. Estimated TKV, however, accurately determines MCIC score.

SUBMITTER: Demoulin N

PROVIDER: S-EPMC8589695 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo develop a high-performance, rapid semi-automated method (Sheffield TKV Tool) for measuring total kidney volume (TKV) from magnetic resonance images (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD).MethodsTKV was initially measured in 61 patients with ADPKD using the Sheffield TKV Tool and its performance compared to manual segmentation and other published methods (ellipsoidal, mid-slice, MIROS). It was then validated using an external dataset of MRI scans from 65 patients with ADPKD.ResultsSixty-one patients (mean age 45 ± 14 years, baseline eGFR 76 ± 32 ml/min/1.73 m2) with ADPKD had a wide range of TKV (258-3680 ml) measured manually. The Sheffield TKV Tool was highly accurate (mean volume error 0.5 ± 5.3% for right kidney, - 0.7 ± 5.5% for left kidney), reproducible (intra-operator variability - 0.2 ± 1.3%; inter-operator variability 1.1 ± 2.9%) and outperformed published methods. It took less than 6 min to execute and performed consistently with high accuracy in an external MRI dataset of T2-weighted sequences with TKV acquired using three different scanners and measured using a different segmentation methodology (mean volume error was 3.45 ± 3.96%, n = 65).ConclusionsThe Sheffield TKV Tool is operator friendly, requiring minimal user interaction to rapidly, accurately and reproducibly measure TKV in this, the largest reported unselected European patient cohort with ADPKD. It is more accurate than estimating equations and its accuracy is maintained at larger kidney volumes than previously reported with other semi-automated methods. It is free to use, can run as an independent executable and will accelerate the application of TKV as a prognostic biomarker for ADPKD into clinical practice.Key points• This new semi-automated method (Sheffield TKV Tool) to measure total kidney volume (TKV) will facilitate the routine clinical assessment of patients with ADPKD. • Measuring TKV manually is time consuming and laborious. • TKV is a prognostic indicator in ADPKD and the only imaging biomarker approved by the FDA and EMA.

Project description:BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrated that metabolic reprogramming may play a key role in cystic epithelial proliferation resulting in cyst growth in ADPKD. Height corrected total kidney volume (ht-TKV) accurately reflects cyst burden and predicts future loss of kidney function. We hypothesize that specific plasma metabolites will correlate with eGFR and ht-TKV early in ADPKD, both predictors of disease progression, potentially indicative of early physiologic derangements of renal disease severity.MethodsTo investigate the predictive role of plasma metabolites on eGFR and/or ht-TKV, we used a non-targeted GC-TOF/MS-based metabolomics approach on hypertensive ADPKD patients in the early course of their disease. Patient data was obtained from the HALT-A randomized clinical trial at baseline including estimated glomerular filtration rate (eGFR) and measured ht-TKV. To identify individual metabolites whose intensities are significantly correlated with eGFR and ht-TKV, association analyses were performed using linear regression with each metabolite signal level as the primary predictor variable and baseline eGFR and ht-TKV as the continuous outcomes of interest, while adjusting for covariates. Significance was determined by Storey's false discovery rate (FDR) q-values to correct for multiple testing.ResultsTwelve metabolites significantly correlated with eGFR and two triglycerides significantly correlated with baseline ht-TKV at FDR q-value < 0.05. Specific significant metabolites, including pseudo-uridine, indole-3-lactate, uric acid, isothreonic acid, and creatinine, have been previously shown to accumulate in plasma and/or urine in both diabetic and cystic renal diseases with advanced renal insufficiency.ConclusionsThis study identifies metabolic derangements in early ADPKD which may be prognostic for ADPKD disease progression.Clinical trialHALT Progression of Polycystic Kidney Disease (HALT PKD) Study A; Clinical www.clinicaltrials.gov identifier: NCT00283686; first posted January 30, 2006, last update posted March 19, 2015.