Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease

Perrone, Ronald D.; Mouksassi, Mohamad Samer; Romero, Klaus; Czerwiec, Frank S.; Chapman, Arlene B.; Gitomer, Berenice; Torres, Vicente E.; Miskulin, Dana C.; Broadbent, Steve; Marier, Jean‐François

doi:10.1016/j.ekir.2017.01.003

Cited by 99 publications

(94 citation statements)

References 25 publications

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“…Further, both the US Food and Drug Administration and the European Medicines Agency formally qualified total kidney volume (TKV) as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials [15].…”

Section: Introductionmentioning

confidence: 99%

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

et al. 2018

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Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m²). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

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Section: Introductionmentioning

confidence: 99%

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

et al. 2018

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“…The selection of participants mainly on the basis of the estimated GFR was justified by the fact that the estimated GFR is an excellent predictor of disease progression when the rate is already declining. 33,34 Nevertheless, it remains possible that additional selection criteria regarding genotype or age-adjusted total kidney volume could have further enriched the trial population for patients who would have rapid disease progression. 30,31 We did not study whether the effect of tolvaptan on the estimated GFR was mediated or paralleled by an effect on kidney volume; renal hemodynamic or other mechanisms could have also played a role.…”

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confidence: 99%

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

et al. 2017

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BACKGROUNDIn a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V 2 -receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODSWe conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m 2 of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m 2 were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTSThe change from baseline in the estimated GFR was −2.34 ml per minute per 1.73 m 2 (95% confidence interval [CI], −2.81 to −1.87) in the tolvaptan group, as compared with −3.61 ml per minute per 1.73 m 2 (95% CI, −4.08 to −3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m 2 ; 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONSTolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145.)

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“…The Polycystic Kidney Disease Outcomes Consortium recently established a therapeutic data standard for ADPKD [21]. This allowed for observational data from multiple sources, including the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) [21], to be integrated into a single data set that included ≤30 years of follow-up TKV data from 2,355 patients with ADPKD [22]. Analysis of this dataset showed that baseline TKV had a significant impact on the risk of a 30% decline in estimated glomerular filtration rate (eGFR) and progression to ESRD, independent of baseline eGFR and age [22].…”

Section: Introductionmentioning

confidence: 99%

“…This allowed for observational data from multiple sources, including the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) [21], to be integrated into a single data set that included ≤30 years of follow-up TKV data from 2,355 patients with ADPKD [22]. Analysis of this dataset showed that baseline TKV had a significant impact on the risk of a 30% decline in estimated glomerular filtration rate (eGFR) and progression to ESRD, independent of baseline eGFR and age [22]. The recent CRISP III study utilized 14.5 years of follow-up data in patients with ADPKD and showed that baseline TKV adjusted for height (htT-KV) was an independent predictor of a ≥30 and ≥57% decline in eGFR from baseline, with a significant correlation between the annual rate of htTKV increase and eGFR decline [23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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Background: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder; it is defined by progressive renal cyst formation and subsequent renal enlargement that leads to end-stage renal disease. Until recently, only symptomatic treatments for ADPKD existed. However, therapies that address the underlying pathophysiology of ADPKD are now available and accurate identification of the rate of disease progression is essential. Summary: Published data on the different imaging modalities for measuring kidney and cyst volumes in ADPKD are reviewed. The advantages and drawbacks of the different techniques for calculating kidney volume from renal imaging are also examined, including the use of manual planimetry, stereology, and the ellipsoid equation, as well as the prospect of semi- and fully automatic techniques. The translation of these approaches into clinical practice and their role in informing treatment decisions is discussed. Key Messages: These new therapies require the accurate monitoring of disease progression, which along with diagnosis and prognosis, relies on the effective use of renal imaging techniques. There is growing support for the use of total kidney volume as a measure of cyst burden and as a prognostic predictor of renal function in ADPKD, showing promise as a marker of disease progression.

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Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease

Cited by 99 publications

References 25 publications

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

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

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