A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model

McEwan, Phil; Wilton, Hayley Bennett; Ong, Albert; Ørskov, Bjarne; Sandford, Richard; Scolari, Francesco; Cabrera, Maria-Cristina V.; Walz, Gerd; O'Reilly, K.; Robinson, Paul

doi:10.1186/s12882-017-0804-2

Cited by 45 publications

(40 citation statements)

References 29 publications

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“…Through ionic mechanisms presented herein, it or other structurally similar non-peptide compounds that can be preferentially used for oral intake, is able to influence the functional activities of endocrine or renal tubular cells, if similar findings occur in vivo . Our findings also highlight an important alternative aspect that needs to be taken into account, inasmuch as the aquaretic effects of TLV in different pathologic disorders including polycystic kidney disease, cirrhosis or heart failure, are evaluated (Ghali et al, 2009; Graziani et al, 2012; Mancinelli et al, 2016; Clark et al, 2017; Sweeney and Avner, 2017; (Torres et al, 2017; van Gastel and Torres, 2017; Wu et al, 2017a; Chebib et al, 2018; Edwards et al, 2018; Imamura and Kinugawa, 2018; Matsukawa et al, 2018; McEwan et al, 2018; Müller et al, 2018; Oguro et al, 2018b; Poch et al, 2018; Sen et al, 2018; Takimura et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Chang

Chan

et al. 2019

Front. Pharmacol.

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Tolvaptan (TLV), an oral non-peptide antagonist of vasopressin V 2 receptor, has been increasingly used for managements in patients with hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion. However, none of the studies have thus far been investigated with regard to its possible perturbations on membrane ion currents in endocrine or neuroendocrine cells. In our electrophysiological study, the whole-cell current recordings showed that the presence of TLV effectively and differentially suppressed the amplitude of delayed rectifier K + ( I K(DR) ) and M-type K + current ( I K(M) ) in pituitary GH 3 cells with an IC 50 value of 6.42 and 1.91 μM, respectively. This compound was also capable of shifting the steady-state activation curve of I K(M) to less depolarized potential without any appreciable change in the gating charge of this current. TLV at a concentration greater than 10 μM also suppressed the amplitude of erg -mediated K + current or the activity of large-conductance Ca 2+ -activated K + channels; however, this compound failed to alter the amplitude of hyperpolarization-activated cation current in GH 3 cells. In vasopressin-preincubated GH 3 cells, TLV-mediated suppression of I K(M) remained little altered. Under current-clamp condition, we also observed that addition of TLV increased the firing of spontaneous action potentials in GH 3 cells and further addition of flupirtine could reverse TLV-mediated elevation of the firing. In Madin-Darby canine kidney (MDCK) cells, the K + current elicited by long ramp pulse was also effectively subject to inhibition by this compound. Findings from the present study were thus stated as saying that the suppression by TLV of multiple type K + currents could be direct and independent of its antagonism of vasopressin V 2 receptors. Our study also reveals an important aspect that should be considered when assessing aquaretic effect of TLV or its structurally similar compounds.

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Section: Discussionmentioning

confidence: 99%

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Chang

Chan

et al. 2019

Front. Pharmacol.

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“…Another prediction instrument is the ADPKD Outcomes Model (ADPKD-OM), a fixed-time increment stochastic simulation model based on disease progression equations for HtTKV and estimated glomerular filtration rate (eGFR). The model was internally validated with data from the placebo arm of the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3:4 tolvaptan study [43]. Finally, a neural network for eGFR prediction was suggested.…”

Section: Early Identification Of Patients For Future Therapy: Whom Anmentioning

confidence: 99%

Unmet needs and challenges for follow-up and treatment of autosomal dominant polycystic kidney disease: the paediatric perspective

Rechter

Bammens

Schaefer

et al. 2018

Clinical Kidney Journal

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Awareness is growing that the clinical course of autosomal dominant polycystic kidney disease (ADPKD) already begins in childhood, with a broad range of both symptomatic and asymptomatic features. Knowing that parenchymal destruction with cyst formation and growth starts early in life, it seems reasonable to assume that early intervention may yield the best chances for preserving renal outcome. Interventions may involve lifestyle modifications, hypertension control and the use of disease-modifying treatments once these become available for the paediatric population with an acceptable risk and side-effect profile. Until then, screening of at-risk children is controversial and not generally recommended since this might cause psychosocial and financial harm. Also, the clinical and research communities are facing important questions as to the nature of potential interventions and their optimal indications and timing. Indeed, challenges include the identification and validation of indicators, both measuring and predicting disease progression from childhood, and the discrimination of slow from rapid progressors in the paediatric population. This discrimination will improve both the cost-effectiveness and benefit-to-risk ratio of therapies. Furthermore, we will need to define outcome measures, and to evaluate the possibility of a potential therapeutic window of opportunity in childhood. The recently established international register ADPedKD will help in elucidating these questions. In this review, we provide an overview of the current knowledge on paediatric ADPKD as a future therapeutic target population and its unmet challenges.

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“…The model showed that differences in baseline TKV can markedly affect time to ESRD, and that younger patient cohorts with large kidneys would enter ESRD at a younger age. For example, the predicted age of progression to ESRD in a patient aged 30 with eGFR 110 mL/min/1.73 m 2 and a TKV of 1,000 mL, would be 49-54 years, compared with 60-65 years for a patient aged 45 years with eGFR 80 mL/ min/1.73 m 2 and a TKV of 1,000 mL [54].…”

Section: Adpkd Outcomes Modelmentioning

confidence: 99%

“…The APDKD outcomes model was developed using TKV and eGFR progression rates derived from the placebo arm of the TEMPO 3: 4 trial [54]. The model simulates disease progression of hypothetical patient cohorts over prespecified time horizons, taking into account covariates including age, sex, and baseline TKV.…”

Section: Adpkd Outcomes Modelmentioning

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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A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model

Cited by 45 publications

References 29 publications

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor

Unmet needs and challenges for follow-up and treatment of autosomal dominant polycystic kidney disease: the paediatric perspective

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

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