106
views
0
recommends
+1 Recommend
0 collections
    4
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1–3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

          The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration.

            The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level generally is a late event in chronic kidney disease (CKD); thus, there is great interest in considering alternative end points for clinical trials to shorten their duration, reduce sample size, and extend their conduct to patients with earlier stages of CKD. However, the relationship between lesser declines in GFR and the subsequent development of kidney failure has not been well characterized. The National Kidney Foundation and Food and Drug Administration sponsored a scientific workshop to critically examine available data to determine whether alternative GFR-based end points have sufficiently strong relationships with important clinical outcomes of CKD to be used in clinical trials. Based on a series of meta-analyses of cohorts and clinical trials and simulations of trial designs and analytic methods, the workshop concluded that a confirmed decline in estimated GFR of 30% over 2 to 3 years may be an acceptable surrogate end point in some circumstances, but the pattern of treatment effects on GFR must be examined, specifically acute effects on estimated GFR. An estimated GFR decline of 40% may be more broadly acceptable than a 30% decline across a wider range of baseline GFRs and patterns of treatment effects on GFR. However, there are other circumstances in which these end points could lead to a reduction in statistical power or erroneous conclusions regarding benefits or harms of interventions. We encourage careful consideration of these alternative end points in the design of future clinical trials.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials.

              The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.
                Bookmark

                Author and article information

                Journal
                Nephrol Dial Transplant
                Nephrol. Dial. Transplant
                ndt
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                March 2016
                29 January 2016
                29 January 2016
                : 31
                : 3
                : 337-348
                Affiliations
                [1 ]Department of Nephrology, University Medical Center Groningen, University of Groningen , Groningen, The Netherlands
                [2 ]Department of Nephrology, Hacettepe University Faculty of Medicine , Ankara, Turkey
                [3 ]Department II of Internal Medicine and Centre for Molecular Medicine Cologne, University of Cologne , Cologne, Germany
                [4 ]Department of Renal Medicine, Aarhus University Hospital , Aarhus, Denmark
                [5 ]Department of Biomedicine, Aarhus University , Aarhus, Denmark
                [6 ]Department of Nephrology, Second University of Naples , Naples, Italy
                [7 ]Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital , and ‘Grigore T. Popa’ University of Medicine , Iasi, Romania
                [8 ]Institute of Physiology, University of Zurich , Zurich, Switzerland
                [9 ]Division of Nephrology, UCL Medical School , Brussels, Belgium
                [10 ]Renal Division, University of Würzburg , University Hospital , Wurzburg, Germany
                [11 ]Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen-Nürnberg (FAU) , Erlangen, Germany
                [12 ]Department of Nephrology and Urology, Bambino Gesù Children's Hospital-IRCCS , Rome, Italy
                [13 ]Department of Nephrology, Hôpital Necker , Paris Descartes University , Paris, France
                [14 ]Service de Néphrologie, Hémodialyse et Transplantation Rénale, Hôpital La Cavale Blanche, Centre Hospitalier Régional Universitaire de Brest , Brest, France
                [15 ]Division of Nephrology, Ambroise Paré Hospital, Assistance Publique Hôpitaux de Paris , Boulogne-Billancourt/Paris, France
                [16 ]Inserm U-1018, Equipe 5 , Villejuif, France
                [17 ]University of Paris Saclay and Paris Ouest—Versailles-Saint-Quentin-en-Yvelines (UVSQ) , France
                [18 ]Academic Nephrology Unit, University of Sheffield Medical School , Sheffield, UK
                [19 ]IIS-Fundacion Jimenez Diaz-UAM and REDINREN , Madrid, Spain
                [20 ]Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital , Heidelberg, Germany
                [21 ]Inherited Kidney Diseases Nephrology Department, Fundació Puigvert Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autònoma de Barcelona , Barcelona, Spain
                [22 ]REDINREN , Barcelona, Spain
                [23 ]Renal Division, Ghent University Hospital , Ghent, Belgium
                [24 ]Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice , Katowice, Poland
                [25 ]CNR-IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension Unit, Reggio Calabria c/o Ospedali Riuniti , Reggio Calabria, Italy
                Author notes
                Correspondence and offprint requests to: Ron T. Gansevoort; E-mail: r.t.gansevoort@ 123456umcg.nl
                Article
                gfv456
                10.1093/ndt/gfv456
                4762400
                26908832
                84873266-2a2f-4f9b-a051-b05bd3870cd3
                © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 22 December 2015
                : 22 December 2015
                Categories
                Cutting-Edge Renal Science
                Ndt Perspectives

                Nephrology
                adpkd,tolvaptan,vasopressin v2 receptor antagonist
                Nephrology
                adpkd, tolvaptan, vasopressin v2 receptor antagonist

                Comments

                Comment on this article