An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International

Abstract

The approval of the vasopressin V2-receptor antagonist tolvaptan – based on the landmark TEMPO 3:4 trial – has marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD). This development has advanced patient care in ADPKD from general measures to prevent progression of chronic kidney disease to targeting disease specific mechanisms. However, considering the long-term nature of this treatment as well as potential side effects, evidence-based approaches to initiate treatment only in patients with rapidly progressing disease are crucial. In 2016, the position statement issued by the ERA was the first society-based recommendation on the use of tolvaptan and has served as a widely-used decision-making tool for nephrologists. Since then, considerable practical experience regarding the use of tolvaptan in ADPKD has accumulated. More importantly, additional data from REPRISE, a second randomized clinical trial (RCT) examining the use of tolvaptan in later stage disease has added important evidence to the field, as have post-hoc studies of these RCTs. To incorporate this new knowledge, we provide an updated algorithm to guide patient selection for treatment with tolvaptan and add practical advice for its use.

Management of autosomal dominant polycystic kidney disease in the era of disease-modifying treatment options

“…The definition of rapid progression is evolving. There is currently controversy on treating MIC 1C, where the United States practical guide favors treating with tolvaptan, whereas the updated recommendations from the European Renal Association-European Dialysis and Transplantation Association and PKD International advise seeking additional confirmatory evidence of rapid progression such as age-adjusted GFR, genotyping, predicting renal outcome in ADPKD (PROPKD) score, or family history [ 26 ]. While there is no consensus, international guidelines will likely be developed through an upcoming Kidney Disease: Improving Global Outcomes (KDIGO) workgroup.…”

“…If there is a discordance between htTKV, age, and decline in kidney function, an alternative diagnosis such as ADTKD and other mimickers of ADPKD should be considered as described above. When interpreting TKV, it is prudent to adjust to the age at time of imaging and ensure [26]. While there is no consensus, international guidelines will likely be developed through an upcoming Kidney Disease: Improving Global Outcomes (KDIGO) workgroup.…”

Drugs in Clinical Development to Treat Autosomal Dominant Polycystic Kidney Disease

“…There is no international consensus on the definition of rapidly progressive ADPKD [ 16 ]. The European Renal Association (ERA) has recently published an updated position statement regarding in which ADPKD patients to prescribe tolvaptan [ 17 ]. This paper defines rapidly progressive disease as an annual estimated glomerular filtration rate (eGFR) decline of ≥ 3.0 mL/min/1.73 m 2 .…”

Zystennieren: Genetische Testung und richtige Einordnung klinisch-therapeutisch zunehmend bedeutsam

“…Diese teure und von massiver Polyurie begleitete Therapie ist aber nur zugelassen für Patienten mit „rapid progressivem“ Krankheitsverlauf, d. h. die zu Lebzeiten mit einer terminalen Niereninsuffizienz rechnen müssen. Zur Auswahl geeigneter Patienten empfiehlt die europäische Fachgesellschaft ERA-EDTA die Genetik und Berücksichtigung des Mutationstyps als Teil des PRO-PKD-Scores 18 19 . Ein rechtzeitiger Beginn der Therapie (also nicht erst nach dokumentiertem raschen Nierenfunktionsverlust) kann das Eintreten der Dialysepflichtigkeit um Jahre verzögern.…”