Understanding variation between kidney centres in implementation of tolvaptan in the management of autosomal dominant polycystic kidney disease: a multiple case study

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) affects an estimated 12.5 million people worldwide and 70,000 in the United Kingdom (UK). Tolvaptan is the only disease-modifying therapy available. Despite national guidelines, prescribing varies across UK kidney centres. The aim was to explore the organisational, individual, and contextual factors influencing implementation of tolvaptan care pathways. Methods We conducted a multiple case study of three UK kidney centres in the National Health Service. Cases were selected based on their prescribing practices. Within each case, semi-structured interviews, patient consultation observations and document analyses were performed (December 2024–September 2025). Data were analysed using framework analysis and mapped to the Consolidated Framework for Implementation Research (CFIR). Results Twelve healthcare professional interviews, twenty-three patient consultation observations, and eight documents were analysed. Implementation was primarily influenced by factors in the ‘Outer Setting’, ‘Inner Setting’, and ‘Individuals’ domains of the CFIR. At the ‘Outer Setting’, Cases 2 and 3 benefited from prior participation in the tolvaptan effectiveness clinical trials, and use of professional networks, to facilitate a rapid launch of a new pathway without additional funding. This enabled early adoption compared to Case 1. At the ‘Inner Setting’, Case 2’s centralised, specialist-led pathway allowed the systematic application of eligibility criteria and timely initiation of tolvaptan, while Case 1’s distributed pathway could cause variable application of eligibility criteria and delays in initiation. Case 3 had a hybrid pathway combining aspects from the other cases, but faced capacity challenges due to high patient volumes. At the ‘Individuals’ level, proactive consultant nephrologists led the management of the tolvaptan pathway in Case 2 which could improve treatment access, whereas less experienced staff in Case 1 appeared to limit early use. Case 3 reported occasional off-guideline use potentially contributing to higher use relative to other centres nationally. Conclusion Without additional dedicated funding, tolvaptan was implemented within existing structures. Centralised, specialist-led models appeared to enable more consistent implementation and prescribing, while distributed or hybrid pathways introduced potential variation from guidelines which could lead to fewer initiations in eligible patients and more initiations in non-eligible patients. These insights may guide implementation of other rare disease therapies to improve equity and access.