SP033
WHAT DIFFERENCE A FORMULA MAKES? ELIGIBILITY FOR TOLVAPTAN THERAPY FOR ADPKD - HOW TO SELECT THOSE WHO WILL BENEFIT THE MOST FROM TREATMENT?

Introduction and Aims: Excitement about ADPKD has never been greater with the European regulatory approval of the use of Tolvaptan (Januvia) in progressive disease in 2015. But, what exactly constitutes progressive ADPKD? Tempo 3:4 was of course a trial examining the change in total kidney volume as the primary outcome. But in clinical practice this is hard - often impossible - to measure. GFR is easier to use, of course, but even here, there are nuances and considerations, not the least which CKD formula / methodology to deploy. We wanted to examine the impact of age, and of different CKD formulae, on the likely numbers of patients eligible for treatment, from our ADPKD cohort. In addition, we wanted to see how well BP is currently controlled in this condition, using the same cohort with reference to the HALT-PKD study from 2014.

Methods: We searched our electronic databases and patient files to construct a "long list" of patients with ADPKD, of all ages, genders, races, and with an MDRD eGFR of 30-90 mls/min. We also then used clinical and laboratory data to complete an analysis of each patient, including their current BP levels in clinic, and, the type of BP treatment if any in use. We compared the results from MDRD formula derived eGFR to CKD-Epi creatinine (2009) formulae derived eGFR (all creatinines traceable). We audited the clinic BP against HALT-PKD criteria (intensive BP 95-110/60-75 mm Hg) and standard BP (120-130/70-80 mm Hg).

Results: We were able to locate 125 patients - likely representing around 75% of the patients which according to epidemiological predictions would be expected to be in our nephrology patient catchment area. There were 40 men, 85 women, 7 patients were Afro-Caribbean. Mean (SD) age was 45.5 (13) years. Age range was 17 to 85 years. Creatinine was 105 (30), MDRD GFR 60 (19), CKD-Epi GFR 68 (23), Systolic BP 135 (15) / Diastolic BP 81 (11). 59 patients were taking ACE/ARB Rx, but overall, 40 were on no BP Rx at all. 32 patients were on more than 1 BP drug. 15 were taking diuretics (bendroflumethazide in 11 cases).Analysing by eGFR - MDRD showed 7 patients with an eGFR > 90 and none with > 100 mls/min. However, using CKD-Epi there were 21 > 90 and 14 > 100 mls/min. Of course, all of these would be ineligible for treatment. If an upper age limit to receive Rx of say 50 were applied, as some have advocated (as Tempo 3:4 had age inclusion range of 18-50), then 39 / 125 patients (~ 25%) would be ineligible as well.With respect to BP, only 12% of patients were controlled to the HALT-PKD intensive BP, and 29% to the standard BP, domains. 40 patients had SBP > 140 and 22 DBP > 90 mm Hg. This meant that 59% of patients had imperfectly controlled outpatient BP levels.

Conclusions: While the use of the CKD-Epi creatinine (2009) formula, advocated by NICE in the UK, may potentially refine assessment, and may bring greater accuracy, it is of course completely UNfamiliar to patients, who have been taught to use and understand MDRD eGFR for a decade now. Equally, an upper age limit for inclusion needs to be very carefully calibrated to ensure fairness to all. Many patients might now be severely disappointed by finding they are barred from receiving valuable treatment either through an unfamiliar eGFR result, or, by the application of an arbitrary age cut-off.BP control in this cohort when compared to contemporary standards was sub-optimal, and thus much more effort in controlling BP should be a corollary of the assessment for, and use of, disease-modifying drugs in ADPKD (e.g. trying to attain HALT-PKD standards).