Research Viewpoints Predicting “Rapid Progression” of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

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Furlano M, Loscos I, Martí T, Bullich G, Ayasreh N, Rius A, Roca L, Ballarín J, Ars E, Torra R: Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression. Am J Nephrol 2018;48:308–317

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive form of Chronic Kidney Disease (CKD), although there is extensive variability in the progression rate even among families with a presumed identical genetic mutation. This complicates the choice of treatment modalities as Tolvaptan, a vasopressin V2 receptor antagonist, is only approved for treatment of a “rapidly progressive” (RP) phenotype of ADPKD. Several “decision-making” algorithms are available for early identification of “rapid progessors” (eGFR decline of ≥ 5ml/min/1.73m2/year or > 2.5ml/min/1.73m2/year over 5 years) so that Tolvaptan therapy can be appropriately applied.

Furlano and colleagues asses the ERA-EDTA Working Group (WG) algorithm using an expanded definition that included both age and baseline eGFR parameters in a cross-sectional analysis with an 18 month time-frame.

A total of 305 subjects with ADPKD were examined, 73 of whom were eligible for assessment of “rapidly progressive“ definition using:

Historical eGFR decline
Historical Total Kidney Volume (TKV) growth (by MRI)
Changes in kidney length (by ultrasound)
Age / height adjusted TKV (Mayo Clinic)
PKD1 / PKD2 mutation analysis can substitute for gender, blood pressure and kidney enlargement (PROPKD criteria)
A family history of end-stage renal disease (ESRD) due to ADPKD at age < 58 years

A total of 48 patients met the criteria for RP (15.7 % of the overall cohort), 33 % of those 18 – 50 years of age who had a baseline eGFR of > 45 ml/min/1.73m2. In patients ages 18 – 55 years of age with a baseline eGFR of > 25 and < 45 ml/min/1,73m2 the overall proportion of patients with RP rose to 27 % and a further increase in treatment eligibility was observed for patients with a well preserved initial eGFR if serial imaging tools are taken into account.

This study clearly illustrates how selection criteria influence the percentage of subjects with ADPKD with presumed RP. With the most conservative approach (ERA-EDTA WG) about 1:6 patients will become eligible for Tolvaptan treatment. With expanded criteria, using age and baseline eGFR, the percentage eligibility can rise to about 1:4 patients.

These expanded criteria need additional external validation, as the decision to initiate Tolvaptan therapy in ADPK is one having major consequences.