Abstracts EAU20 Virtual Congress and Theme Week
243
Hexametaphosphate as a potential new therapy for kidney stones
Eur Urol Open Sci 2020;19(Suppl 2):e429
Robinson T.E.1, Hughes E.A.B.1, Wiseman O.J.2, Cox S.C.1, Grover L.M.1
1
University of Birmingham, School of Chemical Engineering, Birmingham, United Kingdom, 2Cambridge University Hospital, Dept. of Urology,
Cambridge, United Kingdom
Introduction & Objectives: Incidence of kidney stones is increasing across all demographics, with a lifetime risk of 10 – 15% in the Western world.
Citrate therapy is often utilised because it raises urine pH and chelates calcium, the primary component of the vast majority of stones, however
recurrence is common even in patients who receive this treatment. Hexametaphosphate (HMP) is an inorganic oligophosphate, which is used in
the food and minerals industries in part because it is a potent divalent cation chelator. The objective of this study is to assess whether HMP may be
a more potent alternative to citrate therapy.
Materials & Methods: The ability of HMP to dissolve the common components of kidney stones was tested in vitro via light extinction and residual
mass methods. The efficacy at dissolving calcium oxalate, the most frequent stone component, was then directly compared to citrate. The zeta
potential and size of the calcium oxalate particles was also measured over time, in artificial urine doped with HMP or citrate. Finally, the efficacy
was tested ex vivo against human kidney stones.
Results: HMP was found to be effective at dissolving calcium oxalate and phosphate, in addition to struvite, but did not affect uric acid or cystine,
showing that HMP dissolves divalent cationic salts. When compared to citrate, HMP was found to be more than 12 times as effective a dissolution
agent of calcium oxalate. Interestingly, while calcium oxalate suspensions treated with HMP cleared increasingly over time, those treated with citrate
were found to reprecipitate. The zeta potential of particles treated in HMP became significantly more negative, suggesting long-term electrostatic
stability. This was not the case for citrate, which facilitated aggregation of particles. Finally, in calcium-based human kidney stones, HMP was
shown to be up to 16 times as effective a dissolution agent as citrate.
Conclusions: HMP is effective at dissolving calcium oxalate, phosphate and struvite, which make up the vast majority of stones, and is significantly
more effective than citrate at doing so. It also increases the negative charge of the particles to prevent aggregation, which is by far the fastest
growth mechanism of stones in vivo. In contrast, citrate does not significantly alter the zeta potential and facilitates the particles to mass into large
aggregates. Finally, HMP is able to dissolve human stones and is up to 16 times as effective as citrate at doing so. This evidence suggests that
HMP may be a more potent therapy than citrate for cationic stones, and warrants investigation of HMP for the prevention of stones in vivo.
Eur Urol Open Sci 2020;19(Suppl 2):e429