Physico-chemical basis for struvite stone formation.
Doctoral thesis, UCL (University College London).
Introduction: Struvite stones (magnesium ammonium phosphate) account for 10-15% of renal stones and can grow rapidly forming staghorn calculi. With limited medical therapies available and surgery the mainstay of treatment, an understanding of the physico-chemical conditions causing struvite crystallization allows development of strategies to prevent their formation. At present, very little is known about the physico-chemical conditions that result in struvite crystallisation. This lack of understanding has two bases: i) the particular ionised concentrations of the reactants (e.g. Mg2+, NH4+, and phosphate) in the urine are unknown; ii) the prevailing chemical conditions that would modulate crystallisation are also unclear (e.g. pH, osmolality, other urinary constituents).Recent advances in the development of ion-selective electrodes allows accurate determination of urinary constituents in small (<1ml) undiluted samples. Methods: We have furthered developed an NH4+-ion selective electrode and magnesium ion-selective electrode to measure the urinary concentrations of each to aid our understanding of struvite deposition. [NH4+] and [Mg2+] were measured using plastic dip cast ion-selective electrodes dispersed in suitable plasticisers, using nonactin for NH4+ and several different neutral ligands for Mg2+. Data were validated against standardised and developing methodology, including colour spectrophotometry and computational algorithms. Urine samples were also subjected to analysis using clinical biochemical techniques. Results: We characterised an NH4+-ion selective electrode and made the first measurements of [NH4+] in undiluted urine samples, in normal subjects and those with stone disease. This technique was validated using colour spectrophotometry and then the technique was used to validate a computational algorithm. We have developed and characterised the Mg2+-ion-selective electrode but Ca2+ caused significant interference. Conclusions: Direct measurement of the urinary [NH4+] has been achieved for the first time with a value of about 25mM. This exciting new technique may now provide clinicians with an important point-of-care investigative tool in diagnosing and monitoring struvite calculogenesis.
|Title:||Physico-chemical basis for struvite stone formation|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of Urology|
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