title: Agglomeration inhibition reflected stone-forming activity during long-term potassium citrate therapy in calcium stone formers.
abstract: OBJECTIVE
  The agglomeration of preformed crystals of calcium oxalate has been hypothesized to be the rate-limiting step in renal stone-forming activity (SFA). The effect of urine on the in vitro inhibition of agglomeration of seed crystals of calcium oxalate monohydrate, designated [tm], has been used to monitor SFA in calcium oxalate stone formers (CaOxSF). The objective of the present study was to determine whether [tm] could be used to help monitor the long-term effectiveness of oral potassium citrate therapy (K-Cit-Rx) in CaOxSF.
  
  
  METHODS
  Clinic and radiographic (or ultrasound) reports were evaluated for 80 patients, aged 20 to 72 years, 55 men and 25 women, who were treated with oral K-Cit for recurrent calcium oxalate urolithiasis at the Ochsner Stone Clinic between January 1992 and July 1996. Seventy-five of these patients had at least one 24-hour citrate excretion rate of less than 3.0 mm/day before or after K-Cit-Rx. SFA graded on a scale of -2 to +2 by radiographic criteria was combined with information on stone passage to evaluate clinical stone status, and 24-hour urine collections were evaluated for volume, pH, calcium, citrate, uric acid, oxalate, creatinine, and [tm] on free diet before and after 6 to 53 months of K-Cit-Rx. Historical information on procedures performed for urolithiasis before and on K-Cit-Rx was also reviewed.
  
  
  RESULTS
  K-Cit-Rx resulted in increased urine pH (P <0.0001) and decreased calcium (P=0.0475), [tm] (P=0.0045), number of stones passed per year (P=0.0016), and remedial procedures per year (P <0.0001). Patients taking allopurinol in addition to K-Cit required higher doses (P <0.0001) of K-Cit to control their disease, had lower pretreatment urine pH (P=0.0493), and showed greater increase in urine citrate (P=0.0092) than those on K-Cit alone. Those taking high-dose K-Cit were younger (P=0.0363) and showed greater decrease in SFA (P=0.0005) than those taking lower doses. A small group of 10 medication refractory patients, who retained (n=9) or increased (n=1) their stone burden during K-Cit-Rx, was identified. Compared with the medication-responsive group, the refractory patients were older (P=0.0124), and had greatly increased SFA (P <0.0001) and higher (P=0.0347) urine pH before and during (P=0.0173) treatment (data not shown).
  
  
  CONCLUSIONS
  The data confirm that [tm] can be used not only to verify previously documented stone formation rate but also to help evaluate the long-term effectiveness of therapy. In this report, changes in [tm] after K-Cit-Rx reflected decreased stone formation rate and decreased remedial procedures.
authors.affiliation: Department of Urology, Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Fuselier
authors.forename: K
authors.initials: K
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Lindberg
authors.forename: F E
authors.initials: FE
authors.lastname: Husserl
authors.forename: F E
authors.initials: FE
authors.lastname: Cole
authors.forename: D J
authors.initials: DJ
authors.lastname: Kok
authors.forename: D
authors.initials: D
authors.lastname: Whitehead
authors.forename: D J
authors.initials: DJ
authors.lastname: Galliano
authors.forename: D T
authors.initials: DT
authors.lastname: Erwin
mesh_terms: D000328:Adult; D000368:Aged; D002129:Calcium Oxalate / Q000032:analysis*; D003460:Crystallization; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019357:Potassium Citrate / Q000627:therapeutic use*; D012044:Regression Analysis; D013997:Time Factors; D014545:Urinary Calculi / Q000737:chemistry / Q000188:drug therapy* / Q000652:urine*
chemical_list: D004232:Diuretics; D002129:Calcium Oxalate; D019357:Potassium Citrate