| Eligibility |
Inclusion Criteria:
The study will enroll patients with calcium, cystine and uric acid stone composition.
Patients will be at least 18 years of age, with no upper limit of age. Patients will sign
an informed consent form (ICF). We will seek participants who have experienced any USD
events including renal colic with spontaneous stone passage, emergency room visits, or
urological interventions, in the previous 5 years in order to encourage enrollment and
adherence to the protocol. We will include all racial and ethnic groups, and both men and
women. Besides stone composition, standard demographic data including gender, age, and body
mass index will be collected.
Patients who are taking alkalinizing medications for prevention of USD including KCit,
potassium bicarbonate, sodium citrate and sodium bicarbonate will be eligible for
participation in the study. The patient's usual dose, however, will be discontinued for the
2 weeks which make up the two study periods. This maneuver will not be an important risk
for stones for several reasons: 1) the period off alkali altogether will be one week; 2)
the one week of Moonstone will offer a significant amount of alkali, likely as much or more
than the patients' usual prescription doses; 3) participants will continue to adhere to
fluid intake and dietary prescriptions.
These data are intended to be included in an RO-1 resubmission due November 5. We will
therefore aspire to include 10 patients with calcium stones, 3 patients with cystine stones
and 3 patients with uric acid stones.
Exclusion Criteria:
Investigators will exclude patients taking thiazides (indapamide, hydrochlorothiazide, and
chlorthalidone). Our reasoning is that most calcium stone patients are not taking thiazides
and such patients may be total body potassium-depleted (not necessarily reflected by serum
potassium. Potassium depletion reduces citrate excretion (through effects on intracellular
pH in the proximal tubule) so that patients taking thiazides could start with lower urine
citrate excretion and have less of an increment in the Moonstone periods. The order of the
periods might affect the magnitude of urine chemistry changes in those two periods.
Patients with chronic kidney disease tend to have reduced urinary citrate excretion due to
mild metabolic acidosis. We will therefore exclude patients with estimated glomerular
filtration rates (eGFRs) less than 60 ml/min/1.73 m2 calculated by the CKD-EPI equation.
eGFRs will have been measured in the preceding year at a time when urinary tract
obstruction due to USD was not present. We will also exclude women who are pregnant or
nursing and people with any medical, psychiatric, debilitating disease/disorder, or social
condition that in the judgment of the investigator would interfere with or serve as a
contraindication to adherence to the study protocol or ability to give informed consent, or
affect the overall prognosis of the patient.
The study will also exclude patients with a previous history of gastrointestinal
intolerance, or any other intolerance of alkalinizing preparations. The proportion of USD
patients who do not tolerate KCit is not clear. The Cochrane review on this topic states
that there are adverse events reported with citrate therapy, but the effect was not
statistically significant, in part because of incomplete reporting. Based on our
experience, we usually cite this problem to affect about 10% of stone formers, with older
people more frequently affected. We therefore do not think this exclusion criterion will
have a sizable effect on enrollment.
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