Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence.

BACKGROUND: Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited. METHODS: In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed. RESULTS: In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo. CONCLUSIONS: Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).

Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. METHODS: The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. DISCUSSION: The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.

[Hyperkalemia - what the general practitioner must know]. / Hyperkaliämie - was der Hausarzt wissen muss.

Hyperkalemia can be a challenge for the general practitioner as it can prove to be benign as well as life-threatening. From a diagnostic point of view, four possibilities have to be differenciated: a pre-analytical cause, potassium release through cell lysis, a potassium shift, a reduced renal excretion of potassium. The first differential diagnosis can often be carried out by a thorough medical history, in particular the medication intake. Also, the first clinical and laboratory investigations can take place at the general practitioner's clinic. If the hyperkalemia proves to be a true hyperkalemia or cannot be explained by poly-medication and known diseases of the patient, not yet identified renal, endocrine or cardiac diseases should be searched for. If a serious condition is identified as the cause of hyperkalemia the patient should be referred to a specialized clinic.

Une hyperkaliémie peut représenter un challenge au cabinet médical car elle peut aussi bien s'avérer bénigne que menaçante pour la vie du patient. Sur le plan diagnostique, quatre possibilités sont à différencier: une cause pré-analytique, la libération de potassium par une lyse cellulaire, un déplacement du potassium, une diminution de l'excrétion rénale du potassium. Le premier diagnostic différentiel s'effectue souvent par une anamnèse précise, en particulier une anamnèse médicamenteuse. De même, les premières investigations cliniques et de laboratoire peuvent être faites au cabinet médical. Si l'hyperkaliémie ne s'avère pas être une pseudohyperkaliémie ou si une polymédication et la maladie de base ne suffisent pas à l'expliquer, une cause rénale, endocrinologique ou cardiaque ­ jusque-là méconnue ­ doit être recherchée. Si la cause de l'hyperkaliémie est une affection grave, le patient devrait être adressé à une consultation spécialisée.