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.

Chronic and acute consequences of a post-dialysis urokinase lock on permanent hemodialysis catheter function.

BACKGROUND: To treat permanent hemodialysis (HD) catheter dysfunctions due to thrombosis, as an alternative to pre- and intradialytic instillations/infusions of fibrinolytic agents, for practical reasons, a post-dialysis urokinase lock is often preferred. This study aimed to analyze the consequences on catheter function and the cost/effectiveness of an intermittent post-dialysis urokinase lock. METHODS: A prospective open experimental study enrolling 10 dialysis patients with a Tesio twin catheter locked with either heparin 5,000 IU/mL or escalating urokinase doses. Catheter function was monitored measuring the blood flow obtained with an aspiration pressure of -180 mmHg for 28 consecutive HD sessions. RESULTS: No differences were noticed between the blood flow obtained before and after the lock of the catheter with 5000 U/lumen of urokinase (phase 1), but also with 10,000 U/lumen (phase 2) of urokinase. The incidence of catheter dysfunction episodes in the wash-out in the 1st and in the 2nd urokinase phases were, respectively: 13, 6 and 3% (p<0.05 for both 13 vs. 6% and 13 vs. 3%). 47,000 U of urokinase were necessary to avoid one dysfunction episode potentially treatable with an intradialytic urokinase lock of 10,000 U. Between the average blood flow measured in the initial wash out (230 +/- 27 ml/min) and in the 1st (236 +/- 32 ml/min) and also in the 2nd (247 +/- 34 ml/min) urokinase phases significant differences were noticed (p<0.01 and p<0.05, respectively). CONCLUSIONS: The post-dialysis lock with urokinase is associated with an increase in the catheter blood flow and a re-duction in the occurrence of dysfunction episodes. However, the modest impact on dialysis quality and the apparent unfavorable cost/effectiveness of the prophylactic treatment, call for an investigation of its potential advantages in a larger study.

Telaprevir-induced renal impairment: three clinical cases and a review of the literature.

Telaprevir (TPV) is one of the NS3/4A serine protease inhibitors on the market for the treatment of chronic hepatitis C genotype 1 in combination with peginterferon alpha and ribavirin. Well-documented potential adverse reactions of TPV are hematological, skin, and gastro-intestinal disorders. Until now, there were no conclusive data from clinical trials about renal adverse reactions of TPV. We report here three cases of renal impairment that occurred after a few days of TPV treatment and resolved in about 2 weeks after stopping the drug. Two of the patients were hospitalized because of this serious adverse drug reaction. Therefore, renal impairment seems to be a new adverse drug reaction of TPV and clinicians should be aware of this potentially serious complication of chronic hepatitis C therapy.

Usefulness of artificial neural networks to predict follow-up dietary protein intake in hemodialysis patients.

BACKGROUND: Artificial neural networks (ANN) represent a promising alternative to classical statistical and mathematic methods to solve multidimensional nonlinear problems. The aim of the study was to verify, by comparing the performance of ANN with that of experienced nephrologists, whether ANN are useful tools in hemodialysis to predict the follow-up (=1 month after the observation used for the prediction) dietary protein intake (PCR), and whether their performance is influenced by the size of the population and by the data pool used to built the model. METHODS: A combined retrospective and prospective observational study was performed in two Swiss dialysis units (84 chronic hemodialysis patients, 500 monthly clinical observations and biochemical test results). Using mathematical models based on linear regressions to evaluate the variables, ANN were built and then prospectively and interinstitutionally compared with the ability of six experienced nephrologists to predict the follow-up PCR. RESULTS: ANN compared with nephrologists gave a more accurate correlation between estimated and calculated follow-up PCR (P < 0.001). The same superiority of ANN was also seen in the ability to detect a follow-up PCR <1.00 g/kg/day expressed as a percentage of correct predictions, sensitivity, specificity, and predictivity. The interinstitutional performance of the ANN is positively influenced by the size and the variability of the population used to build the mathematical model. CONCLUSION: The use of ANN significantly improves the ability of the experienced nephrologist to estimate and to detect an unsatisfactory (<1.00 g/kg/day) follow-up PCR. The size of the population selected to build the ANN is critical for his performance.