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Randomized double-blind placebo-controlled trial assessing the efficacy of standard and low dose hydrochlorothiazide treatment in the prevention of recurrent calcium nephrolithiasis

English title Randomized double-blind placebo-controlled trial assessing the efficacy of standard and low dose hydrochlorothiazide treatment in the prevention of recurrent calcium nephrolithiasis
Applicant Fuster Daniel Guido
Number 166785
Funding scheme Investigator Initiated Clinical Trials (IICT)
Research institution Klinik für Nephrologie und Hypertonie Universitätsklinik Inselspital Bern
Institution of higher education University of Berne - BE
Main discipline Internal Medicine
Start/End 01.06.2016 - 30.04.2023
Approved amount 2'438'923.00
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Keywords (6)

Secondary prevention; Hydrochlorothiazide; Nephrolithiasis; Dose response; Thiazide; Hypercalciuria

Lay Summary (German)

Lead
In dieser klinischen Studie wird die Wirksamkeit des Medikaments Hydrochlorothiazid zur Vorbeugung von Rückfällen kalziumhaltiger Nierensteine getestet.
Lay summary

Inhalt und Ziele des Forschungsprojektes:

Nierensteine sind ein weltweites Gesundheitsproblem, etwa 10 % aller Menschen sind mindestens einmal im Leben davon betroffen. Nierensteine sind äusserst schmerzhaft, treten wiederholt auf und verursachen hohe direkte und indirekte Kosten. Eine effektive und kostengünstige Vorbeugung gegen Rückfälle von Nierensteinen ist deshalb äusserst wünschenswert.

Etwa 80-90% aller Nierensteine enthalten Kalzium, eine vermehrte Ausscheidung von Kalzium im Urin ist die häufigste Stoffwechselstörung bei Patienten mit Nierensteinen. Thiazide reduzieren die Kalziumausscheidung im Urin und werden daher seit Jahrzehnten zur Vorbeugung von Rückfällen kalziumhaltiger Nierensteine eingesetzt. Deren Wirksamkeit wurde in den letzten 30 Jahren in mehreren Studien getestet. Leider war die Durchführung dieser Studien mangelhaft, die Gesamtzahl der untersuchten Patienten klein und es wurden hohe Medikamentendosen getestet, welche häufig Nebenwirkungen verursachen. Zur Zeit ist daher der Stellenwert der Thiazide in der Behandlung von Patienten mit Nierensteinen unklar. Ziel dieser Studie ist es, die Wirksamkeit von normal- und tiefdosiertem Hydrochlorothiazid zur Vorbeugung von Rückfällen kalziumhaltiger Nierensteine zu testen. 

3. Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts:

Das Nierensteinleiden gehört zu den häufigsten menschlichen Erkrankungen. Mit dieser klinischen Studie soll eine grosse Wissenslücke in der Nierensteinbehandlung geschlossen werden. Die Resultate dieser Studie werden die Behandlung von Nierensteinpatienten weltweit beeinflussen.

Direct link to Lay Summary Last update: 13.06.2016

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers
Moor Matthias B., Dhayat Nasser A., Schietzel Simeon, Grössl Michael, Vogt Bruno, Fuster Daniel G. (2022), Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers, in Urolithiasis, 1-8.
Mechanisms Underlying Calcium Nephrolithiasis
Alexander R.T., Fuster D.G., Dimke H. (2022), Mechanisms Underlying Calcium Nephrolithiasis, in Annual Review of Physiology, 84(1), 559-583.
Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers
Fuster Daniel G, Morard Gaétan A, Schneider Lisa, Mattmann Cedric, Lüthi David, Vogt Bruno, Dhayat Nasser A (2022), Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers, in Nephrology Dialysis Transplantation, 37(2), 335-348.
Predictors of Bone Mineral Density in Kidney Stone Formers
Dhayat Nasser A., Schneider Lisa, Popp Albrecht W., Lüthi David, Mattmann Cedric, Vogt Bruno, Fuster Daniel G. (2022), Predictors of Bone Mineral Density in Kidney Stone Formers, in Kidney International Reports, 7(3), 558-567.
De novo vasculitis after mRNA-1273 (Moderna) vaccination
Anderegg Manuel A., Liu Michael, Saganas Charalampos, Montani Matteo, Vogt Bruno, Huynh-Do Uyen, Fuster Daniel G. (2021), De novo vasculitis after mRNA-1273 (Moderna) vaccination, in Kidney International, 100(2), 474-476.
The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism
Bargagli Matteo, Arena Maria, Naticchia Alessandro, Gambaro Giovanni, Mazzaferro Sandro, Fuster Daniel, Ferraro Pietro Manuel (2021), The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism, in Nutrients, 13(7), 2328-2328.
Effect of Tolvaptan Treatment on Acid−Base Homeostasis in ADPKD Patients
Bargagli Matteo, Ferraro Pietro Manuel, Dhayat Nasser, Anderegg Manuel, Fuster Daniel (2021), Effect of Tolvaptan Treatment on Acid−Base Homeostasis in ADPKD Patients, in Kidney International Reports, 6(6), 1749-1749.
Metabolische Abklärung von NierensteinenLeave no stone unturned
Bonny Olivier, Bosshard Piet (2021), Metabolische Abklärung von NierensteinenLeave no stone unturned, in Therapeutische Umschau, 78(5), 235-240.
Metaphylaxe von Nierensteinen mittels medikamentöser und diätetischer MassnahmenKeep it simple
Fuster Daniel G. (2021), Metaphylaxe von Nierensteinen mittels medikamentöser und diätetischer MassnahmenKeep it simple, in Therapeutische Umschau, 78(5), 241-246.
Und welcher Steintyp sind Sie?Formen, Häufigkeit, Pathogenese und spezifische Ursachen von Steintypen
Dhayat Nasser Abdalla (2021), Und welcher Steintyp sind Sie?Formen, Häufigkeit, Pathogenese und spezifische Ursachen von Steintypen, in Therapeutische Umschau, 78(5), 229-234.
Acute decrease of urine calcium by amiloride in healthy volunteers under high-sodium diet
Harmacek Dusan, Blanchard Anne, Wuerzner Gregoire, Maillard Marc, Jeunemaitre Xavier, Azizi Michel, Bonny Olivier (2021), Acute decrease of urine calcium by amiloride in healthy volunteers under high-sodium diet, in Nephrology Dialysis Transplantation, 1.
Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1
Garrelfs Sander F., Frishberg Yaacov, Hulton Sally A., Koren Michael J., O’Riordan William D., Cochat Pierre, Deschênes Georges, Shasha-Lavsky Hadas, Saland Jeffrey M., van’t Hoff William G., Fuster Daniel G., Magen Daniella, Moochhala Shabbir H., Schalk Gesa, Simkova Eva, Groothoff Jaap W., Sas David J., Meliambro Kristin A., Lu Jiandong, Sweetser Marianne T., Garg Pushkal P., Vaishnaw Akshay K., Gansner John M., McGregor Tracy L., et al. (2021), Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1, in New England Journal of Medicine, 384(13), 1216-1226.
Severe hypomagnesemia
Schietzel Simeon, Moor Matthias B., Fuster Daniel G. (2021), Severe hypomagnesemia, in Journal of Nephrology, 1.
Urine and stone analysis for the investigation of the renal stone former: a consensus conference
Williams James C., Gambaro Giovanni, Rodgers Allen, Asplin John, Bonny Olivier, Costa-Bauzá Antonia, Ferraro Pietro Manuel, Fogazzi Giovanni, Fuster Daniel G., Goldfarb David S., Grases Félix, Heilberg Ita P., Kok Dik, Letavernier Emmanuel, Lippi Giuseppe, Marangella Martino, Nouvenne Antonio, Petrarulo Michele, Siener Roswitha, Tiselius Hans-Göran, Traxer Olivier, Trinchieri Alberto, Croppi Emanuele, Robertson William G. (2021), Urine and stone analysis for the investigation of the renal stone former: a consensus conference, in Urolithiasis, 49(1), 1-16.
The sodium/proton exchanger NHA2 regulates blood pressure through a WNK4-NCC dependent pathway in the kidney
Anderegg Manuel A., Albano Giuseppe, Hanke Daniela, Deisl Christine, Uehlinger Dominik E., Brandt Simone, Bhardwaj Rajesh, Hediger Matthias A., Fuster Daniel G. (2021), The sodium/proton exchanger NHA2 regulates blood pressure through a WNK4-NCC dependent pathway in the kidney, in Kidney International, 99(2), 350-363.
The solute carrier SLC16A12 is critical for creatine and guanidinoacetate handling in the kidney
Verouti Sophia N, Lambert Delphine, Mathis Déborah, Pathare Ganesh, Escher Geneviève, Vogt Bruno, Fuster Daniel G (2021), The solute carrier SLC16A12 is critical for creatine and guanidinoacetate handling in the kidney, in American Journal of Physiology-Renal Physiology, ajprenal.0-ajprenal.0.
Recurrence prevention of kidney stones - pharmacologic and dietary measures
Fuster Daniel G. (2021), Recurrence prevention of kidney stones - pharmacologic and dietary measures, in Therapeutische Umschau, 241-246.
Sodium-hydrogen exchanger 6 (NHE6) deficiency leads to hearing loss, via reduced endosomal signalling through the BDNF/Trk pathway
Kucharava Krystsina, Brand Yves, Albano Giuseppe, Sekulic-Jablanovic Marijana, Glutz Andrea, Xian Xunde, Herz Joachim, Bodmer Daniel, Fuster Daniel G., Petkovic Vesna (2020), Sodium-hydrogen exchanger 6 (NHE6) deficiency leads to hearing loss, via reduced endosomal signalling through the BDNF/Trk pathway, in Scientific Reports, 10(1), 3609-3609.
Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers
Fuster Daniel G, Morard Gaétan A, Schneider Lisa, Mattmann Cedric, Lüthi David, Vogt Bruno, Dhayat Nasser A (2020), Association of urinary sex steroid hormones with urinary calcium, oxalate and citrate excretion in kidney stone formers, in Nephrology Dialysis Transplantation, 1.
Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1
Olinger Eric, Hofmann Patrick, Kidd Kendrah, Dufour Inès, Belge Hendrica, Schaeffer Céline, Kipp Anne, Bonny Olivier, Deltas Constantinos, Demoulin Nathalie, Fehr Thomas, Fuster Daniel G., Gale Daniel P., Goffin Eric, Hodaňová Kateřina, Huynh-Do Uyen, Kistler Andreas, Morelle Johann, Papagregoriou Gregory, Pirson Yves, Sandford Richard, Sayer John A., Torra Roser, Venzin Christina, et al. (2020), Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1, in Kidney International, 98(3), 717-731.
Oral chemolysis is an effective, non-invasive therapy for urinary stones suspected of uric acid content
Tsaturyan Arman, Bokova Elizaveta, Bosshard Piet, Bonny Olivier, Fuster Daniel G., Roth Beat (2020), Oral chemolysis is an effective, non-invasive therapy for urinary stones suspected of uric acid content, in Urolithiasis, 1.
Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan
Bargagli Matteo, Dhayat Nasser A., Anderegg Manuel, Semmo Mariam, Huynh-Do Uyen, Vogt Bruno, Ferraro Pietro Manuel, Fuster Daniel G. (2020), Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan, in Clinical Journal of the American Society of Nephrology, 15(7), 1007-1014.
Parathyroid Hormone and Plasma Phosphate Are Predictors of Soluble α-Klotho Levels in Adults of European Descent
Dhayat Nasser A, Pruijm Menno, Ponte Belen, Ackermann Daniel, Leichtle Alexander Benedikt, Devuyst Olivier, Ehret Georg, Guessous Idris, Pechère-Bertschi Antoinette, Pastor Johanne, Martin Pierre-Yves, Burnier Michel, Fiedler Georg-Martin, Vogt Bruno, Moe Orson W, Bochud Murielle, Fuster Daniel G (2020), Parathyroid Hormone and Plasma Phosphate Are Predictors of Soluble α-Klotho Levels in Adults of European Descent, in The Journal of Clinical Endocrinology & Metabolism, 105(4), e1135-e1143.
Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients Treated With Tolvaptan
Anderegg Manuel A., Dhayat Nasser A., Sommer Grit, Semmo Mariam, Huynh-Do Uyen, Vogt Bruno, Fuster Daniel G. (2020), Quality of Life in Autosomal Dominant Polycystic Kidney Disease Patients Treated With Tolvaptan, in Kidney Medicine, 1-29.
Impact of potassium citrate on urinary risk profile, glucose and lipid metabolism of kidney stone formers in Switzerland
Wiegand Anna, Fischer Gioia, Seeger Harald, Fuster Daniel, Dhayat Nasser, Bonny Olivier, Ernandez Thomas, Kim Min-Jeong, Wagner Carsten A, Mohebbi Nilufar (2019), Impact of potassium citrate on urinary risk profile, glucose and lipid metabolism of kidney stone formers in Switzerland, in Clinical Kidney Journal, 1-12.
A preliminary survey of practice patterns across several European kidney stone centers and a call for action in developing shared practice
Ferraro Pietro Manuel, Arrabal-Polo Miguel Ángel, Capasso Giovambattista, Croppi Emanuele, Cupisti Adamasco, Ernandez Thomas, Fuster Daniel G., Galan Juan Antonio, Grases Felix, Hoorn Ewout J., Knauf Felix, Letavernier Emmanuel, Mohebbi Nilufar, Moochhala Shabbir, Petkova Kremena, Pozdzik Agnieszka, Sayer John, Seitz Christian, Strazzullo Pasquale, Trinchieri Alberto, Vezzoli Giuseppe, Vitale Corrado, Vogt Liffert, Unwin Robert J., et al. (2019), A preliminary survey of practice patterns across several European kidney stone centers and a call for action in developing shared practice, in Urolithiasis, 47(3), 219-224.
Nephrolithiasis secondary to inherited defects in the thick ascending loop of henle and connecting tubules
Faller Nicolas, Dhayat Nasser A., Fuster Daniel G. (2019), Nephrolithiasis secondary to inherited defects in the thick ascending loop of henle and connecting tubules, in Urolithiasis, 47(1), 43-56.
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
Dhayat Nasser A., Faller Nicolas, Bonny Olivier, Mohebbi Nilufar, Ritter Alexander, Pellegrini Lisa, Bedino Giulia, Schönholzer Carlo, Venzin Reto M., Hüsler Carina, Koneth Irene, Del Giorno Rosaria, Gabutti Luca, Amico Patrizia, Mayr Michael, Odermatt Urs, Buchkremer Florian, Ernandez Thomas, Stoermann-Chopard Catherine, Teta Daniel, Rintelen Felix, Roumet Marie, Irincheeva Irina, Trelle Sven, et al. (2018), 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, in BMC Nephrology, 19(1), 349-349.
Incomplete Distal Renal Tubular Acidosis and Kidney Stones
Fuster Daniel G., Moe Orson W. (2018), Incomplete Distal Renal Tubular Acidosis and Kidney Stones, in Advances in Chronic Kidney Disease, 25(4), 366-374.
Distinct phenotype of kidney stone formers with renal phosphate leak
Dhayat Nasser A, Vogt A, Lüthi D, Schneider L, Mattmann C, Fuster Daniel G. (2018), Distinct phenotype of kidney stone formers with renal phosphate leak, in Nephrol Dial Transplant, 1.
Säure-Basen-Störungen und Nierensteine
Fuster D. G. (2018), Säure-Basen-Störungen und Nierensteine, in Der Nephrologe, 13(1), 30-36.
Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis
Pathare Ganesh, Dhayat Nasser A., Mohebbi Nilufar, Wagner Carsten A., Bobulescu Ion A., Moe Orson W., Fuster Daniel G. (2018), Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis, in Kidney International, 1.
Thiaziddiuretika in der Prophylaxe kalziumhaltiger Nierensteine – die NOSTONE Studie.
Fuster Daniel G. (2018), Thiaziddiuretika in der Prophylaxe kalziumhaltiger Nierensteine – die NOSTONE Studie., in Nieren- und Hochdruckkrankheiten, 1.
Thiazide Diuretic Dose and Risk of Kidney Stones in Older Adults: A Retrospective Cohort Study.
Fuster Daniel, AlexanderTodd R, McArthurEric, JandocRacquel, WelkBlayne, GargAmit X, QuinnRobert R (2018), Thiazide Diuretic Dose and Risk of Kidney Stones in Older Adults: A Retrospective Cohort Study., in Can J Kidney Health Dis, 1.
Acute regulated expression of pendrin in human urinary exosomes
Pathare Ganesh, Dhayat Nasser, Mohebbi Nilufar, Wagner Carsten A., Cheval Lydie, Neuhaus Thomas J., Fuster Daniel G. (2017), Acute regulated expression of pendrin in human urinary exosomes, in Pflügers Archiv - European Journal of Physiology, 1.
Antihypertensive medication and risk of kidney stones: a Canadian wake-up call
Fuster Daniel G (2017), Antihypertensive medication and risk of kidney stones: a Canadian wake-up call, in Hypertension Research, 1.
Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC)
Pathare Ganesh, Anderegg Manuel, Albano Giuseppe, Lang Florian, Fuster Daniel G., Elevated FGF23 Levels in Mice Lacking the Thiazide-Sensitive NaCl cotransporter (NCC), in Scientific Reports, 1.

Collaboration

Group / person Country
Types of collaboration
Kantonsspital Sion Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, Cantonal Hospital of Aarau Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Kantonsspital Bellinzona Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Clinical Trial Unit, Department of Clinical Research / University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Division of Urology, University Hospital of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, University Hospital of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Kantonsspital Luzern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, University Hospital of Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, University Hospital of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, Cantonal Hospital of Lugano Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, University Hospital of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, Cantonal Hospital of St. Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Division of Nephrology, University Hospital of Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Kantonsspital Chur Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research Weekly Research Conference Individual talk Thiazides and kidney stone recurrence –results of the randomized NOSTONE trial 25.02.2022 Dallas, United States of America Fuster Daniel Guido;
Fortbildungsveranstaltung Universitätsklinik für Urologie Inselspital Bern Individual talk Erste NOSTONE Studienresultate 27.01.2022 Bern, Switzerland Fuster Daniel Guido;
ERA-EDTA Jahreskongress Talk given at a conference Urate transporters, gout and urate nephropathy 07.06.2021 Berlin, Germany Bonny Olivier;
ERA EDTA Jahreskongress Talk given at a conference RNAi THERAPEUTICS: A NEW APPROACH TO MANAGING PRIMARY HYPEROXALURIA 07.06.2021 Berlin, Germany Fuster Daniel Guido;
Osteoporosis and Metabolic Bone disease Association Talk given at a conference Diagnosis and treatment of hypophosphatemia 12.05.2021 Virtual, Switzerland Bonny Olivier;
ISN, world congress of nephrology 2021 Talk given at a conference Kidney stone at the summit in Switzerland 14.04.2021 Montréal, Canada Bonny Olivier;
Nephrologie Symposium Kantonsspital Fribourg Individual talk Maladie rénale lithiasique 16.03.2021 Fribourg, Switzerland Bonny Olivier;
Annual Meeeting of the American Society of Nephrology 2020 Poster Thiazides in the recurrence prevention of calcareous nephrolithiasis - the NOSTONE Study 22.10.2020 Virtueller Kongress wegen COVID19 (ursprünglich geplant in Denver, CO), United States of America Bonny Olivier; Roth Beat; Cereghetti De Marchi Grazia Maria; Dhayat Nasser; Fuster Daniel Guido;
Annual Meeting of the Swiss Society of Nephrology Poster Thiazides in the recurrence prevention of calcareous nephrolithiasis - the NOSTONE Study 05.12.2019 Interlaken, Switzerland Fuster Daniel Guido; Tamò Luca; Bonny Olivier;
Annual Meeeting of the American Society of Nephrology Poster Thiazides in the recurrence prevention of calcareous nephrolithiasis - the NOSTONE Study 07.11.2019 Washington DC, United States of America Fuster Daniel Guido; Bonny Olivier; Tamò Luca;
4th Swiss Kidney Stone Symposium 2019 Talk given at a conference Hydrochlorothiazide and skin cancer: what should we tell to the stone patients? 26.09.2019 Bern, Switzerland Roth Beat; Bossart Jenny; Fuster Daniel Guido; Tamò Luca; Bonny Olivier;
4th International Meeting on Nephrolithiasis in Verona, Italy Talk given at a conference Secondary prevention of nephrolithiasis 22.06.2019 Verona, Italy Tamò Luca; Bonny Olivier; Fuster Daniel Guido;
Annual Meeting of the Swiss Society of Nephrology Poster Thiazides in the recurrence prevention of calcareous nephrolithiasis - the NOSTONE Study 06.12.2018 Interlaken, Switzerland Fuster Daniel Guido; Bossart Jenny; Bonny Olivier; Tamò Luca;
Thiazide in der Rezidivprophylaxe kalziumhaltiger Nierensteine Individual talk Vortragsreihe Spital Zweisimmen für Hausärzte und Assistenten 30.10.2018 Zweisimmen, Switzerland Fuster Daniel Guido;
3rd Swiss Kidney Stone Symposium 2018 Talk given at a conference Incomplete distal tubular acidosis in nephrolithiasis - a phantom ? 25.01.2018 Bern, Inselspital, Switzerland Roth Beat; Tamò Luca; Amrein Karin; Bonny Olivier; Fuster Daniel Guido;
Annual Meeting of the Swiss Society of Nephrology Poster Thiazides in the recurrence prevention of calcareous nephrolithiasis - the NOSTONE Study 07.12.2017 Fribourg, Switzerland Tamò Luca; Fuster Daniel Guido; Bonny Olivier; Roth Beat;
Nephrologisches Forums München Individual talk Thiaziddiuretika in der Prophylaxe 19.09.2017 München, Germany Fuster Daniel Guido;
Randomized double-blind placebo-controlled trial assessing the efficacy of standard and low dose hydrochlorothiazide treatment in the prevention of recurrent nephrolithiasis Talk given at a conference Oral presentation of Study to all Swiss Nephrologists at the Annual Meeting of the Swiss Society of Nephrology 09.12.2016 Interlaken, Switzerland Fuster Daniel Guido; Tamò Luca; Bonny Olivier; Roth Beat;
Randomized double-blind placebo-controlled trial assessing the efficacy of standard and low dose hydrochlorothiazide treatment in the prevention of recurrent nephrolithiasis Poster Poster presentation of NOSTONE study 08.12.2016 Interlaken, Switzerland Bonny Olivier; Roth Beat; Tamò Luca; Fuster Daniel Guido;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions NOSTONE Studienresultate Western Switzerland 2022
Print (books, brochures, leaflets) How it works - Kidney stones Italian-speaking Switzerland Western Switzerland German-speaking Switzerland Rhaeto-Romanic Switzerland 2018
Print (books, brochures, leaflets) Newsletter Kantonsspital Graubünden German-speaking Switzerland 2018
Media relations: radio, television Reins, calculs et paraplégie RTS Western Switzerland 2018
New media (web, blogs, podcasts, news feeds etc.) Studieninformationsseite Klinik für Nephrologie, Kantonsspital St. Gallen Web German-speaking Switzerland 2018
Media relations: print media, online media Thiazide in der Prävention kalziumhaltiger Nierensteine - die NOSTONE Studie Jahresbericht Department for Biomedical Research, Inselspital German-speaking Switzerland 2018
New media (web, blogs, podcasts, news feeds etc.) Webpage NOSTONE Studie Internet International Rhaeto-Romanic Switzerland Italian-speaking Switzerland Western Switzerland German-speaking Switzerland 2017
Media relations: print media, online media Presentation of Study Homepage Inselspital German-speaking Switzerland 2016
Media relations: print media, online media Presentation of study Newsletter Department of Clinical Research, Inselspital German-speaking Switzerland 2016

Associated projects

Number Title Start Funding scheme
172974 Mechanisms of thiazide-induced glucose intolerance 01.05.2017 Project funding

Abstract

Introduction:Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8 % in men and 9.4 % in women. Without specific treatment, 5- and 20-year recurrence rates are 40 % and 75 %, respectively. 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. About 80-90 % of stones are composed of calcium oxalate with various admixtures of calcium phosphate. Increased excretion of calcium in the urine, hypercalciuria, is the most common metabolic abnormality encountered in patients with recurrent nephrolithiasis. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. The effect of thiazides to reduce the risk of stone recurrence has been attributed to their ability to decrease urinary calcium excretion. However, other factors, such as reduction of urinary pH and urinary oxalate excretion, probably contribute to this effect. Efficacy of thiazides on recurrence prevention of calcareous nephrolithiasis was tested in 11 RCTs. With the exception of two trials, thiazides significantly reduced stone recurrence. Most of these trials are from the 1980’s and 90’s and the cumulative number of patients studied is remarkably low for such a prevalent disease. Our systematic review of these RCTs revealed major methodological deficiencies in all trials, including: lack of double-blinding and intention-to-treat analysis, unclear allocation concealment, lack of adverse event and drop out reporting and unknown baseline risk of disease severity. Furthermore, high doses of thiazides were employed in all trials, in the case of the best studied thiazide, hydrochlorothiazide, up to 100 mg daily. At such high doses, side effects occur frequently and include electrolyte disturbances, orthostatic hypotension, gout, impaired glucose tolerance, skin rashes and erectile dysfunction. Nowadays, thiazides are widely used in the treatment of recurrent nephrolithiasis and arterial hypertension, but at significantly lower doses. In the case of recurrent nephrolithiasis, however, this practice is not supported by randomized evidence and consequently, we do not know whether the currently employed low dose thiazide regimens are effective in reducing the risk for stone recurrence.Rationale: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.Objective:We plan to conduct a 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. More specifically, we aim to assess the dose-response relationship for three different dosages of hydrochlorothiazide.Methodology:We will include 412 adult (>18 years old) 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 with active pharmacologic metaphylaxis or with secondary causes of calcareous nephrolithiasis will be excluded from the study. Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. All patients will receive counseling for state-of-the art non-pharmacologic interventions to prevent stone recurrence according to current guidelines.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.
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