Moor MB, Bonny O (2016), Ways of calcium reabsorption in the kidney., in Am J Physiol Renal Physiol
Li Y, Bonny O (2015), [Oxalate: a poorly soluble organic waste with consequences]., in Praxis
Rathod A, Bonny O, Guessous I, Suter PM, Conen D, Erne P, Binet I, Gabutti L, Gallino A, Muggli F, Hayoz D, Péchère-Bertschi A, Paccaud F, Burnier M, Bochud M (2015), Association of urinary calcium excretion with serum calcium and vitamin D levels., in Clin J Am Soc Nephrol
muller me, Forni Ogna V, Maillard M, Stoudmann C, Zweiacker C, Anex C, Wuerzner G, Burnier M, Bonny O (2015), Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system., in Pflugers Arch
Albano G, Moor M, Dolder S, Siegrist M, Wagner CA, Biber J, Hernando N, Hofstetter W, Bonny O, Fuster DG (2015), Sodium-dependent phosphate transporters in osteoclast differentiation and function., in PLoS One
Ernandez T, Bonny O (2014), [Kidney stone as a cardiovascular risk marker]., in Rev Med Suisse
Clémençon B, Luscher BP, Fine M, Baumann MU, Surbek DV, Bonny O, Hediger MA (2014), Expression, purification, and structural insights for the human uric acid transporter, GLUT9, using the Xenopus laevis oocytes system., in PLoS One
Bonny O Bochud M. (2014), Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes., in Nephrol Dial Transplant.
Bonny O Edwards A. (2013), Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow., in Am J Physiol Renal Physiol
, 304(5), F585-600.
O'Seaghdha CM Wu H Yang Q Kapur K Guessous I Zuber AM Köttgen A Stoudmann C Teumer A Kutali (2013), Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations., in PLoS Genet.
Wöhrle S Henninger C Bonny O Thuery A Beluch N Hynes NE Guagnano V Sellers WR Hofmann F Kne (2013), Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets, in J Bone Miner Res
, 28(4), 899-911.
Ernandez T Stoermann Chopard C Bonny O Iselin C Martin PY Jaeger P. (2013), Renal stone disease: collaborative management between primary care and specialized physicians, in Rev Med Suisse.
van der Hagen E.A. Lavrijsen M. van Zeeland F. Praetorius J. Bonny O. Bindels R.J. and J, Coordinated regulation of TRPV5-mediated Ca2+ transport in primary distal convolution cultures., in Pflugers Arch.
Albano G Dolder S Siegrist M Mercier-Zuber A Auberson M Stoudmann C Hofstetter W Bonny O Fus, Increased bone resorption by osteoclast-specific deletion of the sodium/calcium exchanger isoform 1 (NCX1)., in Pflugers Arch.
, 469(2), 225-233.
Piazzon N, Bernet F, Guihard L, Leonhard WN, Urfer S, Firsov D, Chehade H, Vogt B, Piergiovanni S, Peters DJ, Bonny O, Constam DB, Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression., in J Transl Med
, 2015 Mar 30(13), 103.
Kidney stones bring excruciating pain to 10% of the population at least once in their lifetime and represent an increasing and significant burden for the health system. Eighty-five percent of kidney stones are made of calcium and 10% of uric acid, and hypercalciuria and hyperuricosuria constitute two major risk factors for stone formation. The therapeutical armamentarium for kidney stone is limited and basic research is poorly supported in the field. This grant request aims at boosting a translational research program addressing critical aspects of renal calcium and uric acid handling related to kidney stone formation, and developing new therapeutical approaches. Two independent projects addressing timely and key questions on renal calcium handling (project A) and on uric acid handling (project B) are presented here with their specific aims.Project A. Renal calcium handling and hypercalciuria.The final control of renal calcium reabsorption takes place in the distal convoluted and connecting tubules (DCT/CNT) of the nephron, where calcium is reabsorbed through apical calcium channels (TRPV5/6), and basolateral sodium/calcium exchangers (NCX1) and calcium ATPases (PMCA). The role of NCX1 in this process is elusive, but a mathematical model of calcium reabsorption in the DCT/CNT predicts that NCX1 maybe a major regulator of transepithelial calcium transport.•Aim A1. Role of NCX1 in calcium handling. I established a NCX1 kidney-specific knockout mouse model (NCX1(fl/fl;KSP-cre)), and showed that these mice are hypercalciuric, thus verifying the importance of NCX1 in renal calcium handling. In order to identify new regulatory mechanisms of calcium reabsorption, I propose to analyze the transcriptome of microdissected DCT/CNT tubules isolated from control and NCX1(fl/fl;KSP-cre) mice. New regulatory pathways will be studied in vitro and in vivo. •Aim A2. NCX1 and the hypocalciuric effect of thiazides. Thiazides are diuretics acting on DCT cells that are widely used as kidney stone preventive treatment, due to their stimulatory effect on calcium reabsorption by an unknown mechanism. Thiazides may produce their hypocalciuric effect by interfering with the sodium/calcium exchange in the DCT/CNT and NCX1. This hypothesis will be tested on NCX1(fl/fl;KSP-cre) mice.•Aim A3. Calcium-oxalate kidney stone prevention by sodium thiosulfate. Sodium thiosulfate was effective in treating kidney stone formers in small series, but concerns about side effects on bones have been raised. Sodium thiosulfate will be given to a calcium-oxalate stone forming mouse model that will be developed from the hypercalciuric NCX1(fl/fl;KSP-cre) mice. Measured outcomes will be the number of stones and the bone phenotype.Project B. Uric acid handling and hyperuricosuria.Glut9 (SLC2A9) is a recently identified urate transporter which is expressed in the kidney. Transepithelial Glut9-mediated urate transport is poorly understood in the kidney.•Aim B1. Localization and sorting of Glut9 isoforms in the kidney. Precise description of the localization and sorting of the two known Glut9 isoforms will be assessed in the kidney and in DCT/CNT cells, using isoform-specific antibodies newly developed.•Aim B2. Glut9 structure/function. Domains and residues critical for urate transport will be studied in the Xenopus oocyte expression system. •Aim B3. In vivo role of Glut9 in the mouse kidney. Glut9 kidney-specific knockout mice will help characterize the precise role of Glut9 in the kidney.The results of this research will have important implications in elucidating the molecular mechanisms of calcium and urate transport in the kidney and identify potential new therapeutical approaches for treating patients suffering of kidney stones.