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Michibata U, Maruyama M, Tanaka Y, Yoshimura M, Yoshikawa HY, Takano K, Furukawa Y, Momma K, Tajiri R, Taguchi K, Hamamoto S, Okada A, Kohri K, Yasui T, Usami S, Imanishi M, Mori Y. The impact of crystal phase transition on the hardness and structure of kidney stones. Urolithiasis 2024; 52:57. [PMID: 38563829 PMCID: PMC10987347 DOI: 10.1007/s00240-024-01556-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/06/2024] [Indexed: 04/04/2024]
Abstract
Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.
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Affiliation(s)
- Uta Michibata
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
| | - Mihoko Maruyama
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan.
- Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto, 606-8522, Japan.
| | - Yutaro Tanaka
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Masashi Yoshimura
- Institute of Laser Engineering, Osaka University, 2-6, Yamadaoka, Suita City, 565-0871, Osaka, Japan
| | - Hiroshi Y Yoshikawa
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
| | - Kazufumi Takano
- Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto, 606-8522, Japan
| | - Yoshihiro Furukawa
- Department of Earth Science, Tohoku University, 6-3 Aza-Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan
| | - Koichi Momma
- National Museum of Nature and Science, 4-1-1 Amakubo, Tsukuba, 305-0005, Japan
| | - Rie Tajiri
- Tajiri Thin Section Laboratory, 3-1-11 Sannose, Higashiosaka, 577-0849, Osaka, Japan
| | - Kazumi Taguchi
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Shuzo Hamamoto
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Atsushi Okada
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Kenjiro Kohri
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Takahiro Yasui
- Department of Nephro-urology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho- cho, Mizuho-Ku, Nagoya, 467-8601, Japan
| | - Shigeyoshi Usami
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
| | - Masayuki Imanishi
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
| | - Yusuke Mori
- Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, 565-0871, Japan
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Quantitative analysis of calcium oxalate monohydrate and dihydrate for elucidating the formation mechanism of calcium oxalate kidney stones. PLoS One 2023; 18:e0282743. [PMID: 36893192 PMCID: PMC9997882 DOI: 10.1371/journal.pone.0282743] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 02/21/2023] [Indexed: 03/10/2023] Open
Abstract
We sought to identify and quantitatively analyze calcium oxalate (CaOx) kidney stones on the order of micrometers, with a focus on the quantitative identification of calcium oxalate monohydrate (COM) and dihydrate (COD). We performed Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and microfocus X-ray computed tomography measurements (microfocus X-ray CT) and compared their results. An extended analysis of the FTIR spectrum focusing on the 780 cm-1 peak made it possible to achieve a reliable analysis of the COM/COD ratio. We succeeded in the quantitative analysis of COM/COD in 50-μm2 areas by applying microscopic FTIR for thin sections of kidney stones, and by applying microfocus X-ray CT system for bulk samples. The analysis results based on the PXRD measurements with micro-sampling, the microscopic FTIR analysis of thin sections, and the microfocus X-ray CT system observation of a bulk kidney stone sample showed roughly consistent results, indicating that all three methods can be used complementarily. This quantitative analysis method evaluates the detailed CaOx composition on the preserved stone surface and provides information on the stone formation processes. This information clarifies where and which crystal phase nucleates, how the crystals grow, and how the transition from the metastable phase to the stable phase proceeds. The phase transition affects the growth rate and hardness of kidney stones and thus provides crucial clues to the kidney stone formation process.
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Ibis F, Yu TW, Penha FM, Ganguly D, Nuhu MA, van der Heijden AEDM, Kramer HJM, Eral HB. Nucleation kinetics of calcium oxalate monohydrate as a function of pH, magnesium, and osteopontin concentration quantified with droplet microfluidics. BIOMICROFLUIDICS 2021; 15:064103. [PMID: 34853626 PMCID: PMC8610605 DOI: 10.1063/5.0063714] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 10/31/2021] [Indexed: 05/02/2023]
Abstract
A droplet-based microfluidic platform is presented to study the nucleation kinetics of calcium oxalate monohydrate (COM), the most common constituent of kidney stones, while carefully monitoring the pseudo-polymorphic transitions. The precipitation kinetics of COM is studied as a function of supersaturation and pH as well as in the presence of inhibitors of stone formation, magnesium ions (Mg2+), and osteopontin (OPN). We rationalize the trends observed in the measured nucleation rates leveraging a solution chemistry model validated using isothermal solubility measurements. In equimolar calcium and oxalate ion concentrations with different buffer solutions, dramatically slower kinetics is observed at pH 6.0 compared to pHs 3.6 and 8.6. The addition of both Mg2+ and OPN to the solution slows down kinetics appreciably. Interestingly, complete nucleation inhibition is observed at significantly lower OPN, namely, 3.2 × 10-8 M, than Mg2+ concentrations, 0.875 × 10-4 M. The observed inhibition effect of OPN emphasizes the often-overlooked role of macromolecules on COM nucleation due to their low concentration presence in urine. Moreover, analysis of growth rates calculated from observed lag times suggests that inhibition in the presence of Mg2+ cannot be explained solely on altered supersaturation. The presented study highlights the potential of microfluidics in overcoming a major challenge in nephrolithiasis research, the overwhelming physiochemical complexity of urine.
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Affiliation(s)
- Fatma Ibis
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
| | - Tsun Wang Yu
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
| | - Frederico Marques Penha
- Department of Chemical Engineering, KTH Royal Institute of Technology, Teknikringen 42, SE100-44 Stockholm, Sweden
| | - Debadrita Ganguly
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
| | - Manzoor Alhaji Nuhu
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
| | - Antoine E. D. M. van der Heijden
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
| | - Herman J. M. Kramer
- Complex Fluid Processing, Process & Energy Department, Delft University of Technology, Leeghwaterstraat 39, 2628 CB Delft, The Netherlands
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A Combined Experimental and Modelling Study on Solubility of Calcium Oxalate Monohydrate at Physiologically Relevant pH and Temperatures. CRYSTALS 2020. [DOI: 10.3390/cryst10100924] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Accurate Calcium Oxalate Monohydrate (COM) solubility measurements are essential for elucidating the physiochemical mechanism behind the formation of kidney stones, nephrolithiasis. Yet the reported solubility values of COM in ultrapure water, arguably the simplest solvent relevant for nephrolithiasis, vary significantly depending on implemented method. To address this variation, we present an experimental study of the solubility of COM validated by a model based on the Debye–Hückel theory describing the solution chemistry and the complex formation. We also carefully monitor potential pseudopolymorphic/hydrate transitions during the solubility measurements with in-situ and ex-situ methods. Our results indicate that the solubility of COM in ultrapure water is a weak function of temperature. However, the measured solubility varies significantly in buffer solutions across physiologically relevant pH values at body temperature. The proposed model explains observed trends as a combined effect of ionic strength, protonation reactions, and soluble complex formation. Moreover, it predicts solubility of COM in buffer solutions remarkably well using our measurements in ultrapure water as input, demonstrating the consistency of presented approach. The presented study parleying experiments and modelling provides a solid stepping stone to extend the physiochemical understanding of nephrolithiasis to more realistic solutions laden with biological complexity.
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Karaolanis G, Lionaki S, Moris D, Palla VV, Vernadakis S. Secondary hyperoxaluria: a risk factor for kidney stone formation and renal failure in native kidneys and renal grafts. Transplant Rev (Orlando) 2014; 28:182-187. [PMID: 24999029 DOI: 10.1016/j.trre.2014.05.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 05/18/2014] [Accepted: 05/21/2014] [Indexed: 12/22/2022]
Abstract
Secondary hyperoxaluria is a multifactorial disease affecting several organs and tissues, among which stand native and transplanted kidneys. Nephrocalcinosis and nephrolithiasis may lead to renal insufficiency. Patients suffering from secondary hyperoxaluria, should be promptly identified and appropriately treated, so that less renal damage occurs. The aim of this review is to underline the causes of hyperoxaluria and the related pathophysiologic mechanisms, which are involved, along with the description of seven cases of irreversible renal graft injury due to secondary hyperoxaluria.
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Affiliation(s)
- Georgios Karaolanis
- Transplantation Unit, Laiko General Hospital, Medical School of Athens, Athens, Greece.
| | - Sophia Lionaki
- Nephrology and Transplantation Unit, Laiko Hospital, Athens, Greece
| | - Demetrios Moris
- Transplantation Unit, Laiko General Hospital, Medical School of Athens, Athens, Greece
| | | | - Spiridon Vernadakis
- Transplantation Unit, Laiko General Hospital, Medical School of Athens, Athens, Greece
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Giardina S, Scilironi C, Michelotti A, Samuele A, Borella F, Daglia M, Marzatico F. In vitro anti-inflammatory activity of selected oxalate-degrading probiotic bacteria: potential applications in the prevention and treatment of hyperoxaluria. J Food Sci 2014; 79:M384-90. [PMID: 24471378 DOI: 10.1111/1750-3841.12344] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 11/25/2013] [Indexed: 01/06/2023]
Abstract
UNLABELLED Oxalate (Ox) is a very common component of the human diet, capable to collect in the renal tissue and bind calcium to form calcium oxalate (CaOx) crystals. A supersaturation of CaOx crystal may cause nephrocalcinosis and nephrolithiasis. The inflammation derived from the CaOx crystal accumulation, together with innate or secondary renal alterations, could strongly affect the renal function. In this case a consumption of probiotics with either oxalate-degrading activity at intestinal level and systemic anti-inflammatory activity could be an alternative approach to treat the subjects with excess of urinary oxalate excretion. 11 strains of lactic acid bacteria (Lactobacilli and Bifidobacteria), already included in the list of bacteria safe for the human use, were investigated for their capability to degrade oxalate by mean of RP-HPLC-UV method and modulate inflammation in an in vitro model system based on peripheral blood mononuclear cells. Four promising bacterial strains (Lactobacillus plantarum PBS067, Lactobacillus acidophilus LA-14, Bifidobacterium breve PBS077, Bifidobacterium longum PBS078) were identified as innovative biological tools for the prevention and the therapeutic treatment of hyperoxaluria and the inflammatory events associated to the Ox accumulation. PRACTICAL APPLICATION The oxalate-degrading activity of some probiotics and their capability to modulate the release of inflammation mediators could be exploited as a new nutraceutical and therapeutic approach for the treatment of oxalate accumulation and the related inflammatory state.
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Affiliation(s)
- Silvana Giardina
- Farcoderm Srl, Via Angelini, 21-27028, San Martino Siccomario (PV), Italy
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Rodgers A, Allie-Hamdulay S, Jackson G. Therapeutic action of citrate in urolithiasis explained by chemical speciation: increase in pH is the determinant factor. Nephrol Dial Transplant 2005; 21:361-9. [PMID: 16249202 DOI: 10.1093/ndt/gfi211] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The therapeutic action of citrate in the management of calcium oxalate urolithiasis has been attributed to the depletion of free calcium ions by complexation of the latter by citrate itself. However, little attention has been given to the nature of such complexes and the chemical conditions which control their formation because it is very difficult to measure them in solution. We therefore modelled the theoretical formation of these complexes in urine following administration of a citrate-containing preparation, using a powerful speciation program, JESS (Joint Expert Speciation System), which has been widely used to model metal-ligand equilibria in biological systems but which has hitherto not been applied in urolithiasis research. This program has an extensive database of thermodynamic constants and is able to calculate mixed ligand speciation. METHODS Urine data obtained before and after citrate administration in four groups of subjects (male and female normals and stone formers) were used as input for JESS to calculate the speciation of calcium, citrate and oxalate. The program was also used to examine the effects of varying different urinary components on the nature and concentration of the various species. RESULTS The speciation predicted the formation of a key calcium-citrate-phosphate species (previously unreported in urolithiasis research), which accounts for a significant percentage of the complexation of the free calcium. Moreover, the formation of this complex was found to be dependent on an increase in urinary pH rather than on an increase in urinary citrate concentration per se. CONCLUSION The therapeutic action of citrate in the management of calcium oxalate urolithiasis is due to the formation of a pH dependent calcium-citrate-phosphate complex which reduces the concentration of the free calcium ion species, thereby reducing the risk of stone formation.
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Affiliation(s)
- Allen Rodgers
- Department of Chemistry, University of Cape Town, Rondebosch, South Africa 7701.
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