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Rocha DR, Matos ACC, Heilberg IP. Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent? Curr Opin Nephrol Hypertens 2025; 34:138-142. [PMID: 39878021 DOI: 10.1097/mnh.0000000000001047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
PURPOSE OF REVIEW This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. RECENT FINDINGS Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. SUMMARY Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.
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Affiliation(s)
- Daniel Ribeiro Rocha
- Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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Dong C, Zhou J, Su X, He Z, Song Q, Song C, Ke H, Wang C, Liao W, Yang S. Understanding formation processes of calcareous nephrolithiasis in renal interstitium and tubule lumen. J Cell Mol Med 2024; 28:e18235. [PMID: 38509735 PMCID: PMC10955165 DOI: 10.1111/jcmm.18235] [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: 09/18/2023] [Revised: 02/07/2024] [Accepted: 02/28/2024] [Indexed: 03/22/2024] Open
Abstract
Kidney stone, one of the oldest known diseases, has plagued humans for centuries, consistently imposing a heavy burden on patients and healthcare systems worldwide due to their high incidence and recurrence rates. Advancements in endoscopy, imaging, genetics, molecular biology and bioinformatics have led to a deeper and more comprehensive understanding of the mechanism behind nephrolithiasis. Kidney stone formation is a complex, multi-step and long-term process involving the transformation of stone-forming salts from free ions into asymptomatic or symptomatic stones influenced by physical, chemical and biological factors. Among the various types of kidney stones observed in clinical practice, calcareous nephrolithiasis is currently the most common and exhibits the most intricate formation mechanism. Extensive research suggests that calcareous nephrolithiasis primarily originates from interstitial subepithelial calcified plaques and/or calcified blockages in the openings of collecting ducts. These calcified plaques and blockages eventually come into contact with urine in the renal pelvis, serving as a nidus for crystal formation and subsequent stone growth. Both pathways of stone formation share similar mechanisms, such as the drive of abnormal urine composition, involvement of oxidative stress and inflammation, and an imbalance of stone inhibitors and promoters. However, they also possess unique characteristics. Hence, this review aims to provide detailed description and present recent discoveries regarding the formation processes of calcareous nephrolithiasis from two distinct birthplaces: renal interstitium and tubule lumen.
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Affiliation(s)
- Caitao Dong
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Jiawei Zhou
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Xiaozhe Su
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Ziqi He
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Qianlin Song
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Chao Song
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Hu Ke
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Chuan Wang
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Wenbiao Liao
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
| | - Sixing Yang
- Department of UrologyRenmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina
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Steely A, Worcester E, Prochaska M. Contrasting Response of Urine Stone Risk to Medical Treatment in Calcium Oxalate versus Calcium Phosphate Stone Formers. KIDNEY360 2024; 5:228-236. [PMID: 38251931 PMCID: PMC10914189 DOI: 10.34067/kid.0000000000000362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/11/2024] [Indexed: 01/23/2024]
Abstract
Key Points Thiazide treatment successfully lowered urine calcium and both calcium oxalate and calcium phosphate supersaturations in both types of stone formers (SFs). Alkali therapy may not confer the same benefits on calcium phosphate SFs as it does on calcium oxalate SFs. Background Randomized controlled trials have shown that both thiazide diuretics and potassium citrate (K-Cit) can prevent calcium stone recurrence, but most participants formed calcium oxalate (CaOx) stones. While thiazides are expected to lower risk of calcium phosphate (CaP) stone formation, the effect of K-Cit on risk of CaP stone formation is unclear. Methods To study the effect of common calcium stone treatments, we analyzed the 24-hour urines of CaOx and CaP stone formers (SFs) by four treatment types: Lifestyle, K-Cit, Thiazide, or Both medications. Results Patients treated with thiazides reduced urine calcium in both CaOx (M =−74.4, SD =94.6 mg/d) and CaP (M =−102, SD =99.7 mg/d) SFs while those on K-Cit had no change in urine calcium. Among CaOx SFs, urine citrate rose in patients administered K-Cit with or without thiazide, but citrate did not rise significantly in CaP SFs. Urine pH rose in all CaOx SFs, but among CaP SFs, only rose in patients receiving K-Cit. CaOx supersaturation (SS) decreased in all patients who received Thiazide, and decreased among CaOx SFs treated with K-Cit. CaP SS decreased in both CaOx SFs (M =−0.46, SD =0.86) and CaP SFs (M =−0.76, SD =0.85) treated with Thiazide, except CaOx SFs who received Both. Patients treated with K-Cit alone increased CaP SS in CaOx SFs (M =0.25, SD =0.79). Conclusions Patients treated with Thiazide lowered urine calcium and SS in both stone groups. Patients treated with K-Cit had no significant changes in urine calcium and had a decrease in CaOx SS in CaOx SFs. The study raises questions about the best preventive treatment for patients with CaP stones and suggests that K-Cit may not confer the same benefits on CaP SFs as it does on CaOx SFs.
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Affiliation(s)
- Audrey Steely
- Department of Medicine, University of Chicago, Chicago, Illinois
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Novais EJ, Narayanan R, Canseco JA, van de Wetering K, Kepler CK, Hilibrand AS, Vaccaro AR, Risbud MV. A new perspective on intervertebral disc calcification-from bench to bedside. Bone Res 2024; 12:3. [PMID: 38253615 PMCID: PMC10803356 DOI: 10.1038/s41413-023-00307-3] [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: 10/15/2023] [Revised: 12/04/2023] [Accepted: 12/05/2023] [Indexed: 01/24/2024] Open
Abstract
Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.
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Affiliation(s)
- Emanuel J Novais
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
- Unidade Local de Saúde do Litoral Alentejano, Orthopedic Department, Santiago do Cacém, Portugal
| | - Rajkishen Narayanan
- Rothman Orthopedic Institute at Thomas Jefferson University, Philadelphia, PA, USA
| | - Jose A Canseco
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
- Rothman Orthopedic Institute at Thomas Jefferson University, Philadelphia, PA, USA
| | - Koen van de Wetering
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - Christopher K Kepler
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
- Rothman Orthopedic Institute at Thomas Jefferson University, Philadelphia, PA, USA
| | - Alan S Hilibrand
- Rothman Orthopedic Institute at Thomas Jefferson University, Philadelphia, PA, USA
| | - Alexander R Vaccaro
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
- Rothman Orthopedic Institute at Thomas Jefferson University, Philadelphia, PA, USA
| | - Makarand V Risbud
- Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R, Hasan S, Hamza MB. Renal calcification in children with renal tubular acidosis: What a paediatrician should know. World J Clin Pediatr 2023; 12:295-309. [PMID: 38178934 PMCID: PMC10762599 DOI: 10.5409/wjcp.v12.i5.295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/15/2023] [Accepted: 10/16/2023] [Indexed: 12/08/2023] Open
Abstract
Renal tubular acidosis (RTA) can lead to renal calcification in children, which can cause various complications and impair renal function. This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification, highlighting essential aspects for clinical management. The article analyzed relevant studies to explore the prevalence, risk factors, underlying mechanisms, and clinical implications of renal calcification in children with RTA. Results show that distal RTA (type 1) is particularly associated with nephrocalcinosis, which presents a higher risk of renal calcification. However, there are limitations to the existing literature, including a small number of studies, heterogeneity in methodologies, and potential publication bias. Longitudinal data and control groups are also lacking, which limits our understanding of long-term outcomes and optimal management strategies for children with RTA and renal calcification. Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications. In addition, alkaline therapy remains a cornerstone in the treatment of RTA, aimed at correcting the acid-base imbalance and reducing the formation of kidney stones. Therefore, early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children. Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama, Bahrain, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama, Manama 26671, Manama, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Samir Hasan
- Department of Pediatrics, Faculty of Medicine, Tanta University Hospital, Tanta 31511, Algharbia, Egypt
| | - Mohamed Basiony Hamza
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
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Vrielinck J, Janssens GPJ, Chantziaras I, Cools A, Maes D. Urolithiasis Problems in Finishing Pigs. Vet Sci 2023; 10:688. [PMID: 38133239 PMCID: PMC10748364 DOI: 10.3390/vetsci10120688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/27/2023] [Accepted: 11/29/2023] [Indexed: 12/23/2023] Open
Abstract
This paper describes cases of urolithiasis in fattening pigs on two farms (A and B). Bladder rupture due to urethral obstruction with calculi was the principal finding during the necropsy of the pigs. An in-depth diagnostic examination was performed to elucidate possible pathophysiological mechanisms, namely Fourier-transform infrared spectrophotometry (FT-IR) analysis of the uroliths, blood analysis (farm A: 5 samples, farm B: 10 samples) for assessing concentrations of minerals, the bone resorption marker cross-linked C-telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), and vitamin D components, biochemical urinalysis (farm A: 5 samples, farm B: 7 samples), microscopic examination of urinary sediment (Farms A and B: 7 samples each), mineral composition of the feed, and analysis of the drinking water. Calcium carbonate was the main component found in stones from both farms, and calcium carbonate and struvite were the main components found in crystals from farms A and B, respectively. On farm A, urinary calcium excretion and urinary pH were high; on farm B, urinary phosphorus was high and urinary calcium was low with a normal urinary pH. The mineral compositions of the feed and drinking water were similar on both farms and could therefore not explain the difference between the two farms. Disturbances in calcium and phosphorus absorption and homeostasis might have been involved in these problems. Further research should focus on the calcium, phosphorus, and vitamin D levels in the feed and take into account other factors, such as the absorption and excretion of minerals due to gut and urinary microbiota.
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Affiliation(s)
- Joris Vrielinck
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium; (G.P.J.J.); (I.C.)
- Veterinary Practice, Hospitaalstraat 38, 8906 Ieper-Elverdinge, Belgium
| | - Geert P. J. Janssens
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium; (G.P.J.J.); (I.C.)
| | - Ilias Chantziaras
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium; (G.P.J.J.); (I.C.)
| | - An Cools
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium; (G.P.J.J.); (I.C.)
| | - Dominiek Maes
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium; (G.P.J.J.); (I.C.)
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Goldfarb DS, Modersitzki F, Asplin JR, Nazzal L. Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones. Urolithiasis 2023; 51:96. [PMID: 37479949 DOI: 10.1007/s00240-023-01468-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 07/05/2023] [Indexed: 07/23/2023]
Abstract
A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.
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Affiliation(s)
- David S Goldfarb
- Nephrology Division, NYU Langone Health and NYU Grossman School of Medicine, Nephrology Section/111G, 423 E. 23 St., New York, NY, 10010, USA.
| | - Frank Modersitzki
- Nephrology Division, NYU Langone Health and NYU Grossman School of Medicine, Nephrology Section/111G, 423 E. 23 St., New York, NY, 10010, USA
| | | | - Lama Nazzal
- Nephrology Division, NYU Langone Health and NYU Grossman School of Medicine, Nephrology Section/111G, 423 E. 23 St., New York, NY, 10010, USA
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Gopala SK, Joe J, Chandran J. Effects of lemon-tomato juice consumption on crystal formation in the urine of patients with calcium oxalate stones: A randomized crossover clinical trial. Curr Urol 2023; 17:25-29. [PMID: 37692132 PMCID: PMC10487295 DOI: 10.1097/cu9.0000000000000178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/11/2022] [Indexed: 01/31/2023] Open
Abstract
Background Dietary supplementation with citrate-containing juices may serve as an effective alternative to potassium citrate therapy for preventing calcium oxalate stone recurrence. This study was performed to evaluate whether consumption of lemon-tomato juice can decrease the tendency for stone formation in the urine of calcium oxalate stone formers. Materials and methods The study was conducted as a prospective interventional randomized crossover clinical trial with a repeated-measures design. Twenty-two patients with calcium oxalate stones and no metabolic abnormalities in the urine treated with lithotripsy at a tertiary care center from August 2017 to July 2018 were recruited. After a 14-hour overnight fasting, urine samples were collected after the patients consumed either milk only or milk and lemon-tomato juice. Their urine was tested for multiple parameters, including urine pH, specific gravity, calcium-creatinine ratio, and supersaturation with sodium oxalate, followed by optical density measurement via spectrophotometry. Results There were no significant differences in the background characteristics between the 2 groups. The optical density of the urine samples obtained after consumption of milk only was significantly higher than that after consumption of milk and lemon-tomato juice (mean = 0.131 for milk only vs. 0.053 for milk and lemon-tomato juice, p < 0.001). The urine calcium-creatinine ratio was similar between the groups (mean = 0.141 for milk only vs. 0.076 for milk and lemon-tomato juice, p = 0.019). Conclusions The addition of lemon-tomato juice as a source of citrate in the diet significantly decreases the established risk factors for calcium oxalate stone formation in patients. This study was prospectively registered at CTRI under number CTRI/2017/04/008312 on April 7, 2017.
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Affiliation(s)
- Sathish K. Gopala
- Department of Urology, Government Medical College Thiruvananthapuram, Kerala, India
| | - Jim Joe
- Department of Biochemistry, Government Medical College Kottayam, Kerala, India
| | - Jithesh Chandran
- Department of General Surgery, Government Medical College Konni, Kerala, India
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Vrielinck J, Janssens GPJ, Chantziaras I, Cools A, Maes D. Effect of Feed Supplementation with Tripotassium Citrate or Sodium Chloride on the Development of Urinary Calcium Oxalate Crystals in Fattening Pigs. Vet Sci 2022; 9:614. [PMID: 36356091 PMCID: PMC9699466 DOI: 10.3390/vetsci9110614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/22/2022] [Accepted: 10/31/2022] [Indexed: 11/09/2022] Open
Abstract
The present study investigated whether dietary supplementation of tripotassium citrate or NaCl reduced the prevalence of calcium oxalate dihydrate (COD) uroliths in fattening pigs on a farm with a high prevalence of COD uroliths. Each group (control, TPC, NaCl) consisted of three batches of approximately 260 fattening pigs each. Performance, water intake, markers for bone resorption (CTX) and bone formation (osteocalcin) and urinalysis from samples taken at the farm and in the slaughterhouse were investigated. Performance parameters, feed and water intake, CTX and osteocalcin were not significantly different between the groups (p > 0.05). The main crystals found were struvite, COD, calcite and amorphous crystals. The prevalence of COD crystals was lower in samples from the slaughterhouse in each group. Microscopic and biochemical examination of urine showed large differences between samples from the farm and the slaughterhouse. In conclusion, there were no beneficial effects of feed supplementation with TPC or NaCl on the prevalence of COD crystals but TPC has a clear promoting influence on the development of alkaline calcite crystals. Urinalysis from samples taken at the slaughterhouse does not fully reflect the situation on the farm.
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Affiliation(s)
- Joris Vrielinck
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium
- Veterinary Practice, Hospitaalstraat 38, 8906 Ieper-Elverdinge, Belgium
| | | | - Ilias Chantziaras
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium
| | - An Cools
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium
| | - Dominiek Maes
- Faculty of Veterinary Medicine, Ghent University, 9000 Ghent, Belgium
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The advances of calcium oxalate calculi associated drugs and targets. Eur J Pharmacol 2022; 935:175324. [DOI: 10.1016/j.ejphar.2022.175324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 09/23/2022] [Accepted: 10/11/2022] [Indexed: 11/20/2022]
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Gelli R, Pucci V, Ridi F, Baglioni P. A study on biorelevant calciprotein particles: Effect of stabilizing agents on the formation and crystallization mechanisms. J Colloid Interface Sci 2022; 620:431-441. [DOI: 10.1016/j.jcis.2022.04.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/04/2022] [Accepted: 04/05/2022] [Indexed: 11/27/2022]
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Abstract
PURPOSE OF REVIEW Evaluation of the kidney stone patient includes measurement of 24 h urine chemistries. This review summarizes the application of physiologic principles to the interpretation of urine chemistries, using sulfate and ammonium to estimate diet acid load, and the renal response. RECENT FINDINGS There has been increased recognition of the need to measure urine ammonium excretion in the clinical setting in order to understand renal acid excretion. Some 24 h urine kidney stone panels include ammonium measurements, providing an opportunity to apply this measurement to clinical practice. In order to better interpret ammonium excretion, one needs an estimate of dietary acid load to understand the driving forces for ammonium excretion. Sulfate is also included in some kidney stone panels and functions as an estimate of diet acid load. Combining these analytes with urine pH, the clinician can quickly estimate dietary stone risk as well as potential bowel disease, acidification disorders, and the presence of urease producing bacteria; all of which can affect stone risk. SUMMARY Measurement of ammonium and sulfate excretion along with urine pH provide important insights into the acid/alkali content of diet, presence and severity of bowel disease, presence of renal acidification disorders, and urinary infection.
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Affiliation(s)
- John R Asplin
- Litholink Corporation, Laboratory Corporation of America Holdings, Chicago, Illinois, USA
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Role of Citrus Fruit Juices in Prevention of Kidney Stone Disease (KSD): A Narrative Review. Nutrients 2021; 13:nu13114117. [PMID: 34836376 PMCID: PMC8625077 DOI: 10.3390/nu13114117] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/12/2021] [Accepted: 11/13/2021] [Indexed: 01/04/2023] Open
Abstract
To explore the relationship between citrus fruit juices (oranges, grapefruits, and lemonades) and kidney stone disease (KSD). METHODS A systematic review was performed using the Medline, EMBASE, and Scopus databases, in concordance with the PRISMA checklist for all English, French, and Spanish language studies regarding the consumption of citrus fruit juices and the relationship to urinary stone disease. The main outcome of interest was the association of citrus fruit juices with KSD. RESULTS Thirteen articles met the criteria for inclusion in the final review. Three large epidemiological studies found that grapefruit juice was a risk factor for stone formation, while orange juice did not increase the risk for KSD. Ten small prospective clinical studies found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect and while lemon juice has a protective effect by raising urinary citrate levels, it lacked a significant alkalinizing effect on urine pH. Orange juice and grapefruit juices significantly increased urinary oxalate levels, while orange juice also had a high carbohydrate content. CONCLUSION While orange juice seems to play a protective role against stone formation, grapefruit was found to raise the risk of KSD in epidemiological studies but had a protective role in smaller clinical studies. Lemon juice had a smaller protective role than orange juice. Larger amounts of, as well as more accurate, data is needed before recommendations can be made and a high carbohydrate content in these juices needs to be taken into consideration.
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14
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Study of risk factor of urinary calculi according to the association between stone composition with urine component. Sci Rep 2021; 11:8723. [PMID: 33888737 PMCID: PMC8062512 DOI: 10.1038/s41598-021-87733-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 03/30/2021] [Indexed: 01/22/2023] Open
Abstract
Urolithiasis is a common urinary disease with high recurrence. The risk factor for the recurrence of calculi is not very clear. The object of the present study was to evaluate the association between calculi composition and urine component and analyse the risk factor for the recurrence of urolithiasis. In this study, a total of 223 patients with calculi and healthy control were enrolled, and the components of the calculi and urina sanguinis collected before surgery were analysed. Of the 223 patients, 157 were males and 66 were females. According to the stone composition, the case group was subdivided into three groups. 129 patients had single calcium oxalate stones, 72 had calcium oxalate stones mixed with other stones and 22 had other type of stones excluding calcium oxalate stones. Urine biochemicals were analysed and the associations were found between the chemicals in each group. Multivariate logistic analysis demonstrated that reduced urinary magnesium and uric oxalic acid were independent risk factors when comparing all cases with normal controls. Only decreased urinary magnesium was found to be a risk factor comparing the single calcium oxalate group with normal control group. Low level of urinary magnesium and uric oxalic acid were found to be risk factors comparing the mixed calcium oxalate group with normal control group. No risk factor was found comparing the other stone group with normal control group. In conclusion, there were clear relationships between stone components and urine chemicals. Urine chemicals might be risk factors to predicate the occurrence of urolithiasis.
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Robinson TE, Hughes EAB, Wiseman OJ, Stapley SA, Cox SC, Grover LM. Hexametaphosphate as a potential therapy for the dissolution and prevention of kidney stones. J Mater Chem B 2020; 8:5215-5224. [PMID: 32436557 DOI: 10.1039/d0tb00343c] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The incidence of kidney stones is increasing worldwide, and recurrence is common (50% within 5 years). Citrate, the current gold standard therapy, which is usually given as potassium or sodium salts, is used because it raises urine pH and chelates calcium, the primary component of up to 94% of stones. In this study hexametaphosphate (HMP), a potent calcium chelator, was found to be 12 times more effective at dissolving calcium oxalate, the primary component of kidney stones, than citrate. HMP was also observed to be effective against other common kidney stone components, namely calcium phosphate and struvite (magnesium ammonium phosphate). Interestingly, HMP was capable of raising the zeta potential of calcium oxalate particles from -15.4 to -34.6 mV, which may prevent stone growth by aggregation, the most rapid growth mechanism, and thus avert occlusion. Notably, HMP was shown to be up to 16 times as effective as citrate at dissolving human kidney stones under simulated physiological conditions. It may thus be concluded that HMP is a promising potential therapy for calcium and struvite kidney stones.
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Affiliation(s)
- Thomas E Robinson
- School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK. and Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston, B15 2SQ, UK
| | - Erik A B Hughes
- School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
| | - Oliver J Wiseman
- Department of Urology, Cambridge University Hospital, Cambridge, CB2 0QQ, UK
| | - Sarah A Stapley
- Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston, B15 2SQ, UK
| | - Sophie C Cox
- School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
| | - Liam M Grover
- School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.
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Abou Chakra M, Dellis AE, Papatsoris AG, Moussa M. Established and recent developments in the pharmacological management of urolithiasis: an overview of the current treatment armamentarium. Expert Opin Pharmacother 2019; 21:85-96. [DOI: 10.1080/14656566.2019.1685979] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Mohamed Abou Chakra
- Department of Urology, Al Zahraa Hospital, University Medical Center, Beirut, Lebanon
| | - Athanasios E. Dellis
- Department of Surgery, School of Medicine, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios G. Papatsoris
- 2nd Department of Urology, School of Medicine, Sismanoglio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Mohamad Moussa
- Department of Urology, Al Zahraa Hospital, University Medical Center, Beirut, Lebanon
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Affiliation(s)
- Lada Beara-Lasic
- Nephrology Division, NYU Langone Medical Center, New York Harbor Veterans Affairs Healthcare System, New York, New York and
| | - David S Goldfarb
- Nephrology Division, NYU Langone Medical Center, New York Harbor Veterans Affairs Healthcare System, New York, New York and .,Department of Medicine and Physiology, New York University School of Medicine, New York, New York
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18
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Hydroxycitrate: a potential new therapy for calcium urolithiasis. Urolithiasis 2019; 47:311-320. [PMID: 30915494 DOI: 10.1007/s00240-019-01125-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 03/04/2019] [Indexed: 02/07/2023]
Abstract
Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.
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Goldfarb DS. Editorial: Controversies in kidney stones and other chronic kidney disease topics. Curr Opin Nephrol Hypertens 2019; 28:128-129. [PMID: 30585853 PMCID: PMC6452882 DOI: 10.1097/mnh.0000000000000485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- David S Goldfarb
- Nephrology Division, New York University Langone Health, NY Harbor VA Medical Center, NYU School of Medicine, New York, New York, USA
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