|
1
|
Omić H, Eder M, Herkner H, Seitz C, Kikić Ž, Schrag TA. Study protocol for a randomized single-center cross-over study: Dapagliflozin treatment in recurring kidney stone patients. PLoS One 2025; 20:e0322034. [PMID: 40273182 PMCID: PMC12021238 DOI: 10.1371/journal.pone.0322034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 03/05/2025] [Indexed: 04/26/2025] Open
Abstract
INTRODUCTION Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality. OBJECTIVES We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output. METHODS This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases-one with dapagliflozin and one with placebo-will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency. DISCUSSION Dapagliflozin's pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.
Collapse
Affiliation(s)
- Haris Omić
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Michael Eder
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Harald Herkner
- Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
| | - Christian Seitz
- Department of Urology, Medical University of Vienna, Vienna, Austria.
| | - Željko Kikić
- Department of Urology, Medical University of Vienna, Vienna, Austria.
| | - Tarek Arno Schrag
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
2
|
Meher D, Agarwal V, Das S, Choudhury A, Sahoo D, Sahu SK, Prusty B, Das B. Idiopathic Hypercalciuria: A Comprehensive Review of Clinical Insights and Management Strategies. Cureus 2025; 17:e81778. [PMID: 40330359 PMCID: PMC12054780 DOI: 10.7759/cureus.81778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 04/05/2025] [Indexed: 05/08/2025] Open
Abstract
Idiopathic hypercalciuria (IH) is a metabolic condition characterized by excessive calcium excretion in urine without identifiable secondary causes, such as hyperparathyroidism or malignancy. It is a significant clinical entity due to its association with kidney stones, nephrocalcinosis, and osteoporosis, leading to reduced quality of life and long-term complications. This comprehensive review discusses the pathophysiology, clinical manifestations, diagnostic strategies, and management approaches for IH. The disorder arises from a multifaceted interplay of renal, intestinal, and skeletal factors. Impaired renal tubular calcium reabsorption, heightened intestinal calcium absorption, and increased bone resorption are key contributors to its pathogenesis. Genetic predispositions, including mutations in calcium-regulating receptors and transporters, further complicate its etiology. Patients often present with kidney stones, bone pain, or reduced bone mineral density, although asymptomatic cases are not uncommon. Diagnosing IH requires a thorough evaluation to exclude secondary causes, with 24-hour urinary calcium excretion serving as a crucial diagnostic marker. Management focuses on mitigating complications and improving quality of life through hydration, dietary modifications, and pharmacological therapy. Thiazide diuretics are the cornerstone of treatment, effectively reducing urinary calcium levels and preventing stone formation. Adjunctive measures include citrate supplementation and lifestyle interventions such as weight management and adequate physical activity. For patients with severe nephrolithiasis or nephrocalcinosis, surgical intervention may be necessary. Despite significant advancements, IH remains a diagnostic and therapeutic challenge due to its diverse clinical presentations and underlying mechanisms. A multidisciplinary approach, incorporating tailored medical and dietary strategies, is essential for optimal management. Future research into its genetic and molecular basis holds promise for developing more targeted interventions and improving patient outcomes. This review aims to provide a practical, up-to-date guide for clinicians managing this complex yet common metabolic disorder.
Collapse
Affiliation(s)
- Dayanidhi Meher
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Vishal Agarwal
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Sambit Das
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Arun Choudhury
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Devadarshini Sahoo
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Sandeep K Sahu
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Binod Prusty
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Bijay Das
- Endocrinology, Diabetes and Metabolism, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| |
Collapse
|
|
3
|
Xiang J, Lv M, Luo Y, Ke K, Zhang B, Wang M, Zhang K, Li H. Mechanistic studies of Ca 2+-induced classical pyroptosis pathway promoting renal adhesion on calcium oxalate kidney stone formation. Sci Rep 2025; 15:6669. [PMID: 39994305 PMCID: PMC11850917 DOI: 10.1038/s41598-025-91460-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 02/20/2025] [Indexed: 02/26/2025] Open
Abstract
This study aims to investigate the role of hypercalciuria and pyroptosis in the formation of calcium oxalate kidney stones. Bioinformatics analysis was performed to compare the correlation of pyroptosis scores and cell adhesion scores between Randall's plaques and normal tissues from kidney stone patients. For the in vitro experiments, we investigated the effects of high concentrations of Ca2+ on the pyroptosis and adhesion levels of renal tubular epithelial cells and examined the adhesion levels and crystal aggregation of the cells in high Ca2+ concentrations environment by knockdown and overexpression of the key pyroptosis gene, GSDMD, and we verified the effects of Ca2+ concentration on pyroptosis and adhesion levels, kidney injury, and crystal deposition by in vivo experiments. Bioinformatic results showed that the scores of pyroptosis and cell adhesion in Randall's plaques of patients with kidney stones were significantly higher than those in normal tissues, and pyroptosis was highly positively correlated with cell adhesion. In vitro and in vivo experiments showed that high concentrations of Ca2+ activated the NLRP3/Caspase-1/GSDMD pathway of pyroptosis through ROS and up-regulated the expression of adhesion-related proteins, and GSDMD could regulate the adhesion level of renal tubular epithelial cells by mediating the level of pyroptosis, thereby affecting the adhesion and deposition of calcium oxalate crystals. Our findings reveal that the Ca2+-induced classical pyroptosis pathway may be a potential mechanism to promote calcium oxalate kidney stone formation, which provides new insights into the etiology of kidney stones.
Collapse
Affiliation(s)
- Jinjie Xiang
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Maoxin Lv
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Yuhui Luo
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Kunbin Ke
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Baiyu Zhang
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Mengyue Wang
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Kun Zhang
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China
| | - Hao Li
- Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
| |
Collapse
|
|
4
|
Skolarikos A, Somani B, Neisius A, Jung H, Petřík A, Tailly T, Davis N, Tzelves L, Geraghty R, Lombardo R, Bezuidenhout C, Gambaro G. Metabolic Evaluation and Recurrence Prevention for Urinary Stone Patients: An EAU Guidelines Update. Eur Urol 2024; 86:343-363. [PMID: 39069389 DOI: 10.1016/j.eururo.2024.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/22/2024] [Accepted: 05/13/2024] [Indexed: 07/30/2024]
Abstract
BACKGROUND AND OBJECTIVE The aim of this review was to define patients who are at high risk of recurrence of urolithiasis, to delineate diagnostic and therapeutic algorithms for each type of stone, and to clarify general guidelines and recommendations for prevention of recurrence. METHODS A professional research librarian carried out literature searches for all sections of the urolithiasis guidelines, covering the timeframe between 1976 and June 2023. KEY FINDINGS AND LIMITATIONS For every patient with urolithiasis, an attempt should be made to analyse the stone. Patients should be given general instructions on how to prevent recurrence, including adequate fluid and calcium intake, and low consumption of sodium and protein. Identifying and correcting the causative factors is a cornerstone in preventing the recurrence of urolithiasis. Diagnostic and therapeutic algorithms by stone composition are available. Every patient should undergo baseline metabolic screening, while patients with calcium stones, who are at high risk of relapse and complications, should undergo extensive metabolic screening with two 24-h urine collections and should receive targeted therapy. Patients with uric acid, infection, or cystine stones are at high risk of relapse. All patients at high risk of recurrence should be closely monitored, especially those not complying with therapy in the long term. CONCLUSIONS AND CLINICAL IMPLICATIONS Metabolic stone evaluation and patient follow-up are highly recommended to prevent urolithiasis recurrence.
Collapse
Affiliation(s)
- Andreas Skolarikos
- National and Kapodistrian University of Athens, 2nd Department of Urology, Sismanogleio Hospital, Athens, Greece.
| | - Bhaskar Somani
- Department of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Andreas Neisius
- Department of Urology, Hospital of the Brothers of Mercy Trier, Medical Campus University Mainz, Trier, Germany
| | - Helene Jung
- Urinvejskirurgisk Afdeling, Sygehus Lillebælt, Vejle, Denmark
| | - Alec Petřík
- Department of Urology, Region Hospital, Ceske Budejovice, Czechia
| | - Thomas Tailly
- Servicio de Urología, Hospital Universitario de Gante, Gante, Belgium
| | - Niall Davis
- Department of Urology, Connolly Hospital, Dublin, Ireland
| | - Lazaros Tzelves
- National and Kapodistrian University of Athens, 2nd Department of Urology, Sismanogleio Hospital, Athens, Greece
| | - Rob Geraghty
- Department of Urology, Freeman Hospital, Newcastle-upon-Tyne, UK
| | | | - Carla Bezuidenhout
- European Association of Urology Guidelines Office, Arnhem, The Netherlands
| | - Giovanni Gambaro
- Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy
| |
Collapse
|
|
5
|
Liu M, Liu Z, Huang F, Chen H, Yang Z, Zhu Z. A high-calcium environment induced ectopic calcification of renal interstitial fibroblasts via TFPI-2-DCHS1-ALP/ENPP1 axis to participate in Randall's plaque formation. Urolithiasis 2024; 52:122. [PMID: 39196305 DOI: 10.1007/s00240-024-01622-y] [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: 06/12/2024] [Accepted: 08/17/2024] [Indexed: 08/29/2024]
Abstract
Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.
Collapse
Affiliation(s)
- Minghui Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zhi Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Urology, The Second Affiliated Hospital of Guizhou Medical University, Kaili, 556000, Guizhou, China
| | - Fang Huang
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Critical Care Medicine, Hunan Provincial Clinical Research Center for Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Hequn Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zhongqing Yang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Zewu Zhu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| |
Collapse
|
|
6
|
Bargagli M, Anderegg MA, Fuster DG. Effects of thiazides and new findings on kidney stones and dysglycemic side effects. Acta Physiol (Oxf) 2024; 240:e14155. [PMID: 38698738 DOI: 10.1111/apha.14155] [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: 02/22/2024] [Revised: 04/08/2024] [Accepted: 04/22/2024] [Indexed: 05/05/2024]
Abstract
Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.
Collapse
Affiliation(s)
- Matteo Bargagli
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Swiss National Centre of Competence in Research (NCCR) Kidney.CH, University of Zürich, Zürich, Switzerland
- Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Manuel A Anderegg
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Swiss National Centre of Competence in Research (NCCR) Kidney.CH, University of Zürich, Zürich, Switzerland
- Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Daniel G Fuster
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Swiss National Centre of Competence in Research (NCCR) Kidney.CH, University of Zürich, Zürich, Switzerland
- Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland
| |
Collapse
|
|
7
|
García Pascual L, Simó-Servat A, Puig-Jové C, García-González L. Normocalcemic hyperparathyroidism after successful parathyroidectomy for single parathyroid adenoma: Prevalence, etiological factors, predictive markers, treatment and evolution. ENDOCRINOL DIAB NUTR 2023; 70:640-648. [PMID: 38000970 DOI: 10.1016/j.endien.2023.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 09/14/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND AND OBJECTIVE Postparathyroidectomy normocalcemic hyperparathyroidism (PPNCHPPT) is a frequent situation for which we have no information in our country. The objective is to know our prevalence of PPNCHPPT, the associated etiological factors, the predictive markers, the treatment administered and the evolution. PATIENTS AND METHOD Retrospective observational cross-sectional study on 42 patients. Twelve patients with PPNCHPPT and 30 without PPNCHPPT are compared. RESULTS HPPTNCPP prevalence: 28.6%. Etiological factors: vitamin D deficiency: 75%; bone remineralization: 16.7%; renal failure: 16.7%; hypercalciruria: 8.3%. No change in the set point of calcium-mediated parathormone (PTH) secretion was observed, but an increase in the preoperative PTH/albumin-corrected calcium (ACC) ratio was observed. Predictive markers: PTH/ACC ratio (AUC 0.947; sensitivity 100%, specificity 78.9%) and PTH (AUC 0.914; sensitivity 100%, specificity 73.7%) one week postparathyroidectomy. EVOLUTION follow-up 30 ± 16.3 months: 50% normalized PTH and 8.3% had recurrence of hyperparathyroidism. Patients with PPNCHPPT less frequently received preoperative treatment with bisphosphonates and postoperative treatment with calcium salts. CONCLUSIONS This is the first study in our country that demonstrates a mean prevalence of PPNCHPPT, mainly related to a vitamin D deficiency and a probable resistance to the action of PTH, which can be predicted by the PTH/ACC ratio and PTH a week post-intervention and often evolves normalizing the PTH. We disagree with the etiological effect of hypercalciuria and the change in the PTH/calcemia regulation set point, and we acknowledge the scant treatment administered with calcium salts in the postoperative period.
Collapse
Affiliation(s)
- Luis García Pascual
- Servei d'Endocrinologia, Hospital Universitari Mútua de Terrasa, Terrassa, Spain.
| | - Andreu Simó-Servat
- Servei d'Endocrinologia, Hospital Universitari Mútua de Terrasa, Terrassa, Spain
| | - Carlos Puig-Jové
- Servei d'Endocrinologia, Hospital Universitari Mútua de Terrasa, Terrassa, Spain
| | - Lluís García-González
- Servei de Cirurgia General i Aparell Digestiu, Hospital Universitari Arnau de Vilanova, Lleida, Spain
| |
Collapse
|
|
8
|
Lemoine S, Dahan P, Haymann JP, Meria P, Almeras C. 2022 Recommendations of the AFU Lithiasis Committee: Medical management - from diagnosis to treatment. Prog Urol 2023; 33:911-953. [PMID: 37918992 DOI: 10.1016/j.purol.2023.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/27/2023] [Accepted: 08/01/2023] [Indexed: 11/04/2023]
Abstract
The morphological-compositional analysis of urinary stones allows distinguishing schematically several situations: dietary, digestive, metabolic/hormonal, infectious and genetic problems. Blood and urine testing are recommended in the first instance to identify risk factors of urinary stone disease in order to avoid recurrence or progression. The other objective is to detect a potential underlying pathology associated with high risk of urinary stone disease (e.g. primary hyperparathyroidism, primary or enteric hyperoxaluria, cystinuria, distal renal tubular acidosis) that may require specific management. Lifestyle-diet measures are the basis of the management of all stone types, but pharmacological treatments may be required. METHODOLOGY: These recommendations were developed using two methods: the Clinical Practice Recommendation (CPR) method and the ADAPTE method, depending on whether the question was considered in the European Association of Urology (EAU) recommendations (https://uroweb.org/guidelines/urolithiasis) [EAU 2022] and their adaptability to the French context.
Collapse
Affiliation(s)
- S Lemoine
- Hospices Civils de Lyon, SFNDT, SP, Lyon, France
| | - P Dahan
- Nephrology Department, Clinique Saint-Exupéry, SFNDT, Toulouse, France
| | - J P Haymann
- Inserm, UMRS 1155 UPMC, Tenon Hospital, SP, Paris, France; Service d'Explorations Fonctionnelles Multidisciplinaires, Tenon Hospital, Paris, France
| | - P Meria
- Service d'Urologie, Hôpital Saint Louis, AP-HP-Centre Université Paris Cité, Paris, France
| | - C Almeras
- UroSud, clinique La Croix du Sud, Quint-Fonsegrives, France.
| |
Collapse
|
|
9
|
Di X, Xiang L, Jian Z, Xia Z, Luo D. Association between urinary phthalate metabolites and nephrolithiasis in adults: A cross-sectional analysis with NHANES 2007-2018. CHEMOSPHERE 2023; 337:139436. [PMID: 37422213 DOI: 10.1016/j.chemosphere.2023.139436] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 07/04/2023] [Accepted: 07/05/2023] [Indexed: 07/10/2023]
Abstract
Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.
Collapse
Affiliation(s)
- Xingpeng Di
- Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Liyuan Xiang
- Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, China; Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, China
| | - Zhongyu Jian
- Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Ziyuan Xia
- College of Architecture and Environment, Sichuan University, Chengdu, China.
| | - Deyi Luo
- Department of Urology and Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
| |
Collapse
|
|
10
|
Siener R, Pitzer MS, Speller J, Hesse A. Risk Profile of Patients with Brushite Stone Disease and the Impact of Diet. Nutrients 2023; 15:4092. [PMID: 37764875 PMCID: PMC10534559 DOI: 10.3390/nu15184092] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/18/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023] Open
Abstract
This study examined the profile of patients and the impact of diet on the risk of brushite stone formation under controlled, standardized conditions. Sixty-five patients with brushite nephrolithiasis were enrolled in the study. Metabolic, dietary, and 24 h urinary parameters were collected under the habitual, self-selected diet of the patients and the balanced mixed, standardized diet. The [13C2]oxalate absorption, ammonium chloride, and calcium loading tests were conducted. All patients had at least one abnormality on the usual diet, with hypercalciuria (84.6%), increased urine pH (61.5%), and hyperphosphaturia (43.1%) being the most common. Absorptive hypercalciuria was present in 32.1% and hyperabsorption of oxalate in 41.2%, while distal renal tubular acidosis (dRTA) was noted in 50% of brushite stone formers. The relative supersaturation of brushite did not differ between patients with and without dRTA. Among all recent brushite-containing calculi, 61.5% were mixed with calcium oxalate and/or carbonate apatite. The relative supersaturation of brushite, apatite, and calcium oxalate decreased significantly under the balanced diet, mainly due to the significant decline in urinary calcium, phosphate, and oxalate excretion. Dietary intervention was shown to be effective and should be an integral part of the treatment of brushite stone disease. Further research on the role of dRTA in brushite stone formation is needed.
Collapse
Affiliation(s)
- Roswitha Siener
- University Stone Center, Department of Urology, University Hospital Bonn, 53127 Bonn, Germany
| | - Maria Sofie Pitzer
- University Stone Center, Department of Urology, University Hospital Bonn, 53127 Bonn, Germany
| | - Jan Speller
- Department of Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany
| | - Albrecht Hesse
- University Stone Center, Department of Urology, University Hospital Bonn, 53127 Bonn, Germany
| |
Collapse
|
|
11
|
Jung HD, Lee JY, Kang DH, Ko K, Koh DH, Kwon O, Koo KC, Kim KT, Kim MS, Kim BS, Kim HW, Park J, Bang W, Oh KJ, Yoon YE, Lee KS, Lee DS, Lee SH, Lee S, Lee HJ, Jung W, Cho DS, Cho SY, Choo MS, Choi JY, Choi T, Han DH, Han BK, Jeon SH, Paick S, Seo IY, Kim HJ. Korean Society of Endourology and Robotics (KSER) recommendation on the diagnosis, treatment, and prevention of urolithiasis. Investig Clin Urol 2023; 64:325-337. [PMID: 37417557 DOI: 10.4111/icu.20230102] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 04/26/2023] [Accepted: 05/22/2023] [Indexed: 07/08/2023] Open
Abstract
This article provides evidence-based recommendations and expert opinions to aid urologists in making optimal decisions regarding managing urolithiasis in various clinical scenarios. The most frequently asked questions by urologists in their clinical practice have been collected and answered in the form of FAQs; based on the latest evidence and expert opinions. The natural history of urolithiasis is divided into active treatment and silent phases, with the active treatment stage divided into typical and special situations and peri-treatment management. The authors address 28 key questions, offering practical guidance for the proper diagnosis, treatment, and prevention of urolithiasis in clinical practice. This article is expected to be served as a valuable resource for urologists.
Collapse
Affiliation(s)
- Hae Do Jung
- Department of Urology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Joo Yong Lee
- Department of Urology, Severance Hospital, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea
- Center of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea
| | - Dong Hyuk Kang
- Department of Urology, Inha University College of Medicine, Incheon, Korea
| | - Kyungtae Ko
- Department of Urology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Dong Hoon Koh
- Department of Urology, Konyang University College of Medicine, Daejeon, Korea
| | - Ohseong Kwon
- Department of Urology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Kyo Chul Koo
- Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Taek Kim
- Department of Urology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Myung Soo Kim
- Department of Urology, Ewha Womans University College of Medicine, Seoul, Korea
| | - Bum Soo Kim
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyeon Woo Kim
- Department of Urology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Juhyun Park
- Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woojin Bang
- Department of Urology, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Kyung-Jin Oh
- Department of Urology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Young Eun Yoon
- Department of Urology, Hanyang University College of Medicine, Seoul, Korea
| | - Ki Soo Lee
- Department of Urology, Dong-A University College of Medicine, Busan, Korea
| | - Dong Sup Lee
- Department of Urology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Sang Hyub Lee
- Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea
| | - Seungsoo Lee
- Department of Urology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Hun Joo Lee
- Department of Urology, Busan Adventist Hospital, Busan, Korea
| | - Wonho Jung
- Department of Urology, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Dae Sung Cho
- Department of Urology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Yong Cho
- Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Min Soo Choo
- Department of Urology, SMG-SNU Boramae Medical Center, Seoul, Korea
| | - Jae Young Choi
- Department of Urology, Yeungnam University College of Medicine, Daegu, Korea
| | - Taesoo Choi
- Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea
| | - Deok Hyun Han
- Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | - Seung Hyun Jeon
- Department of Urology, Kyung Hee University School of Medicine, Seoul, Korea
| | - Sunghyun Paick
- Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Ill Young Seo
- Department of Urology, Wonkwang University Hospital, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Korea
| | - Hyung Joon Kim
- Department of Urology, Konyang University College of Medicine, Daejeon, Korea.
| |
Collapse
|
|
12
|
Shin S, Boadi EA, Bandyopadhyay BC. Ablation of TRPC3 compromises bicarbonate and phosphate transporter activity in mice proximal tubular cells. Clin Exp Pharmacol Physiol 2023; 50:247-255. [PMID: 36433745 PMCID: PMC10258833 DOI: 10.1111/1440-1681.13741] [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: 05/11/2022] [Revised: 11/19/2022] [Accepted: 11/21/2022] [Indexed: 11/28/2022]
Abstract
Proximal tubular (PT) cells reabsorb most calcium (Ca2+ ), phosphate (PO4 3- ), bicarbonate (HCO3 - ), and oxalate (C2 O4 2- ) ions. We have shown that mice lacking Transient Receptor Potential Canonical 3 (TRPC3-/- ) channel are moderately hypercalciuric with presentation of luminal calcium phosphate (CaP) crystals at the loop of Henle (LOH). However, other predisposing factors for such crystal deposition are unknown. Thus, we examined the distinctions in functional status of HCO3 - , PO4 3- , and C2 O4 2- transporters in PT cells of wild type (WT) and TRPC3-/- mice by whole-cell patch clamp techniques to assess their contribution in the development of LOH CaP crystals. Here we show the development of concentration dependent HCO3 - -induced currents in all PT cells, which was confirmed by using specific HCO3 - channel inhibitor, S0859. Interestingly, such activities were diminished in PT cells from TRPC3-/- mice, suggesting reduced HCO3 - transport in absence of TRPC3. While PO4 3- -induced currents were also concentration dependent in all PT cells (confirmed by PO4 3- channel inhibitor, PF-06869206), those activities were reduced in absence of TRPC3, suggesting lower PO4 3- reabsorption that can leave excess luminal PO4 3- . Next, we applied thiosulfate (O3 S2 2 - ) as a competitive inhibitor of the SLC26a6 transporter upon C2 O4 2- current activation and observed a reduced C2 O4 2- -induced conductance which was greater in TRPC3-/- PT cells. Together, these results suggest that the reduced activities of HCO3 - , PO4 3- , and C2 O4 2- transporters in moderately hypercalciuric (TRPC3-/- ) PT cells can create a predisposing condition for CaP and CaP tubular crystallization, enabling CaP crystal formation in LOH of TRPC3-/- mice.
Collapse
Affiliation(s)
- Samuel Shin
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, Columbia, USA
| | - Eugenia Awuah Boadi
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, Columbia, USA
| | - Bidhan C. Bandyopadhyay
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, Columbia, USA
- Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, Columbia, USA
| |
Collapse
|
|
13
|
Zheng X, Zhu W, Zeng G. A case-based review of dietary management of calcium oxalate stones. World J Urol 2023; 41:1269-1274. [PMID: 36826485 DOI: 10.1007/s00345-023-04324-z] [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: 10/17/2022] [Accepted: 01/17/2023] [Indexed: 02/25/2023] Open
Abstract
PURPOSE The purpose of this paper is to help patients with calcium oxalate stones to access prevention and treatment options with dietary management. METHODS Typical cases in our hospital and other hospitals were selected for case review; combined with literature review through PubMed search, comprehensive analysis and suggestions were put forward. RESULTS By retrieving the literature with sufficient evidence, selecting, and summarizing, analysis of dietary liquid, oxalate and oxalate precursors, calcium, protein, fruits and vegetables, salt, high dietary fiber, and other content with high evidence index was carried out, respectively. CONCLUSION Through the retrospective analysis of typical cases and literature review, the importance of diet management in the prevention and treatment of calcium oxalate stones was emphasized again, and suggestions were put forward to promote the prevention and treatment of calcium oxalate stones.
Collapse
Affiliation(s)
- Xiaopeng Zheng
- 1Department of Urology, Guangdong Key Laboratory of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Haizhu District, Kangda Road 1#, Guangzhou, 510230, Guangdong, China
| | - Wei Zhu
- 1Department of Urology, Guangdong Key Laboratory of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Haizhu District, Kangda Road 1#, Guangzhou, 510230, Guangdong, China
| | - Guohua Zeng
- 1Department of Urology, Guangdong Key Laboratory of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Haizhu District, Kangda Road 1#, Guangzhou, 510230, Guangdong, China.
| |
Collapse
|
|
14
|
Pediatric Nephrolithiasis. Healthcare (Basel) 2023; 11:healthcare11040552. [PMID: 36833086 PMCID: PMC9957182 DOI: 10.3390/healthcare11040552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/30/2023] [Accepted: 02/10/2023] [Indexed: 02/15/2023] Open
Abstract
The prevalence of pediatric nephrolithiasis has increased dramatically in the past two decades for reasons that have yet to be fully elucidated. Workup of pediatric kidney stones should include metabolic assessment to identify and address any risk factors predisposing patients to recurrent stone formation, and treatment should aim to facilitate stone clearance while minimizing complications, radiation and anesthetic exposure, and other risks. Treatment methods include observation and supportive therapy, medical expulsive therapy, and surgical intervention, with choice of treatment method determined by clinicians' assessments of stone size, location, anatomic factors, comorbidities, other risk factors, and preferences and goals of patients and their families. Much of the current research into nephrolithiasis is restricted to adult populations, and more data are needed to better understand many aspects of the epidemiology and treatment of pediatric kidney stones.
Collapse
|
|
15
|
Abstract
Primary hyperparathyroidism (PHPT) is classically characterized by hypercalcemia with elevated or inappropriately normal parathyroid hormone (PTH) levels. Elevated PTH levels in the presence of normal calcium levels are not infrequently found during the evaluation of metabolic bone disorders or kidney stone disease. This can be caused by secondary hyperparathyroidism (SHPT) or normocalcemic primary hyperparathyroidism (NPHPT). NPHPT is due to autonomous parathyroid function whereas SHPT is caused by a physiologic stimulation to PTH secretion. Many medical conditions and medications can contribute to SHPT, and differentiation between SHPT and NPHPT may be difficult. Cases are presented to illustrate examples. In this paper, we review the distinction between SHPT and NPHPT as well as end organ effects of NPHPT and outcomes of surgery in NPHPT. We suggest that the diagnosis of NPHPT be made only after careful exclusion of causes of SHPT and consideration of medications that can increase PTH secretion. Further, we advise a conservative approach to surgery in NPHPT.
Collapse
Affiliation(s)
- Joseph L Shaker
- Correspondence: Joseph L. Shaker, MD, W129N7155 Northfield Dr, Menomonee Falls, WI 53051, USA.
| | - Robert A Wermers
- Department of Medicine and Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
16
|
Van de Perre E, Bazin D, Estrade V, Bouderlique E, Wissing KM, Daudon M, Letavernier E. Randall’s plaque as the origin of idiopathic calcium oxalate stone formation: an update. CR CHIM 2022. [DOI: 10.5802/crchim.102] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
17
|
Khattar V, Wang L, Peng JB. Calcium selective channel TRPV6: Structure, function, and implications in health and disease. Gene 2022; 817:146192. [PMID: 35031425 PMCID: PMC8950124 DOI: 10.1016/j.gene.2022.146192] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 12/20/2021] [Accepted: 01/07/2022] [Indexed: 12/14/2022]
Abstract
Calcium-selective channel TRPV6 (Transient Receptor Potential channel family, Vanilloid subfamily member 6) belongs to the TRP family of cation channels and plays critical roles in transcellular calcium (Ca2+) transport, reuptake of Ca2+ into cells, and maintaining a local low Ca2+ environment for certain biological processes. Recent crystal and cryo-electron microscopy-based structures of TRPV6 have revealed mechanistic insights on how the protein achieves Ca2+ selectivity, permeation, and inactivation by calmodulin. The TRPV6 protein is expressed in a range of epithelial tissues such as the intestine, kidney, placenta, epididymis, and exocrine glands such as the pancreas, prostate and salivary, sweat, and mammary glands. The TRPV6 gene is a direct transcriptional target of the active form of vitamin D and is efficiently regulated to meet the body's need for Ca2+ demand. In addition, TRPV6 is also regulated by the level of dietary Ca2+ and under physiological conditions such as pregnancy and lactation. Genetic models of loss of function in TRPV6 display hypercalciuria, decreased bone marrow density, deficient weight gain, reduced fertility, and in some cases alopecia. The models also reveal that the channel plays an indispensable role in maintaining maternal-fetal Ca2+ transport and low Ca2+ environment in the epididymal lumen that is critical for male fertility. Most recently, loss of function mutations in TRPV6 gene is linked to transient neonatal hyperparathyroidism and early onset chronic pancreatitis. TRPV6 is overexpressed in a wide range of human malignancies and its upregulation is strongly correlated to tumor aggressiveness, metastasis, and poor survival in selected cancers. This review summarizes the current state of knowledge on the expression, structure, biophysical properties, function, polymorphisms, and regulation of TRPV6. The aberrant expression, polymorphisms, and dysfunction of this protein linked to human diseases are also discussed.
Collapse
Affiliation(s)
- Vinayak Khattar
- Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Lingyun Wang
- Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Ji-Bin Peng
- Division of Nephrology, Department of Medicine, Nephrology Research and Training Center, Department of Urology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| |
Collapse
|
|
18
|
Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F. Secondary Osteoporosis. Endocr Rev 2022; 43:240-313. [PMID: 34476488 DOI: 10.1210/endrev/bnab028] [Citation(s) in RCA: 155] [Impact Index Per Article: 51.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 02/07/2023]
Abstract
Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.
Collapse
Affiliation(s)
- Peter R Ebeling
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia
| | - Hanh H Nguyen
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Department of Endocrinology and Diabetes, Western Health, Victoria 3011, Australia
| | - Jasna Aleksova
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Amanda J Vincent
- Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Monash Centre for Health Research and Implementation, School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria 3168, Australia
| | - Phillip Wong
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| | - Frances Milat
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria 3168, Australia.,Department of Endocrinology, Monash Health, Clayton, Victoria 3168, Australia.,Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
| |
Collapse
|
|
19
|
Bollerslev J, Rejnmark L, Zahn A, Heck A, Appelman-Dijkstra NM, Cardoso L, Hannan FM, Cetani F, Sikjaer T, Formenti AM, Björnsdottir S, Schalin-Jäntti C, Belaya Z, Gibb F, Lapauw B, Amrein K, Wicke C, Grasemann C, Krebs M, Ryhänen E, Makay Ö, Minisola S, Gaujoux S, Bertocchio JP, Hassan-Smith Z, Linglart A, Winter EM, Kollmann M, Zmierczak HG, Tsourdi E, Pilz S, Siggelkow H, Gittoes N, Marcocci C, Kamenický P, the 2021 PARAT Working Group. European Expert Consensus on Practical Management of Specific Aspects of Parathyroid Disorders in Adults and in Pregnancy: Recommendations of the ESE Educational Program of Parathyroid Disorders. Eur J Endocrinol 2022; 186:R33-R63. [PMID: 34863037 PMCID: PMC8789028 DOI: 10.1530/eje-21-1044] [Citation(s) in RCA: 94] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022]
Abstract
This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.
Collapse
Affiliation(s)
- Jens Bollerslev
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Medical Clinic, Oslo University Hospital, Oslo, Norway
- Correspondence should be addressed to J Bollerslev Email
| | - Lars Rejnmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Alexandra Zahn
- Schön-Klinik Hamburg, Department of Endocrine Surgery, Hamburg, Germany
| | - Ansgar Heck
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Specialized Endocrinology, Department of Endocrinology, Medical Clinic, Oslo University Hospital, Oslo, Norway
| | - Natasha M Appelman-Dijkstra
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center (LUMC), Leiden, the Netherlands
| | - Luis Cardoso
- Centro Hospitalar e Universitário de Coimbra, i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal
| | - Fadil M Hannan
- Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK
| | - Filomena Cetani
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Tanja Sikjaer
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Anna Maria Formenti
- Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Sigridur Björnsdottir
- Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden
| | - Camilla Schalin-Jäntti
- Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Zhanna Belaya
- The National Medical Research Centre for Endocrinology, Moscow, Russia
| | - Fraser Gibb
- Edinburgh Centre for Endocrinology & Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Bruno Lapauw
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Karin Amrein
- Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Corinna Wicke
- Thyroid Center, Luzerner Kantonsspital, Luzern, Switzerland
| | - Corinna Grasemann
- Division of Rare Diseases, Department of Pediatrics, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Michael Krebs
- Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Eeva Ryhänen
- Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Özer Makay
- Division of Endocrine Surgery, Department of General Surgery, Ege University Hospital, Izmir, Turkey
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy
| | - Sébastien Gaujoux
- Department of Digestive, Hepatobiliary and Endocrine Surgery, Paris Descartes University, Cochin Hospital, Paris, France
| | - Jean-Philippe Bertocchio
- Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Nephrology Department, Boulevard de l’Hôpital, Paris, France
| | - Zaki Hassan-Smith
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Agnès Linglart
- Université de Paris Saclay, AP-HP, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Filière OSCAR, Service d’Endocrinologie et Diabète de l’Enfant, Hôpital Bicêtre Paris Saclay, Le Kremlin Bicêtre, France
| | - Elizabeth M Winter
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center (LUMC), Leiden, the Netherlands
| | - Martina Kollmann
- Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
| | - Hans-Georg Zmierczak
- Reference Centre for Rare Bone, Calcium and Phosphate Disorders – University Hospital Ghent, Ghent, Belgium
| | - Elena Tsourdi
- Center for Healthy Aging, Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany
| | - Stefan Pilz
- Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Heide Siggelkow
- Endokrinologikum Göttingen, Georg-August-University Göttingen, Göttingen, Germany
| | - Neil Gittoes
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Peter Kamenický
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate, Le Kremlin-Bicêtre, France
| | | |
Collapse
|
|
20
|
Penido MGMG, Tavares MDS. Beyond kidney stones: Why pediatricians should worry about hypercalciuria. World J Clin Pediatr 2021; 10:137-150. [PMID: 34868890 PMCID: PMC8603641 DOI: 10.5409/wjcp.v10.i6.137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/08/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of urolithiasis (UL) is increasing, and it has become more common in children and adolescents over the past few decades. Hypercalciuria is the leading metabolic risk factor of pediatric UL, and it has high morbidity, with or without lithiasis as hematuria and impairment of bone mass. The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria (IH), and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown. A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life. However, it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass. The peak bone mass is achieved by late adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference in order to achieve the peak of optimal bone mass. The bone mass acquired during childhood and adolescence is a major determinant of adult bone health, and its accumulation should occur without interference. This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood. Pediatricians should be aware of this pediatric problem and investigate their patients. They should have the knowledge and ability to diagnose and initially manage patients with IH, with or without UL.
Collapse
Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
- Pediatric Nephrology Unit, Pediatric Department, Clinics Hospital, Universidade Federal de Minas Gerais, CEP 30130100, Belo Horizonte, Minas Gerais, Brazil
| | - Marcelo de Sousa Tavares
- Pediatric Nephrology Unit, Nephrology Center, Santa Casa de Belo Horizonte Hospital, CEP 30150320, Belo Horizonte, Minas Gerais, Brazil
| |
Collapse
|
|
21
|
Cusano NE. Evaluation and Management of Elevated Parathyroid Hormone Levels in Normocalcemic Patients. Med Clin North Am 2021; 105:1135-1150. [PMID: 34688419 DOI: 10.1016/j.mcna.2021.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Primary hyperparathyroidism is a common endocrine disorder. It used to present as a highly symptomatic disease before the advent of the multichannel autoanalyzer, now usually presenting as mild asymptomatic hypercalcemia. A newer presentation has been increasingly identified in the past two decades, normocalcemic primary hyperparathyroidism, presenting with elevated parathyroid hormone concentrations and consistently normal serum calcium. These patients are usually symptomatic, with parathyroid hormone levels measured in the evaluation for kidney stones or osteoporosis. It is important to exclude causes of secondary hyperparathyroidism. This review will focus on the evaluation and management of elevated parathyroid hormone levels in normocalcemic patients.
Collapse
Affiliation(s)
- Natalie E Cusano
- Division of Endocrinology, Department of Medicine, Lenox Hill Hospital, 110 East 59th Street, Suite 8B, New York, NY, USA.
| |
Collapse
|
|
22
|
Islam AK. Advances in the diagnosis and the management of primary hyperparathyroidism. Ther Adv Chronic Dis 2021; 12:20406223211015965. [PMID: 34178298 PMCID: PMC8202248 DOI: 10.1177/20406223211015965] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 04/20/2021] [Indexed: 12/26/2022] Open
Abstract
The parathyroid glands, one of the last organs to be discovered, are responsible for maintaining calcium homeostasis, and they continue to present the clinician with diagnostic and management challenges that are reviewed herein. Primary hyperparathyroidism (PHPT) comprises the vast majority of pathology of the parathyroid glands. The classic variant, presenting with elevated calcium and parathyroid hormone levels, has been studied extensively, but the current body of literature has added to our understanding of normocalcemic and normohormonal variants of PHPT, as well as syndromic forms of PHPT. All variants can lead to bone loss, kidney stones, declining renal function, and a variety of neurocognitive, gastrointestinal, and musculoskeletal complaints, although the majority of PHPT today is asymptomatic. Surgery remains the definitive treatment for PHPT, and advances in screening, evolving indications for surgery, new imaging modalities, and improvements in intra-operative methods have greatly changed the landscape. Surgery continues to produce excellent results in the hands of an experienced parathyroid surgeon. For those patients who are not candidates for surgery, therapeutic advances in medical management allow for improved control of the hypercalcemic state. Parathyroid cancer is extremely rare; the diagnosis is often made intra-operatively or on final pathology, and recurrence is common. The mainstay of treatment is normalization of serum calcium via surgery and medical adjuncts.
Collapse
Affiliation(s)
- Ana Kashfia Islam
- Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9159, USA
| |
Collapse
|
|
23
|
Jung HD, Lee JY. Prevention and management of urinary stone. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2020. [DOI: 10.5124/jkma.2020.63.11.684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The prevalence of urolithiasis is increasing not only in South Korea but also around the world. Urolithiasis has a high recurrence rate, therefore, reducing it is very important in the quality of life for stone formers. For this purpose, dietary modifications and drug therapy can be performed through stone analysis and 24-hour urine collection. Stone analysis is recommended for all stone formers, and the 24-hour urine collection is usually recommended for recurrent stone formers or high-risk groups. A general dietary modification for all stone formers includes a sufficient fluid intake, low levels of sodium, sugar, and animal protein, a normal calcium diet, as well as a high amount of citrate intake. Drug therapy should be performed in cases such as the recurrence of stones or increase of the existing ones, even after the application of preservation therapy, such as dietary modification. The ideal drug therapy should prevent the occurrence of urolithiasis, have no side effects, and have a suitable patientsʼ compliance. Follow-up should be performed periodically, through 24-hour urine collections and imaging studies. For follow-up imaging studies, a lowdose non-enhanced computed tomography is recommended, and it can be performed once a year if the patient is in a stable state. To control various and complex metabolic abnormalities in recurrent stone formers, multiple approaches may be required through diet modifications, drug therapy, treatment of the metabolic syndrome, and lifestyle modifications.
Collapse
|
|
24
|
Abstract
The prevalence of urolithiasis in humans is increasing worldwide; however, non-surgical treatment and prevention options remain limited despite decades of investigation. Most existing laboratory animal models for urolithiasis rely on highly artificial methods of stone induction and, as a result, might not be fully applicable to the study of natural stone initiation and growth. Animal models that naturally and spontaneously form uroliths are an underused resource in the study of human stone disease and offer many potential opportunities for improving insight into stone pathogenesis. These models include domestic dogs and cats, as well as a variety of other captive and wild species, such as otters, dolphins and ferrets, that form calcium oxalate, struvite, uric acid, cystine and other stone types. Improved collaboration between urologists, basic scientists and veterinarians is warranted to further our understanding of how stones form and to consider possible new preventive and therapeutic treatment options.
Collapse
|
|
25
|
Sakhr HM, Hassan MH, Desoky T. Possible Associations of Disturbed Neurometals and Ammonia with Glycaemic Control in Type 1 Diabetic Children with Attention Deficit Hyperactivity Disorder. Biol Trace Elem Res 2020; 198:68-76. [PMID: 32020524 DOI: 10.1007/s12011-020-02063-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 01/30/2020] [Indexed: 12/30/2022]
Abstract
The chronicity of type 1 diabetes mellitus (T1DM) is reported to be associated with various psychological disorders. The current study aimed to evaluate the levels of serum ammonia and various neurometals (zinc, copper, and magnesium) in patients with T1DM with and without ADHD and to correlate their levels with glycaemic status. A prospective case-control study was conducted with 60 diabetic children with T1DM (allocated into a group of 20 patients with a diagnosis of ADHD and a group of 40 patients without ADHD) who were comparable to 60 matched controls. Assays of glucose, glycated haemoglobin (HbA1c), ammonia, zinc, copper, and magnesium were performed. Overall, ammonia and copper levels were significantly higher in the diabetic patients especially those with ADHD than in the control group (p ˂ 0.05 for all). The calculated copper/zinc ratio was significantly higher in the diabetic patient group than in the control group and higher in diabetic children with ADHD than in diabetic children without ADHD (p ˂ 0.05 for all). Diabetic children had significantly lower magnesium levels than the controls (p ˂ 0.05), but no significant difference between the diabetic subgroups was detected. A positive correlation between glycaemic control (HbA1c %) and ammonia level was found in the diabetic group and subgroups, and a positive correlation was found between HbA1c % and the Cu/Zn ratio in diabetic children with ADHD (p ˂ 0.05 for all). The current study confirms an association of elevated ammonia and copper/zinc ratio with poor glycaemic control and ADHD development among children with T1DM.
Collapse
Affiliation(s)
- Hala M Sakhr
- Department of Pediatrics, Faculty of Medicine, South Valley University, Qena, Egypt
| | - Mohammed H Hassan
- Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt.
| | - Tarek Desoky
- Department of Neuropsychiatry, Faculty of Medicine, South Valley University, Qena, Egypt
| |
Collapse
|
|
26
|
Sharma A, Bahowairath F, Uduku C, Ostberg JE. Double jeopardy: a patient's tale of two concurrent hypercalcaemic syndromes. BMJ Case Rep 2020; 13:13/8/e237036. [PMID: 32843465 DOI: 10.1136/bcr-2020-237036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Primary hyperparathyroidism (PHPT) is the most common cause of parathyroid hormone (PTH) dependent hypercalcaemia, however there are few reported cases of its co-occurrence in patients with familial hypocalciuric hypercalcaemia (FHH). This case highlights the challenges in managing a rare case of dual pathology. A 49-year-old Caucasian woman with symptoms of hypercalcaemia presented with an adjusted serum calcium of 2.77 mmol/L and PTH of 11.5 pmol/L. Neck ultrasound and sestamibi scan were concordant with a left lower parathyroid adenoma, and a preoperative dual-energy X-ray absorptiometry scan confirmed osteopenia. Parathyroidectomy resulted in a PTH reduction from 11.5 pmol/L to 2.7 pmol/L. Interestingly, her lowest pre-operative adjusted serum calcium of 2.67 mmol/L remained unchanged 14 months post-parathyroidectomy. Twenty-four hours urine calcium:creatinine clearance ratio performed postoperatively was low and sequencing analysis of the calcium-sensing receptor gene confirmed the coexistence of FHH. Although surgery is not indicated in FHH, parathyroidectomy may help reduce hypercalcaemia and its associated complications if there is coexistent PHPT.
Collapse
Affiliation(s)
- Aditi Sharma
- Section of Investigative Medicine, Imperial College London, London, UK
| | - Fatima Bahowairath
- Deaprtment of Endocrine and Diabetes, Watford General Hospital, Watford, Hertfordshire, UK
| | - Chukwuma Uduku
- Section of Investigative Medicine, Imperial College London, London, UK
| | - Julia E Ostberg
- Deaprtment of Endocrine and Diabetes, Watford General Hospital, Watford, Hertfordshire, UK
| |
Collapse
|
|
27
|
Effect of Vitamin D Treatment on Dynamics of Stones Formation in the Urinary Tract and Bone Density in Children with Idiopathic Hypercalciuria. Nutrients 2020; 12:nu12092521. [PMID: 32825353 PMCID: PMC7551195 DOI: 10.3390/nu12092521] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/14/2020] [Accepted: 08/17/2020] [Indexed: 12/14/2022] Open
Abstract
Vitamin D supplementation in patients with urolithiasis and hypercalciuria is considered to be unsafe. We analyzed the impact of vitamin D supplementation on selected health status parameters in children with idiopathic hypercalciuria. The study included 36 children with urolithiasis resulting from excessive calcium excretion. The level of calcium and 25(OH)D (hydroxylated vitamin D - calcidiol) in serum, urinary calcium excretion and the presence of stones in urinary tract were assessed prospectively. Blood and urine samples were collected at the time when the patient was qualified for the study and every three months up to 24 month of vitamin D intake at a dose of 400 or 800 IU/day. At time zero and at 12, and 24 months of vitamin D supplementation, densitometry was performed. Supplementation with vitamin D caused a statistically significant increase in the concentration of 25(OH)D in serum. There were no significant changes in calcium concentration in serum, excretion of calcium in urine but also in bone density. There was no significant increase in the risk of formation or development of stones in the urinary tract. Supplementation with vitamin D (400–800 IU/day) in children with idiopathic hypercalciuria significantly increases 25(OH)D concentration, does not affect calciuria, but also does not improve bone density.
Collapse
|
|
28
|
Irzyniec T, Boryń M, Kasztalska J, Nowak-Kapusta Z, Maciejewska-Paszek I, Grochowska-Niedworok E. The effect of an oral sodium phosphate load on parathyroid hormone and fibroblast growth factor 23 secretion in normo- and hypercalciuric stone-forming patients. Clin Nutr 2020; 39:3804-3812. [PMID: 32386861 DOI: 10.1016/j.clnu.2020.04.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/13/2020] [Accepted: 04/15/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Abnormalities of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) secretion may cause calcium-phosphate (Ca-P) metabolism disorders in nephrolithiasis. Post-phosphate-load alterations in serum Ca, P and PTH, phosphaturia and calciuria enable monitoring hormonal regulation of Ca-P homeostasis. Our study aimed to determine differences in: 1.selected Ca-P metabolism parameters between healthy and kidney-stone-forming individuals, 2.PTH and FGF23 secretion induced by sodium-phosphate-load(NaP-load) in patients with/without hypercalciuria, 3.secretion of Ca-P related hormones in patients with low and normal/high serum concentrations of 25-hydroxyvitamin D3 (25OHD3). METHODS Sodium phosphates NaH2PO4/Na2HPO4-100mmol were administered orally for five days in 19 hypercalciuric [urinary Ca(U-Ca) 6.5 ± 1.7 mmol/d]-HSF, 35 normocalciuric (2.5±1 mmol/d)-NSF stone-forming patients and 19 controls (U-Ca 2.5 ± 1.4 mmol/d)-CG. On days 1 and 5 PTH-,FGF23-,Ca-,P were determined before and after NaP-load. The areas under PTH, FGF23 curves (AUC) were calculated. U-Ca, urinary phosphate (U-P) and sodium (U-Na) were also determined. RESULTS Following NaP-load, patients and controls exhibited expected alterations in Ca-P homeostasis. Despite changes in phosphate and PTH, no differences in FGF23 concentrations were observed. Patients differed from controls in having higher AUCPTH, calciuria and natriuresis, taking longer for PTH and P to normalize and lack of correlation between AUCPTH and phosphaturia. Post-NaP-load hypocalciuric effect of PTH secretion in NSF was less pronounced than in CG. In the HSFs, the hypocalciuric effect was more pronounced than in NSFs, but insufficient to correct hypercalciuria. In all stone-formers with low 25OHD3 concentrations, the AUCFGF23 was significantly increased on first (1215 ± 605vs766 ± 315 p = 0.0457) and fifth days (1211 ± 641vs777 ± 299 p = 0.041) of NaP-load, compared to normal/high 25OHD3-patients. Hypercalciuric patients with low 25OHD3 concentrations had greater AUCPTH5 than those with normal/high 25OHD3 (1005 ± 401vs835 ± 220 p = 0.0341). CONCLUSIONS Compared to controls, kidney-stone-forming patients exhibited enhanced PTH secretion after NaP-load. The HSFs showed a more pronounced hypocalciuric effect than NSFs, but insufficient to correct hypercalciuria. In hypercalciuric stone-formers with low 25OHD3, FGF23 engagement in hyperphosphatemia reduction increased.
Collapse
Affiliation(s)
- Tomasz Irzyniec
- Department of Nephrology/ENDO, Hospital of the Ministry of the Interior and Administration, Ul. Głowackiego 10, 40-052, Katowice, Poland; Department of Health Promotion and Community Nursing, Faculty of Health Sciences, Medical University of Silesia, Ul. Medyków 12, 40-752, Katowice, Poland.
| | - Monika Boryń
- Department of Nephrology/ENDO, Hospital of the Ministry of the Interior and Administration, Ul. Głowackiego 10, 40-052, Katowice, Poland.
| | - Joanna Kasztalska
- Department of Nephrology/ENDO, Hospital of the Ministry of the Interior and Administration, Ul. Głowackiego 10, 40-052, Katowice, Poland.
| | - Zofia Nowak-Kapusta
- Department of Health Promotion and Community Nursing, Faculty of Health Sciences, Medical University of Silesia, Ul. Medyków 12, 40-752, Katowice, Poland.
| | - Izabela Maciejewska-Paszek
- Department of Health Promotion and Community Nursing, Faculty of Health Sciences, Medical University of Silesia, Ul. Medyków 12, 40-752, Katowice, Poland.
| | - Elżbieta Grochowska-Niedworok
- Department of Dietetics, School of Public Health in Bytom, Medical University of Silesia, Ul. Piekarska 19, 41-902, Bytom, Poland.
| |
Collapse
|
|
29
|
Vitale C, Marangella M, Bermond F, Fabbrini L, Tricerri A. Metabolic effects of cholecalciferol supplementation in patients with calcium nephrolithiasis and vitamin D deficiency. World J Urol 2020; 39:597-603. [PMID: 32367158 DOI: 10.1007/s00345-020-03222-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 04/24/2020] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION In this paper, we investigated whether cholecalciferol supplementation may increase the risk of stone recurrence in patients with calcium nephrolithiasis and Vitamin D deficiency. METHODS Thirty-three stone formers (56 ± 17 years old, 12 males) with 25(OH)D < 20 ng/mL were considered. Calcium excretion and urine supersaturation with calcium oxalate (ßCaOx) and brushite (ßbsh) were evaluated, both before and after cholecalciferol supplementation. Values of ß > 1 mean supersaturation. Cholecalciferol was prescribed as oral bolus of 100,000-200,000 IU, followed by weekly (5000-10,000 IU) or monthly (25,000-50,000 IU) doses. Calcium intake varied between 800 and 1000 mg/day. In urine, total nitrogen (TNE) was taken as an index of protein intake, sodium as a marker of dietary intake, and net acid excretion (NAE) as an index of acid-base balance. RESULTS TNE, sodium, and NAE did not change during the study (p = ns). Compared to baseline values, after cholecalciferol, both serum calcium and phosphate did not vary (p = ns); 25(OH)D increased from 11.8 ± 5.5 to 40.2 ± 12.2 ng/mL (p < 0.01); 1.25(OH)2D increased from 41.6 ± 17.6 to 54 ± 16 pg/mL (p < 0.01); PTH decreased from 75 ± 27.2 to 56.7 ± 21.1 pg/mL (p < 0.01); urinary calcium increased from 2.7 ± 1.5 to 3.6 ± 1.6 mg/Kg b.w. (p < 0.01); ßbsh increased from 0.9 ± 0.7 to 1.3 ± 1.3 (p = 0.02); whereas ßCaOx varied but not significantly. Before cholecalciferol supplementation, 6/33 patients were hypercalciuric (i.e., urine Ca ≥ 4 mg/Kg b.w.) and increased to 13/33 after cholecalciferol supplementation (pX2 = 0.03). CONCLUSIONS Cholecalciferol supplementation may increase calcium excretion, or reveal an underlying condition of absorptive hypercalciuria. This may increase both urine supersaturation with calcium salts and stone-forming risk.
Collapse
Affiliation(s)
- Corrado Vitale
- S.C. Nefrologia e Dialisi, A.O. Ordine Mauriziano di Torino, Largo Turati, 62, 10128, Turin, Italy.
| | - Martino Marangella
- Fondazione Scientifica Mauriziana ONLUS, Largo Turati 62, 10128, Turin, Italy
| | - Francesca Bermond
- S.C. Nefrologia e Dialisi, A.O. Ordine Mauriziano di Torino, Largo Turati, 62, 10128, Turin, Italy
| | - Laura Fabbrini
- S.C. Nefrologia e Dialisi, A.O. Ordine Mauriziano di Torino, Largo Turati, 62, 10128, Turin, Italy
| | - Alberto Tricerri
- S.C. Nefrologia e Dialisi, A.O. Ordine Mauriziano di Torino, Largo Turati, 62, 10128, Turin, Italy
| |
Collapse
|
|
30
|
Schini M, Jacques RM, Oakes E, Peel NFA, Walsh JS, Eastell R. Normocalcemic Hyperparathyroidism: Study of its Prevalence and Natural History. J Clin Endocrinol Metab 2020; 105:dgaa084. [PMID: 32072184 PMCID: PMC7069345 DOI: 10.1210/clinem/dgaa084] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 02/18/2020] [Indexed: 12/23/2022]
Abstract
CONTEXT Normocalcemic hyperparathyroidism (NPHPT) is characterized by persistently normal calcium levels and elevated parathyroid hormone (PTH) values, after excluding other causes of secondary hyperparathyroidism. The prevalence of the disease varies greatly and the data on the natural history of this disease are sparse and inconclusive. OBJECTIVES The objectives of this study are to describe the prevalence of NPHPT and its natural history in a referral population and to compare the variability of serum calcium with a group of patients with primary hyperparathyroidism (PHPT). DESIGN A retrospective study was conducted over 5 years. SETTING The setting for this study was a metabolic bone referral center. PATIENTS A total of 6280 patients were referred for a bone mineral density measurement (BMD). MAIN OUTCOME MEASURES The prevalence and natural history of NPHPT and variability of calcium were the main outcome measures. RESULTS We identified NPHPT patients using data from the day of the BMD measurement. We excluded patients with low estimated glomerular filtration rate (eGFR) or vitamin D, or with no measurements available. Based on the evaluation of their medical files, we identified 11 patients with NPHPT (prevalence 0.18%). Only 4 patients had consistent normocalcemia throughout their follow-up, with only 2 also having consistently high PTH. None had consistently normal eGFR or vitamin D.Intermittent hypercalcemia was present in 7 of the 11 NPHPT patients. The mean adjusted calcium was found to be significantly lower in the NPHPT group compared with the PHPT group but higher than the control group. PTH was similar for NPHPT and PHPT. These 2 groups had similar variability in serum calcium. CONCLUSIONS NPHPT patients often have episodes of hypercalcemia. We believe that NPHPT is a mild form of PHPT.
Collapse
Affiliation(s)
- Marian Schini
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Richard M Jacques
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Eleanor Oakes
- Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK
| | - Nicola F A Peel
- Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK
| | - Jennifer S Walsh
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Richard Eastell
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| |
Collapse
|
|
31
|
Schulster ML, Goldfarb DS. Vitamin D and Kidney Stones. Urology 2020; 139:1-7. [PMID: 32032687 DOI: 10.1016/j.urology.2020.01.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/11/2020] [Accepted: 01/21/2020] [Indexed: 12/31/2022]
Abstract
This review explores the relationship between vitamin D supplementation and lithogenesis. A causal relationship has been assumed despite myriad studies demonstrating that therapeutic doses of vitamin D do not increase lithogenic risk. Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations. Additionally, the evidence for who is vitamin D deficient, and the benefits of supplementation in those not at risk for rickets, is sparse. Concerns may be avoidable as vitamin D screening appears unnecessary in most patients, and superior pharmacology is available which increases bone density, while decreasing stone formation.
Collapse
Affiliation(s)
- Michael L Schulster
- Department of Urology, NYU Langone Health, NYU School of Medicine, and New York Harbor VA Healthcare System, New York, NY
| | - David S Goldfarb
- Nephrology Division, NYU Langone Health, NYU School of Medicine, and New York Harbor VA Healthcare System, New York, NY.
| |
Collapse
|
|
32
|
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
| |
Collapse
|
|
33
|
Milart J, Jobs K, Tłustochowicz M, Pogonowska M, Kalicki B. The impact of vitamin D supplementation on vitamin D level, urinary calcium excretion and bone density in patients with hypercalciuria and vitamin D deficiency - preliminary report. DEVELOPMENTAL PERIOD MEDICINE 2019; 22:145-152. [PMID: 30056401 PMCID: PMC8522899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 05/15/2018] [Indexed: 06/08/2023]
Abstract
AIM To study the impact of vitamin D supplementation on vitamin D concentration in plasma, calcium urinary excretion and bone density in patients with urolithiasis in the course of idiopathic hypercalciuria and with a low vitamin D level. MATERIALS AND METHOD Prospective analysis concerning 28 patients (16 boys, 12 girls) aged 6-14 years (average 10.4) in terms of urinary calcium excretion (mg/kg/day and Ca/Creatinine ratio in morning urine sample), 25OHD blood level after 3, 6, 9 and 12 months of individually recommended doses of vitamin D supplementation (400 IU or 800 IU). The doses were determined on the basis of 25 (OH) D deficiency. The children were on a normocalcemic diet. The bone mineral density of the patients was assessed before and after 12 months of vitamin D use at the aforementioned doses. RESULTS There was no statistically significant correlation between 25 (OH) D plasma concentration and urinary calcium excretion measured on Ca /Creatinine ratio in daily urine collection and Ca/Creatinine ratio in the morning urine sample. No statistically significant change in calcium excretion was noted (measured by calciuria in daily urine collection and the calcium to creatinine ratio in the morning urine sample). A statistically significant increase in vitamin D plasma concentration was observed. Improvement in bone mineral density was not statistically significant. CONCLUSIONS Supplementation of vitamin D in the children with idiopathic hypercalciuria and urolithiasis who were examined seems to be safe. The decision to start treatment and the selection of the vitamin D dose should be considered individually. Patients with urolithiasis should be carefully monitored for calcium/phosphate metabolism parameters and the activity of the disease. Supplementation of low doses vitamin D in the children examined did not improve bone mineral density.
Collapse
Affiliation(s)
- Joanna Milart
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| | - Katarzyna Jobs
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| | | | - Milena Pogonowska
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| | - Bolesław Kalicki
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| |
Collapse
|
|
34
|
Marić I, Kizivat T, Smolić M, Smolić R, Opačak-Bernardi T, Šolić K, Roguljić H, Milas Ahić J, Tucak A, Mihaljević I. LIFESTYLE RISK FACTORS AND BONE MASS IN RECURRENT STONE-FORMING PATIENTS: A CROSS-SECTIONAL STUDY IN 144 SUBJECTS. Acta Clin Croat 2019; 58:439-445. [PMID: 31969755 PMCID: PMC6971805 DOI: 10.20471/acc.2019.58.03.06] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 06/13/2018] [Indexed: 11/24/2022] Open
Abstract
Patients with urolithiasis, particularly hypercalciuria, may have reduced bone mineral density (BMD). There are numerous risk factors contributing to reduction of BMD such as advanced age, sedentary lifestyle, smoking, low calcium intake, etc. The aim of our study was to investigate the association of lifestyle risk factors and daily intake of milk and dairy products with determinants of BMD in a group of recurrent calcium stone formers (RSF) compared with healthy subjects (HS). The study was carried out at the Department of Mineral Research, Faculty of Medicine in Osijek, Croatia. The study included 144 subjects, i.e. 56 RSF and 78 HS. BMD was assessed by dual-energy x-ray absorptiometry. A standard self-reported questionnaire was used to collect data on lifestyle risk factors. Current dietary intake was assessed by personal interview that included questions about milk and dairy product intake. Low BMD was observed in 44.64% of RSF and 35.90% of HS. RSF consumed significantly less milk and dairy products than HS. Calcium restriction in dietary recommendations might be unnecessary due to the impact on bone mineral loss in RSF and dual-energy x-ray absorptiometry should be included in the routine evaluation of RSF.
Collapse
|
|
35
|
van der Wijst J, van Goor MK, Schreuder MF, Hoenderop JG. TRPV5 in renal tubular calcium handling and its potential relevance for nephrolithiasis. Kidney Int 2019; 96:1283-1291. [PMID: 31471161 DOI: 10.1016/j.kint.2019.05.029] [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: 03/15/2019] [Revised: 05/21/2019] [Accepted: 05/22/2019] [Indexed: 10/26/2022]
Abstract
Nephrolithiasis or renal stone disease is an increasingly common problem, and its relatively high recurrence rate demands better treatment options. The majority of patients with nephrolithiasis have stones that contain calcium (Ca2+), which develop upon "supersaturation" of the urine with insoluble Ca2+ salts; hence processes that influence the delivery and renal handling of Ca2+ may influence stone formation. Idiopathic hypercalciuria is indeed frequently observed in patients with kidney stones that contain Ca2+. Genetic screens of nephrolithiasis determinants have identified an increasing number of gene candidates, most of which are involved in renal Ca2+ handling. This review provides an outline of the current knowledge regarding genetics of nephrolithiasis and will mainly focus on the epithelial Ca2+ channel transient receptor potential vanilloid 5 (TRPV5), an important player in Ca2+ homeostasis. Being a member of the TRP family of ion channels, TRPV5 is currently part of a revolution in structural biology. Recent technological breakthroughs in the cryo-electron microscopy field, combined with improvements in biochemical sample preparation, have resulted in high-resolution 3-dimensional structural models of integral membrane proteins, including TRPV5. These models currently are being used to explore the proteins' structure-function relationship, elucidate the molecular mechanisms of channel regulation, and study the putative effects of disease variants. Combined with other multidisciplinary approaches, this approach may open an avenue toward better understanding of the pathophysiological mechanisms involved in hypercalciuria and stone formation, and ultimately it may facilitate prevention of stone recurrence through the development of effective drugs.
Collapse
Affiliation(s)
- Jenny van der Wijst
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, the Netherlands
| | - Mark K van Goor
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, the Netherlands
| | - Michiel F Schreuder
- Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, the Netherlands
| | - Joost G Hoenderop
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, the Netherlands.
| |
Collapse
|
|
36
|
Ibeh CL, Yiu AJ, Kanaras YL, Paal E, Birnbaumer L, Jose PA, Bandyopadhyay BC. Evidence for a regulated Ca 2+ entry in proximal tubular cells and its implication in calcium stone formation. J Cell Sci 2019; 132:jcs.225268. [PMID: 30910829 DOI: 10.1242/jcs.225268] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 03/14/2019] [Indexed: 12/14/2022] Open
Abstract
Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca2+ reabsorption, could be a regulator of such CaP crystal formation. However, PT Ca2+ reabsorption is mostly described as being paracellular. Here, we show the existence of a regulated transcellular Ca2+ entry pathway in luminal membrane PT cells induced by Ca2+-sensing receptor (CSR, also known as CASR)-mediated activation of transient receptor potential canonical 3 (TRPC3) channels. In support of this idea, we found that both CSR and TRPC3 are physically and functionally coupled at the luminal membrane of PT cells. More importantly, TRPC3-deficient mice presented with a deficiency in PT Ca2+ entry/transport, elevated urinary [Ca2+], microcalcifications in LOH and urine microcrystals formations. Taken together, these data suggest that a signaling complex comprising CSR and TRPC3 exists in the PT and can mediate transcellular Ca2+ transport, which could be critical in maintaining the PT luminal [Ca2+] to mitigate formation of the CaP crystals in LOH and subsequent formation of calcium stones.
Collapse
Affiliation(s)
- Cliff-Lawrence Ibeh
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington DC, DC 20422, USA
| | - Allen J Yiu
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington DC, DC 20422, USA.,Department of Medicine, Division of Renal Diseases & Hypertension, The George Washington University, Washington DC, DC 20037, USA
| | - Yianni L Kanaras
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington DC, DC 20422, USA
| | - Edina Paal
- Pathology and Laboratory Service, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington DC, DC 20422, USA
| | - Lutz Birnbaumer
- Division of Intramural Research, NIEHS, Research Triangle Park, Durham, NC 27709, USA.,Institute for Biomedical Research (BIOMED), Catholic University of Argentina, C1107AFF Buenos Aires, Argentina
| | - Pedro A Jose
- Department of Medicine, Division of Renal Diseases & Hypertension, The George Washington University, Washington DC, DC 20037, USA.,Department of Pharmacology and Physiology, The George Washington University, Washington DC, DC 20037, USA
| | - Bidhan C Bandyopadhyay
- Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington DC, DC 20422, USA .,Department of Medicine, Division of Renal Diseases & Hypertension, The George Washington University, Washington DC, DC 20037, USA.,Department of Pharmacology and Physiology, The George Washington University, Washington DC, DC 20037, USA
| |
Collapse
|
|
37
|
Bone resorption in dogs with calcium oxalate urolithiasis and idiopathic hypercalciuria. Res Vet Sci 2019; 123:129-134. [PMID: 30641472 DOI: 10.1016/j.rvsc.2019.01.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 11/26/2018] [Accepted: 01/03/2019] [Indexed: 11/23/2022]
Abstract
People with calcium oxalate (CaOx) urolithiasis and idiopathic hypercalciuria (IH) often have evidence of increased bone resorption, but bone turnover has not previously been investigated in dogs with these conditions. The aim of this study was to determine whether a marker of bone resorption, β-crosslaps, differs between dogs with CaOx urolithiasis and IH compared to controls. This retrospective, cross-sectional study used a canine specific ELISA to measure β-crosslaps concentrations in stored frozen serum samples from 20 dogs with CaOx urolithiasis and IH and 20 breed-, sex-, and age-matched stone-free controls (18 Miniature Schnauzers, 14 Bichons Frise, and 8 Shih Tzus). Dogs with CaOx urolithiasis and IH had lower β-crosslaps concentrations relative to controls (P = .0043), and β-crosslaps had a moderate negative correlation with urinary calcium-to-creatinine ratios (r = -0.44, P = .0044). Miniature Schnauzers had lower β-crosslaps concentrations than the other two breeds (P = .0035). The ELISA had acceptable intra-assay precision, but concentrations decreased when samples were repeatedly assayed over time. Assay recovery rates were also below acceptance criteria. In conclusion, Miniature Schnauzers, Bichons Frise, and Shih Tzus with CaOx urolithiasis and IH have evidence of decreased bone resorption compared to stone-free controls. This suggests that other causes of IH, such as intestinal hyperabsorption of calcium, underlie risk for CaOx urolithiasis in these breeds. Results should be confirmed in larger populations and with other β-crosslaps assays and additional biomarkers of bone turnover. The stability of canine serum β-crosslaps after freeze-thaw cycles and storage at various temperatures requires investigation.
Collapse
|
|
38
|
Abstract
Calcium kidney stones are common worldwide. Most are idiopathic and composed of calcium oxalate. Calcium phosphate is present in around 80% and may initiate stone formation. Stone production is multifactorial with a polygenic genetic contribution. Phosphaturia is found frequently among stone formers but until recently received scant attention. This review examines possible mechanisms for the phosphaturia and its relevance to stone formation from a wide angle. There is a striking lack of clinical data. Phosphaturia is associated, but not correlated, with hypercalciuria, increased 1,25 dihydroxy-vitamin D [1,25 (OH)2D], and sometimes evidence of disturbances in proximal renal tubular function. Phosphate reabsorption in the proximal renal tubules requires tightly regulated interaction of many proteins. Paracellular flow through intercellular tight junctions is the major route of phosphate absorption from the intestine and can be reduced therapeutically in hyperphosphatemic patients. In monogenic defects stones develop when phosphaturia is associated with hypercalciuria, generally explained by increased 1,25 (OH)2D production in response to hypophosphatemia. Calcification does not occur in disorders with increased FGF23 when phosphaturia occurs in isolation and 1,25 (OH)2D is suppressed. Candidate gene studies have identified mutations in the phosphate transporters, but in few individuals. One genome-wide study identified a polymorphism of the phosphate transporter gene SLC34A4 associated with stones. Others did not find mutations obviously linked to phosphate reabsorption. Future genetic studies should have a wide trawl and should focus initially on groups of patients with clearly defined phenotypes. The global data should be pooled.
Collapse
Affiliation(s)
- Valerie Walker
- Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
| |
Collapse
|
|
39
|
Martínez García M, Trincado Aznar P, Pérez Fernández L, Azcona Monreal I, López Alaminos ME, Acha Pérez J, Albero Gamboa R. Comparación de los efectos inducidos sobre la calciuria por tiazidas y diferentes dosis de sal en la dieta: implicaciones en la práctica clínica. Nefrologia 2019; 39:73-79. [DOI: 10.1016/j.nefro.2018.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 04/15/2018] [Accepted: 05/06/2018] [Indexed: 10/28/2022] Open
|
|
40
|
Dhayat NA, Faller N, Bonny O, Mohebbi N, Ritter A, Pellegrini L, Bedino G, Schönholzer C, Venzin RM, Hüsler C, Koneth I, Del Giorno R, Gabutti L, Amico P, Mayr M, Odermatt U, Buchkremer F, Ernandez T, Stoermann-Chopard C, Teta D, Rintelen F, Roumet M, Irincheeva I, Trelle S, Tamò L, Roth B, Vogt B, Fuster DG. 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. BMC Nephrol 2018; 19:349. [PMID: 30526528 PMCID: PMC6288917 DOI: 10.1186/s12882-018-1144-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/20/2018] [Indexed: 11/13/2022] Open
Abstract
Background Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. Methods The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. Discussion The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. Trial registration ClinicalTrials.gov, NCT03057431. Registered on February 20 2017.
Collapse
Affiliation(s)
- Nasser A Dhayat
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Nicolas Faller
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Olivier Bonny
- Department of Nephrology, CHUV, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland
| | - Nilufar Mohebbi
- Department of Nephrology, University Hospital Zurich, Zürich, Switzerland
| | - Alexander Ritter
- Department of Nephrology, University Hospital Zurich, Zürich, Switzerland
| | - Lisa Pellegrini
- Department of Nephrology, Regional Hospital Lugano, Lugano, Switzerland
| | - Giulia Bedino
- Department of Nephrology, Regional Hospital Lugano, Lugano, Switzerland
| | - Carlo Schönholzer
- Department of Nephrology, Regional Hospital Lugano, Lugano, Switzerland
| | - Reto M Venzin
- Department of Nephrology, Cantonal Hospital Chur, Chur, Switzerland
| | - Carina Hüsler
- Department of Nephrology and Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Irene Koneth
- Department of Nephrology and Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Rosaria Del Giorno
- Department of Nephrology, Regional Hospital Bellinzona, Bellinzona, Switzerland
| | - Luca Gabutti
- Department of Nephrology, Regional Hospital Bellinzona, Bellinzona, Switzerland
| | - Patrizia Amico
- Medical Outpatient Department, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Michael Mayr
- Medical Outpatient Department, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Urs Odermatt
- Department of Nephrology, Cantonal Hospital Luzern, Luzern, Switzerland
| | - Florian Buchkremer
- Division of Nephrology, Dialysis and Transplantation, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Thomas Ernandez
- Department of Nephrology, HUG, University Hospital Geneva, University of Geneva, Geneva, Switzerland
| | | | - Daniel Teta
- Service de Nephrology, Centre Hospitalier du Valais Romand (CHVR), Sion, Switzerland
| | - Felix Rintelen
- Clinical Trials Unit, University of Bern, Bern, Switzerland
| | - Marie Roumet
- Clinical Trials Unit, University of Bern, Bern, Switzerland
| | | | - Sven Trelle
- Clinical Trials Unit, University of Bern, Bern, Switzerland
| | - Luca Tamò
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.,Clinical Trials Unit, University of Bern, Bern, Switzerland
| | - Beat Roth
- Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Bruno Vogt
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Daniel G Fuster
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
| |
Collapse
|
|
41
|
Abstract
Traditional hypercalcemic primary hyperparathyroidism is a common endocrine disease. Patients with a history of nephrolithiasis or a suspected metabolic bone disease are increasingly being identified with elevated PTH concentrations in the setting of consistently normal serum and ionized calcium concentrations. In the absence of secondary causes of hyperparathyroidism, a diagnosis of normocalcemic primary hyperparathyroidism is reasonable. As most cohorts described in the literature are from referral populations, involvement of the skeleton and the kidneys is common, two traditional target organs of primary hyperparathyroidism. Data from small cohorts show patients with normocalcemic disease respond similarly to hypercalcemic primary hyperparathyroidism with regard to medical and surgical approaches. In normocalcemic patients, multiglandular disease may be more common. In this article, we review the available literature on the epidemiology, diagnosis, clinical features, medical and surgical management of this newer phenotype of primary hyperparathyroidism.
Collapse
Affiliation(s)
- Natalie E Cusano
- Division of Endocrinology, Department of Medicine, Lenox Hill Hospital, 110 East 59th St, Suite 8B, New York, NY, 10022, USA.
| | - Cristiana Cipriani
- Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
| | - John P Bilezikian
- Metabolic Bone Diseases Unit, Division of Endocrinology, Department of Medicine, College of Physician and Surgeons, Columbia University, 630 West 168th St, New York, NY, 10032, USA.
| |
Collapse
|
|
42
|
Rakowska M, Królikowska K, Jobs K, Placzyńska M, Kalicki B. Pathophysiology and symptoms of renal colic in children - a case report. DEVELOPMENTAL PERIOD MEDICINE 2018. [PMID: 30281523 PMCID: PMC8522885 DOI: 10.34763/devperiodmed.20182203.265269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Urolithiasis is a disease characterized by the presence of stones in the kidney or urinary tract. It is often detected accidentally during an ultrasound or an abdominal x-ray performed for other reasons. However, the first symptom of kidney stone disease can be severe pain called renal colic. Pain caused by a colic attack is characterized by sudden onset. In half of the cases it is associated with nausea or vomiting and can lead to hypotension and fainting. The exact location and radiation of the pain depends on the location of the stone in the urinary tract. The first most commonly performed study is abdominal ultrasound with estimation of the deposit size and evaluation of urinary tract obstruction. Alternative or complementary studies are: an abdominal x-ray where radiopaque deposits can be shown, or unenhanced helical computed tomography of the abdomen. The severity of pain depends on the individual pain threshold and on the change in hydrostatic pressure in the part of the urinary system above the obstruction. Prolonged deposition of the stone in one place causes the activation of autoregulatory mechanisms to lower the pressure of the upper urinary tract, which limits the pain. The basic treatment for renal colic is analgetic therapy. The most commonly used drugs are NSAIDs and opiates. Another important component of renal colic treatment are medications that facilitate urinary stone passage by reducing oedema or limiting urethral contractions, such as: calcium channel blockers, alpha blockers, phosphodiesterase inhibitors. Intensive hydration is not currently recommended. Patients who are unlikely to spontaneously excrete the stone are eligible for minimally invasive treatment. The risk of urolithiasis recurring is high, reaching up to 40% in 5 years and up to 50% in 10 years. However, it can be reduced by proper prevention. The paper describes the pathophysiology of pain in renal colic, the treatment methods, and the case of a boy with recurrent renal colic.
Collapse
Affiliation(s)
- Magda Rakowska
- Department of Paediatrics, Nephrology and Allergology Military Institute of Medicine, Warsaw, Poland,Magda Rakowska Klinika Pediatrii, Nefrologii i Alergologii Dziecięcej Wojskowy Instytut Medyczny ul. Szaserów 128, 04-141 Warszawa tel. 261-817-217
| | - Katarzyna Królikowska
- Department of Paediatrics, Nephrology and Allergology Military Institute of Medicine, Warsaw, Poland
| | - Katarzyna Jobs
- Department of Paediatrics, Nephrology and Allergology Military Institute of Medicine, Warsaw, Poland
| | - Małgorzata Placzyńska
- Department of Paediatrics, Nephrology and Allergology Military Institute of Medicine, Warsaw, Poland
| | - Bolesław Kalicki
- Department of Paediatrics, Nephrology and Allergology Military Institute of Medicine, Warsaw, Poland
| |
Collapse
|
|
43
|
Sorokin I, Pearle MS. Medical therapy for nephrolithiasis: State of the art. Asian J Urol 2018; 5:243-255. [PMID: 30364650 PMCID: PMC6197179 DOI: 10.1016/j.ajur.2018.08.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 04/08/2018] [Accepted: 07/11/2018] [Indexed: 12/13/2022] Open
Abstract
The prevalence of nephrolithiasis is increasing worldwide. Understanding and implementing medical therapies for kidney stone prevention are critical to prevent recurrences and decrease the economic burden of this condition. Dietary and pharmacologic therapies require understanding on the part of the patient and the prescribing practitioner in order to promote compliance. Insights into occupational exposures and antibiotic use may help uncover individual risk factors. Follow-up is essential to assess response to treatment and to modify treatment plans to maximize therapeutic benefit.
Collapse
Affiliation(s)
- Igor Sorokin
- Department of Urology, University of Massachusetts, Worcester, MA, USA
| | - Margaret S Pearle
- Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA.,Charles and Jane Pak Center for Mineral Metabolism and Bone Research, UT Southwestern Medical Center, Dallas, TX, USA
| |
Collapse
|
|
44
|
Pucci ND, Marchini GS, Mazzucchi E, Reis ST, Srougi M, Evazian D, Nahas WC. Effect of phyllanthus niruri on metabolic parameters of patients with kidney stone: a perspective for disease prevention. Int Braz J Urol 2018; 44:758-764. [PMID: 29617079 PMCID: PMC6092661 DOI: 10.1590/s1677-5538.ibju.2017.0521] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 02/13/2018] [Indexed: 11/22/2022] Open
Abstract
Phyllanthus niruri (P.niruri) or stone breaker is a plant commonly used to reduce stone risk, however, clinical studies on this issue are lacking. OBJECTIVE To prospectively evaluate the effect of P. niruri on the urinary metabolic parameters of patients with urinary lithiasis. MATERIALS AND METHODS We studied 56 patients with kidney stones <10mm. Clinical, metabolic, and ultrasonography assessment was conducted before (baseline) the use of P. niruri infusion for 12-weeks (P. niruri) and after a 12-week (wash out) Statistical analysis included ANOVA for repeated measures and Tukey's/McNemar´s test for categorical variables. Significance was set at 5%. RESULTS Mean age was 44±9.2 and BMI was 27.2±4.4kg/m2. Thirty-six patients (64%) were women. There were no significant changes in all periods for anthropometric and several serum measurements, including total blood count, creatinine, uric acid, sodium, potassium, calcium, urine volume and pH; a significant increase in urinary potassium from 50.5±20.4 to 56.2±21.8 mg/24-hour (p=0.017); magnesium/creatinine ratio 58±22.5 to 69.1±28.6mg/ gCr24-hour (p=0.013) and potassium/creatinine ratio 39.3±15.1 to 51.3±34.7mg/gCr24- hour (p=0.008) from baseline to wash out. The kidney stones decreased from 3.2±2 to 2.0±2per patient (p<0.001). In hyperoxaluria patients, urinary oxalate reduced from 59.0±11.7 to 28.8±16.0mg/24-hour (p=0.0002), and in hyperuricosuria there was a decrease in urinary uric acid from 0.77±0.22 to 0.54±0.07mg/24-hour (p=0.0057). CONCLUSIONS P.niruri intake is safe and does not cause significant adverse effects on serum metabolic parameters. It increases urinary excretion of magnesium and potassium caused a significant decrease in urinary oxalate and uric acid in patients with hyperoxaluria and hyperuricosuria. The consumption of P.niruri contributed to the elimination of urinary calculi.
Collapse
Affiliation(s)
- Nidia D. Pucci
- Divisão de Nutrição e Dietética, Instituto Central, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina. São Paulo, Brasil
| | - Giovanni S. Marchini
- Divisão de Urologia, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brasil
| | - Eduardo Mazzucchi
- Divisão de Urologia, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brasil
| | - Sabrina T. Reis
- Laboratório de Investigação Médica, Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brasil
| | - Miguel Srougi
- Divisão de Urologia, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brasil
| | - Denise Evazian
- Divisão de Nutrição e Dietética, Instituto Central, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina. São Paulo, Brasil
| | - William C. Nahas
- Divisão de Urologia, Hospital das Clínicas, Universidade de São Paulo, Faculdade de Medicina, São Paulo, Brasil
| |
Collapse
|
|
45
|
Milart J, Jobs K, Tłustochowicz M, Pogonowska M, Kalicki B. The Impact of Vitamin D Supplementation on Vitamin D Level, Urinary Calcium Excretion and Bone Density in Patients with Hypercalciuria and Vitamin D Deficiency − Preliminary Report. DEVELOPMENTAL PERIOD MEDICINE 2018. [PMCID: PMC8522899 DOI: 10.34763/devperiodmed.20182202.144152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Aim To study the impact of vitamin D supplementation on vitamin D concentration in plasma, calcium urinary excretion and bone density in patients with urolithiasis in the course of idiopathic hypercalciuria and with a low vitamin D level. Materials and method Prospective analysis concerning 28 patients (16 boys, 12 girls) aged 6-14 years (average 10.4) in terms of urinary calcium excretion (mg/kg/day and Ca/Creatinine ratio in morning urine sample), 25OHD blood level after 3, 6, 9 and 12 months of individually recommended doses of vitamin D supplementation (400 IU or 800 IU). The doses were determined on the basis of 25 (OH) D deficiency. The children were on a normocalcemic diet. The bone mineral density of the patients was assessed before and after 12 months of vitamin D use at the aforementioned doses. Results There was no statistically significant correlation between 25 (OH) D plasma concentration and urinary calcium excretion measured on Ca /Creatinine ratio in daily urine collection and Ca/Creatinine ratio in the morning urine sample. No statistically significant change in calcium excretion was noted (measured by calciuria in daily urine collection and the calcium to creatinine ratio in the morning urine sample). A statistically significant increase in vitamin D plasma concentration was observed. Improvement in bone mineral density was not statistically significant. Conclusions Supplementation of vitamin D in the children with idiopathic hypercalciuria and urolithiasis who were examined seems to be safe. The decision to start treatment and the selection of the vitamin D dose should be considered individually. Patients with urolithiasis should be carefully monitored for calcium/phosphate metabolism parameters and the activity of the disease. Supplementation of low doses vitamin D in the children examined did not improve bone mineral density.
Collapse
Affiliation(s)
- Joanna Milart
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland,Joanna Milart Klinika Pediatrii, Nefrologii i Alergologii Dziecięcej Wojskowy Instytut Medyczny ul. Szaserów 128, 04-141 Warszawa tel. 261-817-217
| | - Katarzyna Jobs
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| | | | - Milena Pogonowska
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| | - Bolesław Kalicki
- Department of Paediatrics, Paediatric Nephrology and Allergology, Military Institute of Medicine, Warsaw, Poland
| |
Collapse
|
|
46
|
Abstract
Renal stone disease is a worldwide problem which carries significant morbidity. It frequently requires specialist urology intervention. Patients with recurrent disease and those at high risk require specialist investigations and review. Certain cases benefit from medical and surgical intervention. In this review, we discuss the pathophysiology, risk assessment, specialist investigations and various interventions, their rationale and evidence base. This review aims to provide an update of the previous publication in 2001 in this journal on this topic.
Collapse
Affiliation(s)
- Adie Viljoen
- Department of Chemical Pathology, Lister Hospital, Stevenage UK
| | - Rabia Chaudhry
- Department of Chemical Pathology, Lister Hospital, Stevenage UK
| | - John Bycroft
- Department of Urology, Lister Hospital, Stevenage, UK
| |
Collapse
|
|
47
|
Role of FGF23 in Pediatric Hypercalciuria. BIOMED RESEARCH INTERNATIONAL 2018; 2017:3781525. [PMID: 29457024 PMCID: PMC5804327 DOI: 10.1155/2017/3781525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/26/2017] [Accepted: 10/22/2017] [Indexed: 01/29/2023]
Abstract
Background This study explored the possible role of FGF23 in pediatric hypercalciuria. Methods Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine. Results There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre-Treated patients, 73 RU/mL, was not different from controls, in Treated patients it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre-Treated patients (p = 0.02). In all patients, there was a correlation between FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and higher serum phosphate (p = 0.007) versus Pre-Treated patients. Conclusions Pharmacological treatment of hypercalciuric patients resulted in significantly lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum phosphate concentration, without significant changes in PTH. Further studies are indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.
Collapse
|
|
48
|
Seeger H, Kaelin A, Ferraro PM, Weber D, Jaeger P, Ambuehl P, Robertson WG, Unwin R, Wagner CA, Mohebbi N. Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers. BMC Nephrol 2017; 18:349. [PMID: 29202723 PMCID: PMC5715611 DOI: 10.1186/s12882-017-0755-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 11/14/2017] [Indexed: 11/10/2022] Open
Abstract
Background Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. Methods We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. Results Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201 ± 89 at baseline to 128 ± 88 mmol/d for sodium (p < 0.0001), and from 5.67 ± 3.01 to 4.06 ± 2.46 mmol/d (p < 0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39 ± 0.26 vs 0.39 ± 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. Conclusion A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs. Electronic supplementary material The online version of this article (10.1186/s12882-017-0755-7) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Harald Seeger
- Division of Nephrology, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland
| | - Andrea Kaelin
- Division of Nephrology, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland
| | - Pietro M Ferraro
- Division of Nephrology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome, Italy
| | - Damian Weber
- Department of Urology, University Hospital Zurich, Zurich, Switzerland
| | - Philippe Jaeger
- Centre for Nephrology, University College London, London, UK
| | - Patrice Ambuehl
- Division of Nephrology, Stadtspital Waid, Zurich, Switzerland
| | | | - Robert Unwin
- Centre for Nephrology, University College London, London, UK
| | - Carsten A Wagner
- Institute of Physiology, University of Zurich, Zurich, Switzerland.,, National Center for Competence in Research NCCR Kidney, CH, Zurich, Switzerland
| | - Nilufar Mohebbi
- Division of Nephrology, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
| |
Collapse
|
|
49
|
Salcuni AS, Carnevale V, Battista C, Palmieri S, Eller-Vainicher C, Guarnieri V, Pugliese F, Guglielmi G, Desina G, Minisola S, Chiodini I, Scillitani A. Primary aldosteronism as a cause of secondary osteoporosis. Eur J Endocrinol 2017; 177:431-437. [PMID: 28794160 DOI: 10.1530/eje-17-0417] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Revised: 08/03/2017] [Accepted: 08/07/2017] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Patients with primary aldosteronism (PA) have a high prevalence of osteoporosis (OP) and fractures (Fx). We evaluated the presence of PA in patients admitted to our metabolic bone disease outpatient clinic. DESIGN Study conducted on an in- and outpatient basis in a referral Italian endocrinology unit. METHODS A total of 2632 patients were evaluated. 2310 were excluded because they were taking drugs known to affect bone or mineralocorticoids metabolism or were diagnosed to have a secondary cause of osteoporosis. The remaining 322 subjects (304 females, 18 males) took part in the study. Bone mineral density (BMD) and thoracic and lumbar spine vertebral morphometry were performed by dual X-ray absorptiometry. All patients were screened for PA with aldosterone-to-renin ratio. In those who had positive results, confirmatory tests were performed. RESULTS Among 322 subjects, 213 were osteoporotics and 109 were not. PA was diagnosed in eleven out of 213 osteoporotic patients (5.2%) and one out of 109 non-osteoporotic subjects (0.9%, P = 0.066). PA was observed in the 26.1% of patients with the concomitant presence of osteoporosis, hypertension and hypercalciuria. Compared with patients without PA, patients with PA had mean values of urinary calcium excretion, 4.8 ± 2.5 mmol/day vs 7.6 ± 3.2 mmol/day, P < 0.001 and serum PTH levels, 5.4 pmol/L vs 7.3 pmol/L, P < 0.01, significantly higher. CONCLUSIONS PA should be considered among the causes of secondary OP.
Collapse
Affiliation(s)
| | - Vincenzo Carnevale
- Internal Medicine Unit, 'Casa Sollievo della Sofferenza', IRCCS, San Giovanni Rotondo (FG), Italy
| | | | - Serena Palmieri
- Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Cristina Eller-Vainicher
- Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | | | | | | | - Gaetano Desina
- Clinical Pathology Unit, 'Casa Sollievo della Sofferenza', IRCCS, San Giovanni Rotondo (FG), Italy
| | - Salvatore Minisola
- Department of Internal Medicine and Medical Disciplines, 'Sapienza', Rome University, Rome, Italy
| | - Iacopo Chiodini
- Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | | |
Collapse
|
|
50
|
Furrow E, McCue ME, Lulich JP. Urinary metals in a spontaneous canine model of calcium oxalate urolithiasis. PLoS One 2017; 12:e0176595. [PMID: 28467511 PMCID: PMC5415176 DOI: 10.1371/journal.pone.0176595] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 04/13/2017] [Indexed: 12/13/2022] Open
Abstract
Calcium oxalate urolithiasis is a common and painful condition in people. The pathogenesis of this disease is complex and poorly understood. Laboratory animal and in vitro studies have demonstrated an effect of multiple trace metals in the crystallization process, and studies in humans have reported relationships between urinary metal concentrations and stone risk. Dogs are a spontaneous model of calcium oxalate urolithiasis, and the metal content of canine calcium oxalate stones mirrors that of human stones. The aim of this study was to test for a relationship between urinary metals and calcium oxalate urolithiasis in dogs. We hypothesized that urinary metals would differ between dogs with and without calcium oxalate urolithiasis. Urine from 122 dogs (71 cases and 51 stone-free controls) was analyzed for calcium and 12 other metals. The cases had higher urinary calcium, copper, iron, and vanadium and lower urinary cobalt. Higher urinary vanadium in the cases was associated with being fed a therapeutic stone-prevention diet. Urinary calcium had a strong positive correlation with strontium and moderate positive correlations with chromium, nickel, and zinc. The results of this study complement the findings of similar human studies and suggest a potential role of trace metals in calcium oxalate urolithiasis. Further investigation into how trace metals may affect stone formation is warranted.
Collapse
Affiliation(s)
- Eva Furrow
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America
- * E-mail:
| | - Molly E. McCue
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America
| | - Jody P. Lulich
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America
| |
Collapse
|