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      Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

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          Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research.


          A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved.


          Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients.


          This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.

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          Most cited references 143

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          Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study.

           L Borghi,  T Meschi,  F Amato (1996)
          We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake. We studied 101 controls and 199 patients from the first idiopathic calcium stone episode. After a baseline study period the stone formers were divided by randomization into 2 groups (1 and 2) and they were followed prospectively for 5 years. Followup in group 1 only involved a high intake of water without any dietetic change, while followup in group 2 did not involve any treatment. Each year clinical, laboratory and radiological evaluation was obtained to determine urinary stone risk profile (including relative supersaturations of calcium oxalate, brushite and uric acid by Equil 2), recurrence rate and mean time to relapse. The original urine volume was lower in male and female stone formers compared to controls (men with calcium oxalate stones 1,057 +/- 238 ml./24 hours versus normal men 1,401 +/- 562 ml./24 hours, p < 0.0001 and women calcium oxalate stones 990 +/- 230 ml./24 hours versus normal women 1,239 +/- 440 ml./24 hours, p < 0.001). During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients (p = 0.008). The average interval for recurrences was 38.7 +/- 13.2 months in group 1 and 25.1 +/- 16.4 months in group 2 (p = 0.016). The relative supersaturations for calcium oxalate, brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls. During followup, baseline values decreased sharply only in group 1. Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups. We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences. In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy.
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            Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II.

            In older women and men, greater intakes of dietary calcium, potassium, and total fluid reduce the risk of kidney stone formation, while supplemental calcium, sodium, animal protein, and sucrose may increase the risk. Recently, phytate has been suggested to play a role in stone formation. To our knowledge, no prospective information on the role of dietary factors and risk of kidney stone formation is available in younger women. We prospectively examined, during an 8-year period, the association between dietary factors and the risk of incident symptomatic kidney stones among 96 245 female participants in the Nurses' Health Study II; the participants were aged 27 to 44 years and had no history of kidney stones. Self-administered food frequency questionnaires were used to assess diet in 1991 and 1995. The main outcome measure was an incident symptomatic kidney stone. Cox proportional hazards regression models were used to adjust simultaneously for various risk factors. We documented 1223 incident symptomatic kidney stones during 685 973 person-years of follow-up. After adjusting for relevant risk factors, a higher dietary calcium intake was associated with a reduced risk of kidney stones (P =.007 for trend). The multivariate relative risk among women in the highest quintile of intake of dietary calcium compared with women in the lowest quintile was 0.73 (95% confidence interval, 0.59-0.90). Supplemental calcium intake was not associated with risk of stone formation. Phytate intake was associated with a reduced risk of stone formation. Compared with women in the lowest quintile of phytate intake, the relative risk for those in the highest quintile was 0.63 (95% confidence interval, 0.51-0.78). Other dietary factors showed the following relative risks (95% confidence intervals) among women in the highest quintile of intake compared with those in the lowest quintile: animal protein, 0.84 (0.68-1.04); fluid, 0.68 (0.56-0.83); and sucrose, 1.31 (1.07-1.60). The intakes of sodium, potassium, and magnesium were not independently associated with risk after adjusting for other dietary factors. A higher intake of dietary calcium decreases the risk of kidney stone formation in younger women, but supplemental calcium is not associated with risk. This study also suggests that some dietary risk factors may differ by age and sex. Finally, dietary phytate may be a new, important, and safe addition to our options for stone prevention.
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              Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle.

              Our purpose here is to test the hypothesis that Randall's plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non-stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non-stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated.

                Author and article information

                +39.0635034434 , giovanni.gambaro@unicatt.it
                J Nephrol
                J. Nephrol
                Journal of Nephrology
                Springer International Publishing (Cham )
                25 July 2016
                25 July 2016
                : 29
                : 6
                : 715-734
                [1 ]Department of Nephrology and Dialysis, A. Gemelli University Hospital, Catholic University of the Sacred Heart, Rome, Italy
                [2 ]A.S.L. 10, Florence, Italy
                [3 ]Department of Nephrology, University of Chicago Medicine, Chicago, USA
                [4 ]Department of Urology, Indiana University School of Medicine, Indianapolis, USA
                [5 ]Department of Internal Medicine, Southwestern Medical Center, University of Texas, Dallas, USA
                [6 ]Department of Urological Surgery, Sobeh’s Vascular and Medical Center, Dubai, UAE
                [7 ]Department of Nephrology, Medical Center, University of Rochester, Rochester, USA
                [8 ]Renal Division, Brigham and Women’s Hospital, Boston, USA
                [9 ]Department of Nephrology, University of Bern, Bern, Switzerland
                [10 ]Department of Nephrology, New York Harbor VA Health Care System, New York, USA
                [11 ]Department of Nephrology, Sao Paulo University, Sao Paulo, Brazil
                [12 ]Department of Internal Medicine and Nephrology, Klinik Im Park Hospital, Zurich, Switzerland
                [13 ]Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA
                [14 ]Department of Nephrology, A.S.O Ordine Mauriziano Hospital, Turin, Italy
                [15 ]Department of Nephrology, Mayo Clinic, Rochester, USA
                [16 ]Department of Urology, Duke University Medical Center, Durham, USA
                [17 ]Department of Urology, Catholic University of Portugal, Lisbon, Portugal
                [18 ]Southwestern Medical Center, Mineral Metabolism Research, University of Texas, Dallas, USA
                [19 ]Department of Urology, Dr. Lutfi KIRDAR Kartal Research and Training Hospital, Istanbul, Turkey
                [20 ]Department of Urology, University of Bonn, Bonn, Germany
                [21 ]Department of Internal Medicine, University of Naples, Naples, Italy
                [22 ]Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indiana, USA
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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