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Metabolic risk-evaluation and prevention of recurrence in stone disease: does it make sense?

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In this review, aspects on the importance of information on urine composition and selection of the most appropriate regimen for prevention of recurrence are discussed. For patients with urolithiasis the treatment is facilitated by urine analysis with estimates of supersaturation levels. Despite lack of strong scientific evidence for the benefit of selective versus non-selective prevention of recurrence in patients with calcium stone disease, there is currently both convincing and logical information in support of tailored/selective treatment regimens aiming at correction of abnormal target variables. Such an approach is also recommended in the EAU and AUA guidelines. It is important, however, that every preventive regimen is balanced between the effects on urine composition and patients' tolerance to the treatment in order to achieve satisfactory compliance. It is possible that future improved understanding of the causes of calcium stone formation might provide a different therapeutic approach.
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Urolithiasis (2016) 44:91–100
DOI 10.1007/s00240-015-0840-y
Metabolic risk‑evaluation and prevention of recurrence in stone
disease: does it make sense?
Hans‑Göran Tiselius1
Received: 8 June 2015 / Accepted: 5 November 2015 / Published online: 27 November 2015
© Springer-Verlag Berlin Heidelberg 2015
For the medical and metabolic care of patients with uro-
lithiasis, there are two essential questions that immediately
seek an answer. Is prevention of recurrence at all possi-
ble and of value and if so, does prevention of recurrence
require metabolic risk-evaluation?
Before addressing this issue in detail, it is necessary to
know that the risk of recurrent stone formation varies con-
siderably between patients. It has accordingly been shown
that without preventive treatment the recurrence risk for
patients with cystinuria is around 85 % [1]. For infection
and uric acid stone forming patients, despite lack of spe-
cific information, it can be assumed that the recurrence risk
also is very high and probably at similar or even higher
A more variable response to preventive treatment has
been recorded and can be expected in patients who have
formed stones composed of calcium salts; calcium oxa-
late and calcium phosphate. In these patients the average
recurrence risk after 10 years is around 50 % [2, 3] (Fig. 1).
Patients forming brushite stones (calcium hydrogen phos-
phate) have a particularly high recurrence risk as high as
70 % [3, 4]. But for the other calcium stone patients it
stands to reason that while some will only form one stone
during their life-time others are afflicted by a more severe
disease with repeated stone formation and repeated need of
active stone removing interventions. When patients, who
had formed their first and only stone (S), were compared
with those who had formed at least two stones (R) at the
start of follow-up, two different courses were recorded
(Fig. 1). For S-patients less than 30 % have formed one
or several new stones after 10 years. This should be com-
pared with a 10-year recurrence risk of almost 70 % for
R-patients. It thus seems reasonable to assume that whereas
Abstract In this review, aspects on the importance of
information on urine composition and selection of the
most appropriate regimen for prevention of recurrence are
discussed. For patients with urolithiasis the treatment is
facilitated by urine analysis with estimates of supersatura-
tion levels. Despite lack of strong scientific evidence for
the benefit of selective versus non-selective prevention of
recurrence in patients with calcium stone disease, there is
currently both convincing and logical information in sup-
port of tailored/selective treatment regimens aiming at
correction of abnormal target variables. Such an approach
is also recommended in the EAU and AUA guidelines. It
is important, however, that every preventive regimen is
balanced between the effects on urine composition and
patients’ tolerance to the treatment in order to achieve sat-
isfactory compliance. It is possible that future improved
understanding of the causes of calcium stone formation
might provide a different therapeutic approach.
Keywords Calcium stones · Non-calcium stones · Stone
analysis · Serum analysis · Urine analysis · Risk factors ·
Supersaturation · Prevention of recurrence · Dietary
advice · Drinking advice · Pharmacological treatment ·
Selective treatment · Non-selective treatment
* Hans-Göran Tiselius;
1 Division of Urology, Department of Clinical Science,
Intervention and Technology (CLINTEC), Karolinska
Institutet, Stockholm, Sweden
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... The prevalence of urinary stone disease is estimated to be nearly 5% in Germany and 10% in the United States [3,4]. Despite the availability of excellent treatment modalities, the recurrence rate of urinary stones is reported to be up to 50% after 10 years [3,5]. Exact compositional stone analysis is the most important laboratory diagnostic procedure and a crucial prerequisite for an effective treatment and recurrence prevention of urolithiasis [6][7][8]. ...
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Purpose Stone composition can provide valuable information for the diagnosis, treatment and recurrence prevention of urolithiasis. The aim of this study was to evaluate the distribution of urinary stone components and the impact of different crystal forms according to gender and age of patients in Germany. Methods A total of 45,783 urinary stones submitted from 32,512 men and 13,271 women between January 2007 and December 2020 were analyzed by infrared spectroscopy. Only the first calculus obtained per patient was included in the analysis. Results The most common main stone component was calcium oxalate (CaOx) (71.4%), followed by carbonate apatite (CA) (10.2%) and uric acid (UA) (8.3%). Struvite (2.1%), brushite (1.3%), protein (0.5%) and cystine (0.4%) stones were only rarely diagnosed. CaOx (75%) and UA stones (81%) were more frequently obtained from men than women ( p < 0.001). Weddellite (COD) and uric acid dihydrate (UAD) were more common in younger ages than whewellite (COM) and anhydrous uric acid (UAA), respectively, in both men and women. The ratios of COM-to-COD and UAA-to-UAD calculi were approximately 4:1 and 8:1, respectively. The peak of stone occurrence was between the ages of 40 and 59 years. Conclusion Stone composition is strongly associated with gender and age. The peak incidence of calculi in both women and men was in the most active phase of their working life. The distinction between different crystal forms could provide clues to the activity and mechanisms of lithogenesis. Further research is needed in understanding the causative factors and the process of stone formation.
... In 2013, Medicare and private insurers spent over $805 million on services related to the treatment of kidney stones [2]. Moreover, stone disease can be a chronic issue as 50-85% of first-time stone formers will have a second episode [3,4]. With such wide-spread burden also comes significant cost. ...
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Emergency department (ED) visits and hospital admissions (HA) following urologic procedures are a concern for payors, providers, and patients. We seek to quantify ED visits and HA after urologic stone procedures. This is a retrospective cohort study using claims data from the IBM MarketScan Commercial and Medicare Supplement database. Adults with a urologic stone diagnosis and no history of stone procedure in prior 12 months who underwent stone procedures with ureteral stent codes between 2012 and 2017 were included. All-cause vs genitourinary (GU)-related ED visits and HA were evaluated during 30, 60, 90, and 120-day periods following the index urologic stone procedure. 88,047 patients were included in the analytic cohort. For inpatients, rate of all-cause vs GU-related ED visits was 10% vs 9% at 30 days and 19% vs 15% at 120 days. For outpatients, rate of all-cause vs GU-related ED visits was 9% vs 8% at 30 days and 15% vs 12% at 120 days. A similar trend was found when examining HA. Younger patients (18–44 years old) had higher rates of all-cause ED visits following inpatient index stone procedure (13% vs 10% at 30 days, p ≤ 0.0001). Twenty percent of patients have an ED visit or HA up to 120 days after having a stone procedure with most returning with GU-related complaint. Younger patients had the greatest burden among the study cohort. Further studies need to determine causation of these unplanned visits to guide appropriate intervention.
... The prevalence of urinary stones was reported to be 5% in Germany and 10% in the United States [5,6]. The stone recurrence rate, which was estimated to be around 50% after 10 years, is alarmingly high [7,8]. Low urine volume is a major risk factor for kidney stone formation [9]. ...
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Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.
... Kidney stone disease has a high prevalence, incidence, and recurrence rate in the recent decade [5,6]. Because the disease and its recurrence cause a high burden [7], prevention is of utmost importance in this condition [8]. The main target of preventive recommendations is to modify dietary habits and reduce lifestyle risk factors [9]. ...
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Background The dietary habits and lifestyle changes during the COVID-19 pandemic could affect the urinary risk factors in kidney stone formers. In this study, we investigated the effects of the COVID-19 pandemic on 24-h urine metabolites, as a surrogate for dietary intake, in patients with kidney stones, in Tehran, Iran. Methods We evaluated the medical records of all patients with urolithiasis who visited in our stone prevention clinic from the beginning of COVID-19 in Iran to 1 year later (Feb 2020–Feb 2021) and compared it with the patients’ medical records in the same period a year before COVID-19 (Feb 2019–Feb 2020). Results The results of our stone prevention clinic showed a decrease in the number of visits during COVID-19. Twenty-four-hour urine urea, sodium, and potassium were significantly lower, and 24-h urine magnesium was significantly higher during COVID-19. Higher 24-h urine oxalate was only shown in patients with the first-time visit, whereas lower 24-h urine uric acid and citrate were only shown in patients with the follow-up visits. Conclusions COVID-19 pandemics may change some of the dietary habits of the patients, including lower salt, protein, and fruit and vegetable intake. Although economic issues, restricted access, or sanitation issues may be the reason for the undesirable dietary changes, the importance of a quality diet should be discussed with all patients, as possible. Since the number of patients visited in the stone clinic was lower during COVID-19, virtual visits could be an excellent alternative to motivate patients with kidney stones.
b> Introduction: The aim of the study was to survey current practices for preventing recurrent stone disease in an outpatient clinic setting in Germany. Methods: Two invitations to complete an anonymous REDCap® survey were emailed to members of the occupational union of German urologists who work as outpatient urologists (“Berufsverband Deutscher Urologen e.V.”). The survey included questions on diagnostic modalities and counselling to prevent stone disease. Results: A total of 130 outpatient urologists completed the survey. 84.6% of urologists give general advice to first-time stone formers. Recommendations comprise increased fluid uptake in 100%, two-thirds advice on calcium and oxalate intake, and one-third on salt and protein intake. 64.6% perform a metabolic evaluation for high-risk stone formers. However, patients with risk factors other than repeat stone disease are often overlooked. Urologists agreed that a lack of time (73.1%) and reimbursement (64.6%), as well as insufficient patient compliance (60.8%), pose significant challenges. The majority of urologists agreed that training is required. Conclusion: General recommendations for stone formers are usually provided, but nutritional advice tends to be incomplete. Our results raise quality-of-care concerns: Metabolic evaluation of stone formers at high risk of recurrence is uncommon. Structural changes are required due to time constraints, and poor remuneration must be addressed to improve patient care.
Kidney stones arise from a confluence of multiple factors (genetic predisposition, diet, lifestyle and environmental factors). Calcium stones (calcium oxalate, or less commonly calcium phosphate) are the most common type, representing 85% of all cases. The dietary measures to prevent recurrence of calcium oxalate stones are (1) increasing fluid consumption (> 3 L per day); (2) increasing calcium intake to 1200 mg/day; and (3) a balanced acid/base ratio (meat protein vs. alkaline-rich foods). The same measures apply to a much greater extent in the cases of calcium oxalate stones seen with increasing frequency after bariatric surgery (functional short bowel syndrome). Thiazide and thiazide-like diuretics (with a 48% reduction in the rate of kidney stone recurrence), as well as alkaline citrate (75% reduction in the recurrence rate), are suitable drugs to prevent recurrence of calcium kidney stone disease. Kidney stone disease is associated with reduced tubular secretion of H+ ions, due to distal renal tubular acidosis, in 15% of all kidney stone patients (24% of female patients, 11% of males). This is associated with more active kidney stone disease and increased renal parenchymal calcification, and requires lifelong alkali treatment. Conversely, uric acid stones result almost always from excessive urine acidity, because undissociated uric acid with its very low solubility predominates in acidic urine (pH value < 5.3). Highly acidic urine is a result of reduced renal ammonium excretion in the presence of renal tubular insulin resistance, which is often seen in patients with type 2 diabetes and metabolic syndrome. The treatment consists of persistent alkalisation of the urine to pH values around 6.5, supplemented in certain cases by the use of pioglitazone to increase insulin sensitivity.
The purpose of this study in a small group of non-stone-forming Chinese persons was to measure the levels of supersaturation with calcium oxalate and calcium phosphate and pH with the aim of confirming if any of the different short-term urine samples were better for risk evaluation than a 24-h sample. Nine normal men and 1 woman collected urine during 4 periods of the day. Period 1 between 08 and 12 h, Period 2 between 12 and 18 h, Period 3 between 18 and 22 h, and Period 4 between 22 and 08 h. Each sample was analysed for calcium, oxalate, citrate, magnesium and phosphate, and estimates of supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP) were expressed in terms of AP(CaOx) and AP(CaP) index. An estimate of the solute load of CaOx was also calculated. Urine composition for 24-h urine (Period 24) was obtained mathematically from the analysed variables. Urine composition corresponding to 14-h urine portions 22-12 h (Period 14N) and 08-22 h (Period 14 D) were calculated. The lowest pH levels were recorded in Period 1 urine. The highest level of AP(CaOx) index was recorded during Period 1, and the product AP(CaOx) index × 107 × hydrogen ion concentration was significantly higher in Period 1 urine than in 24-h urine (p = 0.02). Also, the product SL(CaOx) × 107 × hydrogen ion concentration was significantly higher in Period 1 urine (p = 0.02). Low AP (CaP) index levels were recorded in Period 4, but also in all periods following dietary loads of calcium and phosphate. With the important reservation that the analytical results were obtained from non-stone-forming persons, the conclusion is that analysis of urine samples collected between 08 and 12 h might be an alternative to 24-h urine. The risk evaluation might advantageously be expressed either in terms of the product AP(CaOx) index × 107 × hydrogen ion concentration or the product SL(CaOx) × 107 × hydrogen ion concentration.
Nierensteine entstehen multifaktoriell (genetische Prädisposition, Ernährung, Lebensstil und Umweltfaktoren). Kalziumsteine (Kalziumoxalat, seltener Kalziumphosphat) sind mit 85 % aller Fälle die häufigste Steinart. Ernährungstechnischen Massnahmen zur Rezidivprophylaxe beim Kalziumoxalatsteinleiden sind 1) Steigerung der Trinkmenge (>3 l pro Tag); 2) Steigerung der Kalziumzufuhr auf 1200 mg/Tag und 3) ausgewogenes Säure-Basen-Verhältnis (Fleischprotein vs. alkalihaltige Nahrungsmittel). In deutlich übersteigertem Ausmass gelten die gleichen Massnahmen beim sich häufenden Kalziumoxalatsteinleiden nach bariatrischer Chirurgie (funktionelles Kurzdarmsyndrom). Zur medikamentösen Rezidivprophylaxe beim Kalziumnierensteinleiden eignen sich Thiazid- und thiazidähnliche Diuretika (Reduktion Steinrezidivrate 48 %) oder Alkalizitrat (Reduktion Steinrezidivrate 75 %). Das Nierensteinleiden ist in 15 % aller Steinpatienten (24 % bei Frauen, 11 % bei Männern) mit einer verminderten tubulären Sekretion von H+-Ionen wegen distaler renal-tubulärer Azidose assoziiert. Diese ist mit einem aktiveren Steinleiden und vermehrten renalen Parenchymverkalkungen vergesellschaftet und bedingt eine lebenslängliche Alkalitherapie. Umgekehrt ist das Harnsäuresteinleiden fast immer Folge eine überhöhten Urinazidität, weil in sauren Urinen (pH-Werte <5,3) überwiegend die sehr schlecht lösliche nichtdissoziierte Harnsäure vorliegt. Die hohe Urinazidität ist Folge einer verminderten renalen Ammoniumausscheidung bei renal-tubulärer Insulinresistenz, wie sie v. a. bei Patienten mit Typ-2-Diabetes und metabolischem Syndrom oft vorkommt. Die Therapie besteht in einer konsequenten Alkalisierung des Urins auf pH-Werte um 6,5, in ausgewählten Fällen ergänzt durch das die Insulinsensitivität steigernde Pioglitazon.
Resumen La litiasis renal es una patología frecuente, constituyendo un importante problema de salud que se asocia, además, con una gran carga económica. La naturaleza de la litiasis varía según factores dietéticos, climáticos y de estilo de vida, entre otros. La mayoría de los pacientes sufrirá un nuevo episodio litiásico en algún momento de su vida, a menos que se pongan en marcha medidas preventivas para evitarlo, cambiando estilos de vida y hábitos dietéticos. Para reducir las recidivas se deben evaluar los factores de riesgo implicados en la litogénesis. El tipo de evaluación dependerá de la composición de los cálculos y de su forma de presentación clínica. Con estos estudios se pueden diagnosticar enfermedades sistémicas y renales de carácter litogénico y permiten adoptar medidas profilácticas precisas que consiguen el control de la recidiva en un gran número de pacientes.
Crystalluria is a frequent finding in the routine examination of urine sediments. In most instances the precipitation of crystals of calcium oxalate, uric acid, triple phosphate, calcium phosphate and amorphous phosphates or urates is caused by transient supersaturation of the urine, ingestion of foods, or by changes of urine temperature and/or pH which occur upon standing after micturition. In a minority of cases, however, crystalluria is associated with pathological conditions such as urolithiasis, acute uric acid nephropathy, ethylene glycol poisoning, hypereosinophilic syndrome. In addition, crystalluria can be due to drugs such as sulphadiazine, acyclovir, triamterene, piridoxylate, primidone, which under the influence of various factors can crystallize within the tubular lumina and cause renal damage. In all these instances the study of crystalluria is diagnostically useful and is also important to follow the course of the disease. However, a proper methodological approach is necessary. This includes the handling of freshly voided urine, the knowledge of the urinary pH, and the use of a contrast phase microscope equipped with polarizing filters.
Although methods of urinary stone removal are becoming evermore effective, the prevalence of urolithiasis is continuously increasing. Epidemiological studies show that 5-10% of the population suffer from urinary stones. Stone removal alone is not a curative measure. Depending on the stone composition, a recurrence rate of 60-100% must be expected. Hence, analysis of the stone material and basic diagnosis of the metabolic origins of urolithiasis are imperative, as well as consistent recurrence prevention in high-risk patients. This revised and updated handbook meets these requirements. It is designed to assist clinicians and healthcare professionals by guiding them through the appropriate diagnostic examinations and the development of effective and safe plans for treatment and prevention. It takes the newest international and European guidelines for urinary stone therapy into account, and includes the latest findings in clinical and laboratory diagnosis, dietary therapy and medication. Furthermore, it offers specific solutions for the treatment of children. Its clear organization makes it a valuable and indispensable reference book, especially for urologists, nephrologists and pediatricians.
An optimum metabolic evaluation strategy for urinary stone patients has not been clearly defined. To evaluate the optimum strategy for metabolic stone evaluation and management to prevent recurrent urinary stones. Several databases were searched to identify studies on the metabolic evaluation and prevention of stone recurrence in urolithiasis patients. Special interest was given to the level of evidence in the existing literature. Reliable stone analysis and basic metabolic evaluation are highly recommended in all patients after stone passage (grade A). Every patient should be assigned to a low- or high-risk group for stone formation. It is highly recommended that low-risk stone formers follow general fluid and nutritional intake guidelines, as well as lifestyle-related preventative measures to reduce stone recurrences (grade A). High-risk stone formers should undergo specific metabolic evaluation with 24-h urine collection (grade A). More specifically, there is strong evidence to recommend pharmacological treatment of calcium oxalate stones in patients with specific abnormalities in urine composition (grades A and B). Treatment of calcium phosphate stones using thiazides is only highly recommended when hypercalciuria is present (grade A). In the presence of renal tubular acidosis (RTA), potassium citrate and/or thiazide are highly recommended based on the relative urinary risk factor (grade A or B). Recommendations for therapeutic measures for the remaining stone types are based on low evidence (grade C or B following panel consensus). Diagnostic and therapeutic algorithms are presented for all stone types based on the best level of existing evidence. Metabolic stone evaluation is highly recommended to prevent stone recurrences. In this report, we looked at how patients with urolithiasis should be evaluated and treated in order to prevent new stone formation. Stone type determination and specific blood and urine analysis are needed to guide patient treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.