Urine and stone analysis for the investigation of the renal stone former: a consensus conference.

The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places.

A diagnostic-therapeutic pathway for patients with kidney stone disease: 2020 update / Percorso diagnostico-terapeutico per il paziente con calcolosi renale: update 2020

The natural history of urinary kidney stone disease includes the risk of relapses and can be associated with the risk of chronic kidney disease, bone and cardiovascular disease. For this reason, a wide clinical-metabolic assessment of the kidney stone patient is of great importance since the first presentation of the stone, to set an appropriate preventive treatment. The proposed diagnostic-therapeutic pathway includes a careful medical history, in order to highlight a secondary kidney stone disease and the main risk factors for kidney stones, chronic renal disease, or cardiovascular and bone disease; a metabolic evaluation on multiple levels, according to the severity of the disease, and the presence or absence of risk factors, and appropriate instrumental investigations. Thus, the information collected makes it possible to set a preventive treatment consisting of general rules and, if necessary, specific pharmacological or nutritional interventions. This paper has been prepared by the Italian Multidisciplinary Study Group for Kidney Stone Disease, and it is addressed to the several professional figures involved in the management of patients suffering from nephrolithiasis, from the emergency doctor to the general practitioner, urologist, nephrologist, radiologist, and dietician. A diagnostic-therapeutic pathway for patients with kidney stone disease was first published on this Journal in 2010. The present contribution aims at amending and updating the article published exactly ten years ago, to serve as an easy-to-use reference and to guide good clinical practice in this field.

Anthropometric variables, physical activity and dietary intakes of patients with uric acid nephrolithiasis.

To evaluate anthropometric variables, energy expenditure by physical activity and nutrient intake of uric acid stone formers (UA-RSFs) compared to non-forming subjects (C). The study included 33 consecutive male patients with a diagnosis of "pure" stones of anhydrous uric acid at infrared spectroscopy and 49 male control subjects with no history of urinary stones. A personal interview was conducted including questionnaires for physical activity and dietary intakes. Anthropometric parametric and blood pressure were measured. Mean age, weight, height, waist circumference, body mass index, systolic and diastolic blood pressure values, dietary energy, carbohydrate intake, lipid intake, dietary acid load, time spent for different physical activities and total energy expenditure for physical activity were not different in UA-RSFs with respect to C. Mean dietary protein (76.2 ± 19.6 vs 65.4 ± 14.7 g/day, P = 0.006) and ethanol intake (10.4 ± 8.8 vs 4.1 ± 8.6, P = 0.002) were higher in UA-RSFs than in C. History of renal disease, heart disease and treatment with thiazides or allopurinol were more frequent and mean serum glucose and triglycerides (104 ± 12 vs 97 ± 11 mg/dl, P = 0.043) (172 ± 77 vs 123 ± 52 mg/dl, P = 0.023) were higher in UA-RSFs. Metabolic syndrome was more frequent in UA-RSFs (57% vs 39%) but not significant (p = 0.09). Increased dietary animal protein (and ethanol) intake can act as co-factors for uric acid stone formation although a more complex and not fully elucidated metabolic background can have an even more crucial role in the pathogenesis of this disease even in the absence of overweight.

A preliminary survey of practice patterns across several European kidney stone centers and a call for action in developing shared practice.

Currently an evidence-based approach to nephrolithiasis is hampered by a lack of randomized controlled trials. Thus, there is a need for common platforms for data sharing and recruitment of patients to interventional studies. A first step in achieving this objective would be to share practice methods and protocols for subsequent standardization in what is still a heterogeneous clinical field. Here, we present the results of a pilot survey performed across 24 European clinical kidney stone centers. The survey was distributed by a voluntary online questionnaire circulated between June 2017 and January 2018. About 46% of centers reported seeing on average 20 or more patients per month. Only 21% adopted any formal referral criteria. Centers were relatively heterogeneous in respect of the definition of an incident stone event. The majority (71%) adopted a formal follow-up scheme; of these, 65% included a follow-up visit at 3 and 12 months, and 41% more than 12 months. In 79% of centers some kind of imaging was performed systematically. 75% of all centers performed laboratory analyses on blood samples at baseline and during follow-up. All centers performed laboratory analyses on 24-h urine samples, the majority (96%) at baseline and during follow-up. There was good correspondence across centers for analyses performed on 24-h urine samples, although the methods of 24-h urine collection and analysis were relatively heterogeneous. Our survey among 24 European stone centers highlights areas of homogeneity and heterogeneity that will be investigated further. Our aim is the creation of a European network of stone centers sharing practice patterns and hosting a common database for research and guidance in clinical care.

Defining metabolic activity of nephrolithiasis - Appropriate evaluation and follow-up of stone formers.

Considering the variation in metabolic evaluation and medical management of kidney stone disease, this consensus review was created to discuss the metabolic activity of nephrolithiasis, define the difference between single and recurrent stone formers, and develop a schema for metabolic and radiologic follow-up. A systematic review of the literature was performed to identify studies of metabolic evaluation and follow-up of patients with nephrolithiasis. Both single and recurrent stone formers share many similarities in metabolic profiles. The study group determined that based on an assessment of risk for stone recurrence and metabolic activity, single and recurrent stone formers should be evaluated comprehensively, including two 24 h urine studies on a random diet. Targeted medication and dietary recommendations are effective for many patients in reducing the risk of stone recurrence. Follow-up of those with stone disease should be obtained depending on the level of metabolic activity of the patient, the risk of chronic kidney disease and the risk of osteoporosis/osteopenia. A standard scheme includes a baseline metabolic profile, a repeat study 3-6 months after initiation of treatment, and then yearly when stable, with abdominal imaging obtained every 1-2 years.

The Risk of Chronic Kidney Disease Associated with Urolithiasis and its Urological Treatments: A Review.

PURPOSE: Urolithiasis can impair kidney function. This literature review focuses on the risk of kidney impairment in stone formers, the specific conditions associated with this risk and the impact of urological surgery. MATERIALS AND METHODS: The PubMed® and Embase® databases were searched for publications on urolithiasis, its treatment, and the risk of chronic kidney disease, end stage renal disease and nephrectomy in stone formers. RESULTS: In general, renal stone formers have twice the risk of chronic kidney disease or end stage renal disease, and for female and overweight stone formers the risk is even higher. Patients with frequent urinary tract infections, struvite stones, urinary malformations and diversions, malabsorptive bowel conditions and some monogenic disorders are at high risk for chronic kidney disease/end stage renal disease. Shock wave lithotripsy or minimally invasive urological interventions for stones do not adversely affect renal function. Declines in renal function generally occur in patients with preexisting chronic kidney disease or a large stone burden requiring repeated and/or complex surgery. CONCLUSIONS: Although the effect size is modest, urolithiasis may cause chronic kidney disease and, thus, it is mandatory to assess patients with renal stones for the risk of chronic kidney disease/end stage renal disease. We suggest that all guidelines dealing with renal stone disease should include assessment of this risk.

Obesity and urolithiasis: evidence of regional influences.

There is evidence that obese patients have an increased risk of renal stone formation, although this relationship could be less evident in some populations. The aim of this study was to evaluate the impact of overweight and obesity on the risk of renal stone formation in a population consuming a Mediterranean diet and to better elucidate the mechanisms underlying the increased risk of urolithiasis observed in obese subjects. We performed a retrospective review of 1698 stone forming patients (mean age 45.9 ± 14.6 years; 984/714 M/F), attending outpatient stone clinics in Milan and Florence, seen between January 1986 and June 2014. Records were reviewed and data collected pertaining to age, gender, weight, height, stone composition, association with diabetes type 2 or gout and metabolic profile of 24-h urine to perform a descriptive study. We estimated prevalence ratios for body mass index (BMI) categories (underweight: BMI <18.5, normal: BMI 18.5-24.9, overweight: BMI 25-29.9 and obese ≥30). Overweight and obesity were present in 40.7 and 8 % of the men and in 19.9 and 8.7 % of the women in the study population. The mean BMI of patients with urolithiasis was found to be 24.5 ± 7.5 kg/m2. BMI values were positively correlated with age (p = 0.000) and mean BMI was higher in males than in females (25.5 ± 8.9 vs 23.2 ± 4.4 kg/m2). In males, rates of overweight and obesity in renal stone formers were higher than the rates reported in the Italian general population in 2004 only for the age group 25-44 years, whereas males in all the other age groups and in females the rates of overweight and obesity in renal stone formers were similar to rates reported in the Italian general population. The rates of overweight and obesity were significantly different in patients with different chemical stone composition. In particular, patients with uric acid stones have rates of overweight and obesity higher than patients with calcium stones or other types of calculi. Also the rates of type 2 diabetes and gout were greater in patients with overweight and obesity. In overweight and obese patients, the urinary excretion of risk factors for stone formation, such as calcium, oxalate and urate, and also of inhibitory substances, such as citrate, were significantly higher than in patients with normal weight or underweight. The prevalence of overweight and obesity in patients with urinary calculi from a country consuming a Mediterranean diet is not higher than in the general population. It should be taken into account that not all the dietary patterns that are associated with obesity may involve a parallel increase in the risk of forming kidney stones and that epidemiological findings from one country could not be confirmed in other countries with different climatic, socioeconomic and cultural features.

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

BACKGROUND: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Decreased transcriptional activity of calcium-sensing receptor gene promoter 1 is associated with calcium nephrolithiasis.

BACKGROUND: CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis. AIMS: We tested SNPs in the CaSR gene regulatory region associated with calcium nephrolithiasis and their effects in kidney. SUBJECTS AND METHODS: One hundred sixty-seven idiopathic calcium stone formers and 214 healthy controls were genotyped for four CaSR gene SNPs identified by bioinformatics analysis as modifying transcription factor binding sites. Strontium excretion after an oral load was tested in 55 stone formers. Transcriptional activity induced by variant alleles at CaSR gene promoters was compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney medulla samples and compared in patients with different CaSR genotype. RESULTS: Only rs6776158 (A>G), located in the promoter 1, was associated with nephrolithiasis. Its minor G allele was more frequent in stone formers than controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed in GG homozygous stone formers. Luciferase fluorescent activity was lower in cells transfected with the promoter 1 including G allele at rs6776158 than cells transfected with the A allele. CaSR mRNA levels were lower in kidney medulla samples from homozygous carriers for the G allele at rs6776158 than carriers for the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects. CONCLUSIONS: Minor allele at rs6776158 may predispose to calcium stones by decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR expression in kidney tubules.

Prevalence of renal stones in an Italian urban population: a general practice-based study.

Kidney stones represent a common condition characterized by significant morbidity and economic costs. The epidemiology of kidney stones is not completely understood and may vary substantially based on geographic, socioeconomic and clinical factors; the present study aims at defining the prevalence and diagnostic patterns of kidney stones in a cohort representative of the general population in Florence, Italy. A sample of 1,543 adult subjects, all Caucasians, was randomly selected from a population of over 25,000 subjects followed by 22 general practitioners (GPs). Subjects were administered a questionnaire requesting the patient's age and sex, any history of kidney stones and/or colics and the prescription of kidney ultrasound (US) examination. GPs data-bases were also interrogated. Crude and adjusted prevalence proportions and ratios (PRs) with corresponding 95% confidence intervals (CIs) were computed. Furthermore, the association between the practice pattern of each physician with respect to US prescription and the prevalence of kidney stones was investigated. The overall prevalence of kidney stones was 7.5% (95% confidence interval 6.2, 8.9%), increasing with age until 55-60 years and then decreasing. About 50% reported recurrent disease. There were no significant differences in prevalence among males and females. GPs who tended to prescribe more US examinations were more likely to have more patients with kidney stones (adjusted PR 1.80, 95% CI 1.11, 2.94; p = 0.020). The present study confirms both the high prevalence and the regional variability of kidney stones. Practice patterns may be involved in such variability.

[Diagnostic and therapeutic approach in patients with urinary calculi]. / Percorso diagnostico-terapeutico per il paziente con calcolosi urinaria.

The natural history of urolithiasis includes the risk of recurrence and of the development of chronic kidney and/or bone disease, which is why a thorough clinical and metabolic evaluation of these patients is of the utmost importance at disease onset. This paper is aimed at identifying the type of urolithiasis, the related risk factors, and the corresponding treatment options. The diagnostic and therapeutic approach described here includes 1) accurate history taking to detect secondary nephrolithiasis and screen for the main risk factors for kidney and bone disease; 2) metabolic evaluation graded according to different complexity levels based on the severity of the disease and the presence of risk factors; 3) carrying out appropriate imaging procedures. The resulting information allows to plan treatment based either on general rules of lifestyle and diet, or on selected medical intervention, if necessary. This report, which is based on current guidelines, was produced by the Gruppo Italiano di Studio Multidisciplinare per la Calcolosi Renale. It is addressed to all professionals involved in the management of patients suffering from nephrolithiasis, first of all general practitioners, who often become involved immediately at the onset of the disease.

Idiopathic hypercalciuria and calcium renal stone disease: our cases.

Renal idiopathic stone disease affects about 8% of the Italian population. The most common form in western countries (70- 80% of the cases) is calcium nephrolithiasis, with stones formed mainly by calcium oxalate and phosphate. One of the main metabolic anomalies that is often associated with calcium nephrolithiasis is hypercalciuria. Primary hypercalciuria is a metabolic defect characterized by an increased renal calcium excretion. This metabolic alteration is present in the general population with a frequency of 5-10%, but can reach 45-50% in subjects affected by nephrolithiasis. We studied 149 patients affected by idiopathic calcium nephrolithiasis.The aim of the present study was to evaluate the association between familiarity for nephrolithiasis and hypercalciuria in this population of patients.

Biochemical evaluation in renal stone disease.

Renal stone disease may ensue from either derangements of urine biochemistries or anatomic abnormalities of kidneys and urinary tract. Genetic, environmental and dietary factors may also cooperate in the pathophysiology of nephrolithiasis. An adequate metabolic evaluation should focus on the urinary excretion of promoters and inhibitors of stone formation as well as on the occurrence of systemic diseases potentially related to secondary nephrolithiasis (i.e., endocrine disturbances, malabsorption, bone diseases). Moreover, metabolic investigations should provide reliable information on patient's dietary habits, guide towards the best therapeutic approach and enable the physician to verify patient's compliance to prescribed therapies.AN EXTENSIVE METABOLIC EVALUATION IS RECOMMENDED IN PATIENTS WITH ACTIVE STONE DISEASE (NAMELY, AT LEAST ONE NEW STONE WITHIN THE LAST TWO YEARS), OR IN THOSE HAVING HAD A SINGLE STONE EPISODE OCCURRED IN PECULIAR CONDITIONS: familial history of disease, childhood, menopause, pregnancy, systemic diseases. Simplified protocols may be adequate in non-active nephrolithiasis or in patients with single stone and no relevant risk factors.In our Stone Centre, a so-called "first level screening" is performed by routine, in order to assess urinary supersaturation with stone forming salts and evaluate the excretion of dietary-related metabolites in urine. Relative blood and urine determinations are reported below.IN VENOUS BLOOD: urea, creatinine, uric acid, Na, K, total and ionised Ca, Mg, P, Cl, alkaline phosphatase, gas analysis. In 24-hr urine samples: urea, creatinine, uric acid, Na, K, Ca, Mg, P, Cl, oxalate, inorganic sulphate, citrate, pH, ammonia and titratable acidity. IN FASTING URINE SAMPLES: Ca, citrate, creatinine, hydroxyproline, Brand's test for cistinuria, urine sediment, urine culture. If the first-level evaluation suggested an abnormal bone turnover, then further determinations are warranted, namely, calciotropic hormones (blood Vitamin D and PTH), markers of bone resorption (urine pyridinium crosslinks, serum crosslaps) and formation (serum osteocalcin) bone mineral density.EVENTUALLY, MORE SOPHISTICATED INVESTIGATIONS ARE REQUIRED TO IMPROVE THE DIAGNOSIS OF PECULIAR DISEASES: serum oxalate and glycolate, urine glycolate and L-glycerate, hepatic AGT activity (primary hyperoxalurias); genetic tests (hereditary nephrolithiasis); acidification tests (renal tubular acidosis).

The general practitioner and nephrolithiasis.

Nephrolithiasis is a multifactorial disease the genesis of which is influenced by genetic, metabolic and environmental factors which determine a series of alterations in the urinary excretion of a number of substances, the cause of the disease itself. The general practitioner is often the first professional to be consulted as regards clinical and therapeutic treatment at the moment of the onset of nephrolithiasis, renal colic, inasmuch as contacted directly by the patient. His role however should not be limited to this initial phase but becomes of strategic importance throughout the subsequent diagnostic procedure; this is especially true with regard to relapses, in correctly placing the patient and, if necessary, referring him/her to the most appropriate specialist area. Running through the entire process which the lithiasic patient encounters from the onset of the disease until therapeutic treatment begins, it is clear how an appropriate initial approach can, in many cases, simplify and optimise such process. On the basis therefore of a complete medical record, and a few simple, biochemical and instrumental tests, the general practitioner is in a position to decide whether to treat the patient directly or to refer him/her to the most appropriate specialist field for investigation at a higher level.Over the last decades nephrolithiasis has progressively changed from being a disease of mainly surgical pertinence to being one of multidisciplinary medical interest in which the figure of the General Practitioner has a primary role, both during the initial diagnostic phase, by means of the correct physio-pathological identification of the problem, and in the subsequent phases as regards the choice and co-ordination of the various specialists involved.