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The aim of this study was to construct the fourth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the metabolic evaluation, prevention, and follow-up of patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of the literature in the PubMed database from January 1976 to June 2022. Each generated recommendation was graded using a modified GRADE methodology. Guideline recommendations were developed that addressed the following topics: initial evaluation, metabolic testing, dietary measures, medical management, and follow-up of recurrent stone formers. It was emphasized by the Panel that prevention of new stone formation is as important as the surgical removal of the stones. Although general preventive measures may be effective in reducing stone recurrence rates in some patients, specific medical and dietary management should be well considered and eventually applied in an individualized manner based on the outcomes of metabolic work-up, stone analysis and some certain patient related factors. A detailed follow-up of each case is essential depending on the metabolic activity of each individual patient., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: One limitation of the use of 24-hour collection is impracticality. We analysed the performance of spot urine measurements to estimate 24-hour excretion in patients with kidney stones., Methods: A total of 74 adult patients from two centres performed a 24-hour urine collection. A sample of the last micturition was sent for spot urine analysis. Twenty patients were asked to collect two additional spot urine samples, one before dinner and the other after dinner. Urinary concentrations of creatinine, calcium, oxalate, uric acid, citrate and magnesium were measured in the 24-hour and each of the spot urine samples. Four approaches were used to estimate 24-hour urinary excretion, multiplying the ratio of the spot urinary analyte to creatinine concentration by (i) measured 24-hour urinary creatinine excretion (Prediction 1), (ii) estimated 24-hour urinary creatinine excretion (Prediction 2), (iii) assumed 1-g 24-hour urinary creatinine excretion (Prediction 3) or (iv) assumed 1.5-g 24-hour urinary creatinine excretion (Prediction 4). For each parameter we computed Lin's concordance correlation coefficients (CCCs), Bland-Altman plots and 95% limits of agreement., Results: The performance of estimates obtained with Prediction 1 and Prediction 2 was similar, except for citrate and uric acid, for which Prediction 2 performed worse. Both approaches performed moderately well: citrate CCC {0.82 [95% confidence interval (CI) 0.75-0.90]}, oxalate [0.66 (95% CI 0.55-0.78)], magnesium [0.66 (95% CI 0.54-0.77)], calcium [0.63 (95% CI 0.50-0.75)] and uric acid [0.52 (95% CI 0.36-0.68)]. The performance of Predictions 3 and 4 was worse., Conclusions: Although spot urine samples may hold promise for clinical and population-based research, at present they have limited utility in clinical practice. Measuring or estimating 24-hour creatinine, rather than assuming a given creatinine excretion, will be necessary in future studies of spot urine samples., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Estimation of state of saturation with stone-forming salt represents a reliable tool to assess the overall risk. The available methods are based on computer-assisted ab initio calculations. Our earlier method URSUS was subsequently substituted by Lithorisk®, a software including visualization of risk profiles. Unfortunately, Lithorisk does not adapt to new versions of Windows® and Macintosh® Apple, neither runs on smartphones or tablets. We propose a novel version of the software which can be directly used online on any device equipped by different operating systems. Upon online connection and after registration, the software is ready for unlimited accesses, in either Italian, English or French. After digiting input variables (urea and creatinine also included) in a fixed dashboard, state of saturation is promptly given. In addition to state of saturation (ß) with calcium oxalate, brushite and uric acid, ß struvite and cystine are available. Both input variables and ß results are graphically depicted as green or red horizontal bars to indicate recommended values. The software was implemented with equations allowing to omit sulphate and ammonium excretion for users with difficult access to these measurements. This simplified version, tested for ßCaOx and ßBsh on 100 urine samples showed close correlation with the full version. The software gives a list of total and free concentrations and soluble complex species distribution. Results can be printed or saved as PDF. So, we propose an easily accessible software to estimate state of saturation usable on any operating system and personal device.

Background : Metabolic and physicochemical evaluation is recommended to manage the condition of patients with nephrolithiasis. The estimation of the saturation state (β values) is often included in the diagnostic work-up, and it is preferably performed through calculations. The free concentrations of constituent ions are estimated by considering the main ionic soluble complexes. It is contended that this approach is liable to an overestimation of β values because some complexes may be overlooked. A recent report found that β values could be significantly lowered upon the addition of new and so far neglected complexes, [Ca(PO 4 )Cit] 4- and [Ca 2 H 2 (PO 4 ) 2 ]. The aim of this work was to assess whether these complexes can be relevant to explaining the chemistry of urine. Methods: The Ca-phosphate-citrate aqueous system was investigated by potentiometric titrations. The stability constants of the parent binary complexes [Cacit] - and [CaPO 4 ] - , and the coordination tendency of PO 4 3- toward [Ca(cit)] - to form the ternary complex, were estimated. β CaOx and β CaHPO4 were then calculated on 5 natural urines by chemical models, including or not including the [CaPO 4 ] - and [Ca(PO 4 )cit] 4- species. Results: Species distribution diagrams show that the [Ca(PO 4 )cit] 4- species was only noticeable at pH > 8.5 and below 10% of the total calcium. β values estimated on natural urine were slightly lowered by the formation of [CaPO 4 ] - species, whereas [Ca(PO 4 )cit] 4- results were irrelevant. Conclusions: While [CaPO 4 ] - species have an impact on saturation levels at higher pHs, the existence of ternary complex and of the dimer is rejected.

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.

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) 2 D 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 (pX 2  = 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.

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., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Introduction: In this paper we investigated whether cholecalciferol supplementation, prescribed to treat vitamin D deficiency in patients with nephrolithiasis, increased the risk of stone recurrence., Methods: Calcium excretion and urine supersaturation with calcium oxalate (βCaOx) and brushite (βbsh) were evaluated in 33 kidney stone formers (aged 56±17; 12 males), both before and after therapy with cholecalciferol, prescribed as oral bolus of 100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000-10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a dietary regimen which included a daily calcium intake of about 800-1000 mg., Results: Urinary nitrogen, sodium and ash-acid excretion did not significantly change during the study. After cholecalciferol supplementation, the main results were as follows: both serum calcium and phosphate did not vary significantly; 25(OH)VitD₃ increased from 11,8±5,5 to 40,2±12,2 ng/mL (p<0,01); 1,25(OH) ₂ VitD₃ increased from 41,6±17,6 to 54,0±16,0 pg/mL (p<0,01); PTH decreased from 75,0±27,2 to 56,7±21,1 pg/mL (p<0,01); daily urinary calcium increased from 2,7±1,5 to 3,6±1,6 mg/Kg b.w. (p<0,01), whereas fasting urinary calcium did not change significantly. After therapy, βbsh increased from 0,9±0,7 to 1,3±1,3 (p=0,02) and βCaOx did not vary significantly. Before cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric, whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation (pX²=0,03)., Conclusions: Cholecalciferol supplementation for vitamin D deficiency may increase both urinary calcium and urine supersaturation in stone formers. If vitamin D supplements are needed in these patients, a careful monitoring of urine metabolic profile is warranted, in order to customize the metaphylaxis accordingly (hydration, potassium citrate, thiazides)., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Objective: This study evaluated the role of body mass index (BMI) and dietary potential renal acid load (PRAL) with urinary saturation for calcium oxalate (US-CaOx), calcium phosphate (US-CaP) and uric acid (US-UA) in renal stone formers., Materials and Methods: A retrospective analysis was conducted of laboratory data collected on 442 renal stone-forming patients. Demographic information, BMI and 24 h urinary samples were collected from patients on their regular diets. PRAL was calculated as the Load of Acid to Kidney Evaluation (LAKE) score through a short questionnaire., Results: Urinary risk factors, but also inhibitors of calcium stone formation such as magnesium, tended to increase in relation to BMI (p = .000). Urinary pH (p = .002) and ammonium/sulfate ratio (p = .000) were negatively related to BMI. This resulted in a positive correlation between BMI and US-UA (p = .000), whereas US-CaOx and US-CaP were not influenced by BMI. LAKE score was positively correlated with US-CaOx (p = .022) and US-CaP (p = .000) as a consequence of the inverse relationship between LAKE score and citrate (p = .000). Multiple linear regression analysis identified BMI (p = .009) and male gender (p = .002) as independent predictors of US-UA, and LAKE score (p = .004) and age (p = .001) as independent predictors of US-CaP., Conclusions: BMI, which depends on excessive intake of energy from food, is not related to an increased biochemical risk of calcium stone formation, which is more dependent on the renal acid load of the diet. In contrast, obesity is associated with an increased risk of uric acid stone formation due to insulin resistance, impaired ammoniagenesis and low urinary pH.

Background: Nephrolithiasis is a common condition with several studies documenting an increased prevalence over the past four decades. EAU and AUA guidelines recommend 24-hour urine metabolic evaluation in high-risk stone formers. Aim of this study is to retrospectively evaluate the first three years of experience with LithoTest® (Biohealth Italia Srl, Turin, Italy) through the analysis of demographic, clinical and biochemical data collected from a large cohort of patients with kidney stones., Methods: We retrospectively analyzed data from the LithoCenter database, including data from outpatient consultations, between January 2007 and December 2009 from all over Italy. LithoTest® was performed through a 24-hour urine collection and included measurements of urine volume and pH, 24-hour excretion of creatinine as well as main cations and anions, including calcium, magnesium sodium potassium, ammonium, uric acid, oxalate, citrate, phosphate, inorganic sulphate and chloride. Urine state of saturation for calcium oxalate (βCaOx), calcium hydrogen phosphate or brushite (βbsh) and uric acid (βUA) were also calculated by means of the computer program LithoRisk. Brand's test for cystinuria was also carried out. Statistical analysis was performed using the S-PSS software v. 22.0., Results: The number of patients with data available for analysis was 435, of whom 236 were male (54%) and 199 female (46%). Complete 24-hour urine measurements were available for all 435 patients. Compared to men, women had significantly lower values for creatinine, urate, oxalate, phosphate, sodium, potassium, magnesium and chloride excretion, whereas 24-hour pH and citrate excretion were higher. No significant differences were found for the other examined variables. βCaOx and βUA were significantly higher in men than women, whereas no significant difference was found for βbsh. There was a direct relationship between calcium and sodium urine excretion. Excessive sodium excretion was recorded in 191 patients (44%) and low urine volumes in 201 (46.2%). Hyperoxaluria was observed in 118 patients (27.3%), hypercalciuria in 115 (26.6%), hyperuricosuria in 153 (35.4%), hypomagnesuria in 96 (22.2%), and hypocitraturia in 134 patients (31%). Hyperexcretion of sodium, hypocitraturia and hyperoxaluria were most frequent in males. βCaOx was significantly higher in the setting of hypercalciuria, hypocitraturia, hyperoxaluria and urine pH below 5.5., Conclusions: Our findings in a large cohort of high-risk stone-forming patients show significant differences in urinary metabolic profiles between men and women. Carrying on the collection and analysis of data by LithoTest® from 2009 to 2015 and matching urinary and dietary data could eventually improve our understanding on the metabolic profile of stone-formers in Italy.

Citrate is a tricarboxylic acid and an intermediate metabolite of Krebs cycle. It contributes to oxidative metabolism of both kidney and liver. Alkaline sodium or potassium salts have the potential to increase alkaline reserve. In the kidney citrate is completely filtered at the glomerulus, undergoing to 10-40% tubular resorption. Renal insufficiency, even early, metabolic acidosis, potassium depletion induce hypocitraturia. Its importance in nephrolithiasis stems from its ability to form soluble complexes with calcium and to interfere with crystal formation, thus exerting a dual inhibition, thermodynamic and kinetic. Moreover, its alkalizing property has shown benefits of bone mineralization. The alkalizing effect is also useful in uric acid and cystine stone disease. Hypocitraturia has a significant incidence in the course of calcium nephrolithiasis, either secondary to aforementioned causes, or in idiopathic and/or familial forms. Citrate is used in the prevention of stone recurrences and given as tripotassic or potassium-magnesium salt, 0.1 mmol/kg/day in 2-3 dosages. In uric acid disease, in addition to prevention, it can induce dissolution of renal stones, provided urine pH is maintained at higher than 6.5 values. As concerns its effects on bone, it was shown to induce both decreases in marker of bone resorption and increases in bone mineral density., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: Primary hyperoxaluria (PH) is a rare autosomal recessive disease commonly arising in childhood and presenting with nephrolithiasis, nephrocalcinosis and/or chronic renal failure. Three genes are currently known as responsible: alanine-glyoxylate aminotransferase (AGXT, PH type 1), glyoxylate reductase/hydroxypyruvate reductase (GRHPR, PH type 2), and 4-hydroxy-2-oxoglutarate aldolase (HOGA1, PH type 3). In our Centre, at the end of 2014 molecular diagnosis of PH1 had been performed in 80 patients, while one patient received a PH2 diagnosis., Materials and Methods: Fifteen patients referred to our Centre and suspected to have PH on clinical grounds were negative for pathogenic variants in the entire coding sequence and exon-intron boundaries of the AGXT gene. Therefore, we extended the analysis to the AGXT promoter region and the GRHPR and HOGA1 genes., Results: Two patients were heterozygous for two novel AGXT-promoter variants (c.-647C > T, c.-424C > T) that were probably non pathogenic. One patient was homozygous for a novel HOGA1 variant of intron 2 (c.341-81delT), whose pathogenicity predicted by in silico splicing tools was not confirmed by a minigene splicing assay in COS-7 and HEK293T cells., Conclusion: New genetic subtypes of PH can be hypothesized in our patients, that may be caused by mutations in other gene encoding proteins of glyoxylate metabolism. Alternatively, some kind of mutations (e.g., deletions/duplications, deep intronic splicing regulatory variants) could be missed in a few cases, similarly to other genetic diseases.

Nephrolithiasis (NL) is one of the most prevalent nontransmissible diseases in western countries. It is being associated with other frequent diseases, including osteoporosis, cardiovascular disease, hypertension, diabetes mellitus, through a putative common link with metabolic syndrome and insulin resistance or altered mineral metabolism. This review will focus on classification, physicochemical basis, risk factors, laboratory and imaging investigations, medical management.Classification as to stone composition includes calcium, uric acid (UA), cystine (Cys), infected, 2-8 dihydroxyadenine and rare NL. According to pathophysiology, NL is classified as primary, secondary to systemic diseases or drugs, caused by renal or metabolic hereditary disorders.A stone can only form in supersaturated environment, and this is sufficient in UA, Cys and infected NL, but not in Ca-NL, which results from the imbalance between supersaturation and inhibition. All types are characterized by derangements of peculiar risk factors. Laboratory investigations aim at identifying type of NL, underlying risk factors and state of saturation, and pathophysiology. This justifies a rationale therapy able to dissolve some types of stones and/or produce reduction in recurrence rate in others.Medical management includes alkali and allopurinol for UA nephrolithiasis (UA-NL), thiols and alkali in Cys-NL, dietary and pharmacological intervention for Ca-NL. Thiazides and alkaline citrate salts are the most widely used drugs in Ca-NL, where they proved efficient to prevent new stones. Other drugs have only been used in particular subsets.Proper medical management and modern urological approaches have already notably improved clinical outcomes. Future studies will further clarify mechanisms of NL with expected new and targeted therapeutic options.

Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet. PTX compared to baseline reduced PTH (4617 vs 15786 pg/mL, p<0.01), calcemia (9.40.5 vs 11.30.9 mg/dL, p<0.01), calciuria (3.62.3 vs 9.24.5 mmol/24h, p<0.01), phosphaturia (18.47.1 vs 21.99.9 mmol/24h, p<0.05), CaOx (4.73.9 vs 9.86.8, p<0.01) and bsh (1.10.9 vs 3.22.2, p<0.01). Cinacalcet decreased both PTH (13379 vs 17187 pg/mL, p<0.05) and calcemia (9.70.6 vs 11.20.8 mg/dL, p<0.001), whereas no change was seen in calciuria (7.42.2 vs 7.42.4 mmol/24h, p=ns), phosphaturia (21.97.3 vs 23.06.5 mmol/24h, p=ns), CaOx (6.92.7 vs 5.42.5, p=ns) and bsh (1.71.1 vs 1.31.3, p=ns). We conclude that in patients with PHPT, PTX is able to decrease the risk for crystallization of calcium salts, whereas calcimimetic Cinacalcet did not. Therefore, in patients with PHPT complicated with nephrolithiasis only PTX can improve urine biochemistries thereby reducing the risk for recurrent calcium stone disease.

An internet survey was set up to assess the geriatric competence and perceived needs of 337 members of the Italian society of nephrology (SIN). The survey assessed how well aware nephrologists are of the typical geriatric conditions and needs of their elderly chronic kidney disease (CKD) patients. SIN associates were also questioned about their current use of comprehensive geriatric assessment, prescription of potentially nephrotoxic drugs, and screening for osteoporosis. The main finding is that CKD and dialysis are almost unanimously perceived as typically geriatric conditions, but knowledge and use of geriatric tools are scanty. While use of potentially inappropriate drugs is rare, almost half of the patients are not screened for osteoporosis. The significant clinical gaps observed could greatly impair the management of older CKD patients, and call for an urgent educational intervention.

Oxalate (Ox) is an end-product of metabolism, important for poor solubility of its calcium salt in biological fluids. Ox can therefore be found in about 70% of urinary calculi. Hyperoxaluria (HOx) defined as Ox exceeding 0.5 mmol)/day, may cause nephrolithiasis/nephrocalcinosis and may be classified as dietary (DH), enteric (EH) or primary (PH). Fractional intestinal absorption of Ox is less than 10%, but increases to over 20% at calcium intakes below 200 mg/day. DH is often related to low-calcium diets. EH is caused by non-absorbed fatty acids which bind to calcium and lower its concentration in the intestinal lumen. Ox forms more soluble complexes with other cations and results in HOx. Similar mechanisms may cause HOx following bariatric surgery. PHs are the most severe causes of HOx. Three types have so far been described, all being autosomic recessive. PH1 is due to mutations of AGXT gene encoding liver alanine-glyoxylate aminotransferase, PH2 is caused by mutations of GR-HPR gene encoding glyoxylate reductase and PH3 by mutations of HOGA1 encoding for hydroxyl-oxoglutarate aldolase. HOx results from deficient detoxification from glyoxylate, which is oxidized to Ox. The three PHs have different severity, though not always clinically distinguishable. They are identified through genetics and, in PH1, good genotype/phenotype correlations have been established. Thanks to early biochemical and genetic diagnosis, which are crucial to either prevent progression to ESRF or choose adequate transplantation strategies, the outlook of PH patients has dramatically improved in the last decades and will furtherly do in view of new therapeutic strategies.

Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease., Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed., Results: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions., Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels., Children: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

Background: Calcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency., Methods: We evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2-5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20)., Results: The geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or ≥20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating., Conclusion and General Significance: In conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations.

Dabigatran is an oral direct inhibitor indicated for stroke prevention in patients with atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that laboratory test and dose adjustments are not necessary; nevertheless, circumstances of excessive anticoagulation, decreased kidney function, and instances of significant bleeding and thrombosis require laboratory assessment. In order to gather experience in the management of global [activated partial thromboplastin time (APTT) and thrombin time (TT) with extended endpoint] and specific [ecarin chromogenic assay (ECA) and diluted thrombin time (dTT)] laboratory coagulation tests in patients receiving dabigatran with untoward effects, we describe a case in which hemodialysis was used in attempt to remove dabigatran in a patient with excessive anticoagulation, rectal bleeding, and severe anemia. Our experience confirmed that APTT is an unreliable method for the assessment of dabigatran in patients with acute complications because it was often normal in spite of the therapeutic drug plasma levels. Both ECA and dTT showed a linear correlation with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. TT assay, which is highly sensitive to dabigatran, correlated well and linearly not only with low drug levels, but also, because of the introduction of the extended endpoint (400 s), with high concentrations of the drug, and demonstrated to be a simple and reliable alternative to ECA and dTT to assess dabigatran in patients with acute complications.

Nephrolithiasis (NL) has high and increasing prevalence in western countries. Most renal stones contain calcium and/or uric acid and often occur as idiopathic stones, while seldom are caused by genetic disorders. Conversely, cystinuria, xantinuria, 2-8 dihydroxyadeninuria only occur in patients with mutations of corresponding genes. Inherited NL must be suspected in case of early onset, positive family history, severe recurrence rate, associated biochemical disorders, abnormal urinary sediment, renal insufficiency, involvement of other organs or apparatus. Pathophysiology is based on different mechanisms: electrolytic abnormalities, altered tubular transport, acid-base imbalances, cystic renal diseases. Sometimes NL is iatrogenic. Here we review some genetic NL, not only characterized by clinical relevance but also by the scientific interest in view of our better understanding of mechanisms of stone formation. Namely, Dents syndrome, calcium sensing receptor mutations, familial hypopomagnesiemic hypercalciuria (FHHNC), hypophosphatemic rickets (HHRH), renal tubular acidosis (dRTA), primary hyperoxaluria (PH), cystinuria, 2-8 dihydroxyadeninuria (2-8 DHA). We will briefly report on prevalence, genetics, pathophysiology, clinical aspects and treatment. The need for early diagnosis stems from the fact that, for most of these, selective treatment may be highly effective and can prevent progression to ESRD. Lastly, a better knowledge and understanding of genetic NL is a premise to study polymorphisms of candidate genes also in the setting of so-called idiopathic disease.