Search

This chapter reviews a pivotal trial on the role of increased water intake for secondary prevention of recurrent stone formation patients with idiopathic calcium nephrolithiasis. Patients randomized to the intervention arm were instructed to titrate their water intake to a daily urine output of at least 2 liters; patients in the control arms were not given any specific instructions. Increased water intake resulted in fewer stone recurrences, longer time to recurrence, and reduced calcium oxalate and calcium phosphate supersaturation.

BACKGROUND Vitamin D deficiency is a worldwide health concern. It prevails in epidemic proportions all over the Indian subcontinent with a prevalence of 70%-100% in the general population. Vitamin D is important in maintaining calcium and phosphorus homeostasis, but its role in kidney stone disease and its effect on stone formation are still not clear. AIMS AND OBJECTIVES In the present study, association between levels of Vitamin D and nephrolithiasis were studied. MATERIALS AND METHODS 50 patients with nephrolithiasis were selected and were compared with 50 controls matched in terms of age and sex. 25-OH Vitamin D levels were measured in both groups. RESULTS 25-OH Vitamin D levels were low in patients with nephrolithiasis when compared to controls.

Calcium has many important roles in physiology and pathology, such as in ensuring bone integrity, in maintaining haemostasis, and as a cofactor for metabolic enzymes. The kidney is the major organ ...

To establish the relationship between calcium nephrolithiasis, bone densitometry scoring, and bone mineral density (BMD) loss according to bone turnover markers (BTMs) and urinary metabolites.Patients with recurrent calcium nephrolithiasis and idiopathic fasting hypercalciuria (urinary calcium/creatinine ratio0.11) are more likely to have BMD loss that may lead to osteopenia or osteoporosis. In these patients, BTMs may be used as a surrogate for both bone health and stone recurrence. Suspect higher lithogenic states when calcium stone formers have serum beta-crosslaps (resorptive marker) greater than 0.311 ng/ml, serum osteocalcin (formative marker) greater than 13.2 ng/ml, and beta-crosslaps/osteocalcin ratio greater than 0.024.Patients with recurrent calcium nephrolithiasis and fasting hypercalciuria have a higher incidence of osteopenia and osteoporosis, measured by the dual-energy X-ray absorptiometry. These patients present not only with hypercalciuria and increased BTMs (mainly resorptive), but also up to 30% have hypocitraturia and increased urinary calcium/citrate ratio (0.25). On the basis of these results, a diagnostic algorithm was created, classifying hypercalciurics according to their fasting calcium/creatinine and calcium/citrate ratio. Medical therapy for these patients is aimed at improving the dietary habits (normocalcemic, low salt, low animal protein diet), prescribing combinations of potassium citrate, thiazides, and bisphosphonates, and correcting bone and urinary abnormalities that may lower future skeletal and kidney stone risk.

Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole–cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2– and caveolin-1–mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan–deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.

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.

Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986–1998, 853 patients); Group 2, narrow-band era (1999–2004, 467 patients); Group 3, broad-band era (2005–2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend

Background Our purpose is to show the effect of alendronate on patients with recurrent calcium lithiasis and loss of bone mass, and to observe their progress with analytical and densitometric markers.

An increased calcium excretion in 24-hour urine was found in 32 of 42 out-patients with recurrent calcium nephrolithiasis (calcium excretion > 300 mg in males, > 250 mg in females). Subsequent hospitalization of the 32 patients revealed the following diagnosis after a calcium tolerance test: absorptive hypercalciuria in 18, renal hypercalciuria in 4, primary hyperparathyroidism in 2 and dietary hypercalciuria in 7. Normocalciuria in 10 out-patients was confirmed in 6; in one instance there was, however, primary hyperparathyroidism, in 3 there was absorptive hypercalciuria. In one patient it was not possible to classify the hypercalciuria. Total as well as nephrogenic cAMP showed wide scatter and was unsuitable, therefore, in differential diagnosis. In 2 of 3 cases of hyperparathyroidism the serum level of parathormone was distinctly elevated.

Idiopathic calcium nephrolithiasis is a multifactorial disease with a pathogenesis that involves a complex interaction of environmental and individual factors. This review discusses what is known, about monogenic renal calcium stone-related disorders, provides an update on genetic research in calcium nephrolithlasis and such intermediate phenotypes as idiopathic hypercalciuria, discusses the problems that these conditions pose to clinicians and geneticists interested in their pathogenesis, and proposes some method tools potentially useful in this research frame of reference.

While bone involvement is more evident in case of secondary calcium calculosis, such as hyperparathyroidism, medullary sponge disease, hypercalcemic systemic illness and chronic diarrhea syndrome, less known and more controversial is still the link between bone loss and idiopathic calcium nephrolithiasis. In this study 46 patients with idiopathic calcium nephrolithiasis were consecutively enrolled at their customer diet. Our data show that dietary habits, especially an high sodium and animal protein intake, could seem to influence bone loss of the lumbar spine and of the neck. Furthemore a negative correlation has been found between citrate urinary excretion and bone loss, that suggests a protective role of potassium citrate not only on prevention of recurrent calcium nephrolithiasis, but also on bone loss.

Growing evidence has assigned to oxalate a pivotal role in calcium nephrolithiasis pathophysiology. A better understanding of the mechanisms behind intestinal absorption and renal excretion has led to the identification of new treatments. Among these, diet and probiotics appear promising in terms of safety and rationale. However, the discrepancy between in vitro and in vivo results requires further studies to identify the right patient target, the correct dosage, and the real modification of natural and clinical history of nephrolithiasis.

Objective: The object of this study was to investigate the role for measurement of 24-h renal oxalate excretion in the evaluation of idiopathic calcium stone formers. Materials and Methods: Renal excretion rates of oxalate and creatinine were measured in 24-h urines in 46 consecutive male recurrent idiopathic calcium stone formers and 61 healthy males. Furthermore, day-to-day variation in renal oxalate excretion in 10 male recurrent stone formers and 10 healthy males were evaluated by measuring 24-h oxalate excretion on 5 different days in each individual. Concentrations of oxalate in urine were measured using an enzymatic method without ascorbate interference. Results: The cumulative frequency distribution curves of 24-h renal oxalate excretion rates of stone formers and controls were congruent, and there were no statistically significant differences in oxalate excretion rates between stone formers and controls. Mean 24-h oxalate excretion (95%-confidence intervals) was 0.22 (0.18-0.25) mmol and 0.21 (0....

Background Because the causes of stones are uncertain, interventions to prevent recurrence have an insecure foundation. Progress depends on careful evaluation of stone formers. Methods A descriptive retrospective database study of 1983 men and 816 women from the Southampton stones clinic from 1990 to March 2007. Anonymized data from the first attendance were analysed using non-parametric statistical tests. Results Sex ratio (2.43:1), age (median 49 y, 2.5th-97.5th percentiles, 23-77 y men, 20-79 y women), recurrent stone formers (30%) and type of stone were similar to other centres. Women more often had a positive family history (24% versus 19% men), previous urinary infection (31% versus 5%) and structural urinary tract abnormality (14% versus 7%); more men had gout (5% versus 1%) and bladder outlet obstruction (3% versus 4/GFR) < 0.70 mmol/L); 6% men and 1.6% women also had low plasma phosphate. Many variables correlated significantly but often weakly with age. Creatinine clearance, pH and (men) TmPO4/GFR decreased from 50 y, urine creatinine, calcium and citrate from 60 y. Conclusions Risk factors for stones differ between men and women, change with ageing and in some may have a genetic basis. The role of phosphaturia merits further exploration.

Nephrolithiasis is a common disorder, with a rising prevalence in the general population. Its pathogenesis is still unclear, but a role for genetics has long been recognized, especially in cases of the more common calcium nephrolithiasis. Although relatively rare, monogenic causes of hypercalciuria and nephrolithiasis do exist and their timely recognition is important from a prognostic and therapeutic viewpoint. This article reviews the clinical and laboratory findings characterizing inherited causes of nephrolithiasis with a view to helping clinicians to recognize and manage these rare conditions.

Sakhaee et al in this issue have investigated whether the risk of the common calcium nephrolithiasis is associated with the metabolic syndrome (MS). This question is interesting since it deals with a more general problem on whether calcium nephrolithiasis is a ‘systemic disorder’ and entails a cardiovascular risk..

■ Objective: To review dietary factors implicated in the pathogenesis of calcium nephrolithiasis and the pathophysiological mechanisms proposed for each. ■ Data sources: Data were obtained from English language articles published between 1950 and 1991 addressing the evaluation and therapy of patients with nephrolithiasis. The articles are indexed in the National Library of Medicine's MEDLINE data base. ■ Study selection: Studies selected for inclusion in this review were those that identified and discussed dietary factors in the pathophysiology of calcium nephrolithiasis. ■ Data extraction: References were reviewed by the authors with emphasis on study size, randomization, and statistical analysis. ■ Data synthesis: Renal stone formation is the result of genetic, metabolic, and environmental factors. The most important environmental factors relate to diet. Assessment of dietary sodium, calcium, phosphorus, oxalate, protein, fiber, fluid, and exogenous vitamins is mandatory in the initial evaluation of the patient with renal stones. Instruction to correct identified dietary excesses or deficiencies is the first therapeutic intervention for all patients, including those in whom additional drug therapy is ultimately required. ■ Conclusions: Nutritional intervention is central to the evaluation, therapy, and long-term monitoring of the patient with calcium nephrolithiasis.

Background: The purpose of this trial was to evaluate the efficacy of a low-animal-protein diet (LAPD) or a high-fiber diet (HFD) for the prevention of calcium nephrolithiasis recurrence. Methods: We conducted a 4-year randomized trial comparing the effect of 2 diets in 175 idiopathic calcium stone formers. Fifty-five were assigned to a LAPD (25 g/day fiber) and 60 were placed on a normal diet (control group). The primary outcome measure was the time to the first recurrence of calcium nephrolithiasis. Daily urine compositions were analyzed at baseline, at month 4 (M4), M12, M24, M36 and M48. Results: Seventy-three patients completed the trial (23 in the LAPD group, 27 in the HFD group and 23 in the control group). Recurrence was 48% (11/23) in the LAPD group, 63% (17/27) in the HFD group and 48% (11/23) in the control group (p = not significant). During follow-up, urinary calcium levels and other urine parameters did not change significantly in the 3 groups, except for a significant decrease in 24-hour urinary sulfate in the LAPD group. Conclusions: In idiopathic calcium stone formers, neither a LAPD nor a HFD appeared to provide protection against recurrence.

To the Editor: In their interesting review on Randall's plaque, Evan et al.1 go through a number of rodent models where hypercalciuria with/without stones or nephrocalcinosis have been observed, but do not form Randall's plaque-like structures. The list is incomplete, as they themselves pointed out. In our opinion, the Nuf rat model should be added:2 this rat has an activating mutation of the calcium-sensing receptor, which leads to calcifications at various renal levels and – of particular interest – in papillary ducts in up to 63% of heterozygous animals. Whether Randall's plaques exist in such a model is not known and cannot be ascertained from published pictures. Calcification interestingly occurs with no associated hypercalciuria. This model is attractive in relation to human idiopathic calcium stone disease (idiopathic calcium nephrolithiasis). Quite recently, Soldati et al.3 showed that an activating polymorphism of the calcium-sensing receptor is associated with hypercalciuria in idiopathic calcium nephrolithiasis, and Terranegra et al.4 have reported that calcium-sensing receptor SNPs form a haplotype block associated with idiopathic calcium nephrolithiasis and increase the risk of stones by as much as 3.36 times. Looking for the occurrence of Randall's plaques in the Nuf rat might therefore be highly rewarding.

In two earlier publications we reported excellent therapeutic results in patients with recurrent calcium nephrolithiasis, using oral or intravenous i.v. sodium thiosulfate on the one hand, and on treatment of tumorus-soft periarticular tissues calcifications on the other. Thus, we considered useful to measure endogenous thiosulfaturia, using a specific HPLC method, in 25 healthy adult males and 25 patients with recurrent calcium nephrolithiasis. Healthy adult males excreted between 11 and 16 μ M/24 hour of endogenous thiosulfate, while patients with recurrent calcium nephrolithiasis excreted significantly lower amounts of 6 and 10 μ M/24 hour, except one patient, who did not excrete endogenous thiosulfate, reflecting probably a genetic abnormality. Thiosulfate is a unique agent for treatment of recurrent calcium nephrolithiasis as well as some other abnormal calcium depositions. Two doses of 5 mM sodium thiosulfate daily are therapeutically sufficient. © 2004 Kluwer Academic Publishers.

Purpose: Pharmacological treatment of hypocitraturic calcium nephrolithiasis requires as many as 12 tablets, or numerous crystal packages or liquid supplements taken throughout the day. In addition to added cost, this cumbersome regimen decreases patient compliance, which may increase stone recurrence rates. We evaluated the urinary biochemical effects of dietary citrate supplementation in hypocitraturic calcium stone formers in an attempt to decrease or eliminate the need for pharmacological therapy.Materials and Methods: A total of 12 patients who were either noncompliant with or intolerant of pharmacological citrate therapy supplemented their routine diet with citrate in the form of lemonade, consisting of 4 ounces of reconstituted lemon juice (5.9 gm. citric acid) mixed with tap water to a total volume of 2 1. and consumed at uniform intervals throughout the day. Urine specimens (24-hour) were obtained for biochemical analysis after 6 days of lemonade therapy and compared to pre-lemonade basel...

Nephrolithiasis seems to be the result of crystal formation, aggregation and retention in the kidney during crystalluria. These processes have to occur within the short urinary transit time through the kidney being in the order of few minutes. Recently much work was done on rather qualitative aspects of nephrolithiasis like genetics, metabolism and morphology. In this review we try to provide some quantitative information on urinary supersaturation with respect to stone minerals, especially Ca oxalate (CaOx), on the formation and aggregation of CaOx crystals and on crystal retention in the kidney. The paper is centered on idiopathic Ca nephrolithiasis being the most frequent stone disease with only partially known pathogenesis. New aspects of the role of urinary macromolecules in stone formation and of the mechanism of crystal aggregation are provided.

Idiopathic calcium nephrolithiasis (ICN) and hypertension (HY) are both common in affluent countries. Hypercalciuria is reported to be associated with HY1 and hypertensive subjects tend to develop renal stones more often than normals3. Our aim was to evaluate possible differences in blood pressure (BP) between ICN patients and normals and to find possible relationships between BP and metabolic parameters in ICN patients and normals.

Urinary tract infection (UTI) is well known to be a primary factor in the pathogenesis of struvite stones1, yet little data exist on the effect of UTI on idiopathic calcium nephrolithiasis (ICN)2. The aim of this study was to evaluate the prevalence of UTI among patients with ICN and to determine the effect of UTI on the urinary risk factors in ICN.

In an attempt to document the efficacy of potassium citrate in stone formation, 57 patients with active lithiasis (2 or more stones during the preceding 2 years) and hypocitraturia were randomly allocated into 2 groups, with 1 group taking 30 to 60 mEq. potassium citrate daily in wax matrix tablet formation and the other group receiving placebo. In 18 patients receiving potassium citrate for 3 years stone formation significantly declined after treatment from 1.2 +/- 0.6 to 0.1 +/- 0.2 per patient year (p0.0001), in 13 patients (72%) the disease was in remission and all patients showed a reduced stone formation rate individually. In contrast, 20 patients taking placebo medication for 3 years showed no significant change in stone formation rate (1.1 +/- 0.4 to 1.1 +/- 0.3 per patient year) and in only 4 patients (20%) was the disease in remission. The stone formation rate during potassium citrate treatment was significantly lower than during the placebo treatment (0.1 +/- 0.2 versus 1.1 +/- 0.3 per patient year, p0.001). Potassium citrate therapy caused a significant increase in urinary citrate, pH and potassium, whereas placebo did not. Adverse reactions to potassium citrate were mild causing only 2 patients in the potassium citrate group and 1 in the placebo group to withdraw from the study. In summary, our randomized trial showed the efficacy of potassium citrate in preventing new stone formation in idiopathic hypocitraturic calcium nephrolithiasis.

Clinical and biochemical parameters were investigated in a group of patients with medullary sponge kidney (MSK) and compared with tho se of 2 groups of patients with idiopathic calcium nephrolithiasis, single and recurrent stone-formers (SSF and RSF). No sex differences, a more common family history of nephrolithiasis, no tendency to over weight and a higher urinary magnesium excretion were found to be the distinctive features of the patients with MSK with respect to SSF and RSF. Although the high magnesium excretion has been postulated to inhibit calcium oxalate crystallization, its protective effect in MSK is probably overwhelmed by other risk factors such as distal aci dification defects and prolonged transit time in the ectatic ducts.