Urinary Tract Stone Formation Research Articles

Advancements in Urolithiasis Treatment: Current Strategies, Future Challenges, and Integrating Traditional Wisdom into Modern Medicine:A Review

Urolithiasis, the formation of urinary tract stones, remains a prevalent and painful condition that affects millions of individuals worldwide. This article explores the current treatment strategies for urolithiasis, including minimally invasive procedures, dietary modifications, and pharmacological interventions. We also address the ongoing challenges in managing this condition, such as the high recurrence rates and potential complications. Looking to the future, we examine the prospects for innovative technologies, including targeted drug delivery and personalized medicine approaches, to enhance urolithiasis treatment. Furthermore, we discuss the promising potential of integrating traditional knowledge and remedies from various cultures into the modern medical system. This integration not only offers new avenues for preventive and curative therapies but also underscores the importance of preserving and respecting the wisdom of traditional healing practices. By exploring both established and emerging treatment options and considering the implementation of traditional knowledge, this article provides a comprehensive overview of the current state of urolithiasis management, future challenges, and potential solutions. It emphasizes the need for a holistic approach that combines the best of modern medicine with the insights of traditional healing systems to improve the quality of care for urolithiasis patients.

Synergistic inhibition of ureolytic activity and growth of Klebsiella pneumoniae in vitro suggests cobinding of fluoride and acetohydroxamic acid at the urease active site and provides a novel strategy to combat ureolytic bacteria

The ability of ureolytic bacteria to break down stable urea to alkaline ammonia leads to several environmental and health challenges. Ureolytic bacteria such as Helicobacter pylori, Klebsiella pneumoniae, and Proteus mirabilis can become pathogenic and cause persistent infections that can be difficult to treat. Inhibiting urease activity can reduce the growth and pathogenicity of ureolytic bacteria. In the present in vitro study, we investigated the synergistic effects of tannic acid (TA) and the urease inhibitors fluoride (F−) and acetohydroxamic acid (AHA). The concentration of AHA needed for efficient inhibition of the ureolytic activity of K. pneumoniae can be significantly reduced if AHA is coapplied with tannic acid and sodium fluoride (NaF). Thus, only 1.20 μmol l−1 AHA in combination with 0.30 mmol l−1 tannic acid and 0.60 mmol l−1 NaF delayed the onset of ureolytic pH increase by 95.8 % and increased the growth lag phase by 124.3 % relative to untreated K. pneumoniae. At these concentrations, without AHA, TA and NaF increased the onset of the ureolytic pH change by only 37.0 % and the growth lag phase by 52.5 %. The strong inhibition obtained with low concentrations of AHA in triple-compound treatments suggests cobinding of F− and AHA at the urease active site and could reduce the side effects of AHA when it is employed as a drug against e.g. urinary tract infections (UTIs) and blocked catheters. This study reports the basis for a promising novel therapeutic strategy to combat infections caused by ureolytic bacteria and the formation of urinary tract stones and crystalline biofilms on catheters.

Computed Tomography Findings in the Evaluation of Urolithiasis

Background: Urolithiasis, or the formation of urinary tract stones, is a prevalent condition that affects individuals worldwide, predominantly impacting middle-aged and elderly demographics. Computed tomography (CT) has emerged as a superior diagnostic tool for urolithiasis due to its high sensitivity and specificity, offering detailed insights into the size, location, density, and composition of stones. Objective: The objective of this study was to evaluate the efficacy of unenhanced computed tomography in the diagnosis and characterization of urinary tract stones, focusing on their size, location, and associated clinical symptoms. Methods: A cross-sectional study was conducted at the Diagnostic Center of CMH Hospital Lahore over four months, involving 70 patients with suspected or confirmed urolithiasis. Participants were selected using non-probability convenient sampling and underwent 128-slice MDCT imaging without contrast. Data collection included demographic information, clinical symptoms, and CT findings regarding stone characteristics. The ethical standards adhered to the Declaration of Helsinki, with all participants providing informed consent. Results: The study comprised 74.3% male and 25.7% female participants, with the highest prevalence of urolithiasis observed in the 30-40 year age group (32.9%). CT imaging detected stones in 95.7% of the participants, with a significant incidence of smaller stones (1-5 mm) at 31.4%. Hydronephrosis was noted in 85.7% of cases, and hydroureter in 54.3%. The most common stone density ranged from 500-1000 HU (41.4%), and stones were more frequently located on the right side (32.9%). Conclusion: Unenhanced CT proved to be a highly effective diagnostic tool for assessing urinary tract stones, providing essential data on stone size, density, and location, as well as associated clinical symptoms. This modality enhances the ability to tailor treatment strategies effectively, thereby improving patient outcomes.

Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.

The effect of nutritional factors on urolithiasis: A case-control study.

Urolithiasis, a prevalent chronic kidney disease affecting all age groups, can be influenced by nutritional factors. The incidence of urolithiasis in Asian countries ranges from 1% to 19.1%, attributed to geographical and lifestyle differences. In Iran, several risk factors, including ethnicity, dietary habits, gender, and age, are associated with urolithiasis. This study aimed to assess the impact of nutritional factors on kidney and urinary tract stone formation. This case-control study enrolled 127 newly diagnosed urolithiasis patients, and 127 matched healthy participants between February to May 2017. Exclusion criteria included diabetes and acute or chronic renal failure. Data were collected using the Food Frequency Questionnaire (FFQ) and analyzed using chi-square and logistic regression tests. Water (95% CI: 0.09-0.89, OR=0.28), natural juices (95% CI: 0.10-0.65, OR=0.53), mineral water (95% CI: 0.05-0.64, OR=0.18), legumes (95% CI: 0.00-0.38, OR=0.032), butter, cream, or peppermint (95% CI: 0.09-0.95, OR=0.30), and ice cream (95% CI: 0.07-0.54, OR=0.203) had a significant protective effect against kidney and urinary tract stone formation. Conversely, tea consumption (95% CI: 1.15-7.99, OR=4.70), beverages (95% CI: 4.45-23.32, OR=23.32), coffee (95% CI: 1.63-11.78, OR=4.39), bread (95% CI: 1.1-10.59, OR=3.37), meat (95% CI: 1.01-8.01, OR=2.85), liver (95% CI: 3.37-488.90, OR=40.58), fish (95% CI: 2.89-216.39, OR=25.03), and various canned foods (95% CI: 1.34-10.25, OR=3.70) were significantly associated with kidney and urinary tract stone risk. These findings showed that the risk of urinary stones formation had a significant relationship with dietary habits. Therefore, the correct dietary pattern and sufficient fluid consumption may play an important role in preventing urinary stones.

Spectrum of 25 (OH) D3 Status in Urinary Tract Stone Formers in North-Eastern Nigeria

Many studies, none in northeastern part of Nigeria, investigated the association between serum/plasma vitamin D and nephrolithiasis, with no consistent result, couple with the hot weather (as high as 44oC) in most part of the year in Maiduguri and its surroundings, and assay of vitamin D today is not yet part of evaluation of urinary stone formers in Maiduguri, warrant this study to assess status of vitamin D in urinary tract stone formers in Maiduguri. Patients diagnosed with urinary tract stone disease attending Urology Clinic, University of Maiduguri Teaching Hospital and consented were recruited. The first two who consented were recruited per week for a period of 24 months (1st April 2017 to 31st Match 2019) to cover the seasonal changes in weather for the year. Serum for vitamin D is stored at -20oC for batch analysis. Vitamin D was assayed by ELISA technique (Accu-Bind, 100 North Pointe Drive, Lake Forest, California 92630 USA), other parameters were analyzed weekly using autoanalyzer (Cobas C311, ISN, Roche, Germany). Result indicated 58 (36.2%) of patients had Vitamin D values below the optimal level either having deficiency/insufficiency. Forty-nine (30.6%) showed vitamin D concentration above the optimum level out of which 4 (2.5%) had hypervitaminosis D, while 53 (33.1%) patients had optimal vitamin D values. It showed 17 (10.6%) of patients had hypercalcaemia, however, out of the 114 patients with normocalcaemia, 42 (36.5%) had their values at the upper limit of normal (2.6 mmol/L). It also indicated that though 3 of the hypercalcaemic patients had vitamin D insufficiency, majority (14) are either having optimal level or above optimal vitamin D level. Excessive and prolong exposure to ultraviolet sunlight resulting in raised vitamin D synthesis and action is an important factor associated with urinary tract stone formation in this environment cannot be excluded. The high prevalence of hypercalcaemia in the study cannot be accounted for by raised vitamin D alone, therefore measurement of serum vitamin D (25(OH)D) and PTH in evaluation of urinary tract stone formers in this environment is recommended.

MO128: Predisposing Metabolic Factors to Urinary System Stone Formation in Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract BACKGROUND AND AIMS The risk of urinary tract stone formation in patients with autosomal dominant polycystic kidney disease (ADPKD) is 20%, twice as high as in the normal population. The most important reason for this increased tendency to stone disease is thought to be anatomic changes in the kidney. To investigate metabolic factors that predispose to urinary system stone formation in individuals with ADPKD. METHOD A total of 180 volunteers who applied to our outpatient clinic between December 2019 and May 2021 were included in the study. Four groups were formed: patients with ADPKD and urinary system stones (ADPKD + STONE) (n = 42), patients with ADPKD but no stones (ADPKD + STONE FREE) (n = 43), stone patients without ADPKD (STONE) (n = 47) and healthy controls (HEALTHY) (n = 48) groups. Spot urine pH, 24-h urine volume, calcium, uric acid, oxalate, citrate, sodium and magnesium parameters were measured. STONE group data were obtained retrospectively. Along with these parameters, serum electrolyte, parathormone (PTH), ferritin, albumin, creatinine, urea and uric acid values were also compared. A P value of &amp;lt;.05 was considered significant for statistical analysis. RESULTS There was no statistically significant difference between the four groups in terms of age and gender (P &amp;gt; .05). The citrate value in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than the STONE and HEALTHY groups (P &amp;lt; .05). The citrate value in the 24-h urine was significantly lower in the STONE group than in the HEALTHY group (P &amp;lt; .05). The citrate value in 24-h urine did not differ significantly between the ADPKD + STONE and ADPKD + STONE FREE groups (P &amp;gt; .05). In the ADPKD + STONE and ADPKD + STONE-FREE groups, the 24-h urinary calcium value was significantly lower than the STONE and HEALTHY groups (P &amp;lt; .05). In the STONE group, the 24-h urinary calcium value was significantly higher than the HEALTHY group (P &amp;lt; .05). There was no significant difference in the 24-h urinary calcium value between the ADPKD + STONE and ADPKD + STONE FREE groups (P &amp;gt; .05). The uric acid level in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P &amp;lt; .05). The uric acid value in the 24-h urine did not differ significantly between the ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). The uric acid value in 24-h urine did not differ significantly between the STONE and HEALTHY groups (P &amp;gt; .05). Oxalate, sodium and magnesium values in 24-h urine and 24-h urine volume did not differ significantly between the groups (P &amp;gt; .05). Urine pH value was significantly lower in the ADPKD + STONE, ADPKD + STONE-FREE and STONE groups than in the HEALTHY group (P &amp;lt; .05). The pH value did not differ significantly between ADPKD + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). Serum PTH values were significantly higher in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P &amp;lt; .05). The PTH values did not differ significantly between the STONE and HEALTHY groups (P &amp;gt; .05). PTH values did not differ significantly between ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). There was no significant difference between the groups in terms of serum ferritin, sodium, potassium, calcium, phosphorus, magnesium and uric acid values (P &amp;gt; .05). CONCLUSION In our study, 24-h urine citrate level was found to be significantly lower in both ADPKD + STONE and ADPKD + STONE-FREE patients compared to the volunteers in the STONE and HEALTHY groups (P &amp;lt; .05). In conclusion, patients with ADPKD should also be evaluated for hypocitraturia in the outpatient clinic.

Urinary Tract Stones Risk Factors in Patients with Benign Prostatic Hyperplasia in West Java, Indonesia

Background: Urinary tract stones are common in patients with benign prostatic hyperplasia (BPH); therefore, an imaging test is needed for patients who have risk factors for the formation of urinary tract stones. The purpose of this study was to explore the factors associated with the presence of urinary tract stones in patients with BPH as information to conduct imaging tests.Methods: A cross-sectional quantitative analytic study was conducted on medical records of patients with BPH, both with and without urinary tract stones, or patients with urinary tract stones registered at the Department of Urology, Dr. Hasan Sadikin General Hospital, Indonesia, from 2015 to 2018. Data on age, body mass index, hypertension, use of antihypertensive drugs, diabetes mellitus, and hyperuricemia were collected and analyzed using the Mann-Whitney, Chi-square, Fisher exact test, and multivariate logistic regression statistical test to compare variables between BPH with and without urinary tract stones.Results: In total, 235 BPH patients were registered, of whom 74 (31.5%) had urinary tract stones. The median age was 64 years old. There was a relationship between age (p=0.030), diabetes mellitus (p=0.043), and the occurrence of urinary tract stones in patients with BPH. The most dominant risk factor was diabetes mellitus (OR=3.000, 95%CI 1.03-8.69).Conclusions: Age and diabetes mellitus are the risk factors for urinary tract stones in patients with BPH. BPH patients with diabetes mellitus are at a 3-fold risk for urinary tract stones. Diabetes mellitus in BPH patients is an indication to conduct imaging tests.

Mechanisms of Delayed Lower Urinary Tract Stone Formation after Holmium Laser Enucleation of Prostate

Materials and methods: We analysed Holmium Laser Enucleation of Prostate (HOLEP) database consisting of 1300 patients who presented more than 18 months after undergoing the procedure with lower urinary tract symptoms (LUTSvoiding lower urinary tract symptoms, dysuria, haematuria, recurrent urinary tract infections-UTIs) secondary to delayed lower urinary tract stone formation. Information was gathered from the case notes, imaging modalities, operation notes and pathology reports. Results: Three patients were identified who presented with delayed lower urinary tract stone formation 18 months after undergoing HOLEP. Case 1: A 68-year-old presented with a 4-cm mobile bladder stone on a retained prostatic fragment 29 months after HOLEP. Case 2: A 74-year-old presented with 2.5 cm bulbar urethral stone 18 months after HOLEP. Case 3: A 77-year-old presented with dystrophic calcification of the entire prostatic fossa 60 months after HOLEP. Conclusion: Delayed lower urinary tract stone presentation is unusual after HOLEP. Recurrent urethral pain, recurrent UTI, gross haematuria and voiding lower urinary tract symptoms in the presence of a lower urinary tract stone (bladder, prostate and urethra) with a radiolucent centre on a background of HOLEP should raise the suspicion that this may represent calcification on a prostatic tissue fragment or dystrophic calcification of the residual prostate/prostatic fossa. Careful morcellation, inspection of the prostatic fossa on withdrawing the morcellator for large residual prostate fragments still attached to the prostatic bed/bladder neck or simply stuck to the fossa (usually in a clot) will reduce the risk of retainment of such a significant prostatic fragment that can potentially cause complications in the future.

PSIII-36 Increased viscosity enhances water intake and reduces risk of calcium oxalate stone formation in cats

Abstract The control of liquid intake in cats is especially of interest as there is a significant risk of urinary tract stone formation due to their high urinary solute density. Calcium oxalate stone formation is not easily mitigated by dietary manipulation. This study investigated if increasing water viscosity (282 vs 2.9 centipoise; means throughout are viscous water followed by control cats) improved voluntary intake of water and calcium oxalate stone risk. Twelve cats (7 neutered males, 5 spayed females) from 3 to 8 years of age with an average weight 4.7 kg were monitored for 4 months. Each cat spent 2 months consuming viscous water and two months consuming normal water in a crossover design. Water consumption was measured through loss of weight from each pet’s water bowl with an additional bowl of the consumed viscosity placed in the room for evaporative loss measurements. A urine calcium oxalate titrimetric test (COT) was performed to evaluate the risk of calcium oxalate stone formation. In brief, the [Ca+2]/(added Oxalate-2) ratio is calculated (per liter). An increasing index value denotes samples at greater risk of calcium oxalate crystallization. The ratio represents the concentration of ionized calcium and the amount of oxalate that is added to initiate crystallization. The results showed that cats drinking viscous water had a significant increase in water consumption (79.9 vs 65.6 grams P = 0.014). There was a reduction in urine specific gravity (1.042 vs 1.052 P = 0.016), fractional excretion of calcium (0.197 vs 0.280 P = 0.036), urinary calcium concentration (49.8 vs 61.8 ppm P &amp;lt; 0.01) and in stone risk as measured by COT (35.5 vs 82.4 P = 0.029). In conclusion, these data show that there is an increased intake of water when cats are offered water with increased viscosity and increased viscosity was associated with an improvement in measurements of oxalate stone risk.

Etiologic risk factors and vitamin D receptor gene polymorphisms in under one-year-old infants with urolithiasis.

The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged<1year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged<1year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p<0.05). Positive family history came into prominence in the stony group (p<0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p<0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.

Pelvic ultrasound diagnosis of giant vesical calculus in 10 year old boy

Ultrasonography has a vital role to play in the management of children with urinary tract infection as it helps not only in assessing the urinary tract, but also in excluding complication that may arise from the diseases such as a urinary tract stone formation. We report a case of a 10 year old boy with giant vesical calculus to the alert pediatricians to the likelihood of bladder calculus complicating urinary tract infection in our environment and the usefulness of imaging modality both in the clinical work-up and the follow up in order to reduce delay in patient management. It is also presented to alert general practitioners that simple non-invasive and cheap ultrasound has a role to play in making a diagnosis and management.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study

SummaryThe Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.IntroductionThis study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.MethodsWHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).ResultsAmong women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.ConclusionThough based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-012-2224-2) contains supplementary material, which is available to authorized users.

Evaluation of health behaviours in patients with kidney stones in Sari/Iran

Renal stone formation is a common and important problem in urinary tract and the prevalence of the disease is especially rising in recent years due to changing the lifestyle and diet. The aim of this study was to evaluate the health behaviours of patients with kidney stones.This cross‐sectional study was performed on 190 patients with kidney stones who referred to the outpatient department of Hospitals or extracorporeal shock wave lithotripsy clinics in Sari/Iran, during 6 months period in 2009. The people were divided into two safe health behaviours and unsafe health behaviours groups, based on the obtained scores from their health behaviours. Data were analysed using SPSS software and descriptive statistics tests.The mean age of the patients with kidney stones was 39 years. A 51·3% of subjects had positive family history of the disease. A 49·5% of subjects did not have exercise and 38·9% had less than half an hour physical activity per day. There was a significant relationship between the type of kidney stone and type of consumed water, tea, raw vegetables, milk and meat (P &lt; 0·005). There was a significant relationship between family history of disease and exercise and daily activity level as well as the type and amount of water consumption (P &lt; 0·005).Health behaviours can control and prevent the disease progression and influence on recurrence of the disease. Evaluation of health behaviours leading to formation of urinary tract stones in different geographical areas of our country seems to be necessary.

Causes of Hypocitraturia in Recurrent Calcium Stone Formers: Focusing on Urinary Potassium Excretion

Multiple factors associated with hypocitraturia have been identified. However, limited studies addressing the causal relationship to hypocitraturia are available. We therefore conducted this study to determine factors associated with hypocitraturia and show their causal relationship in recurrent calcium stone formers. Dietary review and 24-hour urine samples were obtained from all recurrent calcium stone formers referred for metabolic workup in the stone clinic. One month of oral potassium chloride supplementation was prescribed to stone formers to determine the causal relationship between urinary potassium and citrate levels. Eighty-three subjects, 44 men and 39 women, were recruited to participate in this study. Hypocitraturia (citrate < 300 mg/d [<1.43 mmol/d]) was found in 50.6% of subjects. Four independent urinary variables associated with hypocitraturia were identified, including potassium level, net gastrointestinal alkaline absorption, calcium level, and titratable acid. Urinary potassium level was the strongest predictor of urinary citrate level. Hypocitraturic subjects also had lower fruit intake compared with subjects with high urinary citrate levels. Potassium chloride supplementation to a subgroup of this population (n = 58) resulted in a significant increase in urinary citrate excretion (350.73 +/- 27.25 versus 304.15 +/- 30.00 mg/d [1.67 +/- 0.13 versus 1.45 +/- 0.14 mmol/d]; P < 0.02), but no alteration in fractional excretion of citrate (19.7% +/- 2.7% versus 23.1% +/- 2.4%; P > 0.05). Hypocitraturia was found to be a common risk factor associated with recurrent calcium stone formation and low urinary potassium level, low alkaline absorption, low urinary calcium level, and high titratable acid excretion. Hypocitraturia is predominantly of dietary origin. Estimation of fruit intake should be included in the metabolic evaluation for recurrent calcium stone formation.

Effects of long-duration space flight on calcium metabolism: Review of human studies from Skylab to the present

One of the major effects of prolonged weightlessness seen in long-duration space flights has been an extended loss of bone from the skeleton. The principal characteristics of this loss were shown in the metabolic studies carried out on the Skylab flights of 1, 2 and 3 months in 1973 and 1974. These studies now provide the background for a comprehensive review of the considerable number of subsequent calcium studies in humans during space flights from that time until the present. Because of the close similarities in pattern and degree between space flight and bed rest in effects on calcium metabolism, relevant long-term human bed rest studies have been included. An analysis is presented of the bone calcium loss data with respect to degree, duration and significance, as well as relative failure of reversibility or recovery following flights. Possible mechanisms of bone loss are discussed: the physiological condition of disuse atrophy, increase in bone resorption, decrease (later and lesser) in bone formation, decrease in intestinal calcium absorption, increase in glucocorticoids, along with the threat of urinary tract stone formation and proposed countermeasures. Considerable future research is needed, particularly on mechanisms of bone loss and on countermeasures, to be carried out on the International Space Station and via bed rest studies, before a mission to and return from Mars is undertaken.

Urinary stones following renal transplantation.

Background:The formation of urinary tract stones following renal transplantation is a rare complication. The clinical features of stones after transplantation differ from those of non-transplant patients. Renal colic or pain is usually absent and rarely resembles acute rejection.Methods:We retrospectively studied 849 consecutive kidney transplant patients in The Rogosin Institute/The Weill-Cornell Medical Center, New York who were transplanted between 1980 and 1997 and had functioning grafts for more than 3 months, to determine the incidence of stone formation, composition, risk factors and patient outcome.Results:At our center, urinary stones were diagnosed in 15 patients (1.8%) of 849 functioning renal grafts for 3 or more months. Of the 15 patients, 10 were males and 5 were females in their third and fourth decade. Eight patients received their transplant from living donors and 7 from cadaveric donors. The stones were first diagnosed between 3 and 109 months after transplantation (mean 17.8 months) and 5 patients had recurrent episodes. The stones were located in the bladder in 11 cases (73.3%), transplanted kidney in 3 cases and in multiple sites in one case. The size of stones varied from 3.4 mm to 40 mm (mean 12 mm). The composition of stones was a mixed form of calcium oxalate and calcium phosphate in 5 cases and 4 patients had infected stones consisting of struvite or mixed form of struvite and calcium phosphate. Factors predisposing to stone formation included tertiary hyperparathyroidism (n=8), hypercalciuria (n=5), recurrent urinary tract infection (n=5), hypocitraturia (n=4), and obstructive uropathy (n=2). Many cases had more than one risk factor. Clinically, painless hematuria was observed in 6 patients and dysuria without bacteriuria in 5 patients. None had renal colic or severe pain at any time. There were no changes in graft function at diagnosis and after removal of stones. Five patients passed stones spontaneously and 8 patients underwent cystoscopy for stone removal.Conclusion:Urinary stone formation following kidney transplantation is a rare complication (1.8%). Hyperparathyroidism, hypercalciuria, recurrent urinary tract infection and hypocitraturia are the most common risk factors, but often there are multiple factors which predispose to stone formation. To detect stones and determine their location and size, ultrasonography appears to be the most useful diagnostic tool. Prompt diagnosis, the removal of stones and stone-preventive measures can prevent adverse effects on renal graft outcome.

Role of the Ca2+-Sensing Receptor in Divalent Mineral Ion Homeostasis

The divalent mineral cations Ca2+ and Mg2+ play many and diverse roles both in the function of cells and in extracellular processes. The metabolism of these cations is a complex process involving the coordinated function of several organ systems and endocrine glands. A recently cloned G-protein-coupled receptor responds to extracellular calcium concentration (Ca2+0-sensing receptor, CaSR) and mediates several of the known effects of Ca2+0 on parathyroid and renal function. The CaSR, which is also expressed in a number of other tissues including thyroidal C-cells, brain and gastrointestinal tract, may function as a Ca2+0 sensor in these tissues as well. Thus, Ca2+0 is a first messenger (or hormone) which, via CaSR-mediated activation of second messenger systems (e.g. phospholipases C and A2, cyclic AMP) leads to altered function of these cells. Several mutations in the human CaSR gene have been identified and shown to cause three inherited diseases of calcium homeostasis, clearly implicating the CaSR as an important component of the homeostatic mechanism for divalent mineral ions. Ca2+ and Mg2+ losses from the body are regulated by altering the urinary excretion of these divalent cations. The localization of the CaSR transcripts and protein in the kidney not only provides a basis for a direct Ca2+0 (or Mg2+0)-mediated regulation of Ca2+ (and Mg2+) excretion but also suggests a functional link between divalent mineral and water metabolism. In the kidney, the thick ascending limb of Henle (TAL) plays crucial roles in regulating both divalent mineral reabsorption and urine concentration. Recent studies have suggested models whereby extracellular Ca2+, via the CaSR expressed in the TAL as well as in the collecting duct system, modulates both Ca2+ 0 and Mg2+ 0 as well as water reabsorbtion. When taken together, these studies suggest that the CaSR not only provides the primary mechanism for Ca2+ 0-mediated regulation of parathyroid hormone secretion from parathyroid glands but also for direct modulation of renal divalent mineral excretion and urinary concentrating ability. These latter functions may furnish a mechanism for integrating and balancing water and divalent cation losses that minimizes the risk of urinary tract stone formation. This mechanism can explain hypercalcemia-mediated polyuria (diabetes insipidus).

Differences in the free Ca2+ in undiluted urine from stone formers and normal subjects using a new generation of ion‐selective electrodes

To measure the ionized Ca2+ in urine from normal subjects and patients with urinary tract stones. Urine samples were obtained from 37 normal subjects and 52 stone-formers. Ca2+ was measured using plastic dip-cast ion-selective electrodes; total Ca and other variables were measured by standard analytical techniques. The ionized Ca2+ and the total Ca were greater in stone-formers' urine although the difference was more significant with the Ca2+ data, especially at a standardized pH. Absolute values of the Ca2+ were dependent on the type of reference electrode used. The Ca2+ was a function of urine pH; lower values were recorded as pH increased. Measured values of the Ca2+ did not correlate well with calculated values using a standard computer program. Measurement of the Ca2+ in spot urine samples at a standard pH provides a more discriminative test than total Ca for the presence of urinary tract stones. The pH dependence of the Ca2+ may have important consequences in the formation of urinary tract stones. The poor correlation between measured and computed values of Ca2+ emphasizes the importance of accurate measurement of this variable.

Repeated Percutaneous Nephrolithotomy in Patient with Recurrent Cystine Lithiasis: Preservation of Renal Function

Cystinuria places the patient at continual risk for urinary tract stone formation. Despite aggressive medical therapy, multiple stone recurrences are common, and surgical intervention is often required. Historically, repeated open procedures have been associated with high morbidity. Extracorporeal shock wave lithotripsy has a disappointing record against cystine stones, and percutaneous nephrolithotomy has evolved into the optimal form of surgical therapy for these patients. We report on a patient whose recurrent unilateral cystine calculi necessitated four percutaneous nephrolithotomies with excellent preservation of renal anatomy and function. This result compares favorably with those obtained from repeated open stone procedures in the cystinuric population.