Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study.

BACKGROUND: Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. METHODS: HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. RESULTS: SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. CONCLUSIONS: The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.

Prophylaxis of Recurrent Stone Disease in Outpatient Clinics in Germany: A Quality-of-Care Concern.

INTRODUCTION: The aim of the study was to survey current practices for preventing recurrent stone disease in an outpatient clinic setting in Germany. METHODS: Two invitations to complete an anonymous REDCap® survey were emailed to members of the occupational union of German urologists who work as outpatient urologists ("Berufsverband Deutscher Urologen e.V."). The survey included questions on diagnostic modalities and counselling to prevent stone disease. RESULTS: A total of 130 outpatient urologists completed the survey. 84.6% of urologists give general advice to first-time stone formers. Recommendations comprise increased fluid uptake in 100%, two-thirds advice on calcium and oxalate intake, and one-third on salt and protein intake. 64.6% perform a metabolic evaluation for high-risk stone formers. However, patients with risk factors other than repeat stone disease are often overlooked. Urologists agreed that a lack of time (73.1%) and reimbursement (64.6%), as well as insufficient patient compliance (60.8%), pose significant challenges. The majority of urologists agreed that training is required. CONCLUSION: General recommendations for stone formers are usually provided, but nutritional advice tends to be incomplete. Our results raise quality-of-care concerns: Metabolic evaluation of stone formers at high risk of recurrence is uncommon. Structural changes are required due to time constraints, and poor remuneration must be addressed to improve patient care.

Association between hypertension and 24-h urine composition in adults without urolithiasis in China.

PURPOSE: To explore the association between hypertension and 24-h urine composition in adults without urolithiasis in China. MATERIALS AND METHODS: Blood test and 24-h urine analysis were performed on 958 non-stone formers in six cities to select eligible participants. Eligible participants were divided into hypertension group and non-hypertension group according to WHO guidelines. The 24-h urine compositions between two groups were compared using univariate and multivariate logistic regressions. RESULTS: A total of 584 adults without urolithiasis were included in this analysis. Compared with non-hypertension group, hypertension group had significantly older age, higher BMI, higher prevalence of diabetes mellitus and higher levels of total cholesterol and LDL, but lower eCCr value, lower levels of serum creatinine and serum sodium (all P value < 0.05). In univariable comparisons, hypertension patients had significantly higher level of urine potassium (mean difference [MD] = - 3.89 mmol, 95% confidence interval [CI] - 7.37 to - 0.42, P = 0.014) but lower levels of urine creatinine (MD = 0.80 mmol, 95% CI 0.21-1.39, P = 0.004) and pH (MD = 0.12, 95% CI - 0.01 to 0.25, P = 0.033) than non-hypertension adults. However, no significant difference was found in all 24-h urinary components between two groups (all P value > 0.05) in multivariate Logistic regression analyses. CONCLUSIONS: Our study demonstrated that hypertension did not independently influence the 24-h urine composition in adults without urolithiasis in China; however, we cannot make such an arbitrary conclusion that hypertension was not a risk factor for urolithiasis.

Metabolic evaluation of patients with recurrent, multiple or bilateral renal stones in Jaffna.

INTRODUCTION: A comprehensive evaluation to identify metabolic abnormalities will help design management strategies for prevention of renal stone recurrences. The objective of this study is to identify the metabolic risk factors in a series of patients with recurrent, multiple or bilateral renal stone disease from the Northern Province, Sri Lanka. METHODS: This is a hospital based observational study on patients with recurrent, multiple or bilateral renal stones. Metabolic evaluation workout included, fasting non-tourniquet venous blood sample for serum ionized calcium, creatinine, and uric acid, freshly voided early morning urine sample for pH and laboratory urinalysis, and collection of two sets of 24 hour urine samples on two separate days, for phosphorous, creatinine, oxalate, uric acid, magnesium, calcium and citrate. RESULTS: The mean values of each metabolic parameter measured on the two sets of 24 hour urine samples, were found to be within the normal reference range for the entire 30 patient study group taken as whole, although the mean values for 24 hour urine magnesium (79.79±51.36 mg) and urine calcium (125.02±73.32 mg) were found to be towards the lower limit of normal reference range and the 24 hour urine oxalate (0.38±0.22 mmol) was found to be towards the upper limit of normal reference range. However, 80% of patients individually showed abnormal metabolic results either as single derangement (13 patients, 43.3%) or in multiple combinations of derangements (11 patients, 36.7%). Six patients (20%) did not have any metabolic abnormalities. Hyperoxaluria, hyperuricosuria, hypomagnesuria and hypocitraturia were the metabolic abnormalities identified among the study group. CONCLUSION: A comprehensive metabolic evaluation of each patient with recurrent, multiple or bilateral renal stone disease can help identify metabolic abnormalities, either as a single abnormality or combinations of abnormalities, specific for them. Such patient profiling will help develop bespoke management strategy based on appropriate dietary advice and specific medical treatment towards prevention of further stone formation.

Chronomics of Circulating Plasma Lipid Peroxides and Antioxidant Enzymes in Renal Stone Formers.

The chronome of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of time qualified preventive therapeutic and dietary interventions. One hundred renal stone patients, 20-60 years of age, and 50 clinically healthy volunteers, 21-45 years, were synchronized for 1 week with diurnal activity from 06:00 to 22:00 and nocturnal rest. All subjects took their usual meals three times daily (breakfast around 08:30, lunch around 13:00, and dinner around 20:30) with usual fluid intake. Drugs known to affect free radical system were not taken. Blood samples were collected at 6-h intervals for 24-h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in terms of malondialdehyde (MDA) and blood superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. A marked circadian variation was demonstrated for each studied variable by population-mean cosinor in renal stone patients and healthy participants (p < 0.001). By comparison to healthy subjects, parameter tests indicate that the stone formers had a higher MESOR of MDA, but a lower MESOR of SOD, GPx, GR and CAT. Furthermore, the patients also differed from the healthy controls in terms of their circadian amplitude and acrophase (tested jointly) of all variables (p < 0.001). Mapping the broader time structure with multifrequency circadian characteristics of oxidants and anti-oxidants is needed for exploring their role as marker in the treatment and management of urolithiasis.

Impact of dyslipidemia on 24-h urine composition in adults without urolithiasis.

PURPOSES: To evaluate the influence of dyslipidemia on 24-h urine composition in adults who were non-stone formers (NF). METHODS: Samples for 24-h urine composition were analyzed from 584 NF adults without urolithiasis in a national six-city-based epidemiologic study. The samples were divided into groups based on total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The groups were compared based on demographic data and each component of 24-h urinalysis. RESULTS: The numbers of participants in high TG, high TC, high LDL, and low HDL were 106, 175, 147, and 59, respectively. The high TG group had increased urinary excretions of oxalate [mean difference (MD) = 0.032 mmol, 95% confidence interval (CI): 0.000-0.065] and potassium (MD = 4.298 mmol, 95%CI: 0.182-8.414). Increased urinary excretion of calcium (MD = 0.531 mmol, 95%CI: 0.061-1.001), sodium (MD = 41.561 mmol, 95%CI: 9.179-73.942), and chloride (MD = 45.209 mmol, 95%CI: 12.118-78.299) were found in the high TC group. Interestingly, the high LDL group had a decreased urinary excretion of calcium (MD = - 0.573 mmol, 95%CI: -1.048 to - 0.097), oxalate (MD = - 0.038 mmol, 95%CI: -0.07 to - 0.006), sodium (MD = - 53.285 mmol, 95%CI: -85.823 to - 20.748), and chloride (MD = - 55.809 mmol, 95%CI: -89.035 to - 22.583). Increased urinary excretions of citrate (MD = 0.455 mmol, 95%CI: 0.076-0.835) and magnesium (MD = 0.697 mmol, 95%CI: 0.244-1.149) were found in the low HDL group. CONCLUSIONS: The present study first investigated the effects of dyslipidemia on 24-h urinalysis in NF adults. Of note, high LDL and low HDL were found to be adversely related to kidney stone formation. However, people with high TG and high TC should be cautious of getting kidney stones.

Circadian Periodicity of Circulating Plasma Lipid Peroxides, Uric Acid and Ascorbic Acid in Renal Stone Formers.

Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20-60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21-45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90 ± 0.03 vs. 2.28 ± 0.06; F = 94.929, p < 0.001), a lower MESOR of serum ascorbic acid (0.722 ± 0.010 vs. 0.839 ± 0.10; F = 32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient's response to treatment for further management.

Vascular calcification in kidney stone formers: the impact of age and stone composition.

An increased prevalence of vascular calcification (VC) has been reported in kidney stone formers (KSFs), along with an elevated cardiovascular risk. The aim of the current study is to assess whether VC in these patients develops at a younger age and is influenced by stone composition. This single-center, matched case-control study included KSFs with uric acid or calcium oxalate stones (diagnosed based on stone analysis) and age- and sex-matched controls without a history of nephrolithiasis. The prevalence and severity of abdominal aortic calcification (AAC) and bone mineral density (BMD) were compared between KSFs and non-KSFs. In total, 335 patients were investigated: 134 with calcium oxalate stones, 67 with uric acid stones, and 134 controls. Overall, the prevalence of AAC was significantly higher among calcium stone formers than among the controls (67.9% vs. 47%, p = 0.002). In patients under 60 years of age, those with calcium oxalate stones exhibited both a significantly elevated AAC prevalence (61.9% vs. 31.3%, p = 0.016) and severity (94.8 ± 15.4 vs. 30.3 ± 15.95, p = 0.001) compared to the controls. Within the age group of 40-49, osteoporosis was identified only in the KSFs. Multivariate analysis identified age, smoking, and the presence of calcium stones as independent predictors of AAC. This study highlights that VC and osteoporosis occur in KSFs at a younger age than in non-stone-formers, suggesting potential premature VC. Its pathogenesis is intriguing and needs to be elucidated. Early evaluation and intervention may be crucial for mitigating the cardiovascular risk in this population.

Recurrent Urinary Stone Formers: Imaging Assessment and Endoscopic Treatment Strategies: A Systematic Search and Review.

Background/Objectives: Nephrolithiasis is a heterogeneous disease with a high prevalence and recurrence rate. Although there has been much progress regarding the surgical treatment of stones, a standardized follow-up, especially in recurrent stone formers (SFs), has yet to be decided. This fact leads to the overuse of computed tomography (CT) scans and many reoperations in patients, thus increasing their morbidity and the financial burden on the health systems. This review systematically searched the literature for original articles regarding imaging strategies and endoscopic treatment for patients with recurrent urolithiasis, aiming to identify optimal strategies to deal with these patients. Methods: We systematically searched the Medline database (accessed on 1 April 2024) for articles regarding imaging modalities and endoscopic treatment for patients with recurrent urinary tract lithiasis. Results: No specific follow-up or endoscopic treatment strategy exists for patients with recurrent urolithiasis. CT scan was the imaging modality most used in the studies, followed by X-ray, ultrasonography, and digital tomosynthesis. A transparent algorithm could not be identified. Percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and ureteroscopy (URS) were used in the studies for endoscopic treatment. PCNL showed the best stone-free (SFr) rate and lowest hazard ratio (HR) for reoperation. RIRS showed superiority over extracorporeal shockwave lithotripsy for recurrent SFs, but fragments over 4 mm increased the recurrent rate. URS has an increased HR for reoperation for bilateral stones. Conclusions: The heterogeneity of urolithiasis leaves urologists without a standardized plan for recurrent SFs. Thus, each patient's follow-up should be planned individually and holistically. Pre-stenting is not to be avoided, especially in high-risk patients, and SFr status needs to be the aim. Finally, CT scans should not be generally overused but should be part of a patient's treatment plan. Prospective studies are required to define SFr status, the size of significant residual fragments, and the modalities of intervention and follow-up.

Simple dietary advice targeting five urinary parameters reduces urinary supersaturation in idiopathic calcium oxalate stone formers.

Among 208 kidney stone patients referred within 2 years, 75 patients (66 men, nine women) with truly idiopathic calcium oxalate stones (ICSF) were recruited. Dietary advice (DA) aimed at (1) urine dilution, (2) reduced crystallization promotion (lowering oxalate), and (3) increased crystallization inhibition (increasing citrate). We recommended higher intakes of fluid and calcium with meals/snacks (reducing intestinal oxalate absorption) as well as increased alkali and reduced meat protein (acid) for increasing urinary citrate. The intended effects of DA were elevations in urine volume, calcium (U-Ca) and citrate (U-Cit) as well as reductions in oxalate (U-Ox) and uric acid (U-UA). We retrospectively calculated an adherence score (AS), awarding + 1 point for parameters altered in the intended direction and - 1 point for opposite changes. Calcium oxalate supersaturation (CaOx-SS) was calculated using Tiselius' AP(CaOx) index EQ. DA induced changes (all p < 0.0001) in urine volume (2057 ± 79 vs. 2573 ± 71 ml/day) and U-Ca (5.49 ± 0.24 vs. 7.98 ± 0.38 mmol/day) as well as in U-Ox (0.34 ± 0.01 vs. 0.26 ± 0.01 mmol/day) and U-UA (3.48 ± 0.12 vs. 3.13 ± 0.10 mmol/day). U-Cit only tendentially increased (3.07 ± 0.17 vs. 3.36 ± 0.23 mmol/day, p = 0.06). DA induced a 21.5% drop in AP(CaOx) index, from 0.93 ± 0.05 to 0.73 ± 0.05 (p = 0.0005). Decreases in CaOx-SS correlated with AS (R = 0.448, p < 0.0005), and highest AS (+ 5) always indicated lowering of CaOx-SS. Thus, simple DA can reduce CaOx-SS which may be monitored by AS.

The Impact of Thiazides and Potassium Citrate on Bone Mineral Density Evaluated by CT Scan in Stone Formers.

INTRODUCTION: Thiazides and citrate prevent kidney stones and improve bone mineral density (BMD). The objective of this study was to opportunistically utilize the noncontrast CT (NCCT) scan used for stone detection to identify those with low BMD and follow the impact of potassium citrate and thiazides on longitudinal BMD measurements. MATERIALS AND METHODS: A retrospective analysis was performed on 299 kidney stone patients treated with thiazides and/or potassium citrate for a minimum of 1 year. For each patient, BMD was estimated at L1 with CT attenuation measured in HU. A level of 160 HU was chosen to distinguish normal from low BMD. Pairwise t-test was used to compare the continuous outcomes before and after treatment for the whole cohort and the low BMD subgroup. Linear regression was performed to find if any association exists between the duration of follow-up and the changes in HU. A matched pair t-test was performed to compare among the medications used and the impact of their doses on the HU outcomes. RESULTS: Patients with low BMD (HU <160) comprised (n = 186, 62.2%) the cohort. A total of 16.1% normalized after 1 year of treatment and 68% had an increase in HU. The mean change in HU was 8.6 (p = 0.0001). Linear regression demonstrated no association between the duration of treatment and the HU changes (p = 0.64). Hydrochlorothiazide (HCTZ) 50 mg was more effective at improving BMD (HU +19.7, p = 0.04) compared with 25 mg (+2.9) or 12.5 mg (HU +6.4). Majority of the low BMD subgroup were either postmenopausal women (n = 88) or men with age older than 60 (n = 74) and both showed a significant increase in HU (3.125, 10.731), p-value (0.0453, 0.0007), respectively. CONCLUSION: Stone health and bone health are synergistic. The impact of thiazides and citrates on BMD can be monitored opportunistically with the NCCT scan.

Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones.

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF.