Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a disorder in which urinary solutes precipitate to form aggregates of crystalline material in the urinary space. The incidence of nephrolithiasis has been increasing, and the demographics have been evolving. Once viewed as a limited disease with intermittent exacerbations that are simply managed by urologists, nephrolithiasis is now recognized as a complex condition requiring thorough evaluation and multifaceted care. Kidney stones are frequently manifestations of underlying systemic medical conditions such as the metabolic syndrome, genetic disorders, or endocrinopathies. Analysis of urine chemistries and stone composition provide a window into pathogenesis and direct ancillary studies to uncover underlying diseases. These studies allow providers to devise individualized strategies to limit future stone events. Given its complexity, kidney stone disease is best addressed by a team led by nephrologists and urologists with input from multiple other health professionals including dietitians, endocrinologists, interventional radiologists, and endocrine surgeons. In this installment of AJKD's Core Curriculum in Nephrology, we provide a case-based overview of nephrolithiasis, divided by the individual stone types. The reader will gain a pragmatic understanding of the pathophysiology, evaluation, and management of this condition.Published by Elsevier Inc.

Kidney stone disease (KSD) (alternatively nephrolithiasis or urolithiasis) is a global health care problem that affects almost people in developed and developing countries. Its prevalence has been continuously increasing with a high recurrence rate after stone removal. Although effective therapeutic modalities are available, preventive strategies for both new and recurrent stones are required to reduce physical and financial burdens of KSD. To prevent kidney stone formation, its etiology and risk factors should be first considered. Low urine output and dehydration are the common risks of all stone types, whereas hypercalciuria, hyperoxaluria, and hypocitraturia are the major risks of calcium stones. In this article, up-to-date knowledge on strategies (nutrition-based mainly) to prevent KSD is provided. Important roles of fluid intake (2.5-3.0 L/d), diuresis (>2.0-2.5 L/d), lifestyle and habit modifications (for example, maintain normal body mass index, fluid compensation for working in high-temperature environment, and avoid cigarette smoking), and dietary management [for example, sufficient calcium at 1000-1200 mg/d, limit sodium at 2 or 3-5 g/d of sodium chloride (NaCl), limit oxalate-rich foods, avoid vitamin C and vitamin D supplements, limit animal proteins to 0.8-1.0 g/kg body weight/d but increase plant proteins in patients with calcium and uric acid stone and those with hyperuricosuria, increase proportion of citrus fruits, and consider lime powder supplementation] are summarized. Moreover, uses of natural bioactive products (for example, caffeine, epigallocatechin gallate, and diosmin), medications (for example, thiazides, alkaline citrate, other alkalinizing agents, and allopurinol), bacterial eradication, and probiotics are also discussed. Adv Nutr 2023;x:xx-xx.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Studies on howmetabolic syndrome affects renal stone progression in untreated asymptomatic patients are lacking. Therefore, we investigated the effect of metabolic syndrome on changes in renal stone size.We retrospectively analyzed 820 patients with renal stones incidentally detected on CT during regular health examinations and who underwent follow-up CT evaluations for > 1 year. The patients were divided into two groups according to the presence of metabolic syndrome. Changes in stone size during the follow-up were assessed, and differences were compared according to various factors. Predictors of stone size change on CT were assessed using linear regression analysis.Overall, 820 asymptomatic patients without a history of stone treatments and with a mean follow-up of 52.4 months were included. Of these, 104 (12.7%) had metabolic syndrome and 335 (40.9%) showed stone size increase during the follow-up. The stone size at diagnosis was not significantly different between patients with and without metabolic syndrome (225.3 ± 332.6 vs. 183.9 ± 310.2 mm, p = 0.159); however, a significant difference was observed in the change in stone size at follow-up (148.5 ± 352.0 vs. 81.5 ± 222.4 mm, p = 0.001). Multivariable analysis showed that age (β = - 0.11; - 5.92 to -0.69; p = 0.013), fasting glucose level ≥ 100 mg/dl (β = 0.11; 9.78-99.73; p = 0.017), and metabolic syndrome (β = 0.10; 9.78-99.73; p = 0.017) were factors predictive of stone size changes.Metabolic syndrome, fasting glucose level ≥ 100 mg/dl and young age are positively related to renal stone size changes. Therefore, periodic follow-up and metabolic syndrome management are required in asymptomatic patients with renal stones, especially in young age.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.

Kidney stone disease is a lifestyle-related disease prevalent in developed countries; however, effective medical treatment for the disease is not yet well established. As cellular damage in renal tubular cells (RTCs) is responsible for the disease, here, we focused on the role of macroautophagy/autophagy in RTCs. We found that autophagic activity was significantly decreased in mouse RTCs exposed to calcium oxalate (CaOx) monohydrate crystals and in the kidneys of GFP-conjugated MAP1LC3B (microtubule- associated protein 1 light chain 3 beta) transgenic mice with CaOx nephrocalcinosis induced by glyoxylate. This caused accumulation of damaged intracellular organelles, such as mitochondria and lysosomes, the normal functioning of which is mediated by functional autophagy. An impairment of autophagy was also observed in the mucosa with plaques of CaOx kidney stone formers. We determined that the decrease in autophagy was caused by an upregulation of MTOR (mechanistic target of rapamycin kinase), which consequently resulted in the suppression of the upstream autophagy regulator TFEB (transcription factor EB). Furthermore, we showed that an MTOR inhibitor could recover a decrease in autophagy and alleviate crystal-cell interactions and the formation of crystals associated with increased inflammatory responses. Taken together, we conclude that autophagy compromised by MTOR deregulation is a fundamental feature in the pathology of kidney stone formation, and propose that chemical inhibition of MTOR could be a prospective strategy for disease suppression.: ACTB: actin, beta; CaOx: calcium oxalate; CKD: chronic kidney disease; COM: calcium oxalate monohydrate; LGALS3/galectin-3: lectin, galactose binding, soluble 3; GFP: green fluorescent protein; GOX: glyoxylate; HE: hematoxylin and eosin; MAPLC3B: microtubule- associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NAC: N-acetyl-L-cysteine; ROS: reactive oxygen species; RTC: renal tubular cell; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TEM: transmission electron microscopy; tfLC3: tandem fluorescent-tagged LC3; 3-MA: 3-methyladenine.

Interstitial Randall's plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. The 24-h urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall's plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall's plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.

Urine pH has been thought to be an important factor that can modulate kidney stone formation. Nevertheless, there was no systematic evaluation of such pH effect. Our present study thus addressed effects of differential urine pH (4.0-8.0) on calcium oxalate (CaOx) crystallization, crystal-cell adhesion, crystal internalization into renal tubular cells, and binding of apical membrane proteins to the crystals. Microscopic examination revealed that CaOx monohydrate (COM), the pathogenic form, was crystallized with greatest size, number and total mass at pH 4.0 and least crystallized at pH 8.0, whereas COD was crystallized with the vice versa order. Fourier-transform infrared (FT-IR) spectroscopy confirmed such morphological study. Crystal-cell adhesion assay showed the greatest degree of crystal-cell adhesion at the most acidic pH and least at the most basic pH. Crystal internalization assay using fluorescein isothiocyanate (FITC)-labelled crystals and flow cytometry demonstrated that crystal internalization into renal tubular cells was maximal at the neutral pH (7.0). Finally, there were no significant differences in binding capacity of the crystals to apical membrane proteins at different pH. We concluded that the acidic urine pH may promote CaOx kidney stone formation, whereas the basic urine pH (i.e. by alkalinization) may help to prevent CaOx kidney stone disease.

Background In the kidney, low urinary citrate increases the risk for developing kidney stones, and elevation of luminal succinate in the juxtaglomerular apparatus increases renin secretion, causing hypertension. Although the association between stone formation and hypertension is well established, the molecular mechanism linking these pathophysiologies has been elusive. Methods To investigate the relationship between succinate and citrate/oxalate levels, we assessed blood and urine levels of metabolites, renal protein expression, and BP (using 24-hour telemetric monitoring) in male mice lacking slc26a6 (a transporter that inhibits the succinate transporter NaDC-1 to control citrate absorption from the urinary lumen). We also explored the mechanism underlying this metabolic association, using coimmunoprecipitation, electrophysiologic measurements, and flux assays to study protein interaction and transport activity. Results Compared with control mice, slc26a6(-/-) mice (previously shown to have low urinary citrate and to develop calcium oxalate stones) had a 40% decrease in urinary excretion of succinate, a 35% increase in serum succinate, and elevated plasma renin. Slc26a6(-/-) mice also showed activity-dependent hypertension that was unaffected by dietary salt intake. Structural modeling, confirmed by mutational analysis, identified slc26a6 and NaDC-1 residues that interact and mediate slc26a6's inhibition of NaDC-1. This interaction is regulated by the scaffolding protein IRBIT, which is released by stimulation of the succinate receptor SUCNR1 and interacts with the NaDC-1/sIc26a6 complex to inhibit succinate transport by NaDC-1. Conclusions These findings reveal a succinate/citrate homeostatic pathway regulated by IRBIT that affects BP and biochemical risk of calcium oxalate stone formation, thus providing a potential molecular link between hypertension and lithogenesis.

The NLRP3 inflammasome is a cytosolic multiprotein caspase-activating complex platform involved in innate immunity required for the maturation and release of interleukin (IL)-1β and IL-18. Both cytokines activate their respective receptors present on cells inside and outside kidneys, resulting in the release of other proinflammatory cytokines to set up an inflammatory milieu both within the kidney and systemically. The canonical NLRP3-ASC-caspase-1-IL-1β-IL-18 axis has been shown to contribute to the pathophysiology of several kidney diseases by regulating renal necroinflammation. However, many recent studies have emphasized the inflammasome-independent functions of NLRP3 in chronic kidney disease (CKD) pathogenesis. This review highlights the contribution of the inflammasome-independent functions of NLPR3, for example, in fibrotic tissue remodeling, in tubular epithelial cell apoptosis, and in metabolic pathways, during the development and progression of CKD in various experimental models and humans. Interestingly, therapies targeting the inflammasome effectors (e.g., IL-1 receptor antagonists and IL-1β) have been approved for therapeutic use for NLRP3-dependent diseases; however, no NLRP3 antagonists have been approved for therapeutic use until now. This review highlights the double-edged sword-like functions of NLRP3 in the regulation of renal necroinflammation and fibrosis and therefore emphasizes the urgent need for specific NLRP3 inhibitors because of the broad therapeutic potential they offer for the treatment of CKD.Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

The prevalence of kidney stone disease is rising along with increasing rates of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome.To investigate the associations among the presence and severity of T2DM, glycemic control, and insulin resistance with kidney stone disease.We performed a cross-sectional analysis of all adult participants in the 2007-2010 National Health and Nutrition Examination Survey (NHANES). A history of kidney stone disease was obtained by self-report. T2DM was defined by self-reported history, T2DM-related medication usage, and reported diabetic comorbidity. Insulin resistance was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) definition. We classified glycemic control using glycosylated hemoglobin A1c (HbA1c) and fasting plasma-glucose levels (FPG).Odds ratios (OR) for having kidney stone disease were calculated for each individual measure of T2DM severity. Logistic regression models were fitted adjusting for age, sex, race/ethnicity, smoking history, and the Quételet index (body mass index), as well as laboratory values and components of metabolic syndrome.Correlates of kidney stone disease included a self-reported history of T2DM (OR: 2.44; 95% confidence interval [CI], 1.84-3.25) and history of insulin use (OR: 3.31; 95% CI, 2.02-5.45). Persons with FPG levels 100-126 mg/dl and >126 mg/dl had increased odds of having kidney stone disease (OR 1.28; 95% CI, 0.95-1.72; and OR 2.29; 95% CI, 1.68-3.12, respectively). Corresponding results for persons with HbA1c 5.7-6.4% and ≥ 6.5% were OR 1.68 (95% CI, 1.17-2.42) and OR 2.82 (95% CI, 1.98-4.02), respectively. When adjusting for patient factors, a history of T2DM, the use of insulin, FPI, and HbA1c remained significantly associated with kidney stone disease. The cross-sectional design limits causal inference.Among persons with T2DM, more-severe disease is associated with a heightened risk of kidney stones.Copyright © 2013 European Association of Urology. All rights reserved.

Larger body size may result in increased urinary excretion of calcium, oxalate, and uric acid, thereby increasing the risk for calcium-containing kidney stones. It is unclear if obesity increases the risk of stone formation, and it is not known if weight gain influences risk.To determine if weight, weight gain, body mass index (BMI), and waist circumference are associated with kidney stone formation.A prospective study of 3 large cohorts: the Health Professionals Follow-up Study (N = 45,988 men; age range at baseline, 40-75 years), the Nurses' Health Study I (N = 93,758 older women; age range at baseline, 34-59 years), and the Nurses' Health Study II (N = 101,877 younger women; age range at baseline, 27-44 years).Incidence of symptomatic kidney stones.We documented 4827 incident kidney stones over a combined 46 years of follow-up. After adjusting for age, dietary factors, fluid intake, and thiazide use, the relative risk (RR) for stone formation in men weighing more than 220 lb (100.0 kg) vs men less than 150 lb (68.2 kg) was 1.44 (95% confidence interval [CI], 1.11-1.86; P =.002 for trend). In older and younger women, RRs for these weight categories were 1.89 (95% CI, 1.52-2.36; P<.001 for trend) and 1.92 (95% CI, 1.59-2.31; P<.001 for trend), respectively. The RR in men who gained more than 35 lb (15.9 kg) since age 21 years vs men whose weight did not change was 1.39 (95% CI, 1.14-1.70; P =.001 for trend). Corresponding RRs for the same categories of weight gain since age 18 years in older and younger women were 1.70 (95% CI, 1.40-2.05; P<.001 for trend) and 1.82 (95% CI, 1.50-2.21; P<.001 for trend). Body mass index was associated with the risk of kidney stone formation: the RR for men with a BMI of 30 or greater vs those with a BMI of 21 to 22.9 was 1.33 (95% CI, 1.08-1.63; P<.001 for trend). Corresponding RRs for the same categories of BMI in older and younger women were 1.90 (95% CI, 1.61-2.25; P<.001 for trend) and 2.09 (95% CI, 1.77-2.48; P<.001 for trend). Waist circumference was also positively associated with risk in men (P =.002 for trend) and in older and younger women (P<.001 for trend for both).Obesity and weight gain increase the risk of kidney stone formation. The magnitude of the increased risk may be greater in women than in men.

Most kidney stones are composed of calcium oxalate, and minor changes in urine oxalate affect the stone risk. Obesity is a risk factor for kidney stones and a positive correlation of unknown etiology between increased body size, and elevated urinary oxalate excretion has been reported. Here, we used obese ob/ob (ob) mice to elucidate the pathogenesis of obesity-associated hyperoxaluria. These ob mice have significant hyperoxaluria (3.3-fold) compared with control mice, which is not due to overeating as shown by pair-feeding studies. Dietary oxalate removal greatly ameliorated this hyperoxaluria, confirming that it is largely enteric in origin. Transporter SLC26A6 (A6) plays an essential role in active transcellular intestinal oxalate secretion, and ob mice have significantly reduced jejunal A6 mRNA (- 80%) and total protein (- 62%) expression. While net oxalate secretion was observed in control jejunal tissues mounted in Ussing chambers, net absorption was seen in ob tissues, due to significantly reduced secretion. We hypothesized that the obesity-associated increase in intestinal and systemic inflammation, as reflected by elevated proinflammatory cytokines, suppresses A6-mediated intestinal oxalate secretion and contributes to obesity-associated hyperoxaluria. Indeed, proinflammatory cytokines (elevated in ob mice) significantly decreased intestinal oxalate transport in vitro by reducing A6 mRNA and total protein expression. Proinflammatory cytokines also significantly reduced active mouse jejunal oxalate secretion, converting oxalate transport from net secretion in vehicle-treated tissues to net absorption in proinflammatory cytokines-treated tissues. Thus, reduced active intestinal oxalate secretion, likely secondary to local and systemic inflammation, contributes to the pathogenesis of obesity-associated hyperoxaluria. Hence, proinflammatory cytokines represent potential therapeutic targets.Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Obesity is a significant health concern and is associated with an increased risk of nephrolithiasis, particularly in women. The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are common in these patients. Use of surgical procedures for obesity (bariatric surgery) has risen over the past two decades. Although such procedures effectively manage obesity-dependent comorbidities, several large, controlled studies have revealed that modern bariatric surgeries increase the risk of nephrolithiasis by approximately twofold. In patients who have undergone bariatric surgery, fat malabsorption leads to hyperabsorption of oxalate, which is exacerbated by an increased permeability of the gut to oxalate. Patients who have undergone bariatric surgery show characteristic 24 h urine parameters including low urine volume, low urinary pH, hypocitraturia, hyperoxaluria and hyperuricosuria. Prevention of stones with dietary limitation of oxalate and sodium and a high intake of fluids is critical, and calcium supplementation with calcium citrate is typically required. Potassium citrate is valuable for treating the common metabolic derangements as it raises urinary pH, enhances the activity of stone inhibitors, reduces the supersaturation of calcium oxalate, and corrects hypokalaemia. Both pyridoxine and probiotics have been shown in small studies to reduce hyperoxaluria, but further study is necessary to clarify their effects on stone morbidity in the bariatric surgery population.

To evaluate the association between dyslipidemia and nephrolithiasis risk in a Chinese population.Fasting plasma lipid profiles were measured in a case-control study of 540 nephrolithiasis cases and 656 kidney stone-free controls.Triglycerides (TG) levels were significantly higher, but total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower in nephrolithiasis patients than those in the control group (each p < 0.05). Similar associations were found in both primary and recurrent nephrolithiasis patients except for TC levels. Significantly lower TC and LDL-C levels were found in all patients except those with uric acid stones. Patients with calcium oxalate (CaOx) and uric acid stones had significantly higher TG levels. Individuals with hypertriglyceridemia and low HDL-cholesterolemia were associated with increased risk of nephrolithiasis (OR 1.31, 95% CI 1.01-1.71 and OR 7.57, 95% CI 5.64-10.17, respectively). Conversely, those with hypercholesterolemia and high LDL-cholesterolemia were associated with decreased nephrolithiasis risk (OR 0.60, 95% CI 0.46-0.79 and OR 0.61, 95% CI 0.42-0.90, respectively). The risk remained in patients with CaOx stones.Our results suggest that dyslipidemia was associated with nephrolithiasis risk in a Chinese population, especially in patients with CaOx stones.© 2019 S. Karger AG, Basel.

Chronic kidney diseases (CKD) are usually associated with dyslipidemia. Statin therapy has been primarily recommended for the prevention of cardiovascular risk in patients with CKD; however, the effects of statins on kidney disease progression remain controversial. This study aims to investigate the effects of statin treatment on renal handling of water in patients and in animals on a high-fat diet. Retrospective cohort patient data were reviewed and the protein expression levels of aquaporin-2 (AQP2) and NLRP3 inflammasome adaptor ASC were examined in kidney biopsy specimens. The effects of statins on AQP2 and NLRP3 inflammasome components were examined in mice, 5/6 nephroectomized (5/6Nx) rats with a high-fat diet (HFD), and. In the retrospective cohort study, serum cholesterol was negatively correlated to eGFR and AQP2 protein expression in the kidney biopsy specimens. Statins exhibited no effect on eGFR but abolished the negative correlation between cholesterol and AQP2 expression. Whilst mice showed an increased urine output and a decreased expression of AQP2 protein after a HFD, which was moderately attenuated in deletion mice with HFD. In 5/6Nx rats on a HFD, atorvastatin markedly decreased the urine output and upregulated the protein expression of AQP2. Cholesterol stimulated the protein expression of NLRP3 inflammasome components ASC, caspase-1 and IL-1β, and decreased AQP2 protein abundance, which was markedly prevented by statins, likely through the enhancement of ASC speck degradation via autophagy. Serum cholesterol level has a negative correlation with AQP2 protein expression in the kidney biopsy specimens of patients. Statins can ameliorate cholesterol-induced inflammation by promoting the degradation of ASC speck, and improve the expression of aquaporin in the kidneys of animals on a HFD.© The author(s).

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P<0.03), HOMA index (-13.1+/-0.6 vs. -9.1+/-0.9%, P<0.05), Rq (5.9+/-0.4 vs. 3.1+/-0.5%, P<0.05) and glycosylated haemoglobin (-11.2+/-0.3 vs. -7. 1+/-0.4%, P<0.05). In the whole group of subjects (n=195) and at the end of the study, changes in plasma triglyceride concentrations were significantly correlated with the change in the HOMA index (r=0.44, P<0.001) and age and BMI adjusted-Rq (r=-0.32, P<0.005). Multivariate analyses demonstrated that decline in plasma triglyceride concentration was a significant determinant for explaining the effect of statin on insulin resistance and Rq. In conclusion our study demonstrates that statin administration is useful for controlling dyslipidemia in NIDDM patients and for improving the metabolic control. With regard to this latter aim, atorvastatin seems to be more powerful than simvastatin.

We studied the impact of dyslipidemia on 24-hour urinalysis and stone composition.We retrospectively identified patients with nephrolithiasis who underwent 24-hour urinalysis and lipid profile evaluation within 3 months. Patients were divided into groups based on total cholesterol, high density lipoprotein, nonhigh density lipoprotein and triglycerides. The groups were compared based on demographic data, diabetes, hypertension and each component of 24-hour urinalysis and stone composition. Multivariate analysis and linear regression were performed to control for potential confounders, including age, gender, body mass index, diabetes and hypertension.A total of 2,442 patients with a mean age of 51.1 years were included in study. On multivariate analysis patients with high total cholesterol had significantly higher urinary potassium and calcium, those with low high density lipoprotein or high triglycerides had significantly higher urinary sodium, oxalate and uric acid with lower pH, and those with high nonhigh density lipoprotein had higher urinary sodium and uric acid. Regarding stone composition, high total cholesterol and triglycerides were significantly associated with a higher uric acid stone rate (p = 0.006 and <0.001, respectively). Linear regression showed a significant association of nonhigh density lipoprotein with higher urinary sodium (p = 0.011) and uric acid (p <0.001) as well as triglycerides and higher uric acid (p = 0.017), and lower urinary pH (p = 0.005).There is a link between dyslipidemia and kidney stone risk that is independent of other components of metabolic syndrome such as diabetes and obesity. Specific alterations in the patient lipid profiles may portend unique aberrations in urine physicochemistry and stone risk.Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The goal of this study was to investigate recent changes in stone composition and patient demographics to identify factors influencing stone formation for the purpose of reducing the incidence of urolithiasis and preventing stone recurrence. This retrospective analysis includes patients who underwent percutaneous nephrolithotripsy or ureteroscopy at our institution from 2005 to 2015. Northwestern Medicine Enterprise Data Warehouse was used to retrieve demographic information and stone composition analyses. The composition of mixed stones containing uric acid (UA) and calcium oxalate monohydrate (COM) was analyzed further. Chi-squared tests were used for categorical variables and logistic regression was used to assess trends. From 2005 to 2015, 5268 stones were treated. COM was predominant in 42.2% and only 16.6% were pure. The male/female ratio decreased significantly from 1.8 to 1.08 and patient age increased (p < 0.001) with 45.6% of patients being 60 or older in 2015. Females formed more CO dihydrate (COD; p = 0.008) and struvite (p = 0.001) overall. The incidence of COM (p = 0.007) and UA (p < 0.001) rose significantly in men whereas both sexes saw a decrease in carbonate apatite (CA; p < 0.001). COM increased considerably from 12 to 75% amongst mixed stones with UA over the 11-year span. We concluded that stone formers have become older and more gender-equal. The increase in female patients parallels the increase in female obesity in the US. The rising predominance of COM, including when mixed with UA, and the scarcity of pure stones indicates it may be necessary to develop new approaches to managing and preventing urolithiasis.

Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30% and 50% despite technological and scientific advances. Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities. Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence.All relevant literature up to October 2020, listed in PubMed is reviewed.Clinical guidelines endorse the use of evidence-based medications, such as alkaline agents and thiazides, to reduce urinary mineral supersaturation and recurrence. However, there may be additional steps during stone pathogenesis where medications could moderate stone risk. Idiopathic calcium oxalate stones grow attached to Randall's plaques or plugs. Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs. The renin-angiotensin-aldosterone system (RAAS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, and NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome have all been implicated at specific steps during stone pathogenesis in animal models.In addition to supersaturation-reducing therapies, the use of anti-oxidants, free radical scavengers, and inhibitors of NADPH oxidase, NLRP3 inflammasome, and RAAS may prove beneficial for stone prevention. Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats. Although clinical evidence for their use in stone prevention in humans is limited, experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.© 2023 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.