Sex-specific Stone-forming Phenotype in Mice During Hypercalciuria/Urine Alkalinization.

Sex differences in kidney stone formation are well known. Females generally have slightly acidic blood and higher urine pH when compared with males, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide and calcium gluconate supplementation, respectively, for 4 weeks in wild-type (WT) and moderately hypercalciuric [TRPC3 knockout [KO](-/-)] male and female mice. Our goal was to develop calcium phosphate (CaP) and CaP+ calcium oxalate mixed stones in our animal model to understand the underlying sex-based mechanism of calcium nephrolithiasis. Our results from the analyses of mice urine, serum, and kidney tissues show that female mice (WT and KO) produce more urinary CaP crystals, higher [Ca2+], and pH in urine compared to their male counterparts. We identified a sex-based relationship of stone-forming phenotypes (types of stones) in our mice model following urine alkalization/calcium supplementation, and our findings suggest that female mice are more susceptible to CaP stones under those conditions. Calcification and fibrotic and inflammatory markers were elevated in treated female mice compared with their male counterparts, and more so in TRPC3 KO mice compared with their WT counterparts. Together these findings contribute to a mechanistic understanding of sex-influenced CaP and mixed stone formation that can be used as a basis for determining the factors in sex-related clinical studies.

Plants Used in Mexican Traditional Medicine for the Management of Urolithiasis: A Review of Preclinical Evidence, Bioactive Compounds, and Molecular Mechanisms.

Urolithiasis (UL) involves the formation of stones in different parts of the urinary tract. UL is a health problem, and its prevalence has increased considerably in developing countries. Several regions use plants in traditional medicine as an alternative in the treatment or prevention of UL. Mexico has known about the role of traditional medicine in the management of urinary stones. Mexican traditional medicine uses plants such as Argemone mexicana L., Berberis trifoliata Hartw. ex Lindl., Costus mexicanus Liebm, Chenopodium album L., Ammi visnaga (L.) Lam., Eysenhardtia polystachya (Ortega) Sarg., Selaginella lepidophylla (Hook. & Grev.) Spring, and Taraxacum officinale L. These plants contain different bioactive compounds, including polyphenols, flavonoids, phytosterols, saponins, furanochromones, alkaloids, and terpenoids, which could be effective in preventing the process of stone formation. Evidence suggests that their beneficial effects might be associated with litholytic, antispasmodic, and diuretic activities, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The molecular mechanisms involving these effects could be related to antioxidant, anti-inflammatory, and antimicrobial properties. Thus, the review aims to summarize the preclinical evidence, bioactive compounds, and molecular mechanisms of the plants used in Mexican traditional medicine for the management of UL.

Tea and coffee consumption and the risk of urinary stones-a systematic review of the epidemiological data.

OBJECTIVE: To explore the relationship between the consumption of coffee and tea with urolithiasis. We evaluated large epidemiological and small clinical studies to draw conclusions regarding their lithogenic risk. METHODS: A systematic review was performed using the Medline and Scopus databases, in concordance with the PRISMA statement. English, French, and Spanish language studies regarding the consumption of caffeinated and decaffeinated coffee and tea, and the relationship to urinary stone disease were reviewed. Case reports and letters, unpublished studies, posters, and comments were excluded. RESULTS: As per the inclusion criteria, 13 studies were included in the final review. Most studies, including four large prospective studies and one meta-analysis, reported a reduced risk of stone formation for coffee and tea. Caffeine has a diuretic effect and increases the urinary excretion of calcium, but if these losses are compensated for, moderate caffeine intakes may have little or no deleterious effects. Green and Herbal teas infused for short time had low oxalate content compared to black tea. CONCLUSION: There is no evidence that moderate consumption of coffee raises the risk for stone formation in healthy individuals, provided the recommended daily fluid intake is maintained. The currently available literature supports in general a protective role for tea against the stone formation, mainly for green tea. However, heterogeneity of published data and lack of standardization needs to be addressed before final and clear conclusions can be given to patients and to the public in general.

Tea and coffee consumption and pathophysiology related to kidney stone formation: a systematic review.

OBJECTIVE: To explore the mechanisms behind the potential protective effect of coffee and tea consumption, regarding urinary stone formation, previously demonstrated in large epidemiological studies. METHODS: A systematic review was performed using the Medline, Cochrane library (CENTRAL) and Scopus databases, in concordance with the PRISMA statement. English, French and Spanish language studies, regarding the consumption of caffeinated and decaffeinated coffee and tea, and the relationship to urinary stone formation were reviewed. Meta-analyses, systematic reviews, case reports and letters, unpublished studies, posters and comments abstracts were excluded. RESULTS: As per the inclusion criteria, 13 studies were included in the final review. The major findings show that caffeine increases urinary excretion of calcium, sodium and magnesium, in addition to a diuretic action with consumption > 300-360 mg (approximately four cups of coffee). Together with other components of coffee, this beverage might have potential protective effects against the formation of urinary stones. Tea exerts many protective effects against stone formation, through the accompanying water intake, the action of caffeine and the effects of components with antioxidant properties. CONCLUSION: Caffeine has a hypercalciuric effect, balanced partially by a diuretic effect which appears after consumption of large quantities of caffeine. The current available literature supports in general, a potentially protective role for tea against stone formation, mainly for green tea. Additional standardization in this field of research, through specification of tea and coffee types studied, and their respective compositions, is needed for further clarification of the relation between coffee, tea and urinary stones.

An evaluation of multidrug-resistant (MDR) bacteria in patients with urinary stone disease: data from a high-volume stone management center.

PURPOSE: To investigate the prevalence of MDR bacteria in patients with urinary stones and the risk factors for its formation. METHODS: A retrospective study was performed among patients with urinary stones in Beijing Tsinghua Changgung Hospital from December 2014 to May 2018. Patients with positive urinary cultures and drug sensitivity results were included. MDR were defined as any bacteria that have resistance to at least one agent in at least three classes of antibiotics. Bacteria distribution and resistance patterns were calculated. RESULTS: 1655 patients with urinary stones were eligible for analysis, among which 367 patients had positive urinary culture, yielding 457 isolates of 45 species. Escherichia coli remained the most common organism with a prevalence of 29.3%, followed by Enterococcus faecalis (12.0%), Proteus mirabilis (10.5%), and Klebsiella pneumonia (6.8%). 44.4% isolates were identified as MDR. The three most common Gram-negative bacteria were Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae, with a MDR rate of 84.33%, 62.5%, and 48.39%, respectively. Drug-resistant rates were different between MDR and non-MDR in ampicillin, cefazolin, ceftriaxone, cefepime, gentamicin, amikacin, and levofloxacin (all with p value < 0.05). In multivariate analysis, indwelling catheters (OR 3.1, 95% CI 1.07-8.98) and antibiotics use in the last 3 months (OR 2.14, 95% CI 1.04-4.38) were significantly associated with MDR formation. CONCLUSIONS: MDR bacteria were common among patients with urinary stones in our center and achieved high drug-resistant rates in ampicillin, first-generation and part of third-generation cephalosporins, and fluoroquinolones. Indwelling catheters and antibiotics used in the last 3 months were independent risk factors for MDR formation. Tailored antibacterial strategies still should be established according to the local bacterial spectrum and patient condition.

Efficacy of black seed (Nigella sativa L.) on kidney stone dissolution: A randomized, double-blind, placebo-controlled, clinical trial.

Preclinical studies have shown beneficial effects of black seed (Nigella sativa L.) in the prevention and treatment of renal stones. Hence, we designed a study to evaluate the renal-stone-dissolving efficacy of black seed. Sixty patients with renal stones were randomly enrolled in two arms of a randomized, triple-blind, placebo-controlled, clinical trial. The patients were treated by black seed capsules (500 mg) or placebo two times per day for 10 weeks. Patients were assessed in terms of size of renal stones by using sonography before and after intervention. In the black seed group, 44.4% of patients excreted their stones completely, and the size of the stones remained unchanged and decreased in 3.7% and 51.8% of patients, respectively. In contrast, in the placebo group, 15.3% of the patients excreted their stones completely, 11.5% had reduction in stone size, 15.3% had increase in stone size, and 57.6% had no change in their stone size. The difference in the mean size of renal stones after the study was significant between the two groups (p < 0.05). N. sativa L., as compared with placebo, is demonstrated to have significant positive effects on disappearance or reduction of size of kidney stones.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease.

Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8⁻1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Do Calcium Supplements Predispose to Urolithiasis?

PURPOSE OF REVIEW: The purpose of this study was to investigate the role of calcium supplements, with or without vitamin D, in urinary stone formation in healthy population and in osteoporotic patients as well. Moreover, this review aims to clarify whether or not, and above which dose, they are associated with the risk of lithiasis. RECENT FINDINGS: A research in Medline, Embase, and Scopus databases up to September 2015 was conducted using the following keywords: calcium, supplements, vitamin D, complications, lithiasis, and urinary stone. All types of studies were taken into account (cohort studies, reviews, meta-analyses), and in case they fulfilled the inclusion criteria, they were included in our review. The analysis of the data showed that calcium supplements, probably in association with anti osteoporotic treatment, do not create a predisposition towards lithiasis formation among women suffering from osteoporosis, neither among non-osteoporotic older men. In healthy postmenopausal as well as younger women, the supplements might increase susceptibility to urinary stone formation in long-term basis. The consumption of calcium supplements with the meals could play a protective role in women and younger males. There is certain evidence that supplements containing citrate may be more beneficial over the rest of calcium supplements, particularly when consumed during the meal. Osteoporotic women and healthy men are not at risk of stone formation. On the contrary, healthy women should be aware of the potential risk of developing urinary lithiasis in long-term basis.

Diet-induced acidosis and alkali supplementation.

Western diet, high in protein-rich foods and poor in vegetables, is likely to be responsible for the development of a moderate acid excess leading to metabolism deregulation and the onset or worsening of chronic disturbances. Available findings seem to suggest that diets with high protein/vegetables ratio are likely to induce the development of calcium lithiasis, especially in predisposed subjects. Moreover, some evidence supports the hypothesis of bone metabolism worsening and enhanced bone loss following acid-genic diet consumption although available literature seems to lack direct and conclusive evidence demonstrating pathological bone loss. According to other evidences, diet-induced acidosis is likely to induce or accelerate muscle wasting or sarcopenia, especially among elderlies. Furthermore, recent epidemiological findings highlight a specific role of dietary acid load in glucose metabolism deregulation and insulin resistance. The aim of this review is to investigate the role of acid-genic diets in the development of the mentioned metabolic disorders focusing on the possible clinical improvements exerted by alkali supplementation.

Urinary stones as a novel matrix for human biomonitoring of toxic and essential elements.

Monitoring of body burden of toxic elements is usually based on analysis of concentration of particular elements in blood, urine and/or hair. Analysis of these matrices, however, predominantly reflects short- or medium-term exposure to trace elements or pollutants. In this work, urinary stones were investigated as a matrix for monitoring long-term exposure to toxic and essential elements. A total of 431 samples of urinary calculi were subjected to mineralogical and elemental analysis by infrared spectroscopy and inductively coupled plasma mass spectrometry. The effect of mineralogical composition of the stones and other parameters such as sex, age and geographical location on contents of trace and minor elements is presented. Our results demonstrate the applicability of such approach and confirm that the analysis of urinary calculi can be helpful in providing complementary information on human exposure to trace metals and their excretion. Analysis of whewellite stones (calcium oxalate monohydrate) with content of phosphorus <0.6 % has been proved to be a promising tool for biomonitoring of trace and minor elements.

Determination of Oxalate Content in Herbal Remedies and Dietary Supplements Based on Plant Extracts.

Lifestyle, especially diet, is a prominent risk factor that affects the formation of calcium oxalate stones. Urinary oxalate excretion is directly related to the amount of oral intake and intestinal absorption rate of oxalate. This work evaluated the possibility of increasing oxalate ingestion, which could lead to secondary hyperoxaluria, associated with the intake of herbal remedies and dietary supplements containing plant extracts. A wide variety of 17 commercially available drugs and dietary supplements were analyzed using ion chromatography. The results showed remarkable differences in oxalate contents of the extracts. Total oxalate concentrations ranged from 0.03 to 2.2 mg/g in solid samples and from 0.005 to 0.073 mg/mL in liquid samples. The selected herbal remedies and dietary supplements containing plant extracts represent only a low risk for calcium oxalate stone formers, if the recommended daily dose is not exceeded.

[Urinary stones and bowel diseases: Systematic review]. / Lithiases urinaires et pathologies digestives : une revue de la littérature.

PURPOSE: The aim of the study was to explain the relationship between urinary stones and bowel disease. METHODS: A systematic review was performed on Medline, Embase and Cochrane using following keywords: urinary stones; urolithiasis; bowel; enteric and digestive. The literature selection was based on evidence and practical considerations. RESULTS: Fifty-three articles were selected. Three types of urolthiasis are mainly involved in digestive pathologies: calcium oxalate stones, uric acid and ammonium acid urate stones. Bowel pathologies responsible for stone disease are divided into small bowel diseases, colonic lesions and lack of an oxalate degrading bacteria (Oxalobacter formigenes) in the intestinal flora. Resulting in a decreased urine output, pH, hyperoxaluria, hypocitraturia or a hypomagnesurie. Blood and urinary explorations are the basis of diagnostic management. CONCLUSION: Bowel diseases can be responsible for urolthiasis. Understanding of the mechanisms, and metabolic evaluations can prevent recurrences. Increase fluid intake associated with specific supplementation and diet are the key of the treatment.

The Effect of Shakuyakukanzoto for Renal Colic / 日本東洋医学雑誌

Aim:Shakuyakukanzoto is a Japanese herbal medicine that is known to be useful for the treatment of urinary stone pain. In this study, we investigated the effects of shakuyakukanzoto for acute renal colic.Methods:Twenty-five patients were enrolled in this study. Eleven patients took 5.0 g of shakuyakukanzoto powder, and 14 control patients took non-steroidal anti-inflammatory drugs (NSAIDs) for their acute renal colic. The effects were evaluated before and 15, 30, and 60 minutes after treatment with a numerical rating scale (NRS). We defined scale point zero as not having pain, and scale point ten as having the strongest pain.Results:Mean NRS scores improved from 6.7 ± 2.3 to 3.4 ± 3.5 after 15 minutes (shakuyakukanzoto group), and from 8.3 ± 1.8 to 7.0 ± 1.9 after 15 minutes (control group). NRS scores were improved immediately and significantly in both groups. The NRS score of shakuyakukanzoto group was significantly lower than that of control group at the any time after treatment. No side effects were observed in this study.Conclusion : Shakuyakukanzoto has an immediate effect, and it is more effective than NSAIDs. Shakuyakukanzoto was a useful treatment for acute renal colic.

Antilithic Effects of Extracts from Urtica dentata Hand on Calcium Oxalate Urinary Stones in Rats / 华中科技大学学报（医学）（英德文版）

This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones.The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25％ ethylene glycol (EG) and 1％ ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging.The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE),N-butanol extract (NBE),aqueous extract (AqE) of UDH,Jieshitong (positive control drug),and saline,respectively.Treatment with NBE significantly reduced the elevated levels of urinary calcium,uric acid,phosphate,as well as increased urinary output.Accordingly,the increased calcium,oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats.In addition,NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine.Taken together,these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function.

Effect of pyridoxine (Vitamin-B(6)) supplementation on calciuria and oxaluria levels of some normal healthy persons and urinary stone patients.

Effect of pyridoxine (Vitamin-B(6)) supplementation on calciuria and oxaluria levels of 20 normal healthy persons and 17 urinary stone patients has been studied. Mean 24 hr urinary calcium and oxalate levels of controls (healthy persons) and stone patients were estimated in presupplementation period and at every 20 days interval during supplementation. Stone patients were divided into two groups viz., mild hyperoxaluriacs and moderate hyperoxaluriacs, based on their pre-supplementation (base line) oxaluria levels. 60 days of pyridoxine supplementation, at the rate of 10 mg/day, resulted in a significant decrease (p<0.01 for mild hyperoxaluriacs and p<0.001 for moderate hyperoxaluriacs) in mean 24 hr urinary oxalate levels of urinary stone patients. The corresponding decrement in mean oxaluria level of controls was, however, only mild. The decrease of mean calciuria level of controls as well as stone patients, upon pyridoxine supplementation, were also found to be only mild and not significant. Utility of pyridoxine therapy in oxalate urolithiasis has been discussed in the light of results.