Urinary stone analysis and clinical characteristics of 496 patients in Taiwan.

Evaluate urinary stone components' epidemiological features in urolithiasis individuals and explore potential correlations between stone components and patients' clinical characteristics. A retrospective analysis of urinary stone compositions in 496 patients from a northern Taiwan medical center (February 2006 to October 2021) was conducted. We investigated associations between sex, age, body mass index (BMI), hypertension, diabetes mellitus (DM), hyperlipidemia (HLP), gout, coronary artery disease (CAD), cerebral vascular accident (CVA), chronic kidney disease (CKD), habits, urine pH, and three main stone groups: calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA). Males accounted for 66.5% of cases, with a male-to-female ratio of 1.99:1. Males were negatively associated with CaP stones (OR 0.313, p < 0.001) and positively with UA stones (OR 2.456, p = 0.009). Age showed a negative correlation with CaOx stones (OR 0.987, p = 0.040) and a positive correlation with UA stones (OR 1.023, p < 0.001). DM had a protective effect against CaP stones (OR 0.316, p = 0.004). Gout had a positive association with UA stones (OR 2.085, p = 0.035). Smoking was adversely associated with UA stones (OR 0.350, p = 0.018). Higher urine pH was a risk factor for CaP stones (OR 1.641, p = 0.001) and a protective factor against UA stones (OR 0.296, p < 0.001). These results may provide insights into the pathogenesis of urinary stones and the development of preventative strategies for high-risk populations. Further research is required to confirm and expand upon these findings.

Inhibitory effect of Incarvillea diffusa Royle extract in the formation of calcium oxalate nephrolithiasis by regulating ROS-induced Nrf2/HO-1 pathway in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate (CaOx) kidney stones are widely acknowledged as the most prevalent type of urinary stones, with high incidence and recurrence rates. Incarvillea diffusa Royle (ID) is a traditionally used medicinal herb in the Miao Minzu of Guizhou province, China, for treating urolithiasis. However, the active components and the underlying mechanism of its pharmacodynamic effects remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential inhibitory effect of the active component of ID on the formation of CaOx nephrolithiasis and elucidate the underlying mechanism. MATERIALS AND METHODS: In vivo, a CaOx kidney stone model was induced in Sprague-Dawley (SD) rats using an ethylene glycol and ammonium chloride protocol for four weeks. Forty-eight male SD rats were randomly assigned to 6 groups (n = 8): blank group, model group, apocynin group, and low, medium, and high dose of ID's active component (IDW) groups. After three weeks of administration, rat urine, serum, and kidney tissues were collected. Renal tissue damage and crystallization, Ox, BUN, Ca2+, CRE, GSH, MDA, SOD contents, and levels of IL-1ß, IL-18, MCP-1, caspase-1, IL-6, and TNF-α in urine, serum, and kidney tissue were assessed using HE staining and relevant assay kits, respectively. Protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in kidney tissues was quantified via Western blot. The antioxidant capacities of major compounds were evaluated through DPPH, O2·-, and ·OH radical scavenging assays, along with their effects on intracellular ROS production in CaOx-induced HK-2 cells. RESULTS: We found that IDW could significantly reduce the levels of CRE, GSH, MDA, Ox, and BUN, and enhancing SOD activity. Moreover, it could inhibit the secretion of TNF-α, IL-1ß, IL-18, MCP-1, caspase-1, and decreased protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in renal tissue. Three major compounds isolated from IDW exhibited promising antioxidant activities and inhibited intracellular ROS production in CaOx-induced HK-2 cells. CONCLUSIONS: IDW facilitated the excretion of supersaturated Ca2+ and decreased the production of Ox, BUN in SD rat urine, and mitigated renal tissue damage by regulating Nrf2/HO-1 signaling pathway. Importantly, the three major compounds identified as active components of IDW contributed to the inhibition of CaOx nephrolithiasis formation. Overall, IDW holds significant potential for treating CaOx nephrolithiasis.

Associations of Oxalate Consumption and Some Individual Habits with the Risk of Kidney Stones.

Kidney stone is a highly recurrent disease in the urinary tract system. Most kidney stones are calcium stones, usually consisting of either calcium oxalate or calcium phosphate. Supersaturation of soluble calcium, oxalate, phosphate, and citrate in the urine is the basis for calcium stone formation. Genetics, diet, low physical activity, and individual habits contribute to the formation of kidney stones. In this review, the associations of the risk of kidney stones with oxalate consumption and some individual habits, such as smoking, alcohol drinking, and opium consumption, are summarized.

Oxalate nephropathy in an elderly patient with newly diagnosed celiac disease - a case report.

Oxalate nephropathy, due to secondary hyperoxaluria has widely been described in gastrointestinal diseases. However, reports of oxalate nephropathy in newly diagnosed celiac disease are rare. A 72-year-old Caucasian male presented to the hospital with abdominal discomfort and acute renal insufficiency with a creatinine of 290 µmol/L. The clinical course, laboratory results and urinalysis were suspect for tubular injury. Renal biopsy showed calcium oxalate depositions. Elevated plasma and urine oxalate levels established the diagnosis oxalate nephropathy. The abdominal complaints with steatorrhea and positive anti-tissue transglutaminase antibodies were diagnosed as celiac disease, which was confirmed after duodenal biopsies. Treatment with prednisone, and gluten-free, low oxalate and normal calcium diet, lowered the plasma oxalate levels and improved his renal function. Decreased absorption of free fatty acids can lead to increased free oxalate in the colon due to the binding of free fatty acids to calcium, preventing the formation of the less absorbable calcium oxalate in the colon. Oxalate dispositions in the kidney can lead to acute tubular injury and chronic renal insufficiency. Celiac disease is therefore one of the intestinal diseases that can lead to hyperoxaluria and oxalate nephropathy.

Reversal of Roux-en-Y Gastric Bypass for Successful Salvage of Renal Allograft.

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

Metabolic syndrome in calcium oxalate stones: Is it so important in this type of lithiasis?

INTRODUCTION AND OBJECTIVE: The association of the metabolic syndrome with lithogenesis has been described, especially in uric acid stones. The aim of the work was to analyze the role of the metabolic syndrome in oxalocalcic lithogenesis. MATERIALS AND METHODS: Metabolic evaluation of 151 patients including biochemical, hormonal and 24-urine urine parameters, as well as characteristics associated with metabolic syndrome. The relationship between the characteristics associated with the metabolic syndrome and those related to lithogenesis was evaluated using Spearman's correlation coefficient (SCC), Student's t test and Fisher's exact test. RESULTS: The average body mass index (BMI) was 25.9 (SD 3.7). The median age was 51 years (18.6-84.8) and 64.9% were men. There were no statistically significant differences between hypertension and estradiol, testosterone, triglycerides or cholesterol (P=.191, .969, .454, .345, respectively). Regarding glucose, the mean was 114.5 and 93.5mg/dl in patients with and without hypertension (P=.000). The levels of glucose, estradiol, testosterone or cholesterol did not vary with proteinuria (P=.518, P=.227, P=.095, P=.218, respectively). The mean triglycerides were 185.6 and 108.2mg/dl in patients with and without proteinuria (P=.001). Hypertension and proteinuria were not associated (P=.586). BMI correlated with serum and urinary uric acid and urinary creatinine. CONCLUSIONS: There are few associations between the characteristics of the metabolic syndrome and the anomalies related to lithogenesis. Metabolic syndrome does not seem to have a relevant role in the development of oxalocalcic stones.

Investigation of the potential anti-urolithiatic activity of Alhagi maurorum (Boiss.) grown wild in Al-Ahsa (Eastern Province), Saudi Arabia.

The potential of Alhagi maurorum (Boiss.) aqueous extract (AME), used in traditional medicine for treatment or prevention of urolithiasis, to dissolve calcium oxalate stones in vitro was evaluated. In order to determine the litholytic potential of the extract, Calcium oxalate urinary stones were incubated during 12 weeks under continuous shaking in the presence of AME, Rowanix or NaCl 9 g/mL solution were used as controls. After the incubation period, the residual weight of the treated calculi was determined and the rate of dissolution was calculated. The medium pH variation was measured and changes in the calcium oxalate crystals at the stone surface were assessed using a scanning electron microscope (SEM). The results showed a significant dissolution effect for the extract on the kidney calculi during the experimentation period. At the end of the experiment, the percentages of calculi weight decrease were 41.23, 4.97 and 55.67% for the extract, NaCl solution and Rowanix, respectively. Gas Chromatography analysis revealed mainly the presence of the following phyto-compounds: Cyclopropenone, 2,3-diphenyl; 1-Nonadecanol; methyl-alpha-D-mannopyranoside; cis-9-Hexadecenal. These compounds unarguably play crucial roles in the health care system especially in cancer treatment and many other diseases including urolithiasis. The urinary stone dissolution, independent of medium pH, could be attributed to formation of complexes between the phytochemical compounds in the extract and the calculi.

Antiurolithiatic Potential of Three Sri Lankan Medicinal Plants by the Inhibition of Nucleation, Growth, and Aggregation of Calcium Oxalate Crystals In Vitro.

Background: Deposition and formation of stones in any part of the urinary system is called urolithiasis. CaOx is the predominant component of most stones, and the formation of these stones is a multistep process that includes supersaturation, nucleation, aggregation, growth, and retention. In ayurvedic medicine, medicinal plants are used for the management of kidney stones. The objective of this study was to determine the effect of aqueous, ethanol, and hexane extracts of Drymoglossum piloselloides leaves, Kalanchoe laciniata leaves, and Aegle marmelos flowers against CaOx urolithiasis in vitro. Methods: The crystallization of CaOx monohydrate (COM) and dihydrate (COD) was induced in a synthetic urine system. The nucleation, growth, and aggregation of crystals were measured using spectrophotometric methods. The results were compared against the polyherbal drug, Cystone, under identical concentrations. Crystals generated in the urine were also observed under light microscopy. Statistical differences and percentage inhibitions were calculated using standard formulae and compared. A preliminary phytochemical screening was also performed to detect active phytoconstituents present in the three plants used in the study. Results: The results obtained clearly demonstrated that Kalanchoe laciniata, Aegle marmelos, and Drymoglossum piloselloides have the capacity to inhibit the nucleation, growth, and aggregation of CaOx crystals. Microscopic examination of crystals revealed the presence of more COM than COD crystals but a dose-dependent reduction in crystals was observed in the presence of plant extracts. Hexane, ethanol, and aqueous extracts of all three plants had different capabilities to inhibit nucleation, growth, and aggregation of CaOx crystals but their activities were different at different concentrations. Preliminary phytochemical screening revealed the presence of reducing sugars, proteins, flavonoids, tannins, and polyphenol compound in Kalanchoe laciniata and Drymoglossum piloselloides and reducing sugars, proteins, anthracene glycosides, and saponins in Aegle marmelos. Conclusions: This study provided evidence that Kalanchoe laciniata, Aegle marmelos, and Drymoglossum piloselloides have the potential to be developed as inhibitors of nucleation, growth, and aggregation of CaOx crystals in the treatment of urolithiasis.

Upper urolithiasis in cats with chronic kidney disease: prevalence and investigation of serum and urinary calcium concentrations.

OBJECTIVES: This study aimed to define the prevalence of upper urolithiasis in cats with chronic kidney disease (CKD) in a referral population, and to compare urinary calcium:creatinine ratio (UCa:Cr), and total and ionised calcium between cats with CKD with and without upper urolithiasis. METHODS: The medical records of cats diagnosed with CKD were reviewed for signalment, body weight, diet and prevalence of upper urolithiasis. Cats with preserved urine samples were further classified into two groups: urolithiasis group (upper urolithiasis identified by abdominal ultrasonography) and control group (CKD of unknown origin). Serum biochemical analysis, CKD stage, blood gas analysis, urine specific gravity and UCa:Cr were compared between groups using a two-sample t-test or Mann-Whitney U-test for continuous variable and a χ2 test or Fisher's exact test for categorical variables. Multivariable binary logistic regression analysis was used to identify risk factors. RESULTS: Among the 140 cats with CKD, the prevalence of upper urolithiasis was 73%. Fifty cats (5, 29 and 16 cats with CKD stages 1, 2 and 3, respectively) with urine samples met the inclusion criteria and were included in the analysis. Among cats with CKD, being purebred (odds ratio [OR] = 81.56; P = 0.03) and being fed dry food only (OR = 25.06; P = 0.001) were identified as independent upper urolithiasis risk factors; those with upper urolithiasis were more likely to be exclusively fed with urine-acidifying food (P <0.001) and have increased serum ionised calcium (iCa) (P = 0.044), fractional excretion of calcium (P = 0.45) and UCa:Cr (P = 0.005) than cats with CKD without upper urolithiasis. CONCLUSIONS AND RELEVANCE: Cats with CKD that were purebred, fed dry food and fed urine-acidifying food only often had upper urolithiasis. A higher UCa:Cr may be a result of increased serum iCa and may cause upper urolithiasis.

Discovering inhibitor molecules for pathological crystallization of CaOx kidney stones from natural extracts of medical herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: Kidney stones is one of the common diseases of the urinary system. The primary cause of kidney stone formation is the thermodynamic supersaturation of lithogenic solutes in urine, which desaturates by nucleation, crystal growth and aggregation of minerals and salts, mainly Calcium oxalate (CaOx). One of the potential therapies is to develop drug molecules to inhibit or prevent CaOx crystallization in urine. Traditional Chinese medicines (TCMs) provided an efficient approach for the treatment of kidney stones with a specialized-designed recipe of medicinal herbs. But the action details of these herbs were poorly understood due to their complex components, and whether the effective constituents of herbs have an inhibitory effect on the process of stone formation has not been evaluated. AIM OF THE STUDY: This study aims to develop and identify inhibitor substitutes from a library of kidney stone prescriptions in traditional Chinese medicines to prevent pathological kidney stone formation. MATERIALS AND METHODS: As many as twenty Chinese medicines were extracted and separated into five different polar extracts, the inhibition performance of which on CaOx crystallization was explored by recording and comparing crystallization kinetics. The potential inhibitor molecules in the inhibitory extracts were confirmed by HPLC and their retardation efficacy was evaluated by quantifying nucleation and growth kinetics using colorimetry. Then the inhibitor-COM crystal interactions and specificity were examined by morphology evolution and surface structure analysis. In vitro inhibition performance of inhibitors on crystal growth and attachment of CaOx crystals to human renal epithelial cells were further evaluated by recording the nucleation and adhesive crystal numbers. RESULTS AND CONCLUSION: Water- and n-butanol- soluble extracts from 20 kinds of herbs show almost 100% inhibition percentage, and the n-butanol extracts was found better than commercial drug citrate. Twenty-one molecule substitutes were identified from these extracts, and among them polyphenols display the best inhibition efficacy to retard CaOx crystallization. The high-throughput colorimetric assay and morphology examinations reveals thirteen out of 21 molecules show inhibition potential and disrupt growth of CaOx monohydrate crystals by interacting with exposed Ca2+ and C2O42- on the (100) and (010) surfaces. Moreover, these inhibitors also display pronounced performance in protecting renal epithelial cells by inhibiting nucleation and adhesion of CaOx crystals to cells, thus reducing stone formation. The structure-performance correlation among 19 screened molecules that inhibitors having pKa<3.5, logD (pH = 6) <0, H-number>0.1 mmol are the best in suppressing CaOx crystallization. Our findings provide a novel solution to design and manufacture inhibitor drugs from Chinese medicines for preventing pathological kidney stones formation.

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers.

BACKGROUNDS: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs). METHODS: Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry. RESULTS: Urine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies. CONCLUSIONS: Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

Urinary stone composition analysis and clinical characterization of 1520 patients in central China.

A total of 1520 patients with urinary stones from central China were collected and analysed by Fourier transform infrared spectroscopy between October 1, 2016 and December 31, 2019. For all patients, age, sex, comorbidities, stone location, laboratory examination and geographic region were collected. The most common stone component was calcium oxalate (77.5%), followed by calcium phosphate (8.7%), infection stone (7.6%), uric acid (UA) stone (5.3%)and cystine (0.9%). The males had more calcium oxalate stones (p < 0.001), while infection stone and cystine stones occurred more frequently in females (p < 0.001). The prevalence peak occurred at 41-60 years in both men and women. UA stones occurred frequently in patients with lower urinary pH (p < 0.001), while neutral urine or alkaline urine (p < 0.001) and urinary infection (p < 0.001) were more likely to be associated with infection stone stones. Patients with high levels of serum creatinine were more likely to develop UA stones (p < 0.001). The proportion of UA stones in diabetics was higher (p < 0.001), and the incidence of hypertension was higher in patients with UA stones (p < 0.001). Compared to the other types, more calcium oxalate stones were detected in the kidneys and ureters (p < 0.001), whereas struvite stones were more frequently observed in the lower urinary tract (p = 0.001). There was no significant difference in stone composition across the Qinling-Huaihe line in central China except UA stones, which were more frequently observed in patients south of the line (p < 0.001).

Sex Differences of Kidney Stone Urine Risk Factors after Roux-en-Y Gastric Bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is a bariatric surgical procedure that is associated with higher risk of kidney stones after surgery. We examined urine composition in 18 men and women before and after RYGB to examine differences in kidney stone risk. METHODS: Three 24-h urine collections were performed before and 1 year after RYGB. We analyzed mean urinary values for pre- and post-RYGB collections and compared men and women. RESULTS: Seven men and eleven women completed pre- and post-RYGB urine collections. Pre-RYGB, men had higher calcium oxalate supersaturation (CaOx SS) (7.0 vs. 5.0, p = 0.04) compared with women. Post-RYGB, women had higher urine CaOx SS (13.1 vs. 4.6, p = 0.002), calcium phosphate supersaturation (1.04 vs. 0.59, p = 0.05), and lower urine volumes (1.7 vs. 2.7L, p < 0.001) compared with men. DISCUSSION/CONCLUSION: There are important differences in urine composition by sex that may contribute to higher kidney stone risk in women after RYGB compared with men.

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.

Clinical validation of urinary indole-reacted calcium oxalate crystallization index (iCOCI) test for diagnosing calcium oxalate urolithiasis.

An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. We conducted the prospective cohort study in accordance with the STARD guideline to evaluate the accuracy of urinary iCOCI test (index test) for diagnosing urolithiasis. A total of 281 participants were recruited for the study. Levels of urinary iCOCI were determined in the pre-diagnostic 24-h urine samples. Positive urinary iCOCI (≥ 0.6 COM eqv., g/L) was accounted for 51% (144/281), and the rest of 49% (137/281) were negative. Non-contrast CT imaging (reference standard) was subsequently performed for the definite diagnosis of urolithiasis to divide the participants into two groups, non-stone subjects (NSS, n = 122) and stone-forming subjects (SFS, n = 159). It should be noted that only subjects who currently had urinary stone at the time of study were classified as SFS. Urinary iCOCI levels in the SFS were significantly higher than the NSS. ROC analysis revealed an area under curve (AUC) of 0.893 (95% CI: 0.855-0.932) in separating NSS from all SFS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LH+) and negative likelihood ratio (LH-) of urinary iCOCI test for diagnosis of all urolithiasis were 87%, 80%, 84%, 84%, 83%, 4.44 and 0.16, respectively. Of 159 SFS, 38 were confirmed to have CaOx stones. Among these 38 CaOx SFS, only 2 had negative urinary iCOCI test. The AUC of urinary iCOCI test for separating CaOx SFS from NSS was markedly high (0.946, 95% CI: 0.914-0.978). Sensitivity, specificity, PPV, NPV, accuracy, LH+ and LH- of urinary iCOCI test for diagnosing CaOx urolithiasis were 95%, 86%, 68%, 98%, 88%, 6.80 and 0.06, respectively. Conclusion, we clinically validated that an innovative non-invasive urinary iCOCI test was highly accurate to diagnose urolithiasis, especially CaOx stone. With its high sensitivity and NPV, urinary iCOCI test is clinically intended to use as a screening test for CaOx urolithiasis. LH- of 0.06 indicates that negative result of urinary iCOCI test is highly accurate to rule out the CaOx stone formation. It is noted that urinary iCOCI level is expressed as arbitrary unit, and it is not directly related to the actual physiological level of urinary oxalate.

Measurement of preprandial and postprandial urine calcium to creatinine ratios in male Miniature Schnauzers with and without urolithiasis.

BACKGROUND: We aimed to identify a simple test for excessive calciuresis and predict calcium oxalate (CaOx) disease in Miniature Schnauzers. We investigated the impact of postprandial time on the urine calcium to creatinine ratio (UCa/Cr) in male dogs of this breed, with the goal of improving the utility of the UCa/Cr. HYPOTHESES: (1) Significant differences will exist in preprandial and postprandial UCa/Cr between CaOx urolith-forming and control Schnauzers. (2) The UCa/Cr will increase significantly from the first morning baseline at ≥1 postprandial time point(s) in both control and CaOx urolith-forming dogs. (3) Biochemical abnormalities and other variables may be associated with urolith status. ANIMALS: Twenty-four male Miniature Schnauzer dogs, consisting of 9 with (urolith formers) and 15 without (controls) CaOx uroliths. METHODS: Urine was collected before and 1, 2, 4, and 8 hours after feeding a standardized diet. Receiver operator characteristic curve analysis was performed to identify the UCa/Cr cutoff that most accurately differentiates dogs based on urolith status. RESULTS: Urolith formers had significantly higher mean UCa/Cr over the course of 8 hours. The postprandial change in UCa/Cr was not significant at any time point between or within groups. The cutoff UCa/Cr value of 0.06 had a specificity of 93% (95% confidence interval [CI], 80%-100%) and a sensitivity of 56% (95% CI, 21%-86%) for identifying CaOx urolithiasis. CONCLUSIONS AND CLINICAL IMPORTANCE: Urolith-forming male Miniature Schnauzers have excessive calciuresis, and the postprandial sampling time up to 8 hours is not critical. This simple urine measurement has potential as a marker of CaOx disease.

Gastrin-releasing peptide receptor gene silencing inhibits the development of the epithelial-mesenchymal transition and formation of a calcium oxalate crystal in renal tubular epithelial cells in mice with kidney stones via the PI3K/Akt signaling pathway.

Between 1% and 15% of people are globally affected by kidney stones, and this disease has become more common since the 1970s. Therefore, this study aims to investigate the effects of gastrin-releasing peptide receptor (GRPR) gene silencing via the PI3K/Akt signaling pathway on the development of the epithelial-mesenchymal transition (EMT) and formation of a calcium oxalate crystal in renal tubular epithelial cells (TECs) of kidney stones. A total of 70 clean and healthy C57BL/6J mice were assigned into the normal ( n = 10) and kidney stones groups ( n = 60). The underlying regulatory mechanisms of GRPR were analyzed in concert with the treatment of shGRPR-1, LY294002, and shGRPR-1 + LY294002 in TECs isolated from mice with kidney stones. A series of experiments were conducted for the measurement of urinary oxalate and urinary calcium, the renal calcium salt deposition, the positive rate of GRPR, the expressions of renal TECs related genes and calcium oxalate regulation related genes, and the growth of calcium crystals induced by cells. After treatment of shGRPR-1 and shGRPR-1 + LY294002, levels of urinary oxalate and urinary calcium in the serum, as well as positive rate of GRPR, became relatively low, levels of E-cadherin enhanced, whereas levels of Akt, PI3K, GRPR, extents of PI3K and Akt phosphorylation, α-SMA, Vimentin and FSP-1, OPN, MCP-1, and CD44 decreased and a number of crystals reduced. Taken together, we conclude that GRPR gene silencing suppresses the development of the EMT and formation of the calcium oxalate crystal in renal TECs of kidney stones through the inactivation of the PI3K/Akt signaling pathway.

Quantified water intake in laboratory cats from still, free-falling and circulating water bowls, and its effects on selected urinary parameters.

OBJECTIVES: The study objectives were to determine if the method of water presentation (still [S], circulating [C] or free-falling [FF] bowl systems) influences daily water consumption in cats in a controlled environment, and whether differences in water intake affect urine relative super saturation (RSS) for calcium oxalate and struvite, urine specific gravity (USG), urine osmolality (Uosmol) and urine volume. METHODS: Sixteen healthy laboratory cats fed a dry diet were individually housed with urine collection systems. Each cat underwent a randomized 2 week crossover period with all bowl systems, allowing a 1 week acclimation period between each crossover. Water intake was measured daily by bowl weight, accounting for spillage and evaporation. USG and urine volume were measured daily, whereas other urinary parameters were measured at various time points throughout each 14 day crossover period. RESULTS: Fourteen cats completed the study. Average daily water intake (ml/kg/day), urine volume, USG and urine RSS for struvite and calcium oxalate were not significantly different between water bowls. Uosmol was significantly higher in C compared with S and FF bowl systems (P = 0.009 for both). Three individual cats demonstrated a significant water bowl preference (Cat 4: C >S, P = 0.039; Cat 10: FF >C, P = 0.005; Cat 11: S >C, P = 0.037). CONCLUSIONS AND RELEVANCE: Overall, water bowl type had no appreciable effect on water intake. Uosmol was the only urinary parameter found to be significantly different, and was higher for the C bowl. The implication of this is unknown, considering water intake did not differ significantly between bowls. Alternative methods to increase water intake should be implemented beyond providing unique water bowls in patients where augmented water intake would be beneficial for disease management.