Kidney Stone Composition Research Articles

Kidney stone composition in the Kingdom of Saudi Arabia .

Urolithiasis is a globally-distributed disease; however, its prevalence varies across countries and regions. Countries in the Middle East have been reported to have particularly high nephrolithiasis prevalence rates. To date, however, we have an incomplete understanding of the composition of stones seen in this region. Therefore, we performed a study to characterize stone composition over a 14-year period in the Eastern Province of the Kingdom of Saudi Arabia (KSA). A retrospective review of all adult patients who had the composition of their upper urinary tract calculi analyzed at Johns Hopkins Aramco Healthcare (JHAH) between 1999 and 2013 was performed. Patient demographics and pathology results were obtained from the electronic medical record. A total of 1,747 stones were analyzed in the study period. The results are presented in the Table. Male patients predominated (79%). For both men and women, the majority of stones were calcium oxalate: 85.2% male, 85.9% female. Uric acid stones were the next most common: 10.1% male; 9.0% female. Overall, there were no significant differences between gender with regards to the distribution of stone types. This study represents one of the largest characterizations of stone composition in the Middle East. There remains a significant gender disparity in stone prevalence in the Eastern Province of KSA, with males affected to a significantly greater extent. Calcium oxalate is the most common type of stone, and this is true for both men and women. Future investigations of dietary and environmental factors can build on these initial epidemiologic findings. .

An assessment of kidney stone composition and risk factors: Matched case-control study at Orotta referral hospital in Asmara, Eritrea

An assessment of kidney stone composition and risk factors: Matched case-control study at Orotta referral hospital in Asmara, Eritrea

Phase composition and morphological characterization of human kidney stones using IR spectroscopy, scanning electron microscopy and X-ray Rietveld analysis

Pathological calcification in human urinary tract (kidney stones) is a common problem affecting an increasing number of people around the world. Analysis of such minerals or compounds is of fundamental importance for understanding their etiology and for the development of prophylactic measures. In the present study, structural characterization, phase quantification and morphological behaviour of thirty three (33) human kidney stones from eastern India have been carried out using IR spectroscopy (FT-IR), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Quantitative phase composition of kidney stones has been analyzed following the Rietveld method. Based on the quantitative estimates of constituent phases, the calculi samples have been classified into oxalate (OX), uric acid (UA), phosphate (PH) and mixed (MX) groups. Rietveld analysis of PXRD patterns showed that twelve (36%) of the renal calculi were composed exclusively of whewellite (calcium oxalate monohydrate, COM). The remaining twenty one (64%) stones were mixture of phases with oxalate as the major constituent in fourteen (67%) of these stones. The average crystallite size of whewellite in oxalate stones, as determined from the PXRD analysis, varies between 93 (1) nm and 202 (3) nm, whereas the corresponding sizes for the uric acid and struvite crystallites in UA and PH stones are 79 (1)–155 (4) nm and 69 (1)–123(1) nm, respectively. The size of hydroxyapatite crystallites, 10 (1)–21 (1) nm, is smaller by about one order of magnitude compared to other minerals in the kidney stones. A statistical analysis using fifty (50) kidney stones (33 calculi from the present study and 17 calculi reported earlier from our laboratory) revealed that the oxalate group (whewellite, weddellite or mixture of whewellite and weddellite as the major constituent) is the most prevalent (82%) kidney stone type in eastern India.

Protein Network Analysis and Functional Studies of Calcium Oxalate Crystal-Induced Cytotoxicity in Renal Tubular Epithelial Cells.

Our previous expression study has reported a set of proteins with altered levels in renal tubular cells after exposure to calcium oxalate monohydrate (COM) crystals, which are the main composition of kidney stones. However, their functional significance remained largely unknown. In this study, protein network analysis revealed that the significantly altered proteins induced by COM crystals were involved mainly in three main functional networks, including i) cell proliferation and wound healing; ii) oxidative stress and mitochondrial function; and iii) cellular junction complex and integrity. Cell proliferation and wound healing assays showed that the COM-treated cells had defective proliferation and tissue healing capability, respectively. Oxyblot analysis demonstrated accumulation of the oxidized proteins, whereas intracellular ATP level was significantly increased in the COM-treated cells. Additionally, level of zonula occludens-1 (ZO-1), a tight junction protein, was significantly decreased, consistent with the significant declines in transepithelial resistance (TER) and level of RhoA signaling molecule in the COM-treated cells. These findings indicate significant perturbations in mitochondrial and oxidative stress axis that cause defective cell proliferation, tissue healing capability, junctional protein complex, and cellular integrity of renal tubular epithelial cells exposed to COM crystals that may play important roles in kidney stone pathogenesis.

Prevalence, pathophysiological mechanisms and factors affecting urolithiasis.

The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi. In this review, composition of kidney stones, its prevalence/incidence, explanation of pathophysiological mechanisms and role of various factors; urinary pH, uric acid, parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin, matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm-Horsfall protein, inter-α-inhibitors, have been discussed in detail.

Investigation of Adipose Tissue Fatty Acid Composition in Men with Uronephrolithiasis and Metabolic Syndrome.

BackgroundFatty acids (FA) and their metabolites are closely related to some mechanisms involved in the development of uronephrolithiasis. The aim of this study was to evaluate the relationship between FA composition and type of kidney stones.Material/MethodsAbdominal adipose tissue fatty acid methyl esters of 71 men with nephrolithiasis were identified by GC/MS, and the type of kidney stones was identified using FTIR infrared spectroscopy. Patients were divided into groups according to diagnosis of metabolic syndrome (MS) and type of kidney stone. The composition of FA was compared within different groups of patients with different types of kidney stones and between the patients and healthy individuals (control group) (n=100).ResultsIndividuals with nephrolithiasis had a significantly higher level of monounsaturated fatty acids (MUFA) and a lower level of polyunsaturated fatty acids (PUFA) versus healthy individuals. Patients with MS had a higher level of 18: 1ω9 and a lower level of 16: 1ω7 than patients without MS. Individuals with nephrolithiasis, but without MS, had a higher level of saturated fatty acids (SFA) compared to controls. The level of PUFA was higher in the control group (p<0.0001) compared to individuals with uronephrolithiasis, with or without MS. PUFA, ω – 6 PUFA, and 18: 2ω6 were higher in patients with calcium-based kidney stones without MS versus patients with uric acid kidney stones with MS.ConclusionsThe levels of MUFA were significantly higher and the levels of PUFA were significantly lower in patients with uronephrolithiasis compared to controls.

EVALUATION OF RENAL STONES BY COMPUTED TOMOGRAPHY AND ITS CORRELATION WITH URINE pH AND BIOCHEMICAL ANALYSIS

Introduction: The aim of the study is to assess the composition of renal stones by non chemical analysis that is by use of computed tomography (CT) values in Hounsfield Units (HU) and to compare the results of biochemical stone analysis collected post surgically done in biochemistry lab. Methodology: This is a prospective study, included patients in age group of 25 - 60yrs. Patients who were referred to radiology department from Urology and also patients referred from surgery with complaints of loin pain, groin pain, hematuria, crystalluria were recruited for the study. About 100 patients were screened with first line modality of ultrasound evaluation for identifying the presence of stone in kidney, later on positive confirmation from ultrasound evaluation they were further subjected to CT scan evaluation. Urine was collected from all the patients with renal stones and urine pH was measured. Stones collected post surgically were used for the biochemical analysis to know the chemical composition of the stones RESULTS: The stone removed from the patients of this group contain high calcium content. Most of the stones removed from bladder comprises two categories 1.uric acid (mainly) 2.large stones more than 20 mm size were proved to be calcium stones possibly related to greater sunlight exposure, resulting in increase in insensible fluid losses and increase in vitamin D production. We obtained a reference from hounsfield units value from stones collected post surgically from the urological department. The stones are categorized into three types - Pure highly reflective crystalline white stones, Stones which appears most mostly black, Complex mild yellow stones. Conclusion: CT may enable accurate in vivo characterization of kidney stone composition.

Human kidney stone matrix: Latent potential to restrain COM induced cytotoxicity and inflammatory response

Kidney stone disease is a multi-factorial disorder resulting from the interplay of various risk factors including lifestyle, environment and genetics along with metabolic activities inside the body. However, it is difficult to determine how these factors converge to promote stone disease. Extensive investigations of kidney stone composition at the molecular level have been carried out however; its impact on the complex mechanism of stone formation is still obscure. Hence, an in vitro study was designed to investigate the attenuation of calcium oxalate toxicity by human kidney stone matrix proteins on NRK-52E cells using flowcytometry, Western blotting, RT-PCR and immunofluorescence assays. Morphological alterations in cell-crystal interaction were assessed using scanning electron microscopy. Microscopic studies showed profound impairment of COM crystal structure as a consequence of protein-crystal interactions. RT-PCR analysis and immunocytochemistry of NRK-52E cells revealed the up-regulation of inflammatory and stress biomarkers OPN and HSP-70, respectively, in response to COM toxicity; which diminished significantly in the presence of kidney stone matrix proteins. The results of present study propose that the mechanism undertaken by matrix proteins to attenuate COM induced cytotoxicity could be attributed to the modulation of crystal structure, which subsequently restraint the inflammatory response and apoptotic cell death. The inference drawn through this study could provide better understanding of the intricate process of kidney stone formation.

Adherence to the Mediterranean Dietary Pattern and Incidence of Nephrolithiasis in the Seguimiento Universidad de Navarra Follow-up (SUN) Cohort

Diet plays an important role in the pathogenesis of nephrolithiasis. Limited data are available to investigate the association between a Mediterranean dietary pattern and risk for nephrolithiasis. Prospective cohort study. 16,094 men and women without a history of nephrolithiasis who participated in the Seguimiento Universidad de Navarra Follow-up (SUN) Project. A validated 136-item food frequency questionnaire was used to assess baseline adherence to a Mediterranean dietary pattern that is high in fruits, vegetables, nuts, fish, and legumes, but moderate in alcohol and low in meats, saturated fats, and sugars. A Mediterranean dietary pattern score was calculated and categorized into 3 groups (0-3, 4-6, and 7-9 points). Additional factors included in statistical models were sex, age, body mass index, smoking, physical activity, time spent watching television, following a medical nutritional therapy, water and energy intake, calcium and vitamin D supplementation, and history of hypertension or diabetes. Incidence of nephrolithiasis. Participants were classified as having incident nephrolithiasis if they reported a physician-made diagnosis of nephrolithiasis during follow-up. After a mean follow-up of 9.6 years, 735 new cases of nephrolithiasis were identified. The multivariable HRs of nephrolithiasis for the 2 highest categories of adherence to the Mediterranean dietary pattern, using the lowest category as the reference, were 0.93 (95% CI, 0.79-1.09) and 0.64 (95% CI, 0.48-0.87); P for trend=0.01. The risk for nephrolithiasis was lower with greater consumption of dairy products and vegetables and greater with higher monounsaturated fatty acid to saturated fatty acid ratio. No information for kidney stone composition. Greater adherence to a Mediterranean dietary pattern was associated with reduced risk for incident nephrolithiasis. Additional longitudinal studies are needed.

Application of TXRF and XRPD techniques for analysis of elemental and chemical composition of human kidney stones

Total reflection X‐ray fluorescence analysis and X‐ray powder diffraction were used for elemental and chemical composition analysis of 83 samples of human kidney stones. Samples came from patients after surgical removal of stones. Elements such as P, K, Ca, Fe, Zn, Ni, Br, Sr, and Pb were determined in all samples. Other elements Mg, S, Cl, Ti, V, Cr, Mn, Cu, Se, Rb, I, and Bi were found in some of the analyzed kidney stones (censoring effect). Descriptive statistics were calculated for all elements paying particular attention to the censored elements. From diffraction measurements, the following crystalline substances were determined in the stones: apatite, struvite, uric acid, weddellite, whewellite, magnesium phosphate, and calcium phosphate. Information of chemical composition was applied to classify the analyzed kidney stone into four groups. Statistical analysis of the results included multigroups comparison, testing of element concentration distribution, and elemental correlations in the dependence of kind of kidney stones. The presented studies are part of wider microbiological studies focusing on the correlation between different kinds of bacteria and fungi presented in the samples of kidney stones and their elemental as well as chemical composition. Information on stone composition can be helpful in understanding kidney stone formation and complemented by additional metabolic blood and urine tests. This, in turn, can lead to appropriate medical treatment together with the reduction of the risk as regards forming new stones.

Pediatric Nephrolithiasis: A Review.

The incidence of pediatric nephrolithiasis is on the rise. The composition of kidney stones in children is different than in adults, as most stones in children have a composition of calcium oxalate and calcium phosphate mixed with a small amount of uric acid. The symptoms of pediatric nephrolithiasis are nonspecific. Computed tomography (CT) is the gold standard for diagnosis; however, because of radiation exposure associated with a CT scan, ultrasonography is also an accepted modality for the diagnosis. Extensive metabolic evaluation is important to rule out an underlying metabolic disorder. Urinary decompression, medical expulsion therapy, and surgical interventions such as ureteroscopy and extracorporeal shockwave lithotripsy are some of the options available for treating pediatric nephrolithiasis. [Pediatr Ann. 2017;46(6):e242-e244.].

Consistency of Renal Stone Volume Measurements Across CT Scanner Model and Reconstruction Algorithm Configurations.

The objective of this prospective study is to evaluate the consistency of renal stone volume estimation using dual-energy CT across scanner model and reconstruction algorithm configurations. Patients underwent scanning with routine kidney stone composition protocols on both second- and third-generation dual-source CT scanners. Images were reconstructed using filtered back projection and iterative reconstruction (IR). In addition, a modified IR kernel on the third-generation CT scanner was evaluated. Individual kidney stone volumes were determined and compared. No significant difference was noted in measured volumes between filtered back-projection data, IR data from the second-generation scanner, and the modified IR kernel data (p > 0.05). The third-generation commercially available IR kernel yielded lower volumes than did the other configurations (p < 0.0001). With the use of a modified kernel for the third-generation scanner, patients being monitored for changes in kidney stone volume can undergo scanning performed with second- or third-generation dual-energy CT scanners, and the images obtained can be reconstructed with either filtered back projection or IR without the introduction of bias into kidney stone volume measurements.

Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation

The prevalence of kidney stones has increased globally in recent decades. However, studies investigating the association between temporal changes in the risk of stone formation and stone types are scarce. We investigated temporal changes in stone composition, and demographic, serum and urinary parameters of kidney stone formers from 1980 to 2015. We retrospectively analyzed the records of 1,516 patients diagnosed with either calcium or uric acid stones at an initial visit to a university kidney stone clinic from 1980 to 2015. From 1980 to 2015, the proportion of uric acid stones in all stone formers increased from 7% to 14%. While age and body mass index increased with time inboth uric acid and calcium stone formers, uric acid stone formers were consistently older and had a higher body mass index and lower urinary pH than calcium stone formers. The proportion of females with stones has increased over time but the increase in female gender was more prominent among calcium stone formers. Urinary pH, phosphorus, oxalate and sodium increased with time in calcium stone formers but remained unchanged in uric acid stone formers. After accounting for various parameters of stone risk, the strongest clinical discriminant of uric acid vs calcium stones was urinary pH. Limitations of this study include the retrospective single center design and the available number of patients with stone analysis. From 1980 to 2015, the proportion of uric acid stones increased significantly. With time, there were proportionately more female calcium stone formers but not uric acid stone formers. Urinary pH is the most prominent factor distinguishing uric acid from calcium stones.

Analysis of Methods for Extracting Matrix Proteins from Human Kidney Stones

Five techniques for the extraction of proteins from kidney stones were compared for the purpose of maximizing yield for mass spec analysis. The proteomics of kidney stones may provide insight into the underlying mechanisms of stone formation and why some people are more prone to developing kidney stones than others. Kidney stones contain proteins that may serve as markers for a wide variety of disease states. Mass spectrometry offers the ability to identify and quantify the complete proteome of a kidney stone. To date, there have been only a limited number of research projects aimed at studying the protein composition of kidney stones, possibly due to the difficulty in extracting these proteins while preserving the ability to subject the samples to mass spectrometry. We compared five methods for extracting kidney stone matrix proteins, three from previously published studies and two methods we designed based on previous studies. We were able to establish which methods produced the highest yield of protein for both calcium oxalate and uric acid stones.

Association of serum biochemical panel with mineralogical composition of kidney stone in India

Purpose: The aim is to study the diversity in the composition of kidney stones and its association with the basic biochemical metabolic panel in patients with kidney stone disease (KSD). Methods: A cross-sectional prospective study enrolling consecutive patients with KSD attending a tertiary care hospital in Mangalore (India) was undertaken. Mineral compositions of kidney stones were analyzed using attenuated total reflection-Fourier transform infrared spectroscopy. Kidney stones were classified into different groups according to the composition. Metabolic status was assessed to analyze possible association with the kidney stone. Results: A total of 369 patients (male 305 and female 64) in the age group of 43.05 ± 14.3 years were included in the study and showed a high diversity of kidney stone types with >50% with mixed compositions. A significant association was found between pure stone type and gender as well with age group (P < 0.001). Serum calcium levels in the calcium oxalate stone formers were significantly higher (P < 0.001) than others. Similarly, uric acid stone formers showed higher random blood sugar, blood urea, uric acid, and serum creatinine levels (P < 0.001). Urine pH was also found to be a contributing factor for the stone formation (P < 0.001). Stone recurrence did not differ significantly concerning stone composition as well as metabolic status. Conclusion: The study reports a high diversity of the kidney stone types among patients. This finding highlights the increased cases of mixed stones that may be because of various lifestyle factors resulting in altered metabolic status. This finding warrants mechanistic studies to understand the etiology of stone formation. This will enable to develop novel noninvasive interventional strategies and proper preventive strategies to reduce the risk of KSDs.

Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway

Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin–Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

SU-G-IeP2-15: Virtual Insertion of Digital Kidney Stones Into Dual-Source, Dual- Energy CT Projection Data

Purpose: In order to investigate novel methods to more accurately estimate the mineral composition of kidney stones using dual energy CT, it is desirable to be able to combine digital stones of known composition with actual phantom and patient scan data. In this work, we developed and validated a method to insert digital kidney stones into projection data acquired on a dual-source, dual-energy CT system. Methods: Attenuation properties of stones of different mineral composition were computed using tabulated mass attenuation coefficients, the chemical formula for each stone type, and the effective beam energy at each evaluated tube potential. A previously developed method to insert lesions into x-ray CT projection data was extended to include simultaneous dual-energy CT projections acquired on a dual-source gantry (Siemens Somatom Flash). Digital stones were forward projected onto both detectors and the resulting projections added to the physically acquired sinogram data. To validate the accuracy of the technique, digital stones were inserted into different locations in the ACR CT accreditation phantom; low and high contrast resolution, CT number accuracy and noise properties were compared before and after stone insertion. The procedure was repeated for two dual-energy tube potential pairs in clinical use on the scanner, 80/Sn140 kV and 100/Sn140 kV, respectively. Results: The images reconstructed after the insertion of digital kidney stones were consistent with the images reconstructed from the scanner. The largest average CT number difference for the 4 insert in the CT number accuracy module of the phantom was 3 HU. Conclusion: A framework was developed and validated for the creation of digital kidney stones of known mineral composition, and their projection-domain insertion into commercial dual-source, dual-energy CT projection data. This will allow a systematic investigation of the impact of scan and reconstruction parameters on stone attenuation and dual-energy behavior under rigorously controlled conditions. Dr. McCollough receives research support from Siemens Healthcare

Relationship between Twinkle Artefacts and in vivo Biochemical Composition of Kidney Stones

Introduction: Our aim was to predict the chemical composition of kidney stones according to their twinkle artefact (TA) features obtained by in vivo color Doppler ultrasonography and to determine the potential factors affecting the formation and intensity of TAs. Materials and Methods: A total of 101 patients who met the inclusion criteria were included in the study. All patients were evaluated for TAs using color Doppler ultrasonography. All stones were subjected to chemical analysis. The relationships between the TA and the size and chemical composition of the stone, presence of hydronephrosis and body mass index (BMI) were evaluated statistically. Results: According to the results of the chemical analysis, 66 (65.3%) were calcium oxalate stones. It was found that the in vivo TA intensity did not predict cystine and calcium oxalate monohydrate stones (p > 0.05) and the intensity of TAs increases with increasing BMI (p = 0.002). Conclusion: The present study is the first to show that TAs may not be reliable in overweight patients. The TAs could not predict the chemical composition of stones; so future comprehensive in vivo studies will clarify the role of TAs in the prediction of the stone type preoperatively.

Neutron diffraction as a probe for the characterization of biological entities

Using neutron diffraction as a probe, investigations at the interface between physics, chemistry and medicine can provide major information to clinicians, and the goal of this short review is to assess different information which can be retrieved. Varied research issues can be approached, such as the interaction of tissues with trace elements, the mechanical deformation of prosthesis, and the effect of diseases affecting bone or kidney stone composition and microstructure, as well as the dissolution process induced by drugs on kidney stones.

High Prevalence of Opaline Silica in Urinary Stones From Burkina Faso

To underline peculiar composition of kidney stones and to propose an epidemiologic study of urinary stones in West African countries, where epidemiologic studies are scarce. Only few data are available regarding stone composition in sub-Saharan countries. Recently, a set of 100 stones consecutively removed by surgery in the Department of Urology of the University Hospital of Ouagadougou in Burkina Faso were collected for physical analysis, which provided the opportunity to obtain an epidemiologic profile of stone composition in this country. A total of 100 stones from 64 men, 22 women, 10 boys, and four girls were analyzed by morphologic examination, infrared spectroscopy, and electron microscopy in our laboratory. The results were considered by sex and separately for adults and children. Sixty-five percent of the 100 stones contained calcium oxalate as the main component. Interestingly, the second main component was opaline silica (18%). Furthermore, opaline silica was identified in any proportion in 48% of the stones. The prevalence was sex and age dependent. Opaline silica was detected as the main component in 42% of the nuclei, which underlines its role as one of the main components involved in the initiation of calculi in this country. For the first time, a dramatically high occurrence of a "scarce" urinary stone component, namely opaline silica, was reported in a series of consecutive calculi from a single country. We propose that a regular consumption of clay could be the origin of this phenomenon in these populations.