Pathophysiology Of Nephrolithiasis Research Articles

Research Progress of Drugs in Prevention and Treatment of Nephrolithiasis.

With the improvement of people's living standards,the incidence of nephrolithiasis is increasing year by year.Nephrolithiasis poses a serious threat to the patients due to the unclear etiology,complicated composition of stones,and high recurrence rate after surgery.As the research on the pathogenesis and pathophysiology of nephrolithiasis keeps deepening in recent years,researchers have made achievements in the drug treatment,which has become a hot topic for urologists.This paper reviews the advances in the research on the possible formation mechanism and drug-induced litholysis and prevention for nephrolithiasis,aiming to provide theoretical references for subsequent clinical research.

REVIEW OF THE PHYTOTHERAPY FOR NEPHROLITHIASIS

Nephrolithiasis (kidney stone) cases have a prevalence ranging from 1% to 13%. The disease not only hampers kidney function but also elevates the risk of chronic kidney diseases. The pathophysiology of nephrolithiasis is closely linked to elevated concentrations of calcium, oxalate, and/or uric acid in the urine. Pharmacotherapy to manage nephrolithiasis includes thiazide diuretics, allopurinol, citrate supplements, and alpha-blockers that have been prescribed to relieve symptoms. In addition, there is growing interest in exploring the potential of phytotherapy. This review aims to identify suitable phytotherapy approaches by examining relevant articles on nephrolithiasis. The research methodology involved searching PubMed articles using the keywords of (("Plant Extracts") AND ("Nephrolithiasis")) OR ("Ureterolithiasis"). The articles obtained from the initial search were n =123. 2 authors screened articles for their eligibility. The inclusion criteria were limited to articles written in English, topics related to nephrolithiasis and not other kidney diseases, the botanical names of the plants and the method of extraction are clearly described, complete studies with clear descriptions regarding the methods and results, not synthetic drugs, and not involving medical instruments or laser to remove the stones. Articles included in the review were n = 17. Water and hydro-alcohol were the solvents used to extract the plants. Twenty-two plants have confirmed their anti-nephrolithiasis activity, and nine articles described the assay by in vivo study, two by in vitro study, three by both in vitro and in vivo study, and only one article mentioned a study in humans by a randomized-control trial on a mixture of herbs. It is concluded that Rhizoma alismatis, Poria cocos, Polyporus umbellatus, Atractylodis macrocephalae, and Cinnamomi Cassiae prepared as a mixture in the Wu-Ling-San formula have a potential therapeutic effect on nephrolithiasis, as this formula has been studied in humans.

Risk Factor and Pathophysiology of Nephrolithiasis: A Review Article

Introduction: Nephrolithiasis is a urinary tract stone disease that can be found in the kidneys, ureters, bladder, and urethra. This disease is the three most common diseases in the field of urology besides urinary tract infections and benign prostate enlargement. Kidney stones are the most common, with an estimated lifetime prevalence as high as 15%. Bladder stones have significant morbidity but occur much less frequently than kidney stones. Many factors cause reduced urine flow and cause obstruction, one of which is urine static and decreased urine volume due to dehydration and inadequate fluid intake, this can increase the risk of nephrolithiasis. Low urine flow is a common abnormal symptom. In addition, various conditions that trigger nephrolithiasis such as the composition of various stones are the main factors in identifying the cause of nephrolithiasis. Aims of this article is to review risk factors and pathophysiology of nephrolithiasis. Discussion: Symptoms associated with urinary tract stones depend on the location of the stone, the size of the stone, and any complications that have occurred. Usually, stones in the kidney calyx are asymptomatic. When the stone falls off and descends into the narrow ureter, it becomes symptomatic. Stones generally get stuck in the narrowest part of the ureter, such as the uretero-pelvic junction, when the ureter crosses the iliac vasa, and the uretero-vesical junction. The main symptom of ureteric stones is often an acute onset of pain in the back. This pain can be colicky or not. Colic pain occurs because the peristaltic activity of the smooth muscle of the calical system or ureter increases in an attempt to remove stones from the urinary tract. The increase in peristalsis causes the intraluminal pressure to increase so that there is stretching of the nerve terminals that provide a sensation of pain. The pain can radiate from the pelvis and to the ipsilateral groin. Other symptoms include nausea, vomiting and hematuria. Hematuria can occur macros or microscopy from urinalysis. Hematuria occurs as a result of trauma to the urinary tract mucosa caused by stones. Conclusion: Nephrolithiasis is rock-forming salt reaches a urine concentration that exceeds the equilibrium point between the dissolved component and crystallization occurs. There are several risk factors that nephrolithiasis occurs due to various causes. Therapy and lifestyle changes are interventions that can change risk factors, but there are also risk factors that cannot be changed.

Dyslipidemia is associated with an increased risk of nephrolithiasis.

The pathophysiology of nephrolithiasis is multifactorial. Obesity, diabetes mellitus and hypertension are implicated in its formation. Dyslipidemia (DLD) recently has received attention as well. Congruent with a vascular etiology in stone formation, DLD theoretically would predispose patients to nephrolithiasis. We investigated a possible association of DLD with nephrolithiasis. A random cohort of 60,000 patients was established by collecting the first 5,000 patient charts per month in the year 2000. After excluding pediatric patients, a retrospective study was performed by reviewing age, sex, comorbidities, and last patient follow-up. Median lipid laboratory levels also were reviewed. Descriptive statistics were performed as well as Cox proportional-hazards regression analysis, and univariate and multivariate analyses. 52,184 (22,717 women/29,467 men) patient charts were reviewed. The average age was 31.0±15.2 years. On univariate analysis, DLD was associated with nephrolithiasis with a hazard ratio (HR) of 2.2 [Confidence Interval (CI), 1.9-2.5; p<0.001] and on multivariate analysis HR=1.2 (1.0-1.5; p=0.033). Low-density lipoprotein and triglycerides had no association with stone disease. Patients with high-density lipoprotein (HDL) values <45 for men and <60 for women had an HR of 1.4 (1.1-1.7, 95% CI, p=0.003) on univariate analysis and on multivariate analysis; HR=1.27 (1.03-1.56; p=0.024) for nephrolithiasis. DLD was associated with an increased risk of stone disease though the only specific lipid panel associated with lower nephrolithiasis was HDL. Clinicians should consider obtaining lipid levels with the intent that treatment could potentially not only mitigate atherosclerotic disease but also decrease nephrolithiasis risk.

Pediatric nephrolithiasis and the link to bone metabolism

To review the recent publications describing the link between pediatric nephrolithiasis and bone metabolism. Nephrolithiasis incidence is increasing in children and is associated with low bone mineral density (BMD). Affected children are conceptually at risk for fractures and osteoporosis. In addition to abnormal calcium metabolism, inflammation, genetic makeup and dietary habits are being recognized as important factors in the pathophysiology of nephrolithiasis and low bone density. Findings from retrospective reviews suggest that low BMD in children may be improved with citrate or thiazide treatment. The healthcare burden from low BMD with subsequent osteoporosis and fracture risk is immense with potential far-reaching effects in patient quality of life and healthcare expense. Bone mass is acquired in the pediatric age range, thus it is important to identify and treat at-risk children. Retrospective reviews in pediatric patients indicate that citrate or thiazide diuretic treatment may improve BMD. We now understand that a relationship exists between nephrolithiasis and low BMD. To improve healthcare for our current patients as well as protect their future health it is important to identify low BMD and initiate strategies to improve BMD in 'at-risk' children.

Elevated levels of miR-155 in blood and urine from patients with nephrolithiasis.

Background. Both circulating and urinary miRNAs may represent a potential noninvasive molecular biomarker capable of predicting chronic kidney disease, and, in the present study, we will investigate the serum and urinary levels of miR-155 in patients with nephrolithiasis. Methods. Serum and urinary levels of miR-155 are quantified in 60 patients with nephrolithiasis; the result was compared to 50 healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlations of miR-155/eGFR and miR-155/CRP (C-reactive protein) levels were analyzed as well. Results. The median levels of serum and urinary levels of miR-155 are significantly higher in nephrolithiasis patients than in controls. eGFR inversely correlates with urinary level of miR-155; CRP positively correlates with urinary miR-155. Urinary level of miR-155 inversely correlates with urinary expression of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α and positively correlates with urinary expression of regulated upon activation, normal T-cell expressed, and secreted (RANTES). Conclusion. Serum and urinary levels of miR-155 were significantly elevated in patients with nephrolithiasis, and the upregulation of miR-155 was correlated with decline of eGFR and elevation of CRP. Our results suggested that miR-155 might play important roles in the pathophysiology of nephrolithiasis via regulating inflammatory cytokines expression. Further study on the molecular pathogenic mechanism and larger scale of clinical trial are required.

The relevance of Randall′s plaques

The pathophysiology of nephrolithiasis is not fully understood. The pioneering work of Alexander Randall in the 1940s sought to clarify our understanding of stone formation. This review traces the inception of the theory of Randall's plaques and the refinement of the hypothesis in the early days of kidney stone research. It then reviews the contemporary findings utilizing sophisticated investigative techniques that shed additional light on the pathophysiology and redefine the seminal findings of Dr. Randall that were made 70 years ago.

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5- to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.