Objective New biomarkers for acute kidney injury are needed and urinary Cystatin C is one alternative. The objective was to validate a urinary Cystatin C method on Mindray BS-380 comparing urine samples from the Uppsala Longitudinal Study of Adult Men (ULSAM-77) and urine samples from a reference group for Cystatin C. A visual control for a relationship between Cystatin C and C-reactive protein (CRP) and interleukin 6 (IL-6) respectively was made. Methods Precision, linearity, recovery, interference, and stability of the urine cystatin C method were investigated. Comparisons were made between ULSAM-77 samples and a reference group samples consisting of ordinary people. Results The highest total imprecision was 10.24 % for the sample with the lowest concentration. The second lowest concentration had 4.21 % total variation coefficient. The linearity equation was y = 0.99x – 0.01 with an R2-value of 0.99. The recovery for all concentrations was always 91 % or more. No interference from hemoglobin at a concentration of 10 g/L was found. The samples were stable at +5°C for seven days. The median for the samples from ULSAM-77 was 0.09 mg/L and the median for the reference samples was 0.06 mg/L. There was no obvious relationship between Cystatin C and CRP/IL-6 from ULSAM-77. Conclusion   Reliable data of urinary Cystatin C can be analyzed on a Mindray BS-380. The level of urinary Cystatin C was higher for people age 77 than for those with a median age of 49. There was no correlation between the concentration of Cystatin C in urine and the levels of CRP and IL-6.

Environmental chemicals may affect human health by disrupting endocrine function. Many of the endocrine disrupting chemicals (EDCs) are estrogens or estrogen-like molecules that have been classified as environmental estrogens or xenoestrogens (XEs). XEs include endosulfan, chlordance, nonylphenol, bisphenol A, octylphenol, and coumestrol, etc. Although these compounds have wide structural diversity, but all have in common the and/or other hydrophobic components. Many studies have shown that XEs affect cell viability. For instance, Nonylphenol is used in surfactants or plasticizers and bisphenol A (4, 4¡¦-isopropylidene-2-diphenol) is used as protective coatings on food containers and for composites and sealants in dentistry. Most previous studies have focused on the toxicity of XEs on development process and reproductive system, especially in aquatic ecosystems. Thus, the effects of these two environmental chemicals on the toxicological effect are still controversial. The aim of this study is to investigate the molecular mechanisms of nonylphenol and bisphenol A in induction of cell death in human gastric cancer (SCM-1) cells and Madin Darby canine renal tubular (MDCK) cells. First, WST-1 reduction assays and propidium iodide-staining assay were used to determine cell viability and apoptosis in the present of nonylphenol and bisphenol A. Furthermore, we will use immunoblotting to measure the activity of apoptotic markers caspase-3, mitogen-activated protein kinases (MAPKs) to survey how nonylphenol affects apoptotic pathways. Besides, I will explore bisphenol A whether induces cell death and the mechanisms underlying the [Ca2+]i rise in MDCK cells. The results may be helpful for understanding the pharmacological and toxicological effects of these two environmental chemicals in cells from important organs. Results showed that nonylphenol caused apoptosis via the activation of caspase-3 in cultured human gastric cancer (SCM-1) cells. Although nonylphenol could activate the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Nonylphenol was also found to induce [Ca2+]i increases and pretreatment with BAPTA/AM, a Ca2+ chelator, prevented nonylphenol-induced [Ca2+]i increases, and protect cells from death. These results suggest that nonylphenol induced apoptosis via a Ca2+- and p38 MAPK-dependent pathway. On the other hand, the effect of the environmental contaminant bisphenol A on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether bisphenol A changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Bisphenol A at concentrations between 50-300 £gM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Bisphenol A induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholiapase A2 inhibitor aristolochic acid, store-operated Ca2+ channel blockers nifedipine and SK&F96365; and protein kinase C inhibitor GF109203X. In Ca2+-free medium, pretreatment with the mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) and the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited bisphenol A-induced Ca2+ release. Conversely, pretreatment with bisphenol A abolished thapsigargin (or BHQ)- and CCCP-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished bisphenol-induced [Ca2+]i rise. Bisphenol A caused concentration-dependent decrease in cell viability via apoptosis in a Ca2+-independent manner. Collectively, in MDCK cells, bisphenol A induced [Ca2+]i rises by causing phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and mitochondria and Ca2+ influx via phospholipase A2-protein kinase C-sensitive store-operated Ca2+ channels. Key words: calcium, apoptosis, human gastric cancer cells (SCM-1), Madin Darby canine kidney (MDCK), nonylphenol, bisphenol A.

In Taiwan, the nephritis, nephrotic syndrome and chronic renal failure are occupied the eighth of compatriot's ten major causes of the death; Due to medical improvement in recent years, end stage renal disease with long term hemodialysis patients were increasing day by day, the dialysis cost also go up year by year. According to the statesment of Bureau of National Health Insurance, the whole Taiwan dialysis patients were about 50,000 persons, expensed 28,100 million dollars in one year , each dialysis patient expense 600,000 dollars every year on average, it is the first of clinical expenses . In recent years, the dialysis suppliers get involved in the business of the dialysis clinics, they already were not only the large international factory for selling dialysis material, but also get involved in dialysis clinics about dealing , buying and combining resources, so the dialysis clinics form the two kinds of different manageable type :dialysis supplier and independent operator. This research was cross- sectional study and divided dialysis clinics into dialysis supplier and independent operator, the study choose the different kinds of dialysis clinic patients as samples from Kaohsiung and Pingtung area and carry on the interview of questionnaire by the bedside. Through analyzing the patient¡¦s idiosyncrasy, affect patients in choosing health care providers, patient's satisfaction, life quality, life impact after kidney disease and paying medical care quality indicator of dialysis clinics (average serum albumin with the whole people's clinic of health insurance, dialysis efficiency equally to life), probe into the difference between two kinds of different manageable type of dialysis clinics. The descriptive statistical analysis, explored factor analysis, dependent sample analysis of variance, independent sample analysis of variance and Pearson product-moment correlation analysis, etc. method were employed as statistical analysis. The result of study found, the top five expected satisfaction level of hemodialysis patient were avablility to the peritoneum dialysis service, avablility to consultation of kidney transplantation , medicine safe to value , nutritionist for diets consultation , the availability of nephrology specialists , the expected satisfaction level relatively lean to the professional service , but patient satisfaction relatively lean to the hardware service actually. The whole satisfaction of independent operator in the operation service , professional service , extra service , public relations , geographical position are all superior to dialysis suppliers. The dialysis supplier was superior to the independent operator only in the hardware service. Through this research, hope to make the officer in dialysis center, realize the demand of patients,and offer better service as improving direction in medical quality.

Chronic kidney disease (CKD) is a major cause of illness in dogs, and it is commonly caused by glomerular diseases that result in proteinuria and a progressive decline in renal function. Despite the importance of glomerular lesions, tubulointerstitial fibrosis identified by histologic evaluation of renal biopsies correlates best with renal function. However, performing a renal biopsy is invasive. Most current non-invasive tests for renal function lack adequate sensitivity and specificity for renal disease. Proteinuria can be both a sensitive and specific marker for renal damage. However, its evaluation in veterinary medicine beyond determination of the magnitude of proteinuria (e.g., urine protein:creatinine ratio (UPC)) is limited. Therefore, in this report, further evaluation of the UPC was performed to aid in the monitoring of renal disease progression and response to treatment. In addition, qualitative evaluation of proteinuria was performed in dogs with progressive CKD in order to identify better non-invasive markers for tubulointerstitial injury. The day-to-day variability of the UPC was determined utilizing data obtained from female dogs that are carriers for X-linked hereditary nephropathy (XLHN). Despite an unchanging magnitude of proteinuria in these dogs, substantial variation in their UPC was observed. Using these results, guidelines were suggested to help assess whether disease progression or treatment leads to a significant change in UPC. Qualitative characterization of proteinuria in dogs with CKD was performed using urine from male dogs affected with XLHN, and results were correlated with clinical and histologic findings concerning renal function and damage. The two discovery proteomic techniques utilized (chromatographic chip array and two-dimensional gel electrophoresis) revealed several proteins that have not previously been implicated as markers for canine CKD, providing a basis for future studies. Specific assays for urinary biomarkers of renal injury were used to serially evaluate renal function in these dogs. All proteins evaluated proved to be sensitive markers for renal damage. However, only retinol binding protein provided clear evidence for renal disease progression. These results will provide the foundation for future studies aimed at monitoring urinary biomarkers in dogs with CKD, which will ultimately help veterinarians better diagnose and monitor proteinuric renal disease.

No description available.

Research Objective Patients with chronic kidney disease (CKD) are at increased risk for atherosclerosis and peripheral artery disease (PAD). PAD has received far less attention than coronary artery disease (CAD) in CKD patients. Few studies have examined risk factors for PAD in CKD. We studied the possible related risk factors and benefit of hypertension treatment in CKD patients with PAD. Data Sources We included 129 patients of both sexes with stages 3 to 5 of CKD, as described by the Kidney Outcome Quality Initiatives (K/DOQI ) classification, without receiving dialysis therapy, not previously diagnosed with PAD. Study Design The following information were collected within six month period, including demographic characteristics, history of hypertension, anti-hypertension drug, diabetes, smoking, and pre-existing cardiovascular disease, body mass index (BMI), fasting blood glucose, HbA1c, total cholesterol, triglyceride(TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol(LDL), calcium (Ca), phosphate(P), Albumin, uric acid, urine protein. Ankle-brachial index (ABI) is a noninvasive diagnostic test that is efficient in detecting asymptomatic PAD with ABI <0.9. Findings There were 22 (17.7 %) participants with PAD. Higher systolic blood pressure (SBP), higher diastolic blood pressure (DBP), higher pulse pressure showed strong association with PAD in CKD patients. On further analysis, significant fewer patients treated with calcium channel blocker (CCB) in hypertensive CKD patients with PAD (£q2 =7.055, p =0.008). The multivariate logistic regression analysis in hypertensive patients demonstrated the risk factors for PAD was pulse pressure, and Calcium channel blocker treatment may correlate with decreasing PAD formation (odds ratio= 0.232, 95% CI=0.07-0.73, p =0.013) in CKD patients. Conclusion There is a high prevalence rate of PAD in population of CKD, especially those with hypertension. ABI should be routinely examined in these patients who can benefit earlier from therapeutic measures.

Most patients diagnosed with End Stage Renal Disease (ESRD) undergo hemodialysis. Traditional hemodialysis treatment requires patients spending three to five hours every other day while yielding the high waste level accumulated between treatments. These limitations in the current technology have spurred the development of a portable renal replacement system. The portable system will not only free the patients from visiting the clinic but also allow more frequent treatment that will lead to lower average waste level. To realize a portable system, the size and weight of hemodialysis system components should be reduced. This work analyzes the working principle of the pump and proposes a DC-motor and cam driven finger pump design. In addition, an analytical pump model is created for the optimization of the pump design. In vitro experiment conducted using the pump measured Creatinine levels over time, and the results validitate the design for the portable renal replacement system. The proposed pump design is smaller than 188 cm³ and consumes less than 4W while providing a flow rate of more than 100ml/min (the optimum flow rate for a portable system) for both blood and dialysate flows. The smallest pump of a portable renal replacement system in the literature uses check valves, which considerably increase the overall manufacturing cost and possibility of clogging. Compared to that pump, the proposed pump design achieved reduction in size by 40% and savings in energy consumption by 65% with the removal of valves. This simple and reliable design substantially enables development of a portable renal replacement system.

<p>Diabetic nephropathy is a chronic kidney disease and one of the more severe complications from diabetes mellitus type 2. The glomerular and tubular dysfunctions usually lead to end stage renal disease and the treatments of these patients (dialysis, kidney transplants) are a huge economic burden for the society. Due to an epidemiologic increase of type 2 diabetes, conventional diagnostic markers like creatinine and albumin are not sufficient, since they are only able to identify already existing kidney damage. With targeted metabolomics, the analysis of small molecules produced from metabolism, this project aimed at finding novel and more sensitive metabolic biomarkers from several different classes of metabolites. The different assays were performed with flow injection analysis, high performance liquid chromatography, gas chromatography and mass spectrometry, and with principal component analysis and discriminant analysis, up-and down-regulated metabolites could be identified and their respective biochemical pathways, if possible, explained. In diabetics significantly elevated concentrations of very long chain fatty acids (impaired peroxisomal β-oxidation), urinary sugars and acylcarnitines in plasma could be recognized. Markers indicating kidney damage included significantly increased plasma concentrations of asymmetric dimethylarginine (inhibition of nitric oxide synthase resulting in decreased endothelial functionality) and histamine (indication of uremic pruritus). Oxidative stress was also found to be a potential prognostic marker as indicated by the raised methionine-sulfoxide to methionine ratio in nephrotic patients. To summarize, this project succeeded in identifying metabolic biomarkers both for diabetes type 2 and nephropathy, which in the future might become important tools in slowing down progression or diagnosing these diseases.</p>

Involving patients in medical decisions by acknowledging patients personal values and individual preferences has become an important goal of providing ethical medical care. Despite a general movement towards a model of shared decision-making, many patients do not fully meet their preferred role in practice. The decision whether or not to accept a kidney once it is offered to a patient awaiting transplant has historically been made predominantly by the transplant surgeon with little involvement from the patient. Because dialysis can provide long-term renal replacement, declining a kidney is a viable option. Patient changes over time and inherent heterogeneity of donor kidneys make this an authentic decision requiring careful analysis of costs and benefits from the patient perspective. The purpose of this study is to improve our understanding of how patients and transplant surgeons prioritize different factors when deciding whether or not to accept a kidney that has become available, in order to empower patients to become more involved in the decision-making process. Phase I: We developed a comprehensive list of factors that patients might consider important through qualitative interviews with patients, and deliberation with a transplant surgeon (SK) and a transplant nephrologists (RF). Phase II: We quantified the relative importance of each factor for patients on the transplant list and for transplant surgeons with a computerized survey using Maximum Differences Scaling. We developed relative importance scores using Heirarchical Bayes analysis, and tested for associations between patient characteristics and relative importance scores using Spearmans correlation coefficient and the Mann Whitney U test for continuous and categorical variables respectively. Of the factors evaluated, patients placed the greatest value on Kidney quality, How closely matched you are to the kidney, and How strongly your surgeon feels you should accept the kidney. Relative importance of different factors did not change based on patient demographic characteristics. Patients who are on the waiting list longer give less importance to kidney quality (standard beta estimate -0.23, p value 0.03) and more importance to How difficult it is for you to be matched to a donor (ie whether or not you are sensitized) (standard beta estimate 0.28, p value 0.01). Surgeons placed the greatest value on Kidney quality, How difficult it is for the patient to be matched to a kidney (ie whether or not the patient is sensitized), and The age of the donor. This pilot study suggests a role for standardized education tools to help empower patients to be involved in this difficult decision. Development of decision aids can be guided by the results of this project.

Many patients with end-stage renal disease come to rely on catheters as their only means of hemodialysis when other options are no longer viable. These patients have a very poor quality of life due to their chronic illness as well as many long-term complications related to the use of tunneled catheters. Many prior attempts have been made to understand these catheter-related problems. Yet, they continue to be a major cause of morbidity and mortality in chronic catheter-reliant patients. We hope to examine the rate as well as long term time course of these complications such that in future, we may decrease their occurrence. We predict that over time, chronic catheter use decreases the mean indwell time for each catheterization and increases the incidence of complications. To study this, we conducted a retrospective study looking at all patients who had three or more tunneled catheter exchanges between July 2003 and July 2008. We collected information from Yale IDX database on the patients age and gender, the type of catheter used, the indwell time of the catheter, the vessel used as access, the indication for catheter removal, whether the procedure was performed by a medical doctor (M.D.) or physicians assistant (P.A.) and whether it was a de novo insertion or over-the-wire exchange. We collected a total of 764 data points on 191 patients (89 males and 102 females). They ranged from 8 to 87 years old with a median age of 56 years. Infection was the number one indication for catheter removal at 37%. The rate of infection was 3.34 per 1,000 catheter days. There was no difference in the rate of complications by the side of vessel accessed nor by type of catheter. However, right-sided catheters had a longer indwell time of 117 + 159 days compared to left-sided catheters, 87 + 124 days (p =0.008). There was no significant difference in the indwell duration of first catheter in comparison to all subsequent placements. There was also no difference in complications whether the catheter was exchanged over the wire or placed de novo. Nor were complication rates different among M.D. versus P.A. conducted procedures. We conclude that our rates of infection are similar to other institutions and the vessels located on the right-side of the neck are preferable to left-sided vessels to increase catheter longevity. Future research is needed to better assess how rates and incidences of complications change with long standing catheter-reliance.