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Prevalence, Predictors, and Outcomes Associated with Late Start of Chronic Kidney Disease Care Amongst Adults with End-stage Renal DiseaseSinghal, Rajni 20 December 2011 (has links)
Using Ontario health administrative data, we identified 12,143 adults with chronic kidney disease (CKD) who received outpatient nephrology care prior to start of renal replacement therapy (RRT) in order to study the effect of care-related factors in predicting late start of predialysis care (PDC, defined as first outpatient nephrology visit <6 months prior to RRT start) and to explore covariates which further quantify the PDC received. Lack of an usual provider of primary care (OR 0.76; 95%CI 0.66, 0.87) predicted late start of PDC. In addition to late start of PDC, number of nephrology visits (OR 0.97 per visit; 95% CI 0.96, 0.98), and having seen a nephrologist in only 1 or 2 of the 6 months prior to RRT start (OR 1.33; 95%CI 1.18, 1.51), were also independent predictors of one-year mortality, suggesting that other measures of PDC are needed to better characterize the care received.
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Role of the SDF-1/CXCR4/eNOS Signaling Pathway in Chronic Kidney DiseaseChen, Li-Hao (Henry) 21 November 2012 (has links)
Loss of the renal microvasculature is a common feature of almost all forms of chronic kidney disease (CKD). Here we explored the role of the angiogenic chemokine stromal cell-derived factor-1-alpha (SDF-1) and its cognate receptor CXCR4 in experimental and human CKD. CXCR4 was present on endothelial cells and podocytes, while SDF-1 was detectable on podocytes, arteriolar smooth muscle cells, interstitial fibroblasts and occasional endothelial cells. CXCR4 mRNA was elevated in the kidneys of rats with CKD and chronic antagonism of CXCR4 accelerated renal decline and capillary loss. Acute SDF-1 infusion activated glomerular endothelial nitric oxide synthase (eNOS) in vivo, while functional response to SDF-1 was impaired in glomerular endothelial cells derived from eNOS-/- mice. Finally, CXCR4 mRNA was also found to be increased in biopsies of patients with secondary focal segmental glomerulosclerosis. These observations indicate that local eNOS-dependent SDF-1/CXCR4 signaling exerts a compensatory reno-protective effect in the setting of CKD.
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Early Outgrowth Cells As A Novel Therapy for Chronic Kidney DiseaseYuen, Darren 12 January 2012 (has links)
Chronic kidney disease (CKD) and its cardiac complications represent a large and growing problem in Canada. The progression of CKD is driven by the activation of several final common pathways of injury, including fibrosis and oxidative stress. If left unchecked, these inter-connected processes lead to progressive damage and subsequent organ dysfunction. Current clinical therapies, consisting of aggressive blood pressure control and blockade of the renin-angiotensin system, fail to arrest this progressive injury in a significant number of patients.
Early outgrowth cells (EOCs) represent a novel bone marrow-derived cell population that have been recently described to have tissue protective activity. In this work, we examined the effects of intravascular EOC infusion in two independent models of CKD, demonstrating potent anti-fibrotic renoprotective effects in the subtotally nephrectomized (SNX) rat, a well-established model of non-diabetic progressive CKD, and anti-fibrotic and anti-oxidant effects in the db/db mouse, a commonly used model of type 2 diabetic nephropathy. In the SNX rat, which is characterized by impaired cardiac relaxation reminiscent of a common and high risk clinical CKD phenotype, EOC infusion was also associated with improved cardiac structure and function. In both cases, infused EOCs were not retained in significant numbers within the diseased kidney or heart, but rather localized to distant organs such as the liver, spleen, and bone marrow. We further demonstrated that EOCs release soluble factors with anti-oxidant and anti-fibrotic activity in vitro, and that a cell-free preparation of EOC-derived factors can mimic the reno- and cardiac protective effects of the cells themselves when infused into the SNX rat.
Taken together, our results demonstrate the therapeutic potential of an EOC-based strategy for the treatment of CKD and its cardiac complications, and provide the preclinical rationale for the design of clinical trials of EOC-based therapies for this devastating disease.
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Early Outgrowth Cells As A Novel Therapy for Chronic Kidney DiseaseYuen, Darren 12 January 2012 (has links)
Chronic kidney disease (CKD) and its cardiac complications represent a large and growing problem in Canada. The progression of CKD is driven by the activation of several final common pathways of injury, including fibrosis and oxidative stress. If left unchecked, these inter-connected processes lead to progressive damage and subsequent organ dysfunction. Current clinical therapies, consisting of aggressive blood pressure control and blockade of the renin-angiotensin system, fail to arrest this progressive injury in a significant number of patients.
Early outgrowth cells (EOCs) represent a novel bone marrow-derived cell population that have been recently described to have tissue protective activity. In this work, we examined the effects of intravascular EOC infusion in two independent models of CKD, demonstrating potent anti-fibrotic renoprotective effects in the subtotally nephrectomized (SNX) rat, a well-established model of non-diabetic progressive CKD, and anti-fibrotic and anti-oxidant effects in the db/db mouse, a commonly used model of type 2 diabetic nephropathy. In the SNX rat, which is characterized by impaired cardiac relaxation reminiscent of a common and high risk clinical CKD phenotype, EOC infusion was also associated with improved cardiac structure and function. In both cases, infused EOCs were not retained in significant numbers within the diseased kidney or heart, but rather localized to distant organs such as the liver, spleen, and bone marrow. We further demonstrated that EOCs release soluble factors with anti-oxidant and anti-fibrotic activity in vitro, and that a cell-free preparation of EOC-derived factors can mimic the reno- and cardiac protective effects of the cells themselves when infused into the SNX rat.
Taken together, our results demonstrate the therapeutic potential of an EOC-based strategy for the treatment of CKD and its cardiac complications, and provide the preclinical rationale for the design of clinical trials of EOC-based therapies for this devastating disease.
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The Role of Podocyte Prostaglandin E2 and Angiotensin II Receptors in Glomerular DiseaseStitt, Erin Maureen 24 February 2011 (has links)
The incidence of chronic kidney disease (CKD) is increasing. CKD is characterized by a gradual decrease in renal function leading to end stage renal disease (ESRD). Damage to the glomerular podocytes, is one of the first hallmarks of CKD. We hypothesized that podocyte prostaglandin E2 (PGE2) receptors contribute to the progression of glomerular injury in models of CKD. To test this hypothesis, transgenic mice were generated with either podocyte-specific overexpression or deletion of the PGE2 EP4 receptor (EP4pod+and EP4pod-/- respectively). Mice were next tested in the 5/6 nephrectomy (5/6 Nx) or angiotensin II (Ang II) models of CKD. These studies revealed increased proteinuria and decreased survival for EP4pod+ mice while EP4pod-/- mice were protected against the development of glomerular injury. Furthermore, our findings were supported by in vitro studies using cultured mouse podocytes where an adhesion defect was uncovered for cells overexpressing the EP4 receptor. Additionally, our investigations have demonstrated a novel synergy between angiotensin II AT1 receptors and prostaglandin E2 EP4 receptors. This was revealed by in vitro studies using isolated mouse glomeruli. There we were able to show that Ang II stimulation leads to increased expression of cyclooxygenase 2 (COX-2), the enzyme responsible for synthesis of PGE2, in a p38 mitogen activated protein kinase (MAPK) dependent fashion. Moreover increased PGE2 synthesis was measured in response to Ang II stimulation. We confirmed the presence of this synergy in our cultured mouse podocytes and showed an adhesion defect in response to Ang II stimulation which was COX-2 and EP4 dependent. These findings suggest that Ang II AT1 receptors and PGE2 EP4 receptors act in concert to exacerbate glomerulopathies. Studies using mice with either podocyte-specific overexpression of a dominant negative p38 MAPK or mice with global deletion of the EP1 receptor did not provide conclusive results as to their respective signaling involvement in podocyte injury. Altogether our findings provide novel insight for podocyte PGE2 EP4 and Ang II AT1 receptor signaling in models of CKD. These studies provide novel avenues for pursuing therapeutic interventions for individuals with progressive kidney disease.
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The Effects of Acid-Base Parameters, Oxygen and Heparin on the Ability to Detect Changes in the Blood Status of End-Stage Renal Disease Patients Undergoing Hemodialysis Using Whole Blood-Based Optical SpectroscopyAtanya, Monica 18 April 2011 (has links)
Relative changes are detectable in the blood of end-stage renal disease (ESRD) patients during hemodialysis (HD) treatment using optical spectroscopy. However, the potential impacts of several confounding factors that could affect the detection of these changes have not been evaluated. The objectives of this thesis were to: 1) investigate how the variations and/or changes in acid-base and oxygen parameters during HD treatment can affect the optical signature of whole blood of ESRD patients, 2) to investigate the effect of heparin on the optical properties of whole blood and its impact on our method.
Blood samples were drawn from 23 ESRD patients at 5 time points during a 4 hour HD treatment and sent for blood gas and blood spectroscopy analyses. No significant correlations were found between the changes in the blood transmittance spectra and acid-base and oxygen parameters. This indicates that the perturbations in these parameters due to HD procedures do not confound the detection of changes in the blood transmittance spectra of ESRD patients during HD treatment. Additionally, the effect of heparin in modifying the optical properties of whole blood does not confound the detection of changes in the blood of ESRD patients due to HD treatment using whole blood-based optical spectroscopy.
ANOVA revealed significant (P<0.05) measurable changes in the blood transmittance spectra of ESRD patients during HD treatment. Significant spectral differences (P<0.05) were found between ESRD patients. The lack of uniform spectral characteristics across patients is
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The analysis and research of medical care quality indicator of dialysis clinicsTsai, Ming-kai 11 July 2010 (has links)
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.
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Urine Protein Analysis and Correlation of Urinary Biomarkers with Renal Disease Progression in Dogs with X-Linked Hereditary NephropathyNabity, Mary B. 2010 December 1900 (has links)
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.
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Uremic Toxicity of Indoxyl SulfateNiwa, Toshimitsu 02 1900 (has links)
No description available.
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The Prevalence and Clinical Correlative Factors of Peripheral Arterial Disease in Patients with Chronic Kidney DiseaseYang, Ching-ping 17 June 2009 (has links)
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.
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