No description available.

In the setting of an increasing incidence of endocarditis in the United States, we report a patient with necrotizing crescentic glomerulonephritis (GN) associated with native valve bacterial endocarditis due to Streptococcus parasanguinis. He was started on appropriate antibiotic treatment and subsequent blood cultures showed no growth. However, due to continuing decline in kidney function, immunosuppressive therapy was started. Despite immunosuppressive therapy and antibiotics, renal function did not improve and chronic hemodialysis was required. Due to rarity of condition, there are no definite treatment guidelines available. Antibiotics, steroids, immunosuppressive agents can be of help in most cases. Further research in this regard may help with early diagnosis and better treatment modalities.

No description available.

Raman spectroscopy records the inelastic scattering of photons originating from striking a sample with monochromatic light. Inelastic, or Raman, scattered photons shift in wavelength due to excitation of the vibrational modes of molecules struck by the incident light. The Raman scattered photons are representative of all of the covalent bonds contained within a sample. Raman spectra taken of biological systems such as proteins, bacterial colonies, and liquid waste, are difficult to interpret due to the complexity of their covalent bond landscape and mixtures of molecules in highly variable concentrations. Rather than deconstructing Raman spectra to attempt assignment of specific bonds and functional groups to wavenumber peaks, here we have developed a chemometric analysis pipeline for quantifying the similarities and differences among a set of Raman spectra. This quantification aids in both classification of samples, and in measuring how samples change over time. The chemometric approach for interpretation of Raman spectra was made freely available in a user-friendly format via a MATLAB add-on called the Raman Data Analysis (RDA) Toolbox. Demonstrations of the RDA Toolbox functionalities on Raman spectra taken of various common biological systems are included, such as determination of protein concentration and monitoring bacterial culture growth. The RDA Toolbox and Raman spectroscopy are also used to initiate research in novel areas. Fast and accurate evaluation of enzyme specific activity is required for engineering enzymes, and results of Raman assays, evaluated in the RDA Toolbox, are successfully correlated to absorbance activity assays of an enzyme WT and mutant library. Further development of this research could alleviate the bottleneck of screening mutant libraries in enzyme engineering projects. The Toolbox is then used in a distinctly different application for evaluating urine and spent dialysate samples from patients with end stage renal disease. Categorization between samples from healthy volunteers and patients is accomplished with close to 100% accuracy, and evidence indicating that Raman spectroscopy can serve as an early diagnostic tool for infections of the peritoneal membrane is presented. / PHD / Raman spectroscopy, unlike other forms of spectroscopy, provides a complete picture of the chemical make-up of a sample. However, Raman spectra of biological samples are very difficult to interpret due to the complex mixture of molecules in living systems. Rather than trying to discern what specific molecules are in a sample, we have developed a method for measuring the similarities and differences among a set of Raman spectra. These measurements help us classify samples and monitor how samples change over time. We made a MATLAB add-on called the Raman Data Analysis (RDA) Toolbox to automate our method for interpreting Raman spectra, and made it available online for anyone to download and use. Raman spectroscopy and the RDA Toolbox are used to measure enzyme reaction speed, and the results compare favorably with a traditional method for measuring enzyme reaction speed. The final part of this dissertation focuses on using Raman spectroscopy and the RDA Toolbox to evaluate the health of patients with end stage renal disease (ESRD) by scanning urine and spent dialysate samples to detect failing kidney function or the onset of infection.

End-stage renal disease (ESRD), or kidney failure, is a serious illness with significant health consequences and high-cost treatment options. Since the early 1980s, the number of Canadians with ESRD has more than quadrupled (CIHI, 2001), leading to questions about the current and future impact of the disease on public health, quality of life, health spending, and patients’ productivity. Using an economic burden of illness approach, this thesis estimates ESRD’s “direct” health care costs and “indirect” costs, such as productivity losses due to premature death and short- and long-term disability. It also projects future results under various alternative assumptions using a multi-state discrete time Markov model. The analysis suggests that, although less than 0.1% of Canadians have ESRD, it generated direct health care costs of $1.3 billion in 2000 or $51,099 per person with ESRD. That compares to $3,183 per capita for Canadians overall (CIHI, 2002b). Adding indirect morbidity and mortality costs brings the total to $1.9 billion. Rising ESRD numbers suggest higher costs in the future. Further analysis explored the effect of various assumptions about drivers of past trends, such as population growth, changes in the age structure, and the prevalence of conditions known to cause ESRD (e.g. diabetes). Projections were most sensitive to assumptions about the rate at which new cases are diagnosed. If current trends continue, the total economic burden of the disease can be expected to reach $7.9 billion by 2015 (year 2000 dollars). On the other hand, if the rate of new cases in 2000 were maintained, the economic burden of illness would be $5.7 billion in 2015. Nevertheless, under this and many other assumptions, there is likely to be a significant gap between available organs for transplant and the demand for transplantation. The likely effects of various options for addressing this gap are also explored. / Thesis / Doctor of Philosophy (PhD)

Depression is a substantial psychopathology encountered in the dialysis population yet its association with potentially modifiable psychological antecedents are not well known. Of these potential antecedents, individual’s perception of their condition are likely to play an important role in how they adjust to their illness (Leventhal, Brissette, & Leventhal, 2003). The Common Sense Model suggests that illness representations guide the self-regulation of illness (Leventhal, Meyer, & Nerenz, 1980; Leventhal, Nerenz, & Steele, 1984). The model posits that the interpretation of illness (illness perceptions) influence the response and procedures adopted in order to regulate the illness threat. The overarching aim of the work here is to examine whether illness perceptions predict depression and its trajectory in End-Stage Renal Disease (ESRD) patients, and to establish if depression and illness perceptions are associated with adverse clinical outcomes in these patients. In order to achieve these aims it was first important to establish how best to assess depression and illness representations in the context of ESRD. A pilot study investigated whether the Beck Depression Inventory (BDI) and the Revised Illness Perception Questionnaire (IPQ-R) could be administered to haemodialysis patients (HD) while actively on dialysis. Patients completed the BDI and IPQ-R while on-dialysis and again at a time when off-dialysis (n=40). Level of agreement revealed no discernable difference between BDI and IPQ-R scores across the two conditions, although there was a slight bias with regards to scoring on somatic items of the BDI while on-dialysis. Given these data, on-dialysis assessments were employed in the studies reported. Furthermore the BDI was compared against a diagnostic standard for Major Depressive Disorder (MDD) in order to define an adjusted BDI cut-off score that would indicate potential depressive cases. The data revealed that a BDI≥16 had optimal sensitivity and specificity for MDD. This cut-off score was employed to define patients with “probable” depression. The factor structure of the BDI was the focus in the following chapter. BDI data from two larger studies (reported later in the thesis) were pooled in order to conduct confirmatory factor analysis, testing several proposed structures of the BDI. The analysis revealed that two and three factor solutions had relatively poor fit to the data. A relatively novel bi-factor model proposed by Ward (2006) had the best fit. In this model there is a general depression factor that loaded onto all of the 21 BDI items, and two smaller orthogonal cognitive and somatic factors. These factors collectively explained 91% of the total variance in BDI-II total scores, suggesting that the BDI provides a good overall measure of global depressive symptoms. The first study to examine the association between illness representations and depression was a cross-sectional study of established HD patients (n=215). Nearly 30% of the sample were depressed (BDI≥16), highlighting the extent of depressive symptoms in this patient group. Significant differences between depressed and non-depressed patients with regards to illness perceptions were evident. In logistic regression illness coherence, perceived consequences and treatment control perceptions predicted depression. Interestingly clinical variables including co-morbidity were unrelated to depression. This suggests that it is not disease severity or extra-renal co-morbidity per se that are vulnerabilities for depression, rather it is the interpretation of the disease that appears to be important. The proceeding chapter extended this cross-sectional investigation by examining the trajectory of depression (i.e. change in depression) over the first year of dialysis therapy in relation to illness representations. An incident cohort of dialysis patients (n=160) were seen at a point soon after dialysis initiation and followed up 6 and 12 months thereafter. In particular, differences between patients who start dialysis via planned route (i.e. those with progressive renal failure who had been “worked-up” to dialysis) vs. those who started dialysis suddenly (unplanned starters) were sought. Unplanned starters were more depressed than the planned patients and held different illness perceptions. Structural equation modelling of the baseline data revealed that illness perceptions predicted depression, and that path to dialysis had an indirect effect on depression as mediated through illness perceptions. Over time, depression and illness perceptions appeared to remain relatively stable although there was some evidence of a non-linear decline in depression scores over the follow-up period. In addition, illness identity decreased over time, while illness coherence (understanding) increased. Clinical and demographic factors were not associated with the trajectory of depression as assessed using Latent Growth Models. However several illness perceptions were associated with a change in depression over time, suggesting that patient’s illness representations assist in the regulation (or under-regulation) of mood. The first of two clinical oriented chapters examined the utility of illness representations in explaining fluid non-adherent behaviour. HD patients were categorised as either fluid adherent or non-adherent based upon Inter-dialytic Weight Gain (IDWG). Patients in the upper quartile of percent weight gain were defined as non-adherent (IDWG≥3.21% dry weight). The data revealed that non-adherent patients had lower timeline perceptions as compared to adherent patients. Logistic regression models were evaluated in order to identify predictors of fluid non-adherence. After several demographic and clinical variables had been controlled, lower consequence perceptions predicted non-adherence. This data points to the utility of understanding dialysis patient’s personal illness representations in relation to maladaptive health care behaviour. Finally, the potential association between depression, illness representations and short term survival in incident dialysis patients was evaluated. Patients were followed up for a mean of 545 (±271) days in which there were 27 deaths (16.9%). Patients were censored if they were lost to follow-up, transplanted or recovered renal function. In Cox survival models after controlling for several co-variates including co-morbidity, depression significantly predicted mortality. Furthermore, survival models including illness perceptions revealed that treatment control perceptions were also predictive of mortality. These results suggest that depression and beliefs surrounding treatment control contribute to the survival of dialysis patients. Possible explanations regarding these associations are presented. In conclusion the empirical investigations offered here support the thesis that illness perceptions predict depression in dialysis patients. Moreover there is evidence that illness representations are associated with maladaptive health behaviour (non-adherence) in dialysis patients. Depression and illness representations also predict short-term survival in incident patients after adjusting for important co-variates. Recent studies have shown that altering maladaptive illness perceptions via psychological intervention can have a positive influence upon outcomes (Petrie, Cameron, Ellis, Buick, & Weinman, 2002). Given the evidence presented in this thesis, testing interventions that target maladaptive illness representations in order to improve clinical and psychological outcomes seem highly relevant in this setting.

The study of immune status and biobehavioral measures is limited in professional nursing. The purpose of the pre-pilot study was to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. A within subject descriptive study was conducted as part of a larger pilot study to describe levels of cytokines prior to, during, and after dialysis, examine changes in cytokine levels from immediate pre-dialysis to immediate post-dialysis, and to compare cytokine patterns prior to and after dialysis. Serum cytokine samples were collected pre-dialysis and every 30 minutes during the dialysis treatment and immediately post-dialysis from a convenience sample of 10 patients. Mean age of subjects was 53.5 years and 60% were African American. The sample was equally divided between female and male. Statistical analysis using a nonparametric paired difference test showed that only MIP-1β showed a significant increase from pre-dialysis to post-dialysis. Based on the results of this study, a second descriptive study was conducted. The purpose of the second study was to examine the relationships among disease related factors, perceived stress, depressive symptoms, immune indicators, and HRQOL among patients requiring hemodialysis for ESRD using a PNI framework. Using a descriptive design, participants completed the Perceived Stress Scale (PSS), the Center for Epidemiologic Studies Depression Scale (CES-D), and one quality of life measure, the Functional Assessment of Cancer Therapy-General scale (FACT-G), during the first hour of the dialysis treatment. In addition, blood samples were collected immediately prior to dialysis for cytokine measurement and demographic information was collected from the medical record. The sample included 75 adults with ESRD requiring dialysis who consented and were enrolled in the study. Regression analysis showed significant correlations among the psychosocial variables (p = <0.0001, r = 0.65). Negative correlations were found between perceived stress and health-related quality of life (p = 0.024) and depressive symptoms with health-related quality of life (p = 0.0003). MIP-1 ß was the only cytokine significantly (and positively) correlated with health-related quality of life ( p = 0.0419). Principal component analysis of the cytokine data revealed three factors. A three-factor solution described the cytokine data; Factors 1 and 3 represented a pro-inflammatory response and Factor 2 represented a mixture of pro-inflammatory and anti-inflammatory responses. There was a significant correlation between Factor 1 and depressive symptoms (p = 0.0069). Significant differences in the distributions of Factors 2 and 3 were associated with the presence of cardiovascular disease (CVD) (Chi-square = 4.0, df = 1, p = 0.047), (Chi-square = 4.1, df = 1, p = 0.043), respectively, and Factor 3 with hypertension (HTN) (Chi-square = 7.6. df = 1, p = 0.006). However no relationships were found between the cytokine factors and QOL, PSS, and other variables. Findings suggest that there are relationships among psychosocial variables and possibly biological interactions that may affect perceptions of health-related quality of life among persons with ESRD on hemodialysis.

Abstract This pilot study aimed to establish if an exercise programme utilizing the world’s first manual compression foot-pump, commonly known as “Venous Anti-Stasis Slippers”, could be used as an intervention to improve dialysis efficacy (Kt/V) and the quality of life (QOL) of patients with end stage renal disease (ESRD). The entire population of 34 self-care renal patients at the Flora Clinic renal unit were screened and 19 patients who met the inclusion criteria for the study were invited to participate in this 16 week pilot study. Baseline dialysis efficacy values were obtained from the analysis of routine blood tests and quality of life values were established with the use of the South African English version of the EQ-5D health questionnaire. This was followed by an eight week non-intervention period. Pre-intervention values were then established prior to the implementation of an eight week exercise programme using the manual compression foot pumps. A single group time series design was used and 12 of the initial 19 subjects completed the study by performing seated calf raising exercises, with manual compression foot pumps on their feet, for 20 minutes per hour during the first three hours of their routine dialysis sessions (2 - 3 times per week) over a period of eight weeks. Exercise diaries were kept to record exercise times, heart rates and exercise intensities. At the end of the eight week exercise programme, dialysis efficacy and quality of life values were re-measured. An intention to treat analysis of routine blood test results revealed statistically significant changes in dialysis efficacy (Kt/V) values between baseline (1.70 ± 0.48), pre-intervention (1.39 ± 0.43) and post intervention (1.50 ± 0.47) with a resultant 7.91% improvement in Kt/V values as a result of the exercise programme. There were however no statistically significant changes observed in overall quality of life (QOL) values, but noticeable improvements in self-care ability and a reduction in depression/anxiety scores were observed during this pilot study. The frequency of exercise per week had no significant effect on the changes in Kt/V.

Purpose: To evaluate the diagnostic performance of Coronary Computed Tomography Angiography (CCTA) in predicting Myocardial Perfusion Scintigraphy (MPS) perfusion defects in low likelihood patients with End Stage Renal Disease (ESRD) awaiting transplant. Materials and Methods: In total, 131 consecutive patients with ESRD awaiting transplant were prospectively enrolled in this study (86 men; 54±9years). All patients underwent MPS as per standard of care and in addition non-enhanced CT for calcium scoring (CAC score) and Coronary Computed Tomography Angiography (CCTA). Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC score in predicting MPS perfusion defects were 88%, 35%, 28% and 92%, respectively. The sensitivity, specificity, PPV and NPV of CCTA in predicting MPS perfusion defects at the patient level were 55%, 87%, 57% and 87%, respectively, and 48%, 92%, 41% and 94% at the vessel level. The diagnostic performance of CCTA in predicting MPS perfusion defects improved when patients with CAC score higher than 1000 (15/70, 21%) were excluded from the analysis. In patients with positive CAC score up to 1000 sensitivity, specificity, PPV and NPV at the patient level were 60%, 93%, 75% and 86% respectively. These were 53%, 91%, 36% and 95%, respectively, at the vessel level. Conclusion: Non-enhanced CT for CAC score and CCTA can be considered useful diagnostic tools in the ESRD population, particularly in identifying patients without coronary artery disease. This approach however had limitations in the presence of high CAC score.

Durante a evolução da doença renal crônica (DRC) em cães, um dos mecanismos importantes envolvidos na autoperpetuação e progressão da lesão renal envolvem, teoricamente, o comprometimento inicial do glomérulo pelo mecanismo de hiperfiltração glomerular, e este processo pode acarretar no desenvolvimento de microalbuminúria ou de proteinúria pela presença de proteínas de alto peso molecular (albumina). Com o progredir da doença, as altas concentrações de proteína no filtrado glomerular pode também desencadear lesões tubulares e intersticiais, ocasionando a perda urinária também de proteínas de baixo peso molecular (PM) pelo comprometimento da reabsorção dessas proteínas pelos túbulos renais. Outras teorias de progressão da lesão renal também são suscitadas tais como o comprometimento inicial da porção túbulo-intersticial. Assim, espera- -se que durante a evolução da DRC, a avaliação das proteínas urinárias quanto à qualidade (determinação de albumina e os pesos moleculares) e a quantidade possam trazer informações relevantes sobre a velocidade de progressão e o local da lesão renal. O objetivo deste estudo foi de avaliar, sequencialmente, a albuminúria e a proteinúria (pelos métodos quantitativos e qualitativos - eletroforese de proteínas) dos cães com DRC nos estágios 1, 2 ou 3 ao longo do período de pelo menos 5 meses, e verificar a existência de alterações na intensidade ou no aparecimento de proteinúria e/ou albuminuria. Dezesseis cães (Grupo 1= 5 cães do estágio 1; Grupo 2= 5 cães do estágio 2 e Grupo 3= 6 cães do estágio 3), 9 fêmeas e 7 machos de raças variadas e idades entre 24 a 168 meses, foram acompanhados por 5 a 18 meses e os exames clínico e laboratorial realizados a cada 30 dias. Os cães dos Grupos 1 e 2 apresentaram bom controle clínico, entretanto o Grupo 3 apresentou evolução mais rápida da doença (3 cães vieram a óbito). No Grupo 1, o aumento da razão proteína:creatinina urinária (RPC; variação de 0,154 a 1,14) foi observada somente em um dos cães (no 1) e esta não era decorrente de albuminúria, mas sim da presença de proteínas de baixo peso molecular (lesão tubular) e também foi constatada diminuição progressiva da taxa de filtração glomerular pelo o aumento das concentrações de cistatina C sérica; os demais cães deste grupo apresentaram RPC e razão albumina:creatinina urinária (RAC) normais, entretanto com predomínio de proteínas de baixo peso molecular em 2 cães. No Grupo 2 fato semelhante também foi constatado, nos cães no 6 (inicialmente hipertenso) e 8 em que a RPC variou de 4,89 a 12,77 e 0,5 a 1,0, respectivamente; no cão no6 foi não foi detectada macroalbuminuria, mas somente microalbuminúria e com o predomínio de proteínas de baixo PM (lesão tubular), como também no cão no 8 (ausência de micro ou macroalbuminuria) em que houve o predomínio de 78 a 100% de proteínas de baixo PM e com 3 a 6 bandas. No Grupo 3, proteinúria foi constatada nos cães de no 11, 13 e 15 e a microalbuminúria somente no cão no11; o predomínio de proteínas de baixo PM foi observada nos cães no 11 e 13 e proteinúria mista no cão no 15. Assim, a avaliação sequencial ou seriada da proteinúria, pelo conjunto de informações obtido pela RPC, RAC e eletroforese de proteínas urinárias nos com cães com doença renal crônica, ao longo de um período, trouxe informações mais precisas acerca da qualidade das proteínas, identificando os segmentos do néfron que provavelmente foram comprometidos ao longo da evolução da doença. / During the course of chronic kidney disease (CKD) in dogs, one of the mechanisms involved in the autoperpetuation and progression of renal disease, in theory, is glomerular hyperfiltration, and this process may result in the development of microalbuminuria or proteinuria due to the presence of high molecular weight proteins (albumin). As the disease progresses, the presence of high concentrations of proteins in the glomerular filtrate may also cause the development of interstitial and tubular injuries, and in consequence the presence of low molecular weight proteins in urine as the impairment of tubular reabsorption mechanism of proteins is affected. Other theories of progression of renal injury are also raised such as the initial involvement of the tubulointerstitial segment. Thus, it is expected that during the course of CKD, the evaluation of the quality (determination of albumin and molecular weights) and quantity of urinary proteins may indicate relevant information about the location and rate of progression of renal injury. The objective of this study was to evaluate, longitudinally, albuminuria and proteinuria (by quantitative and qualitative methods - protein electrophoresis) of dogs with CKD in stages 1, 2 and 3 over the period of at least 5 months, and observe the changes in intensity or the appearance of proteinuria and / or albuminuria. Sixteen dogs (Group 1 = 5 dogs in stage 1, Group 2 = 5 dogs in stage 2 and Group 3 = 6 dogs in stage 3), 9 females and 7 males of various breeds and ages ranging from 24 to 168 months, were followed-up for 5-18 months and medical and laboratory monitoring data were recorded every 30 days. Dogs of Groups 1 and 2 showed good clinical control, however the Group 3 had a progressive deterioration of the disease (3 dogs died). In Group 1, the increase in urinary protein-to-creatinine ratio (UPC; ranging from 0.154 to 1.14) was observed in only one dog (no. 1) and albuminuria was not involved, however low molecular weights proteins (LMWP) were detected (tubular injury) and also the progressive decrease in glomerular filtration rate was noticed by the increase of serum concentrations of cystatin C; the remaining dogs in this group demonstrated normal UPC and UAC (urinary albumin-to-creatinine ratio), however the predominance of LMWP in 2 dogs was observed. In Group 2, similar findings were also noticed in CKD dogs no. 6 (initially hypertensive) and 8 , UPC ranged from 4.89 to 12.77 and 0.5 to 1.0, respectively; dog no. 6 demonstrated no macroalbuminuria but only microalbuminuria, and the predominance of LMWP (tubular injury) was observed as well as the dog no. 8 that had 78 to 100% of LMWP with 3 to 6 bands and no micro or macroalbuminuria was detected. Group 3 presented proteinuria in dogs no. 11, 13 and 15 and microalbuminuria was only observed in dog no. 11; the predominance of LMWP was noticed in dogs no.11 and 13, and mixed proteinuria in dog no. 15. Thus, the sequential or longitudinal study of proteinuria by means of several information obtained of UPC, UAC and urine protein electrophoresis in dogs with chronic kidney disease, followed-up over a period, could give more accurate information about the quality of proteins, allowing the possible identification of the segments of the nephron involved that could probably be affected throughout the course of the disease.