Calciphylaxis is a deadly disease seen primarily in patients with end stage renal disease. Literature indicated that improved patient outcomes are seen with routine screenings. Many dialysis providers lack fundamental knowledge that would enable early identification of calciphylaxis in patients with renal disease. The purpose of this project was to design a screening instrument and develop a staff education program that would transform calciphylaxis management by promoting early identification and treatment of the disease. Knowles's theory of andragogy was used as the theoretic framework for the project. Dialysis center staff (n = 26) participated in the education. The number of participants was based on the number of staff working at the partner dialysis site. There were no exclusions as all members of the interdisciplinary team play an important role in calciphylaxis management. Surveys conducted following the education were used to determine whether dialysis staff believed they had acquired the knowledge and skills necessary to identify early signs of calciphylaxis. Descriptive data collected by the surveys indicated 60% of participants were not at all comfortable identifying patients at risk for developing calciphylaxis prior to attending the education presentation. Following the presentation, 68% of participants felt very comfortable identifying at-risk patients, an increase of 82.3%. This project exemplified that calciphylaxis detection is a secondary prevention nursing intervention that has potential for promoting positive social change by improving patient outcomes, reducing mortality rates in the end stage renal disease population, and providing empirical data to inform evidence-based therapies for at-risk patients.

Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet. This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure. Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed. The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium. Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure. Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism. / För att bedöma exponering för kadmium och bly mäts ofta deras koncentrationer i blod eller urin. Dessa studerades i longitudinella data för 48 blyarbetare och 20 individer med normal miljömässig exponering. Blod- och urinprover togs var annan till var tredje månad. Kadmium- och blykoncentrationer mättes sedan i helblod, plasma och urin. Koncentrationer av bly i blod var den biomarkör som hade den största andelen av den totala variationen som kunde förklaras av skillnader mellan individer, och var därför den biomarkör med den bästa förmågan att särskilja på individer med olika medelkoncentration, både för individer med yrkesexponering och normal miljömässig exponering (91 respektive 95% av variansen berodde på vilken individ blodprovet kom ifrån). Justering för urinens utspädning av bly i urin förbättrar oftast urins användbarhet som biomarkör. För bly stämde detta bara hos dem som inte var blyarbetare. Blodkoncentrationer var också den biomarkör med störst andel av den totala variation som kunde förklaras med skillnader mellan individer för kadmium. Kadmium och bly ackumuleras i njure respektive ben och kan ha toxikologiska effekter. Det är välkänt att höga exponeringsnivåer av kadmium orsakar njurskada och även vid lägre exponeringsnivåer har studier funnit samband med markörer för njurfunktion. Exponering för bly påverkar i första hand det centrala nervsystemet. Studier har dock funnit samband mellan koncentrationer av bly i blod och njurens glomerulära filtrationshastighet. Det är oklart både om dessa associationer, vid låga exponeringsnivåer, är viktiga för hälsan och om de verkligen beror på att kadmium och bly orsakar njurskada. För att studera end-stage renal disease användes prospektiva kohorter där personer lämnat blodprov för forskning: Västerbottens interventionsprogram med prover som tagits vid Västerbottens hälsoundersökningar, MONICA-undersökningar i Norr- och Västerbotten, mammografiundersökningarna i Västerbotten och Malmö kost cancer. Sammanlagt ingick över ett hundra tusen individer i dessa kohorter. Med hjälp av det Svenska njurregistret identifierades sedan 118 personer som senare i livet fått end-stage renal disease. Dessa jämfördes med 378 kontroller. För dessa 496 personer tinades blodprovet (närmare bestämt röda blodkroppar) upp och analyserades för kadmium och bly. För att undersöka njurens förmåga till återhämtning studerades tre områden i Kina varav ett tidigare varit kraftigt kadmiumexponerat. Erytrocytkoncentrationer av bly var, utan att ta hänsyn till några andra variabler, associerat med en ökad risk för att utveckla end-stage renal disease (med oddskvoten 1.54 för en interquartile range ökning av erytrocytbly, med ett 95% konfidensintervall 1.18-2.00). Sambanden kvarstod också efter att ha tagit hänsyn till övriga variabler. För erytrocytkadmium var oddskvoten 1.15 med 95% konfidensintervall 0.99-1.34, och sambandet försvagades när hänsyn togs till andra variabler. Associationerna sågs bland män men inte bland kvinnor. Eftersom kadmium vid höga nivåer orsakar njurskada är det också av intresse att studera om påverkan på njuren går över om exponeringen minskas. Totalt följdes 412 individer upp med mätningar av markörer för njurfunktion och kadmiumkoncentrationer i blod och urin. Första undersökningen gjordes 1998, då man just hade slutat äta kadmiumförorenat ris. En andra undersökning gjordes 2006. Andelen individer med avvikande albuminvärde i urin var lägre vid uppföljningen jämfört med vid baslinjen, men ingen minskning sågs för markörer för tubulär förmåga att återta proteiner. Åttioprocent av kadmium i celler är bundet till proteinet metallotheonin, vilket skyddar mot cellskada, men har också en roll i transporten av kadmium från levern till njurarna. En tidigare studie har visat att njurens känslighet för kadmiumexponering var associerad med genetiska skillnader i detta protein. För att studera genetiska associationer studerades de 412 personerna i den kinesiska studien [då också individernas genotyper av metallotheonin-polymorfierna MT1A rs11076161 (G/A), MT2A rs10636 (G/C) och MT2A rs28366003 (A/G) bestämdes]. Genetiken spelade roll för sambandet mellan förmåga att återta proteiner och kadmium men påverkade inte förändring av njurfunktion efter att man slutat äta kadmiumförorenat ris. Kadmium- och blykoncentrationer i blod är de biomarkörer, av koncentrationer i blod, plasma och urin, med den bästa förmågan att skilja på individer med olika medelkoncentrationer. Justering för urinutspädning påverkade andelen av den totala variationen som kunde förklaras av skillnader mellan individer i stor utsträckning för individer med normal miljömässig exponering men inte bland yrkesexponerade, vilket tyder på en skillnad i hur utsöndringen går till. Associationen mellan end-stage renal disease och låg exponering för bly, uppmätta i prospektiva erytrocytprover, ger orsak till oro, men ytterligare studier behövs för att kunna utvärdera om detta är ett kausalt samband. En kadmiumrelaterad skada av den glomerulära filtrationen är reversibel efter en kraftig reducering i exponering, men detta är inte fallet för tubulär skada. De tubulära njureffekterna av kadmiumexponering kan påverkas av metallotheonin-polymorfier.

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

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.

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.

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

The Severity of Renal Disease Scale (SORDS) was developed to provide a single score reflecting disease severity of renal patients independent of confounding psychosocial influences. This study examined SORDS' reliability and validity and its relevance as a research tool assessing the psychological effect of illness severity. Data was collected from 127 renal patients (predialysis, HD, CAPD). SORDS was compared with the Endstage Renal Disease Severity Index (ESRD-SI), the SF-36, the Beck Depression Inventory - 2nd Edition and a subset of BDI-II items reflecting cognitive features only at differing stages of renal disease and time on dialysis. SORDS and ESRD-SI data from twenty-two CAPD patients was included in reliability analyses. SORDS reliability estimates were low suggesting that the use of SORDS with medical chart data at this time is problematic. SORDS should be used only by medical practitioners who are aware of patients' standing on SORDS variables. There was however strong support for SORDS' validity. Validity was demonstrated by correlations between SORDS and the ESRD-SI. Compared to the ESRD-SI, SORDS was better able to discriminate between dialysis and pre-dialysis patients. SORDS and ESRD-SI scores were related to self-perceptions of decreased health status on the SF-36 independent of dialysis duration and age. SORDS utility in psychosocial research with renal patients was demonstrated by a finding that disease severity differentially impacts levels of depression for HD versus CAPD patients independent of age or dialysis duration. At the lowest level of illness severity as assessed by SORDS, CAPD patients scored in the moderate range of depression and were significantly more depressed than HD patients. Using the same analyses but with the ESRD-SI, no differences in level of depression were detected. These results imply a relationship between adjustment to treatment and illness severity. It is concluded that SORDS is a valid index of renal disease severity and that illness severity as assessed by SORDS may have an important role as a moderator variable in psychosocial research with renal patients. These results may have important implications for treatment assignment and psychosocial assessment and intervention of renal patients and their families.

Our epidemiology research found that the incident and prevalent rates for Diabetes mellitus (DM) and Diabetic End Stage Renal Disease (DM-ESRD) were at rise in Saskatchewan between year 1980 and 2005. Combining concerns regarding the rising trends reported by research studies with the concerns of the significant health and financial burden imposed by DM-ESRD on individuals and societies, we sought to project the number of DM-ESRD patients in Saskatchewan up to year 2025 with the cost required for caring for those patients. An agent-based model (ABM) is developed to simulate DM to ESRD progression, treatments for DM-ESRD patients, and the assessments and waiting list processes preparing patients for kidney transplants. The model parameters were estimated from a wide variety of data sources. The agent based modeling approach is chosen for projections regarding the DM-ESRD situation in Saskatchewan because of its advantage in capturing heterogeneities of individual patients, ability to retain biographical information on patients, capacity to capture time-varying competing risks, better presentations features and easy integration with existing models built in either agent based or System Dynamic methods. The approach was also attractive due to its flexibility for future expansion to represent social networks. The model projects the incident and prevalent case count, cost, and person years lived for the DM-ESRD population in Saskatchewan between year 1980 and 2025. The projections captured the great challenges brought by the fast growing number of DM-ESRD patients and substantial cost associated with managing the disease. In addition to producing projection results, the research presented here demonstrates how the model can be used by policy makers to experiment and evaluate different policy/interventions in a safe context. By capturing both the individual level records and population level statistics, the model provide a wealth of data for detailed analysis, which can help health policy makers gain insights in the current and future diabetic-ESRD situation in the province, aiding in resources planning for managing the fast-growing ESRD population and the growing need for dialysis services.

Background and Purpose: Physical activity is significantly lower in the end-stage renal disease (ESRD) population compared with age-matched sedentary controls. Self-efficacy is a significant contributing factor to exercise behaviour in the healthy and various chronic disease populations; however, little information is available on self-efficacy and exercise in the ESRD population. The purpose of this study was to examine the relationship between self-efficacy and physical activity levels in individuals with ESRD and to determine factors which may contribute to this relationship. Participants: Patients (127 hemodialysis and 5 peritoneal dialysis) were recruited from the Kingston General Hospital renal units. Methods: Self-efficacy was measured using the Exercise Self-Efficacy Scale (ESES) and the Chronic Disease Self-Efficacy Scale (CDSES). Physical activity was measured using the Human Activity Profile (HAP). Responses on the HAP resulted in 2 scores: the maximum activity score (MAS) and the adjusted activity score (AAS). Contributing factors, such as age, co-morbidities, length on dialysis (vintage), medications, dialysis efficacy (Kt/V), albumin, prealbumin, total protein, protein catabolic rate (PCR) and hemoglobin (HgB) were collected from patient records. Results: The average MAS and AAS scores were 62.5±15.6 and 49.1± 21.0 (SD), respectively, which are substantively lower than those in the healthy population. Serum albumin was the sole contributing factor to physical activity such that AAS in those with lower levels of albumin (24-30g/L, 31-34 g/L) was less than those with higher levels of albumin (p<0.05). Both MAS and AAS were significantly lower in those with diabetes (n=66) compared to those without (n=66), as was the difference between MAS and AAS. Age and self-efficacy explained 51% of the variance in MAS. Age, self-efficacy and serum albumin level explained 59% of variance in AAS. Discussion and Conclusion: Individuals on dialysis have lower functional capability within their maximal energy ability at any age and this difference is more pronounced among those with diabetes. Physical activity was substantially influenced by an individual’s self-efficacy, age and serum albumin level. These findings indicate that self-efficacy must be taken into account and used to promote greater participation in physical activity in the ESRD population. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2010-04-27 09:47:12.764

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