[show abstract][hide abstract] ABSTRACT: The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for anemia management in patients with chronic kidney disease provides the structural and evidence base for the Canadian Society of Nephrology commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 11 of the 61 KDIGO guideline statements. Specifically, we agreed that a therapeutic trial of iron is appropriate in cases in which a reduction in erythropoiesis-stimulating agent (ESA) dosage or avoidance of ESA and transfusion is desired, transferrin saturations are >30%, and ferritin concentrations are >500 μg/L. However, we concluded that there is insufficient evidence to support an upper target or threshold for ferritin and transferrin saturation levels. We agree with the initiation of ESA treatment when hemoglobin (Hb) level is 90-100 g/L; however, we specifically state that an acceptable range for Hb level is 95-115 g/L, with a target of 100-110 g/L, and add caution to individualization above this range due to concerns regarding the safety of ESAs. We agree that ESAs should be used with considerable caution in patients with active malignancy, history of stroke, or history of malignancy, and we suggest initiating ESA therapy at Hb level of 90 g/L and to aim for a Hb level in the range of 90-105 g/L. The reader is encouraged to note the level of evidence and review the entire KDIGO anemia guideline to interpret the guideline statements and commentary appropriately.
American Journal of Kidney Diseases 09/2013; · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Calcific uremic arteriolopathy (CUA) is a rare but serious disorder affecting 4% of dialysis patients. Intravenous sodium thiosulfate (IV STS) has been shown as an effective treatment. In Canada, the average cost of IV STS is about CAD 12,000 per month, while the cost of compounded oral STS is CAD 45 per month. Methods: Prospective cohort where all patients diagnosed with CUA during the year 2011 were included. They were treated initially with IV STS. Afterwards, each patient had a baseline bone scan and was started on oral STS for a total of 6 months followed by a repeat bone scan. A single radiologist, blinded to the dates of both scans for a given patient, read all scans. Results: Four patients were studied. The intravenous dose used was 25 g three times a week for an average duration of 131 days. After the maintenance therapy, 2 patients developed further regression of the lesions, 1 had stable lesions, and 1 got worse; however, nonadherence to the drug was confirmed. The oral medication was well tolerated with no reported side effects. Conclusion: Oral STS, after IV STS, seems to stabilize, or even improve CUA lesions, and therefore could be useful as maintenance therapy, especially since its cost is much more reasonable than IV STS and due to the ongoing shortage of the IV formulation.
American Journal of Nephrology 01/2013; 37(2):104-109. · 2.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: Central venous catheters (CVCs) are associated with early mortality in dialysis patients. However, some patients progress to end stage renal disease after an acute illness, prior to reaching an estimated glomerular filtration rate (eGFR) at which one would expect to establish alternative access (fistula/peritoneal dialysis catheter). The purpose of this study was to determine if exclusion of this "acute start" patient group alters the association between CVCs and mortality.
We conducted a retrospective cohort study of 406 incident dialysis patients from 1 Jan 2006 to 31 Dec 2009. Patients were classified as acute starts if 1) the eGFR was >25 ml/min/1.73 m2, ≤3 months prior to dialysis initiation and declined after an acute event (n = 45), or 2) in those without prior eGFR measurements, there was no supporting evidence of chronic kidney disease on history or imaging (n = 12). Remaining patients were classified as chronic start (n = 349).
98 % and 52 % of acute and chronic starts initiated dialysis with a CVC. There were 148 deaths. The adjusted mortality hazard ratio (HR) for acute vs. chronic start patients was 1.84, (95 % CI [1.19-2.85]). The adjusted mortality HR for patients dialyzing with a CVC compared to alternative access was 1.19 (95 % CI [0.80-1.77]). After excluding acute start patients, the adjusted HR fell to 1.03 (95 % CI [0.67-1.57]).
A significant proportion of early dialysis mortality occurs after an acute start. Exclusion of this population attenuates the mortality risk associated with CVCs.
[show abstract][hide abstract] ABSTRACT: Hyperphosphatemia is a common and potentially harmful condition in patients with end-stage kidney disease. In Canada, first-line treatment of hyperphosphatemia consists primarily of calcium carbonate (CC). Lanthanum carbonate (LC) and sevelamer hydrochloride (SH) are non-calcium phosphate binders that have been used as second-line therapy in patients intolerant of or not responsive to CC.
The primary objective of the present study was to assess the costs and clinical benefits of second-line use of LC after therapy failure with CC in patients receiving dialysis, from a Canadian payer perspective. The secondary objective was to perform an economic comparison between second-line LC therapy and second-line SH therapy, from a Canadian payer perspective. Short-term outcomes were treatment response and cost per additional responder, and long-term outcomes were survival, number of all-cause hospitalizations, and quality of life.
A cost-effectiveness Markov model was populated with simulated cohorts of 1000 patients receiving incident dialysis, followed life-long. Patients not responsive to CC with a serum phosphate concentration >1.78 mmol/L (>5.5 mg/dL) received a trial regimen with LC. Patients not responsive to LC returned to CC therapy. Patient data from a randomized controlled trial of 800 patients receiving dialysis were used. Extensive (probabilistic) sensitivity analyses were performed. When available, model parameters were based on Canadian data or from a Canadian perspective. All costs are in 2010 Canadian dollars (C$).
Results of the model estimated that in patients responsive to second-line LC therapy, survival increased, on average, 0.44 years (95% confidence interval [CI], 0.35-0.54) per patient when compared with continued CC therapy. The mean (range) costs per patient in the first year of treatment with LC was C$2600 (C$2400-C$2800). Over patients' lifetimes, the second-line LC strategy resulted in a gain of 48.8 (37.1-61.3) life-years and 29.3 (21.4-38.1) quality-adjusted life-years (QALYs). The cost-effectiveness of the second-line LC strategy was C$7900 (C$1800-C$14,600) per life-year and C$13,200 (C$3000-C$25,100) per QALY gained. Most sensitivity analyses did not change the cost-effectiveness outcomes; however, including unrelated future costs raised the incremental cost-effectiveness ratio to C$159,500 (95% confidence interval, C$133,300-C$191,600) per QALY gained. Compared with second-line SH therapy, second-line LC therapy had similar effectiveness and was 23% less expensive.
Second-line treatment with LC is cost-effective in the treatment of end-stage kidney disease in patients with hyperphosphatemia, from a Canadian payer perspective. Second-line treatment with LC is less expensive, with similar effectiveness as second-line treatment with SH. The primary limitation of health economic evaluations of phosphate binders is the relative scarcity of clinical data on the association between phosphate concentration and long-term outcome.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: There is a concern that some, especially older people, are not referred and could benefit from transplantation. METHODS: We retrospectively examined consecutive incident end stage renal disease (ESRD) patients at our center from January 2006 to December 2009. At ESRD start, patients were classified into those with or without contraindications using Canadian eligibility criteria. Based on referral for transplantation, patients were grouped as CANDIDATE (no contraindication and referred), NEITHER (no contraindication and not referred) and CONTRAINDICATION. The Charlson Comorbidity Index (CCI) was used to assess comorbidity burden. RESULTS: Of the 437 patients, 133 (30.4%) were CANDIDATE (mean age 50 and CCI 3.0), 59 (13.5%) were NEITHER (age 76 and CCI 4.4), and 245 (56.1%) were CONTRAINDICATION (age 65 and CCI 5.5). Age was the best discriminator between NEITHER and CANDIDATES (c-statistic 0.96, P <0.0001) with CCI being less discriminative (0.692, P <0.001). CANDIDATES had excellent survival whereas those patients designated NEITHER and CONTRAINDICATION had high mortality rates. NEITHER patients died or developed a contraindication at very high rates. By 1.5 years 50% of the NEITHER patients were no longer eligible for a transplant. CONCLUSIONS: There exists a relatively small population of incident patients not referred who have no contraindications. These are older patients with significant comorbidity who have a small window of opportunity for kidney transplantation.
[show abstract][hide abstract] ABSTRACT: To determine whether warfarin prolongs the time to first mechanical-catheter failure.
This was a multicenter parallel-group randomized controlled trial with blinding of participants, trial staff, clinical staff, outcome assessors, and data analysts. Randomization was in a 1:1 ratio in blocks of four and was concealed by use of fax to a central pharmacy. Hemodialysis patients with newly-placed catheters received low-intensity monitored-dose warfarin, target international normalized ratio (INR) 1.5 to 1.9, or placebo, adjusted according to schedule of sham INR results. The primary outcome was time to first mechanical-catheter failure (inability to establish a circuit or blood flow less than 200 ml/min).
We randomized 174 patients: 87 to warfarin and 87 to placebo. Warfarin was associated with a hazard ratio (HR) of 0.90 (P=0.60; 95% confidence interval [CI], 0.57, 1.38) for time to first mechanical-catheter failure. Secondary analyses were: time to first guidewire exchange or catheter removal for mechanical failure (HR 0.78; 95% CI, 0.37, 1.6); time to catheter removal for mechanical failure (HR 0.67; 95% CI, 0.19, 2.37); and time to catheter removal for any cause (HR 0.89; 95% CI, 0.42, 1.81). Major bleeding occurred in 10 participants assigned to warfarin and seven on placebo (relative risk, 1.43; 95% CI, 0.57, 3.58; P=0.61).
We found no evidence for efficacy of low-intensity, monitored-dose warfarin in preventing mechanical-catheter failure.
Clinical Journal of the American Society of Nephrology 05/2011; 6(5):1018-24. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abnormal mineral metabolism is associated with increased morbidity and mortality in dialysis patients. Therefore, the goal of this study was to compare a) mineral metabolism control among a cohort of Canadian peritoneal dialysis (PD) patients to K/DOQI-defined targets and b) the effect of different treatment strategies on mineral metabolism parameters.
We looked at a cohort of 317 Canadian PD patients from 9 clinics that used the PhotoGraph™ software program which tracks mineral metabolism management. Serum phosphorus (P), calcium (Ca) and intact parathyroid hormone (iPTH) values were collected for the patients. Data were categorized and analyzed by the type of phosphate binder prescribed, vitamin D use, and dosing and reimbursement criteria for the phosphate binder, sevelamer.
The majority of patients achieved K/DOQI-set targets for serum P. Patients who resided in Quebec (QC), which had greater access to sevelamer, had lower mean concentrations of P and Ca, were less likely to take Ca-based phosphate binders (CBBs) exclusively and were exposed to less exogenous Ca than in Ontario (ON).
Availability of the phosphate binder sevelamer and reduced doses of elemental Ca were associated with more mineral metabolism parameters within suggested target ranges. Further studies that focus on patient outcomes are warranted.
[show abstract][hide abstract] ABSTRACT: Macrocytosis occurs in chronic hemodialysis (CHD) patients; however, its significance is unknown. The purpose of this study was to establish the prevalence and distribution of macrocytosis, to identify its clinical associations and to determine if macrocytosis is associated with mortality in stable, chronic hemodialysis patients.
We conducted a single-centre prospective cohort study of 150 stable, adult CHD patients followed for nine months. Macrocytosis was defined as a mean corpuscular volume (MCV) > 97 fl. We analyzed MCV as a continuous variable, in tertiles and using a cutoff point of 102 fl.
The mean MCV was 99.1 ± 6.4 fl, (range 66-120 fl). MCV was normally distributed. 92 (61%) of patients had an MCV > 97 fl and 45 (30%) > 102 fl. Patients were not B12 or folate deficient in those with available data and three patients with an MCV > 102 fl had hypothyroidism. In a logistic regression analysis, an MCV > 102 fl was associated with a higher Charlson-Age Comorbidity Index (CACI) and higher ratios of darbepoetin alfa to hemoglobin (Hb), [(weekly darbepoetin alfa dose in micrograms per kg body weight / Hb in g/L)*1000]. There were 23 deaths at nine months in this study. Unadjusted MCV > 102 fl was associated with mortality (HR 3.24, 95% CI 1.42-7.39, P = 0.005). Adjusting for the CACI, an MCV > 102 fl was still associated with mortality (HR 2.47, 95% CI 1.07-5.71, P = 0.035).
Macrocytosis may be associated with mortality in stable, chronic hemodialysis patients. Future studies will need to be conducted to confirm this finding.
[show abstract][hide abstract] ABSTRACT: Abnormalities in mineral metabolism in chronic kidney disease are associated with increased morbidity and mortality. The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines were established in 2003 to address issues in the management of mineral and bone metabolism. The goal of this study was to compare (i) mineral metabolism control among Canadian haemodialysis (HD) patients with K/DOQI-defined targets and Dialysis Outcomes and Practice Patterns Study II (DOPPS II) data and (ii) the effect of different treatment strategies.
A cross-sectional study of 2215 HD patients was conducted. Phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) and calcium-phosphate product (CaXP) were analysed. In addition, management was compared between provinces with more or less restricted access to the phosphate binder sevelamer.
K/DOQI targets for P, Ca, iPTH and CaXP K/DOQI targets were met by 59.7%, 58.6%, 29.7% and 83.3%, respectively. A greater proportion of patients were within target compared with those in DOPPS II (2002-2004). Targets were more likely to be reached by patients residing in provinces with formularies allowing less restricted access to sevelamer: P: 61.8% vs 55.7% (P = 0.01); CaXP: 85.5% vs 79.1% (P = 0.0006). As expected, patients in provinces with more restrictive formularies were more often receiving doses of elemental calcium > 1.5 g/day than those with more open listings (62.1% vs 14.0%, P < 0.0001) and were less likely to receive sevelamer (14.1% vs 42.4%, P = 0.0001).
Mineral metabolism parameters were more frequently within the target range amongst (i) patients in the current study compared with those in the DOPPS II era and (ii) patients in provinces with less restricted access to sevelamer.
[show abstract][hide abstract] ABSTRACT: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. Design and setting: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument.
Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities.
These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.
Clinical Journal of the American Society of Nephrology 08/2009; 4(8):1293-301. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: A topic map is implemented for learning about clinical data associated with a hospital stay for patients diagnosed with chronic kidney disease, diabetes and hypertension. The question posed is: how might a topic map help bridge perspectival differences among communities of practice and help make commensurable the different classifications they use? The knowledge layer of the topic map was generated from existing ontological relationships in nosological, lexical, semantic and HL7 boundary objects. Discharge summaries, patient charts and clinical data warehouse entries rectified the clinical knowledge used in practice. These clinical data were normalized to HL7 Clinical Document Architecture (CDA) markup standard and stored in the Clinical Document Repository. Each CDA entry was given a subject identifier and linked with the topic map. The ability of topic maps to function as the infostructure ;glue' is assessed using dimensions of semantic interoperability and commensurability.
Health Informatics Journal 01/2009; 14(4):267-78. · 0.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship between quality of life (QofL) and anemia has been the subject of recent debates; it has been suggested that the QofL changes associated with the treatment of anemia of chronic kidney disease (CKD) or ESRD patients should not be used in making decisions to treat anemia in CKD patients.
This study examines the relationship between Kidney Disease Quality of Life (KDQofL) questionnaire domains and hemoglobin (Hgb) levels in 1200 patients with stage 3, 4, and 5 CKD followed in seven centers. QofL measures were compared in a stepwise fashion for hemoglobin levels of <11, 11 to <12, 12 to <13, and > or =13. ANOVA was used to examine the relationship between QofL scores and Hgb level, age, CKD stage, and albumin level; a history of diabetes, congestive heart failure, or myocardial infarction; use of erythropoetic-stimulating agents (ESA); and the interaction of hemoglobin level and ESA.
The results demonstrate that with increasing Hgb levels there is a statistically significant increase in all four physical domains, the energy/vitality domain, and the physical composite score of the SF-36, and the general health score on the kidney disease component of the questionnaire. The most dramatic improvements in these various domains occurred between the <11 and the 11 to 12 group.
Higher Hgb levels are associated with improved QofL domains of the KDQofL questionnaire. These findings have implications for the care of CKD patients in terms of the initiation of and the Hgb target of ESA therapy.
Clinical Journal of the American Society of Nephrology 12/2008; 4(1):33-8. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts.
We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices.
Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant.
Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.
[show abstract][hide abstract] ABSTRACT: The need to educate patients in order to enable them to participate in making appropriate choices for all therapeutic options in end stage renal disease would seem obvious yet there are many barriers to providing such information. We measured 'perceived knowledge' of the therapeutic options for end stage renal disease in a cohort of patients with chronic kidney disease in established treatment programs. A self administered questionnaire was given to 676 patients with stage 3-5 chronic kidney disease as part of the CRIOS study designed to identify trends in practice patterns and outcomes over a 4 year period. The median patient age was 66, about three-fourths were Caucasian and almost half were diabetic. When patients were asked to rate their level of knowledge, about one-third reported limited or no understanding of their chronic kidney disease and no awareness regarding their treatment options. A significant and substantial number of patients indicated they had no familiarity with transplant, hemodialysis, and continuous ambulatory or automated peritoneal dialysis. Perceived knowledge improved with the progression of kidney disease and frequency of nephrology visits; however, only about half of patients with 4 or more nephrology appointments in the prior year reported knowing of hemodialysis, continuous ambulatory peritoneal dialysis or transplant. Age, gender and disease had no impact on levels of patient knowledge, but African-Americans reported having significantly less understanding than Asians or Caucasians. These findings suggest that the lack of perception concerning the treatment options chronic kidney and end stage renal disease reflects, in part, problems with the education of patients by nephrologists and not a lack of referral of these patients to nephrologists for care. The discrepancy of perceived knowledge between African-Americans and other races needs special attention.
Kidney International 08/2008; 74(9):1178-84. · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pragmatic interoperability problems arise when the intended effect of a communication differs from its actual effect. To avert these problems, we seek an information model which supports semantic interoperability among electronic health resources used for communication and reasoning. The model must support information exchange among clinicians caring for patients with a chronic disease. We use a formative evaluation to assess the solution, a Boundary Infostructure for eHealth, against these objectives. The infostructure components HL7 Clinical Document Architecture, SNOMED CT, ICD-10-CA, Primary Renal Diagnosis, ICD9 and the Chronic Kidney Disease Discharge Summary Template are boundary objects. The five communities of practice in the CHAMP model provide a basis for context of use. We compare content in electronic discharge summaries (N=4) with the markers of disease progression taken from the Western Health Information Collaborative Chronic Disease Management data standard. Early results indicate that we can increase usefulness of clinical documents but data entry is a barrier. The formative evaluation points out the need for a nosological system that can serve the interests of all parties concerned and enable shared understanding. An evaluation of how well SNOMED CT addresses that need is reserved for future work.