The BC ADPKD Network: A Comprehensive Provincial Approach to Support Specialized and Locally Delivered Multidisciplinary ADPKD Care.

PURPOSE: With evolving evidence around the progression, assessment, and management of autosomal dominant polycystic kidney disease (ADPKD), care of the disease has become increasingly complex. Needs assessments in British Columbia (BC) described variability in knowledge and comfort with incorporating these new aspects of ADPKD care into clinical practice. Undercapture of early-stage ADPKD patients in existing renal databases was also identified as an unmet need. SOURCES OF INFORMATION: A multidisciplinary group of clinicians and patient partners with interest and expertise in ADPKD and/or multidisciplinary kidney care informed the project work. An existing provincial renal database was used to support the provincial ADPKD registry. METHODS: A formalized, comprehensive provincial ADPKD Network was created within the existing infrastructure of multidisciplinary kidney clinics (MDCs) in BC. The Network is coordinated provincially and implemented locally. It incorporates robust data collection, education, creation, and dissemination of dedicated clinical tools; collaboration between clinics and clinicians across the province; and ongoing evaluation and continuous quality improvement. KEY FINDINGS: Over the 5 years since its inception, the BC ADPKD Network has enabled increased and earlier identification of British Columbians living with ADPKD and a shift in practice toward increased and earlier enrollment of ADPKD patients into MDCs. A host of tailored ADPKD clinical tools have been created and implemented in all MDCs across the province to support existing MDC staff in the delivery of more standardized and specialized ADPKD care. A collaborative provincial clinician network founded on Local Clinical Champions has been established to support ongoing experience sharing between clinics. An evaluation framework has been established to evaluate outcomes and enable ongoing refinement of the Network. LIMITATIONS: The provincial ADPKD registry is undergoing enhancements to enable more comprehensive capture of APDKD-specific information such as total kidney volume and genetic results, but at present, this remains a limitation. It remains to be seen whether the activities of the ADPKD Network will improve long-term clinical outcomes and care experiences of patients living with ADPKD, and a long-term sustainability assessment of this model of care will be required. IMPLICATIONS: The structure, tools, and coordinated and collaborative clinician network established through this comprehensive provincial ADPKD Network may be valuable in addressing the variability and gaps in existing ADPKD care while allowing patients and families across BC to receive enhanced care locally, in their usual kidney care environments.

JUSTIFICATION: L'évolution des données entourant la progression, l'évaluation et la prise en charge de la polykystose autosomique dominante (ADPKD) complexifie de plus en plus son traitement. En Colombie-Britannique (C.-B.), une évaluation des besoins a décrit la variabilité des connaissances et le niveau de confort quant à l'intégration de ces nouveaux aspects des soins pour l'ADPKD dans la pratique clinique. La capture des patients atteints d'ADPKD à un stade précoce dans les bases de données rénales existantes a également été reconnue comme un besoin non satisfait. SOURCES: Les travaux ont été orientés par un groupe multidisciplinaire de cliniciens et de patients partenaires possédant une expertise dans le domaine de l'ADPKD ou dans les soins rénaux multidisciplinaires. Une base de données provinciale existante sur les maladies rénales a été utilisée en appui au registre provincial de l'ADPKD. MÉTHODOLOGIE: Un réseau provincial complet et structuré pour l'ADPKD a été créé au sein de l'infrastructure existante des cliniques rénales multidisciplinaires (CRM) de la Colombie-Britannique. Le réseau est coordonné à l'échelle provinciale et mis en œuvre localement. Le réseau englobe une collecte rigoureuse des données, de l'éducation, la création et la diffusion d'outils cliniques dédiés, la collaboration entre les cliniques et les cliniciens de toute la province, de même que l'évaluation et l'amélioration continues de la qualité. PRINCIPAUX RÉSULTATS: Au cours des cinq années qui ont suivi sa création, le réseau ADPKD de la C.-B. a permis d'identifier en plus grand nombre et plus précocement les Britanno-Colombiens vivant avec l'ADPKD. On a également pu observer un virage dans la pratique vers une plus vaste et une plus précoce inclusion des patients atteints d'ADPKD dans les CRM. De plus, une foule d'outils cliniques sur mesure ont été créés et mis en œuvre dans tous les CRM de la province afin d'appuyer le personnel des CRM existantes dans la prestation de soins normalisés et plus spécialisés pour l'ADPKD. Un réseau coopératif provincial de cliniciens, fondé sur les champions cliniques locaux, a été créé pour favoriser le partage continu de l'expérience entre les cliniques. Enfin, un cadre d'évaluation a été établi pour examiner les résultats et permettre l'amélioration continue du réseau. LIMITES: Le registre provincial de l'ADPKD fait présentement l'objet d'améliorations qui permettront une saisie plus complète de l'information spécifique à l'APDKD, notamment le volume rénal total et les résultats génétiques, mais à l'heure actuelle, ceci demeure une limite. Reste à voir si les activités du réseau ADPKD permettront d'améliorer les résultats cliniques à long terme et les expériences de soins des patients vivant avec l'ADPKD. Une évaluation à long terme de la durabilité de ce modèle de soins sera nécessaire. CONCLUSION: La structure, les outils et le réseau coordonné et collaboratif de cliniciens mis en place par le biais de ce réseau provincial sur l'APDKD peuvent être utiles pour rendre compte de la variabilité et combler les lacunes des soins existantes, tout en permettant aux patients et aux familles de la Colombie-Britannique de recevoir localement de meilleurs soins, soit dans leur milieu de soins rénaux habituel.

The prevalence of hematologic and metabolic abnormalities during chronic kidney disease stages in different ethnic groups.

We conducted an observational cross-sectional study to determine if the prevalence of hematologic and metabolic abnormalities in chronic kidney disease (CKD) varied in different ethnic groups. We used a CKD provincial database where a complete data set at the time of registration was available as well as an estimated glomerular filtration rate (eGFR), which showed using the abbreviated MDRD formula that the patients had CKD of stages 3-5. We included patients with self-reported race of Caucasian, Oriental Asian, or South Asian. Primary outcomes were the prevalence of at least one of the following: anemia, hypocalcemia, hyperphosphatemia, hyperparathyroidism, hypoalbuminemia, and three or more laboratory abnormalities. All definitions were consistent with K/DOQI guidelines. When compared with Caucasians, Oriental Asians and South Asians had a higher prevalence of many of the metabolic abnormalities during most stages of CKD and were more likely to have any abnormality at all levels of eGFR. The prevalence of three or more laboratory abnormalities was higher in Oriental Asians at all stages and in South Asians at some levels of eGFR. These results were unchanged or exaggerated when controlled for age, gender, diabetes, and a primary diagnosis of renal disease. Hence, it appears that South Asians and Oriental Asians have more laboratory abnormalities compared with Caucasians at most levels of eGFR.

Canadian survey of clinical status at dialysis initiation 1998-1999: a multicenter prospective survey.

AIMS: The current growth in end-stage kidney disease populations has led to increased efforts to understand the impact of status at dialysis initiation on long-term outcomes. Our main objective was to improve the understanding of current Canadian nephrology practice between October 1998 and December 1999. METHODS: Fifteen nephrology centers in 7 provinces participated in a prospective data collection survey. The main outcome of interest was the clinical status at dialysis initiation determined by: residual kidney function, preparedness for chronic dialysis as measured by presence or absence of permanent peritoneal or hemodialysis access, hemoglobin and serum albumin. Uremic symptoms at dialysis initiation were also recorded, however, in some cases these symptom data were obtained retrospectively. RESULTS: Data on 251 patients during 1-month periods were collected. Patients commenced dialysis at mean calculated creatinine clearance levels of approximately 10 ml/min, with an average of 3 symptoms. 35% of patients starting dialysis had been known to nephrologists for less than 3 months. These patients are more likely to commence without permanent access and with lower hemoglobin and albumin levels. Even of those known to nephrologists, only 66% had permanent access in place. CONCLUSIONS: Patients commencing dialysis in Canada appear to be doing so in relative concordance with published guidelines with respect to timing of initiation. Despite an increased awareness of kidney disease, a substantial number of patients continues to commence dialysis without previous care by a nephrologist. Of those who are seen by nephrologists, clinical and laboratory parameters are suboptimal according to current guidelines. This survey serves as an important baseline for future comparisons after the implementation of educational strategies for referring physicians and nephrologists.

Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter.

The high prevalence of cardiovascular disease (CVD) in patients with kidney disease is well described. This Canadian, multicenter, observational cohort study reports the prevalence and risk factors of CVD associated with kidney disease, in a cohort of patients with established chronic kidney disease (CKD), who are followed-up by nephrologists. This analysis sought to answer 2 questions: (1) in patients with established CKD, are the prevalence and progression of CVD accounted for by conventional or uremia-related risk factors, and (2) to what extent can progression to renal replacement therapy (RRT) be explained by CVD versus traditional risk factors for kidney disease? This study population consists of 313 patients (predominantly men) who had a mean age of 56 years and a mean creatinine clearance of 36 mL/min. Thirty percent were diabetic. The overall prevalence of CVD was 46%, and was independent of severity of kidney dysfunction (P = 0.700). The median follow-up time was 23 months, for a total of 462 patient years. We note the overall incidence of CVD events (new CVD or worsening of CVD) was 47/244 (20%). The best predictors of new CVD events among those without preexisting CVD were diabetes (odds ratio [OR] = 5.35, P = 0.018) and age (OR = 1.26, P = 0.08). In those with preexisting CVD, low diastolic pressure (DP) (OR =.72, P = 0.004) and high triglycerides (OR = 1.48, P = 0.019) at baseline were independent predictors of progression of CVD. We could not determine an independent impact of kidney function on CVD in the overall cohort. Furthermore, we determined that the presence of CVD itself confers an increased risk for progression to RRT (relative risk [RR] = 1.58, P = 0.047), adjusted for kidney function. This is the first in-depth analysis of CVD in a cohort of patients with established chronic kidney disease who are not on dialysis. The question regarding the impact of the altered biology of uremia in contributing to CVD progression remains unanswered, and clearly needs further study. However, the findings do raise the issue of whether aggressive treatment of CVD and risk factors might, in fact, reduce progression to RRT. Further large-scale, observational studies as well as interventional studies are needed to more clearly understand the complex biology of cardiovascular and kidney disease progression.

Obstacles to residents' conducting research and predictors of publication.

Internal medicine residents at one school identified barriers to and predictors of publishing their research. Insufficient time was the key obstacle to completing research. Residents with previous research experience, senior residents, and men were more likely to publish.

Screening for renal disease using serum creatinine: who are we missing?

BACKGROUND: Appropriate management and timely referral of patients with early renal disease often depend on the identification of renal insufficiency by primary care physicians. Serum creatinine (SCr) levels are frequently used as a screening test for renal dysfunction; however, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate the prevalence of patients who have significantly reduced GFR as calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS: The study included 2781 outpatients referred by community physicians to an urban laboratory network for SCr measurement. GFR was estimated using the C-G formula. Patients were grouped according to the concordance of SCr level abnormalities (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal or =70 years old, 12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available laboratory data for patients with abnormal SCr and abnormal C-G values showed that 2 years prior to the study period, 72% of this group had abnormal SCr, while 18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C-G values. CONCLUSIONS: This study documents the substantial prevalence of significantly abnormal renal function among patients identified by laboratories as having normal-range SCR: Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the early identification of patients with renal impairment.

A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate.

BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.

How reliable is emergency department triage?

STUDY OBJECTIVE: To measure interrater and intrarater agreement for an emergency department triage system. METHODS: A 2-phase experimental study was conducted using previously described in-person scripted encounters with emergency nurses who perform patient triage and attending emergency physicians at a tertiary referral center. Standardized patient scenarios were presented twice over 6 weeks. Participants rated severity for each patient using a 5-tier triage system (nurses only) and estimated the probability of hospital admission, the most appropriate time frame to physician evaluation (5 choices, from "Immediate" to "More than 24 hours"), the need for a monitored ED bed, and the need for diagnostic services. Interrater agreement was measured by a coefficient of agreement for multiple raters and multiple categories. RESULTS: Of the 37 participants (fewer than 90% of those eligible), 19 (51%) completed both phases (12 nurses, 7 physicians). Four (33%) of the nurses assigned the same severity ratings for the 5 cases in phase 2 as they did in phase 1. Intrarater agreement among the 12 nurses rating triage severity was.757. Interrater agreement of nurses and physicians was substantial regarding need for ED monitoring, and moderate to substantial for other triage assessments. CONCLUSION: There was general agreement in interrater assessment of triage classification. Continued work is necessary to more fully delineate areas of variation.

Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin.

Cardiovascular disease occurs in patients with progressive renal disease both before and after the initiation of dialysis. Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis populations and is common in the renal insufficiency population. LVH is associated with numerous modifiable risk factors, but little is known about LV growth (LVG) in mild-to-moderate renal insufficiency. This prospective multicenter Canadian cohort study identifies factors associated with LVG, measured using two-dimensional-targeted M-mode echocardiography. Eight centers enrolled 446 patients, 318 of whom had protocol-mandated clinical, laboratory, and echocardiographic measurements recorded. We report 246 patients with assessable echocardiograms at both baseline and 12 months with an overall prevalence of LVH of 36%. LV mass index (LVMI) increased significantly (>20% of baseline or >20 g/m2) from baseline to 12 months in 25% of the population. Other than baseline LVMI, no differences in baseline variables were noted between patients with and without LVG. However, there were significant differences in decline of Hgb level (-0.854 v -0.108 g/dL; P = 0.0001) and change in systolic blood pressure (+6.50 v -1.09 mm Hg; P = 0.03) between the groups with and without LVG. Multivariate analysis showed the independent contribution of decrease in Hgb level (odds ratio [OR], 1.32 for each 0.5-g/dL decrease; P = 0.004), increase in systolic blood pressure (OR, 1.11 for each 5-mm Hg increase; P = 0.01), and lower baseline LVMI (OR, 0.85 for each 10-g/m2; P = 0.011) in predicting LVG. Thus, after adjusting for baseline LVMI, Hgb level and systolic blood pressure remain independently important predictors of LVG. We defined the important modifiable risk factors. There remains a critical need to establish optimal therapeutic strategies and targets to improve clinical outcomes.

Homocyst(e)ine and vascular access complications in haemodialysis patients: insights into a complex metabolic relationship.

BACKGROUND: As elevated total homocyst(e)ine (tHcy) is associated with increased risk of vascular thrombosis, we hypothesized that the elevated levels of tHcy seen in patients on haemodialysis may be associated with an increased risk of thrombosis of native arteriovenous fistulae (vascular access failure). Our study was designed to investigate the relationship between tHcy and vascular access failure. The relationship between tHcy and mortality was explored as a secondary analysis. METHODS: The study comprised a cross-sectional analysis of 96 haemodialysis patients at a single university-affiliated hospital and a subsequent 9-month prospective follow-up of 88 of the 96 patients. RESULTS: Levels of tHcy (median 30 micromol/l) were elevated. In the initial cross-sectional sample, there was an inverse relationship between tHcy and history of vascular access failure which was not observed in the prospective study. Variables influencing the risk of vascular access failure in the prospective study included history of previous vascular access failure (RR=2.93, P=0.03), use of antiplatelet agents (RR=0.13, P=0.01), increased urea reduction ratio (RR=0.55 for a 5% increase, P=0.01) and increased weight (RR=0.61 for a 10 kg increase, P=0.02). Secondary analysis showed an unexpected inverse relationship between tHcy and mortality (RR=0.033 for 1 log increase in tHcy, P=0.006), such that the lower levels of tHcy were associated with an increased risk of death in short-term follow-up. CONCLUSION: We did not demonstrate a relationship between tHcy and risk of vascular access failure. Patients with the lowest levels of tHcy appeared to be at increased risk of death in this short-term follow-up. The relationship of tHcy to vascular access complications and death in haemodialysis patients appears complex and requires further study.

Determinants of short- and long-term outcome in patients with respiratory failure caused by AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVES: To determine (1) predictors of in-hospital mortality and long-term survival in patients with acute respiratory failure (ARF) caused by acquired immunodeficiency syndrome-related Pneumocystis carinii pneumonia (PCP) and (2) long-term survival for patients with ARF relative to those without ARF. METHODS: A retrospective medical chart review was conducted of all cases of PCP-related ARF for which the patient was admitted to the intensive care unit of a single tertiary care institution between 1991 and 1996. Data were extracted regarding physiologic scores, relevant laboratory values, and duration of previous maximal therapy with combined anti-PCP agents and corticosteroids at entry to the intensive care unit. Duration of survival was determined by Kaplan-Meier methods from date of first hospital admission and compared for patients with and without ARF. RESULTS: There were 41 admissions to the intensive care unit among 39 patients, with 56.4% in-hospital mortality. Higher physiologic scores (Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Lung Injury, and modified Multisystem Organ Failure scores) were predictive of in-hospital mortality. Duration of previous maximal therapy also predicted in-hospital mortality (45% for patients with <5 days of previous maximal therapy vs 88% for those with > or =5 days of previous maximal therapy; P = .03). Combining physiologic scores and duration of previous maximal therapy enhanced prediction of in-hospital mortality. There was no difference in long-term survival between patients with PCP with ARF and those without ARF (P = .80), and baseline characteristics did not predict long-term survival. CONCLUSIONS: In-hospital mortality of patients with acquired immunodeficiency syndrome-related PCP and ARF is predicted by duration of previous maximal therapy and physiologic scores, and their combination enhances predictive accuracy. Long-term survival of patients with ARF caused by PCP is comparable to that of patients with PCP who do not develop ARF, and determinants of in-hospital mortality do not predict long-term survival.

A randomized trial of N-acetylcysteine for prevention of trimethoprim-sulfamethoxazole hypersensitivity reactions in Pneumocystis carinii pneumonia prophylaxis (CTN 057). Canadian HIV Trials Network 057 Study Group.

Hydroxylamine derivatives of sulfamethoxazole may be the reactive metabolites that cause adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMX). The increased frequency of reactions observed in HIV-positive individuals is hypothesized to be due to systemic glutathione deficiency and a decreased ability to scavenge these metabolites. Two hundred and thirty-eight patients were randomized to receive or not receive N-acetylcysteine (3 g of the 20% liquid solution) 1 hour before each dose of TMP-SMX (trimethoprim 80 mg, sulfamethoxazole 400 mg) twice daily, which was initiated as primary Pneumocystis carinii pneumonia prophylaxis. Forty-five patients had to discontinue TMP-SMX within 2 months because of fever, rash, or pruritus including 25 of 102 patients (25%) who were receiving TMP-SMX alone and 20 of 96 patients (21%) who were randomized to TMP-SMX and N-acetylcysteine. The difference between treatment groups is 4% (95% confidence interval [CI]: -16%, +9%). No independent association was found with the hypersensitivity reaction and age, gender, race, HIV risk factor, prior AIDS, concurrent use of fluconazole, or baseline CD4. N-acetylcysteine at a dose of 3 g twice daily could not be shown to prevent TMP-SMX hypersensitivity reactions in patients with HIV infection.

Validation of the modified multisystem organ failure score as a predictor of mortality in patients with AIDS-related Pneumocystis carinii pneumonia and respiratory failure.

STUDY OBJECTIVES: To validate a previously developed multisystem organ failure (MSOF) score with and without the addition of the lactate dehydrogenase (LDH) level as a predictor of survival to hospital discharge in patients with AIDS-related Pneumocystis carinii pneumonia (PCP) and acute respiratory failure (ARF). DESIGN: Retrospective chart review between April 1, 1991, and September 30, 1996. SETTING: University-affiliated tertiary care center in downtown Vancouver, British Columbia, Canada. PATIENTS: All patients with PCP-related ARF admitted to the ICU of St. Paul's Hospital during the study period. INTERVENTIONS: As putative prognostic instruments, data were extracted regarding the APACHE II (acute physiology and chronic health evaluation II), acute lung injury (ALI), AIDS, and modified MSOF scores, as well as LDH levels, at entry to the ICU. Patients were stratified based on an LDH level of < or > or = 2,000 U/L and this threshold was assessed in its predictability of outcome when added to each of the above scores. For APACHE II, the score was categorized in six groups and evaluated with and without inclusion of the LDH. Receiver operating characteristic curves were constructed for LDH and for each score with and without the LDH level to assess accuracy of prediction. The area under each curve was calculated and compared to estimate the statistical significance of observed differences. MEASUREMENTS AND RESULTS: There were 40 admissions to the ICU of 38 patients with 52.5% mortality. The ALI and AIDS scores were not predictive of outcome. The modified MSOF and APACHE II scores were significant predictors of survival and the performance of both was enhanced by the addition of LDH. CONCLUSIONS: Both the APACHE II and the modified MSOF scores were significant predictors of outcome in the patient population studied. These results validate the modified MSOF score as an effective predictor of survival to hospital discharge among patients with AIDS-related PCP who develop ARF and the performance of the score is enhanced by the addition of the LDH level.

Active immunization of patients with HIV infection: a study of the effect of VaxSyn, a recombinant HIV envelope subunit vaccine, on progression of immunodeficiency.

Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its administration was beneficial with respect to slowing disease progression. A 3-year multicenter, randomized, placebo-controlled, double-blinded, efficacy and safety trial of repeated immunization with VaxSyn was used to evaluate the long-term impact on the progression of immunodeficiency. VaxSyn in alum, or alum alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4 counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both virological and immunological parameters were followed. No significant differences were observed between the treatment and placebo control groups in rate of CD4 T cell decline, time to initiation of antiretroviral therapy, incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral infectivity as measured by quantitative HIV coculture assay, and death. This study revealed no effect on either clinical or laboratory virological parameters from the administration of VaxSyn.