Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

PURPOSE OF REVIEW: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. SOURCES OF INFORMATION: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. METHODS: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. KEY FINDINGS: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. LIMITATIONS: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

JUSTIFICATION: (1) Commenter les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC); (2) appliquer les lignes directrices actualisées et fondées sur les données probantes en vue de leur mise en œuvre dans le système de soins de santé canadien; (3) commenter les soins prodigués aux enfants atteints d'insuffisance rénale chronique (IRC) et (4) définir les priorités de recherche des patients Canadiens. SOURCES: Les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC). MÉTHODOLOGIE: Les coprésidents du comité ont sélectionné les membres potentiels sur la base de leur connaissance du secteur de la santé rénale au Canada, tout en visant une bonne représentation de toutes les disciplines concernées, des centres universitaires et communautaires et des différentes régions géographiques. PRINCIPAUX COMMENTAIRES: Nous approuvons un grand nombre des recommandations du KDIGO. Cependant, compte tenu de la rareté des anomalies du calcium et du phosphate et de la faible probabilité d'anomalies graves de la PTH (hormone parathyroïde), nous déconseillons le dépistage et la surveillance des taux de calcium, de phosphate, de PTH et de phosphatase alcaline chez les adultes atteints d'IRC de stade G3. Nous suggérons de mesurer ces paramètres chez les adultes de stade G4 et nous le recommandons pour les patients de stade G5. Chez les enfants, nous appuyons la recommandation de commencer la surveillance des TMO-MRC dès le stade G2, mais nous suggérons de mesurer le calcium ionisé plutôt que les taux de calcium total ou de calcium corrigé en fonction de l'albumine. En ce qui concerne la vitamine D, nous déconseillons le dépistage de routine des carences chez les adultes atteints d'IRC de stade G3 à G5 et G1T à G5T; nous suggérons plutôt de suivre les recommandations visant la population générale pour un apport adéquat en vitamine D. Nous recommandons que la mesure et la prise en charge de la densité minérale osseuse (DMO) se fassent en suivant les recommandations pour la population générale chez les adultes atteints d'IRC de stade G3 et G3T, mais nous déconseillons les tests de DMO de routine chez les adultes de stades G4-G5 et G4T-G5T, de même que chez les enfants atteints d'IRC. En raison de données insuffisantes, nous déconseillons également la pratique systématique d'une biopsie osseuse chez les adultes atteints d'IRC ou d'IRC-TMO, ainsi que chez les enfants atteints d'IRC, bien que nous la considérions comme un important outil de recherche. LIMITES: Le comité s'est appuyé sur le résumé des preuves rédigé par le KDIGO. Le comité de la SCN n'a pas reproduit ou mis à jour les revues systématiques.

Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease: A Canadian Expert Consensus.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD. The purpose of this consensus recommendation is to develop an evidence-informed recommendation for the optimal management of adult patients with ADPKD. This document focuses on the role of genetic testing, the role of renal imaging, predicting the risk of disease progression, and pharmacological treatment options for ADPKD. These areas of focus were derived from 2 national surveys that were disseminated to nephrologists and patients with ADPKD with the aim of identifying unmet needs in the management of ADPKD in Canada. Specific recommendations are provided for the treatment of ADPKD with tolvaptan.

La polykystose rénale autosomique dominante (PKRAD) est le trouble rénal héréditaire le plus fréquent dans le monde. La maladie est caractérisée par la présence de kystes rénaux et par une insuffisance rénale progressive provoquée par l'élargissement progressif des kystes et par une fibrose rénale. Environ 45 à 70% des patients atteints de PKRAD verront leur état évoluer vers l'insuffisance rénale terminale avant l'âge de 65 ans. Bien que les thérapies ciblées et non ciblées aient été testées chez des patients atteints de PKRAD, le tolvaptan est le seul médicament approuvé au Canada pour le traitement de la PKRAD. L'objectif de cette recommandation consensuelle est l'élaboration de recommandations fondées sur des données probantes pour une prise en charge optimale des patients adultes atteints de PKRAD. Ce document met l'accent sur le rôle du dépistage génétique et de l'imagerie rénale, sur les façons de prédire le risque de progression de la maladie et sur les options de traitement pharmacologique de la PKRAD. Ces domaines d'action dérivent de deux enquêtes nationales diffusées aux néphrologues et aux patients canadiens atteints de PKRAD, et qui avaient pour but d'identifier les besoins non satisfaits dans la prise en charge le la PKRAD au Canada. Des recommandations spécifiques sont fournies pour le traitement de la PKD avec le tolvaptan.

A randomised single-blind study to improve health-related quality of life by treating anaemia of chronic kidney disease with Aranesp® (darbepoetin alfa) in older people: STIMULATE.

BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age, and the risk of significant anaemia increases as renal function declines. The objectives of this study were to assess the effect of darbepoetin alfa administration on health-related quality of life (HRQOL) through treatment for anaemia in older patients with CKD. METHODS: In this multicentre, randomised, placebo-controlled trial, older patients (aged ≥ 70 years) with CKD (Stages 3-5, predialysis) and haemoglobin (Hb) < 11.0 g/dL were randomised to darbepoetin alfa (n = 28) or placebo (n = 23). HRQOL was measured using a number of instruments including Short Form-36 (SF-36) and Functional Assessment of Cancer Therapy-Anaemia (FACT-An). RESULTS: The primary endpoint, mean SF-36 Vitality Score at Week 24, was comparable between the darbepoetin alfa (51.4 [95 % CI 48.0, 54.9]) and placebo (46.7 [40.9, 52.5]) groups. Darbepoetin alfa-treated patients experienced statistically significant improvements in some SF-36 and FACT-An Subscale Scores. Mean Hb was higher with darbepoetin alfa (12.5 [12.1, 12.9] g/dL) than with placebo (10.5 [10.1, 11.0] g/dL). The safety profiles were comparable between the treatment groups. The study was limited by only 20 % of the planned patient recruitment being achieved. CONCLUSIONS: Darbepoetin alfa increased Hb and, within study limitations, suggested that improvements in some HRQOL domains in older CKD patients with anaemia may be achieved with more physiological haemoglobin.

An assessment of dialysis provider's attitudes towards timing of dialysis initiation in Canada.

BACKGROUND: Physicians' perceptions and opinions may influence when to initiate dialysis. OBJECTIVE: To examine providers' perspectives and opinions regarding the timing of dialysis initiation. DESIGN: Online survey. SETTING: Community and academic dialysis practices in Canada. PARTICIPANTS: A nationally-representative sample of dialysis providers. MEASUREMENTS AND METHODS: Dialysis providers opinions assessing reasons to initiate dialysis at low or high eGFR. Responses were obtained using a 9-point Likert scale. Early dialysis was defined as initiation of dialysis in an individual with an eGFR greater than or equal to 10.5 ml/min/m(2). A detailed survey was emailed to all members of the Canadian Society of Nephrology (CSN) in February 2013. The survey was designed and pre-tested to evaluate duration and ease of administration. RESULTS: One hundred and forty one (25% response rate) physicians participated in the survey. The majority were from urban, academic centres and practiced in regionally administered renal programs. Very few respondents had a formal policy regarding the timing of dialysis initiation or formally reviewed new dialysis starts (N = 4, 3.1%). The majority of respondents were either neutral or disagreed that late compared to early dialysis initiation improved outcomes (85-88%), had a negative impact on quality of life (89%), worsened AVF or PD use (84-90%), led to sicker patients (83%) or was cost effective (61%). Fifty-seven percent of respondents felt uremic symptoms occurred earlier in patients with advancing age or co-morbid illness. Half (51.8%) of the respondents felt there was an absolute eGFR at which they would initiate dialysis in an asymptomatic patient. The majority of respondents would initiate dialysis for classic indications for dialysis, such as volume overload (90.1%) and cachexia (83.7%) however a significant number chose other factors that may lead them to early dialysis initiation including avoiding an emergency (28.4%), patient preference (21.3%) and non-compliance (8.5%). LIMITATIONS: 25% response rate. CONCLUSIONS: Although the majority of nephrologists in Canada who responded followed evidence-based practice regarding the timing of dialysis initiation, knowledge gaps and areas of clinical uncertainty exist. The implementation and evaluation of formal policies and knowledge translation activities may limit potentially unnecessary early dialysis initiation.

CONTEXTE: Les perceptions et opinions des médecins peuvent influencer le moment d'initiation de la dialyse. OBJECTIF: Examiner les perspectives et opinions des médecins relatives au moment d'initiation de la dialyse. TYPE D'ÉTUDE: Sondage en ligne. ÉCHANTILLON: Unités de dialyse communautaires et académiques au Canada. PARTICIPANTS: Un échantillon représentatif de médecins au Canada. MÉTHODES ET INSTRUMENTS DE MESURE: Nous avons recueilli les opinions des professionnels impliqués en dialyse sur l'initiation de la dialyse basée sur le niveau de eDGF (inférieur ou supérieur à 10,5 mL/min/m2) grâce à un sondage envoyé à tous les membres de la Société canadienne de néphrologie en février 2013. Les réponses aux questions étaient exprimées par une échelle de Likert à 9 catégories. Nous avons préalablement testé le sondage afin d'évaluer sa durée et sa facilité d'administration. L'initiation précoce de la dialyse était définie par un début de dialyse en présence d'un eDGF supérieur ou égal à 10,5 mL/min/m2. RÉSULTATS: Cent quarante et un (taux de réponse de 25%) médecins ont participé au sondage. La majorité provenait de centres urbains et académiques et pratiquait dans des programmes régionaux de suppléance rénale. Très peu de répondants avaient un protocole formel pour le début de la dialyse ou avaient révisés les nouvelles initiations de dialyse (n = 4, 3,1%). La majorité des répondants était soit neutre ou en désaccord avec l'affirmation que l'initiation tardive, comparée à l'initiation précoce, améliore les issues (85-88%), réduit l'utilisation d'une FAV ou de la dialyse péritonéale (84-90%), conduit vers des patients plus malades (83%), ou était rentable (61%). Cinquante-sept pour cent des répondants estimaient que les symptômes urémiques apparaissent plus tôt chez les patients âgés ou souffrant de comorbidités. La moitié (51,8%) des répondants estimait qu'il existe un seuil de DFG où ils débuteraient la dialyse chez un patient asymptomatique. La majorité des répondants initierait la dialyse pour les indications classiques de dialyse, telles que la surcharge volémique (90,1%) et la cachexie (83,7%). Cependant, un nombre significatif de répondants ont rapporté d'autres facteurs qui les conduiraient à initier la dialyse précocement, incluant éviter une urgence (28,4%), la préférence du patient (21,3%) et l'inobservance (8,5%). LIMITES DE L'ÉTUDE: Taux de réponse de 25%. CONCLUSIONS: Bien que la majorité des néphrologues au Canada ait répondu selon les lignes directrices basées sur les données probantes pour le moment d'initiation de la dialyse, des lacunes de connaissance et des incertitudes cliniques existent. La mise en œuvre et l'évaluation de politiques formelles et d'activités de valorisation des connaissances pourraient limiter l'initiation de dialyse précoce non nécessaire.

Risk factors associated with hemodialysis central venous catheter malfunction; a retrospective analysis of a randomized controlled trial.

BACKGROUND: We previously reported a reduction in central venous catheter (CVC) malfunction when using once-weekly recombinant tissue-plasminogen activator (rt-PA) as a locking solution, compared with thrice-weekly heparin. OBJECTIVES: To identify risk factors for CVC malfunction to inform a targeted strategy for rt-PA use. DESIGN: Retrospective analysis. SETTING: Canadian hemodialysis (HD) units. PATIENTS: Adults with newly placed tunnelled upper venous system CVCs randomized to a locking solution of rt-PA(1 mg/mL) mid-week and heparin (5000 u/ml) on the other HD sessions, or thrice-weekly heparin (5000 u/ml). MEASUREMENTS: CVC malfunction (the primary outcome) was defined as: peak blood flow less than 200 mL/min for thirty minutes during a HD session; mean blood flow less than 250 mL/min for two consecutive HD sessions; inability to initiate HD. METHODS: Cox regression was used to determine the association between patient demographics, HD session CVC-related variables and the outcome of CVC malfunction. RESULTS: Patient age (62.4 vs 65.4 yr), proportion female sex (35.6 vs 48.4%), and proportion with first catheter ever (60.7 vs 61.3%) were similar between patients with and without CVC malfunction. After multivariate analysis, risk factors for CVC malfunction were mean blood processed < 65 L when compared with ≥ 85 L in the prior 6 HD sessions (HR 4.36; 95% CI, 1.59 to 11.95), and mean blood flow < 300 mL/min, or 300 - 324 mL/min in the prior 6 HD sessions (HR 7.65; 95% CI, 2.78 to 21.01, and HR 5.52; 95% CI, 2.00 to 15.23, respectively) when compared to ≥ 350 mL/min. LIMITATIONS: This pre-specified post-hoc analysis used a definition of CVC malfunction that included blood flow, which may result in an overestimate of the effect size. Generalizability of results to HD units where trisodium citrate locking solution is used may also be limited. CONCLUSIONS: HD session characteristics including mean blood processed and mean blood flow were associated with CVC malfunction, while patient characteristics were not. Whether targeting these patients at greater risk of CVC malfunction with rt-PA as a locking solution improves CVC longevity remains to be determined.

CONTEXTE: Nous avons précédemment fait rapport d'une réduction du dysfonctionnement du cathéter veineux central (CVC) lors de l'utilisation hebdomadaire de l'activateur tissulaire du plasminogène obtenu par génie génétique (rt-PA) comme solution verrou, plutôt que l'administration d'héparine trihebdomadaire. OBJECTIFS: Déterminer les facteurs de risques de dysfonctionnement du CVC afin d'indiquer une stratégie visée quant à l'utilisation du rt-PA. TYPE D'ÉTUDE: Analyse rétrospective. CONTEXTE: Les services canadiens d'hémodialyse (HD). PARTICIPANTS: Adultes à qui on a nouvellement installé un CVC tunnellisé intravasculaire dans le système veineux supérieur, et qui ont reçu soit une solution verrou de rt-PA (1 mg/ml) en milieu de semaine et de l'héparine (5 000 u/ml) lors des autres séances d'HD, soit de l'héparine trois fois par semaine (5 000 u/ml). MESURES: On a défini le dysfonctionnement du CVC (résultat primaire) comme étant : un débit sanguin de pointe inférieur à 200 mL/min durant trente minutes, au cours d'une séance d'HD; un débit sanguin moyen inférieur à 250 mL/min lors de deux séances d'HD consécutives; l'impossibilité d'entamer l'HD. MÉTHODES: On a eu recours au modèle de régression de Cox pour déterminer l'association entre les données démographiques des participants, les variables relatives au CVC lors des séances d'HD et le résultat d'un dysfonctionnement du CVC. RÉSULTATS: L'âge des participants (62,4 c. 65,4 ans), la proportion des participants de sexe féminin (35,6% c. 48,4%), et la proportion de ceux à qui on a installé un cathéter pour la première fois (60,7% c. 61,3%) étaient similaires entre les patients qui ont subi un dysfonctionnement du CVC et ceux qui n'en ont pas subi. L'analyse multifactorielle révèle que les facteurs de risque liés au dysfonctionnement du CVC sont un traitement moyen du sang < 65 L, comparativement à ≥ 85 L au cours des 6 séances d'HD précédentes (HR 4,36; 95% CI, 1,59 à 11,95), et un débit sanguin moyen < 300 mL/min, ou 300 ­ 324 mL/min lors des 6 séances d'HD précédentes (HR 7,65; 95% CI, 2,78 à 21,01, et HR 5,52; 95% CI, 2,00 à 15,23, respectivement), comparativement à ≥ 350 mL/min. LIMITES DE L'ÉTUDE: Cette analyse prédéterminée et post-hoc reposait sur une définition du dysfonctionnement du CVC qui comprenait le débit sanguin, ce qui pourrait résulter en une surestimation de l'ampleur de l'effet réel. La validité externe des résultats pour les services d'HD qui utilisent le citrate trisodique comme solution verrou pourrait aussi être limitée. CONCLUSIONS: Les caractéristiques des séances d'HD comprenant le traitement moyen du sang et le débit sanguin moyen ont été associées au dysfonctionnement du CVC, alors que les caractéristiques des participants ne l'ont pas été. Il reste à déterminer si le fait de cibler les patients courant un risque accru de dysfonctionnement du CVC avec rt-PA comme solution verrou améliore la longévité du CVC.

Canadian Society of Nephrology commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD.

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.

A nurse-coordinated model of care versus usual care for stage 3/4 chronic kidney disease in the community: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m(2) identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked. RESULTS: The average decline in eGFR over 20 months was -1.9 ml/min per 1.73 m(2). eGFR declined by ≥4 ml/min per 1.73 m(2) within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year. CONCLUSIONS: Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.

Cost-effectiveness analysis of a randomized trial comparing care models for chronic kidney disease.

BACKGROUND AND OBJECTIVES: Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs. RESULTS: Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR. CONCLUSIONS: The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.

Macrocytosis may be associated with mortality in chronic hemodialysis patients: a prospective study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Macrocytosis may be associated with mortality in stable, chronic hemodialysis patients. Future studies will need to be conducted to confirm this finding.

Health-related quality of life and hemoglobin levels in chronic kidney disease patients.

BACKGROUND: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective.

BACKGROUND: The Irbesartan in Reduction of Microalbuminuria trial and the Irbesartan in Diabetic Nephropathy Trial found that irbesartan is renoprotective in patients having hypertension with type 2 diabetes. OBJECTIVE: The objective of this study was to assess whether treatment with irbesartan is cost-effective in Canada relative to conventional care in this patient population and whether it is more cost-effective to treat patients early rather than later in the development of renal disease from the perspective of the Canadian health and social care system. METHODS: The analysis compared 3 alternative strategies for the management of hypertension in patients with type 2 diabetes and early renal disease: (1) conventional hypertensive treatment excluding the use of angiotensin II receptor antagonists (AIIRAs); (2) the early addition of irbesartan (an AIIRA) to conventional treatment; and (3) the late addition of irbesartan to conventional treatment. A Markov model was used to simulate the progression of renal disease (microalbuminuria to death) in hypertensive patients with type 2 diabetes over a 25-year time horizon. Transition probabilities were derived from the 2 randomized controlled trials. A cost-effectiveness analysis was conducted with outcome measured in life-years gained (LYGs). RESULTS: The early addition of irbesartan during microalbuminuria was cost-saving and more effective than both delaying irbesartan treatment until advanced overt nephropathy (AON) (0.45 LYG, Can $54,100 saved) and conventional antihypertensive use (0.62 LYG, $68,400 saved). This was due to the increased drug costs associated with the use of irbesartan being offset by savings arising from delays in the development of overt nephropathy and the subsequent delay to end-stage renal disease (ESRD). Sensitivity analyses confirmed the robustness of the study results. CONCLUSIONS: The early use of irbesartan for patients with hypertension and type 2 diabetes who have yet to develop overt nephropathy is both more effective and less costly than delaying irbesartan treatment until AON and conventional antihypertensive use. Analysis suggests that the earlier irbesartan is added to conventional antihypertensive treatment, the greater the delays in the onset of ESRD and the overall savings in health care resource utilization from the perspective of the Canadian health and social care system.