Comparing survival in patients with chronic kidney disease across three countries - Results from the study of heart and renal protection-extended review.

AIM: This study examined whether survival and causes of death differed between participants enrolled from Australia (AUS), Malaysia (MYL), and New Zealand (NZ) in extended follow-up of the Study of Heart and Renal Protection (SHARP), a randomized controlled trial (RCT) of participants with moderate to severe chronic kidney disease comparing placebo to combination therapy with Simvastatin and Ezetimibe. METHODS: All participants alive at final SHARP study visit in participating centres were eligible for inclusion. Consenting participants were re-enrolled following final SHARP Study visit and followed for 5 years. Data collection included: significant medical events, hospital admissions and requirement for kidney replacement therapy. Data linkage was performed to national kidney and mortality registries. The primary outcome was all-cause mortality compared across the three countries. RESULTS: The SHARP trial randomized 2029 participants from AUS (1043/2029, 51%), MYL (701/2029, 35%), and NZ (285/2029, 14%), with 1136 participants alive and eligible for extended follow-up at the end of SHARP. In multivariable analysis, risk of death was increased for participants in MYL (HR 1.37, 95% CI 1.17-1.61, p < .001) and NZ (HR 1.28, 95% CI 1.04-1.57, p = .02) when compared to AUS participants. Adjustment for kidney transplantation as a competing risk did not explain the variation seen between countries. CONCLUSION: This study allows a better understanding of the differences in long-term mortality risk across participants from AUS, MYL, and NZ in extended follow-up of the SHARP study and demonstrates the feasibility and value of extended follow-up of participants enrolled in RCTs.

Risk factors for incident kidney disease in older adults: an Australian prospective population-based study.

BACKGROUND AND AIM: To determine risk factors for incident chronic kidney disease (CKD) in a large population-based cohort. METHODS: This prospective opt-in population-based cohort study is based on the 45 and Up Study, where New South Wales residents aged ≥45 years were randomly sampled from the Services Australia database and agreed to complete the 45 and Up Study baseline questionnaire and have their responses linked to their health data in routinely collected databases. The primary outcome was the development of incident CKD, defined as eGFR < 60 mL/min/1.73 m2 . CKD incidence was calculated using Poisson regression. Risk factors for incident CKD were assessed using Cox regression in multivariable models. RESULTS: In 39 574 participants who did not have CKD at enrolment, independent factors associated with developing CKD included: older age, regional residence (HR 1.38 (1.27-1.50) for outer regional vs major city), smoking (1.13 (1.00-1.27) for current smoker vs non-smoker), obesity (1.25 (1.16-1.35) for obese vs normal body mass index), diabetes mellitus (1.41 (1.33-1.50)), hypertension (1.53 (1.44-1.62)), coronary heart disease (1.13 (1.07-1.20)), depression/anxiety (1.16 (1.09-1.24)) and cancer (1.29 (1.20-1.39)). Migrants were less likely to develop CKD compared with people born in Australia (0.88 (0.83-0.94)). Gender, partner status and socioeconomic factors were not independently associated with developing CKD. CONCLUSIONS: This large population-based study found multiple modifiable and non-modifiable factors were independently associated with developing CKD. In the Australian setting, the risk of CKD was higher with regional residence. Differences according to socioeconomic status were predominantly explained by age, comorbidities and harmful health-related behaviours.

How Do the Recent Major Randomized Controlled Trials Inform Best Use of the Novel Glucose-Lowering Agents?

BACKGROUND: Type 2 diabetes mellitus (T2DM) is frequently associated with the development of cardiovascular disease and chronic kidney disease (CKD). Some newer glucose-lowering agents confer both cardiac and kidney benefits, as supported by robust data from recent high-quality randomized controlled trials. The decision-making process when selecting glucose-lowering medications for T2DM now extends beyond glycaemia and metabolic effects, and towards additional benefits such as prevention of other complications. SUMMARY: We review the evidence for efficacy in 3 new classes of medication for T2DM and additionally discuss relevant safety issues when considering optimal agents. Key Messages: Clinicians have multiple efficacy and safety factors to consider when selecting agents for glucose lowering in T2DM, and this should help direct individualized selection of pharmacotherapy for patients. New medications offer an opportunity to prevent cardiac and renal complications in people with T2DM.

Effectiveness of corticosteroid compared with non-corticosteroid therapy for the treatment of drug-induced acute interstitial nephritis: a systematic review.

Corticosteroids may hasten recovery in drug-induced acute interstitial nephritis (DI-AIN). However, there is no consensus regarding the effectiveness of corticosteroid compared with non-corticosteroid therapy. We conducted a systematic review of the literature according to Preferred Reporting in Systematic Reviews and Meta-Analysis (PRISMA) guidelines using MEDLINE, EMBASE, CINAHL, Scopus and Web of Science from inception until November 2017 using predefined search terms. Studies that compared the effects of corticosteroid therapy versus non-corticosteroid therapy in the treatment of DI-AIN were included. Outcomes were change in serum creatinine, adverse drug reactions, need for renal replacement therapy (RRT) and death. Due to considerable heterogeneity, a meta-analysis was not performed. There were no randomised controlled trials. Eight retrospective studies met inclusion criteria, with 430 patients (300 received and 130 did not receive corticosteroid therapy) and a median age of 57 (range 29-75) and 58 (22-76) years respectively. When treatment details were reported, prednisone was commenced at 40-60 mg daily in five studies, and two studies commenced intravenous methylprednisolone 1 mg/kg with a treatment duration of 1.5-12 weeks. Non-corticosteroid therapy was poorly defined across all studies. Four studies showed no difference in serum creatinine between corticosteroid and comparator arms, while four studies found a benefit. Adverse drug reactions, need for RRT and deaths were infrequently reported. Risk of bias was high across all domains. The limited evidence does not support the use of corticosteroids in the treatment of DI-AIN. Larger, well-designed trials are needed to help guide clinical management of this condition.

Physical component quality of life reflects the impact of time and moderate chronic kidney disease, unlike SF-6D utility and mental component SF-36 quality of life: An AusDiab analysis.

AIM: Assessing the impact of interventions on the patient experience requires measures that are plausibly responsive to change. In a community cohort of people with and without chronic kidney disease (CKD) markers at baseline, we aimed to evaluate change in commonly used measures of quality of life (QOL) over the passage of 5 years. METHODS: Included were 6400 participants in the Australian Diabetes, Obesity and Lifestyle (AusDiab) surveys with baseline and 5-year CKD and QOL measures. Changes in SF-6D utility, and the Medical Outcomes Study 36-Item Short Form (SF-36) physical (PCS) and mental (MCS) component summary scores, were evaluated with regression analyses according to the baseline presence of reduced estimated glomerular filtration rate (eGFR) (CKD-Epidemiology Collaboration eGFR ≤60 m/min per 1.73 m2 ) or albuminuria (urine albumin:creatinine ratio ≥3.4 mg/mmol). RESULTS: At baseline, eGFR was reduced in 2.4% of participants and 5.1% had albuminuria. Participants with reduced eGFR had a lower SF-6D and PCS, and those with albuminuria a lower PCS, compared with those without, but the differences were explained by known confounders. MCS scores were not affected by the presence of reduced eGFR or albuminuria. Over 5 years all groups exhibited stable SF-6D and MCS scores but declining unadjusted PCS scores. PCS decline was greater for those with reduced eGFR, and remained significant after adjustment (-2.7 (-4.1 to -1.3) vs. -0.8 (-1.1 to -0.6, P < 0.01). Analyses according to CKD stages were essentially unchanged. CONCLUSION: Utility and mental QOL appears stable over 5 years, unaffected by time or markers of CKD health. Physical QOL appeared to deteriorate with time, especially for those with CKD, making it a more likely candidate assessment measure for intervention and health service evaluations.

Muscle strength, mobility, quality of life and falls in patients on maintenance haemodialysis: A prospective study.

AIM: The aim is to explore (i) the relationship between quality of life and physical parameters (muscle strength and mobility) among people undergoing maintenance haemodialysis; (ii) changes in strength and mobility over time and predictors of changes; and (iii) whether strength and mobility were associated with falls. METHODS: We recruited 51 maintenance haemodialysis patients to a prospective longitudinal study. Baseline quality of life was assessed using the SF-36 physical component summary and mental component summary scores. Muscle strength (ankle dorsiflexion strength measured with a hand-held dynamometer), mobility (short physical performance battery) and falls history were assessed at baseline, 12 and 36 months. Associations between variables at baseline were assessed with linear regression models. Changes in physical parameters were evaluated with paired t-tests and prediction of falls assessed by negative binominal regression. RESULTS: Fifty and 34 patients completed 12 and 36 month follow-ups, respectively. Baseline mobility but not muscle strength correlated with physical component summary (P = 0.01 and P = 0.23, respectively). Neither baseline mobility nor muscle strength correlated with mental component summary. At 12 months, muscle strength and mobility had significantly deteriorated (mean ankle dorsiflexion strength 11.0 lb (SD 1.5) from 14.0 lb (SD 2.2), P < 0.01; short physical performance battery 8.5 (SD 2.8) from 9.3 (SD 2.6), P < 0.01). Falls at 12 and 36 months were predicted by baseline mobility (P = 0.06 and P = 0.02, respectively) but not muscle strength. CONCLUSION: Physical parameters appear to be associated with meaningful patient outcomes and showed measurable deterioration over relatively short time frames. Interventions, with the potential to slow physical decline in people receiving maintenance dialysis, such as exercise programmes, warrant further investigation.

Dangers of broth after transplantation.

Serum creatinine is routinely used to monitor renal function in transplant recipients. External factors including diet, exercise and hydration status can also influence serum creatinine concentration on a day-to-day basis. We describe a case of a patient whose serum creatinine increased from 128 to 171 µmol/L after ingestion of creatinine-rich (3098 µmol/L) soup. A renal biopsy was performed but revealed no cause for the rise in creatinine and by the next day, serum creatinine had returned to baseline. We conducted two experiments to examine the effect of soup ingestion by healthy volunteers. We measured the creatinine concentration of various store-bought stock preparations and found creatinine concentrations less than one-quarter of that contained in our patient's homemade soup. A creatinine-rich soup (4334 µmol/L) was ingested by six healthy volunteers age 33 (± 6.5) years with baseline normal serum creatinine 68 (± 14) µmol/L. Mean (standard deviation) serum creatinine increased to 77 (± 11) µmol/L 4 hours after soup ingestion (P = 0.0015, paired t-test). Mean (standard deviation) creatinine clearance, extrapolated from the 4 hour urine collection following soup ingestion, was high (267 ± 198 mL/min) exhibiting a supra-normal creatinine clearance. The rate of serum creatinine rise was lower in volunteers compared with the transplant patient, consistent with the concept of renal functional reserve. Our case highlights the importance of taking dietary changes into account when interpreting serum creatinine as a measure of allograft function.

Health-related quality of life in survivors of acute kidney injury: The Prolonged Outcomes Study of the Randomized Evaluation of Normal versus†Augmented Level Replacement Therapy study outcomes.

AIM: While patients with chronic kidney disease have reduced health-related quality of life (HRQOL), long-term HRQOL of survivors of severe acute kidney injury (AKI) remains unclear. METHODS: We analysed HRQOL from the Prolonged Outcomes Study of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (POST-RENAL) study and compared findings with those from a general Australian adult population enrolled in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. We used a multivariate analysis adjusted for baseline characteristics along with sensitivity analysis using age and sex-matched case controls. RESULTS: In the POST-RENAL study, 282 participants had HRQOL data collected using the SF-12 questionnaire. This was compared with 6330 participants from the AusDiab study. Unadjusted analyses showed that POST-RENAL participants had lower physical component scores (PCS, mean score 40.0 vs 49.8, P<0.0001) and lower mental component scores (MCS, mean score 49.8 vs 53.9, P<0.0001) than the AusDiab group. After age and sex matching, the difference in PCS and MCS remained statistically significant (P<0.0001). Advanced age, reduced renal function and albuminuria (all P ≤ 0.01) were all strongly associated with lower PCS values but not MCS values. After matching subsets of the cohorts on the basis of age, sex and renal function, PCS and MCS were lower in the POST-RENAL group (P<0.0001). CONCLUSION: Survivors of severe AKI in the POST-RENAL study had lower physical and mental components of HRQOL compared with general population, even after adjustment for their reduced renal function. Increasing age and reduced renal function were associated with poorer physical QOL.

Prior Cardiovascular Treatments-A Key Characteristic in Determining Medication Adherence After an Acute Myocardial Infarction.

Objective: To investigate long-term adherence to guideline-recommended cardioprotective medications following hospitalization for an acute myocardial infarction (AMI), and identify characteristics associated with adherence. Methods: An Australian population-based cohort study was used to identify participants who had their first AMI between 2006 and 2014 and were alive after 12 months. Linked routinely collected hospital, and prescription medication claims data was used to study adherence over time. Predictors and rates of adherence to both lipid-lowering medication and renin-angiotensin system blockade at 12 months post-AMI was assessed. Results: 14,200 people (mean age 69.9 years, 38.7% female) were included in our analysis. At 12 months post-AMI, 29.5% (95% CI: 28.8-30.3%) of people were adherent to both classes of medication. Individuals receiving treatment with both lipid-lowering medication and renin-angiotensin system blockade during the 6 months prior to their AMI were over 9 times more likely to be adherent to both medications at 12 months post-AMI (66.2% 95% CI: 64.8-67.5%) compared to those with no prior medication use (treatment naïve) (7.1%, 95% CI: 6.4-7.9%). Prior cardiovascular treatment was the strongest predictor of long-term adherence even after adjusting for age, sex, education and income. Conclusions: Despite efforts to improve long-term medication adherence in patients who have experienced an acute coronary event, considerable gaps remain. Of particular concern are people who are commencing guideline-recommended cardioprotective medication at the time of their AMI. The relationship between prior cardiovascular treatments and post AMI adherence offers insight into the support needs for the patient. Health care intervention strategies, strengthened by enabling policies, are needed to provide support to patients through the initial months following their AMI.

Incidence and Associations of Chronic Kidney Disease in Community Participants With Diabetes: A 5-Year Prospective Analysis of the EXTEND45 Study.

OBJECTIVE: To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in people with diabetes. RESEARCH DESIGN AND METHODS: We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006-2014) that linked the Sax Institute's 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia. The study outcome was the first eGFR measurement <60 mL/min/1.73 m2 recorded during the follow-up period. Participants with eGFR < 60 mL/min/1.73 m2 at baseline were excluded. We used Poisson regression to estimate the incidence of eGFR <60 mL/min/1.73 m2 and multivariable Cox regression to examine factors associated with the study outcome. RESULTS: Of 9,313 participants with diabetes, 2,106 (22.6%) developed incident eGFR <60 mL/min/1.73 m2 over a median follow-up time of 5.7 years (interquartile range, 3.0-5.9 years). The eGFR <60 mL/min/1.73 m2 incidence rate per 100 person-years was 6.0 (95% CI 5.7-6.3) overall, 1.5 (1.3-1.9) in participants aged 45-54 years, 3.7 (3.4-4.0) for 55-64 year olds, 7.6 (7.1-8.1) for 65-74 year olds, 15.0 (13.0-16.0) for 75-84 year olds, and 26.0 (22.0-32.0) for those aged 85 years and over. In a fully adjusted multivariable model incidence was independently associated with age (hazard ratio 1.23 per 5-year increase; 95% CI 1.19-1.26), geography (outer regional and remote versus major city: 1.36; 1.17-1.58), obesity (obese class III versus normal: 1.44; 1.16-1.80), and the presence of hypertension (1.52; 1.33-1.73), coronary heart disease (1.13; 1.02-1.24), cancer (1.30; 1.14-1.50), and depression/anxiety (1.14; 1.01-1.27). CONCLUSIONS: In participants with diabetes, the incidence of an eGFR <60 mL/min/1.73 m2 was high. Older age, remoteness of residence, and the presence of various comorbid conditions were associated with higher incidence.

Prevalence, incidence and risk factors of diabetes in Australian adults aged ≥45 years: A cohort study using linked routinely-collected data.

AIMS: To use linked routinely-collected health data to estimate diabetes prevalence and incidence in an Australian cohort of adults aged ≥45 years, and examine risk factors associated with incident disease. RESEARCH DESIGN AND METHODS: The EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45) Study is a linked data study that combines baseline questionnaire responses from the population-based 45 and Up Study (2006-2009, n = 267,153) with multiple routinely-collected health databases up to December 2014. Among participants with ≥1 linked result for any laboratory test, diabetes status was determined from multiple data sources according to standard biochemical criteria, use of glucose-lowering medication or self-report, and the prevalence and incidence rate calculated. Independent risk factors of incident diabetes were examined using multivariable Cox regression. RESULTS: Among 152,169 45 and Up Study participants with ≥1 linked laboratory result in the EXTEND45 database (mean age 63.0 years; 54.9% female), diabetes prevalence was 10.8% (95% confidence interval [CI] 10.6%-10.9%). Incident disease in those without diabetes at baseline (n = 135,810; mean age 62.5 years; 56.1% female) was 10.0 per 1,000 person-years (95% CI 9.8-10.2). In all age groups, diabetes incidence was lower in women compared to men, an association that persisted in the fully adjusted analyses. Other independent risk factors of diabetes were older age, being born outside of Australia (with the highest rate of 19.2 per 1,000 person-years observed in people born in South and Central Asia), lower education status, lower annual household income, residence in a major city, family history of diabetes, personal history of cardiovascular disease or hypertension, higher body mass index, smoking and long sleeping hours. CONCLUSIONS: Our study represents an efficient approach to assessing diabetes frequency and its risk factors in the community. The infrastructure provided by the EXTEND45 Study will be useful for diabetes surveillance and examining other important clinical and epidemiological questions.

EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (the EXTEND45 Study): Protocol for an Australian Linked Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) and diabetes are the major causes of death and disability worldwide. They are associated with high health service utilization persisting over many years. Their slow progression and wide clinical variation make them eminently suitable for study in population-based cohorts. However, current understanding of their prevalence, incidence, and progression is largely based on studies conducted in clinical populations. OBJECTIVE: This study aims to establish a novel link between an existing population-based cohort (the 45 and Up Study) and routinely collected laboratory and administrative data to facilitate research across the full disease spectrum of CKD and diabetes. METHODS: In the EXTEND45 Study (EXamining OuTcomEs in chroNic Disease in the 45 and Up Study), baseline questionnaire responses of over 260,000 participants of the 45 and Up Study aged ≥45 years living in New South Wales (NSW), collected between January 2006 and December 2009, are linked to data from laboratory service providers as well as national- and state-based administrative datasets via probabilistic linkage. Routinely collected data were obtained for participants who could be linked between January 2005 and July 2013. Laboratory data will enable the identification of early cases of chronic disease and the assessment of clinically relevant biochemical targets during the disease course. Health administrative datasets will allow for the examination of health service use, pharmacological management, and clinical outcomes. RESULTS: The study received ethics approval from the NSW Population and Health Services Research Ethics Committee in February 2014. Data linkage for 267,153 of the 45 and Up Study participants was completed in June 2016, with congruent linkage achieved for 265,086 (99.23%) individuals. To date, the CKD and diabetes cohorts have been identified (published elsewhere), and a diverse portfolio of research projects relating to disease burden, risk factors, health outcomes, and health service utilization is in development. CONCLUSIONS: The EXTEND45 Study represents an unparalleled opportunity to perform extensive research into diseases of considerable public health and clinical importance. Strengths include the population-based nature of the cohort and the availability of longitudinal information on the complete disease pathway for affected individuals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15646.

Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort.

BACKGROUND: There are limited studies on the effects of statins on outcomes in the moderate chronic kidney disease (CKD) population and their trajectory to end-stage kidney disease. OBJECTIVE: To examine the long-term effects of lipid-lowering therapy on all-cause mortality, cardiovascular morbidity, CKD progression, and socioeconomic well-being in Australian, New Zealand, and Malaysian SHARP (Study of Heart and Renal Protection) trial participants-a randomized controlled trial of a combination of simvastatin and ezetimibe, compared with placebo, for the reduction of cardiovascular events in moderate to severe CKD. DESIGN: Protocol for an extended prospective observational follow-up. SETTING: Australian, New Zealand, and Malaysian participating centers in patients with advanced CKD. PATIENTS: All SHARP trial participants alive at the final study visit. MEASUREMENTS: Primary outcomes were measured by participant self-report and verified by hospital administrative data. In addition, secondary outcomes were measured using a validated study questionnaire of health-related quality of life, a 56-item economic survey. METHODS: Participants were followed up with alternating face-to-face visits and telephone calls on a 6-monthly basis until 5 years following their final SHARP Study visit. In addition, there were 6-monthly follow-up telephone calls in between these visits. Data linkage to health registries in Australia, New Zealand, and Malaysia was also performed. RESULTS: The SHARP-Extended Review (SHARP-ER) cohort comprised 1136 SHARP participants with a median of 4.6 years of follow-up. Compared with all SHARP participants who originally participated in the Australian, New Zealand, and Malaysian regions, the SHARP-ER participants were younger (57.2 [48.3-66.4] vs 60.5 [50.3-70.7] years) with a lower proportion of men (61.5% vs 62.8%). There were a lower proportion of participants with hypertension (83.7% vs 85.0%) and diabetes (20.0% vs 23.5%). LIMITATIONS: As a long-term follow-up study, the surviving cohort of SHARP-ER is a selected group of the original study participants, which may limit the generalizability of the findings. CONCLUSION: The SHARP-ER study will contribute important evidence on the long-term outcomes of cholesterol-lowering therapy in patients with advanced CKD with a total of 10 years of follow-up. Novel analyses of the socioeconomic impact of CKD over time will guide resource allocation. TRIAL REGISTRATION: The SHARP trial was registered at ClinicalTrials.gov NCT00125593 and ISRCTN 54137607.

CONTEXTE: On trouve peu d'études faisant état de l'effet des statines sur les issues des patients atteints d'insuffisance rénale chronique (IRC) modérée et sur leur évolution vers l'insuffisance rénale terminale (IRT). OBJECTIF: Observer les effets à long terme d'un traitement hypolipidémiant sur la mortalité toutes causes, la morbidité cardiovasculaire, la progression de l'IRC et le mieux-être socioéconomique des participants australiens, néo-zélandais et malaisiens, à l'essai SHARP; un essai contrôlé à répartition aléatoire qui portait sur l'effet comparatif d'une combinaison de simvastatine et d'ézétimibe, ou d'un placebo, sur la réduction des événements cardiovasculaires en contexte d'IRC modérée à grave. PLAN DE L'ÉTUDE: Il s'agit d'un protocole pour un suivi prospectif et observationnel prolongé. CADRE: Les centres d'Australie, de Nouvelle-Zélande et de Malaisie traitant des patients atteints d'IRC de stade avancé et participant à l'essai SHARP. SUJETS: Tous les participants à l'essai SHARP encore vivants lors de la dernière visite de l'étude. MESURES: Les principaux résultats ont été mesurés par autodéclaration des participants et vérifiés auprès des données administratives de l'hôpital. Les résultats secondaires ont été mesurés à l'aide d'un questionnaire validé évaluant la qualité de vie liée à l'état de santé, une enquête économique de 56 questions. MÉTHODOLOGIE: Les participants ont été suivis tous les six mois en alternant les visites en clinique et les entretiens téléphoniques, jusqu'à cinq ans après la dernière visite prévue lors de l'essai SHARP. On a procédé au couplage des données avec les registres de santé d'Australie, de Nouvelle-Zélande et de Malaisie. RÉSULTATS: La cohorte SHARP-ER était constituée de 1 136 participants à l'essai SHARP et la durée de suivi médiane était de 4,6 ans. En comparaison de l'ensemble des patients ayant participé à l'essai SHARP en Australie, en Nouvelle-Zélande et en Malaisie, la cohorte SHARP-ER était plus jeune (57,2 [48,3-66,4] contre 60,5 [50,3-70,7] ans), comptait moins d'hommes (61,5 % contre 62,8 %) et présentait une plus faible proportion de patients hypertendus (83,7 % contre 85,0 %) ou diabétiques (20,0 % contre 23,5 %). LIMITES: Puisqu'il s'agit d'une étude de suivi à plus long terme, la cohorte de survivants (SHARP-ER) constitue un groupe choisi à partir de l'ensemble des participants à l'essai initial, ce qui pourrait limiter la généralisabilité des résultats. CONCLUSION: L'étude SHARP-ER, avec un suivi total sur dix ans, apportera des informations importantes sur les effets à long terme d'un traitement hypolipidémiant chez les patients atteints d'IRC de stade avancé. De nouvelles analyses des impacts socioéconomiques de l'IRC au fil du temps éclaireront l'affectation des ressources.

Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis.

OBJECTIVE:  To summarise the benefits and harms of ischaemic conditioning on major clinical outcomes in various settings. DESIGN:  Systematic review and meta-analysis. DATA SOURCES:  Medline, Embase, Cochrane databases, and International Clinical Trials Registry platform from inception through October 2015. STUDY SELECTION:  All randomised controlled comparisons of the effect of ischaemic conditioning on clinical outcomes were included. DATA EXTRACTION:  Two authors independently extracted data from individual reports. Reports of multiple intervention arms were treated as separate trials. Random effects models were used to calculate summary estimates for all cause mortality and other pre-specified clinical outcomes. All cause mortality and secondary outcomes with P<0.1 were examined for study quality by using the GRADE assessment tool, the effect of pre-specified characteristics by using meta-regression and Cochran C test, and trial sequential analysis by using the Copenhagen Trial Unit method. RESULTS:  85 reports of 89 randomised comparisons were identified, with a median 80 (interquartile range 60-149) participants and median 1 (range 1 day-72 months) month intended duration. Ischaemic conditioning had no effect on all cause mortality (68 comparisons; 424 events; 11 619 participants; risk ratio 0.96, 95% confidence interval 0.80 to 1.16; P=0.68; moderate quality evidence) regardless of the clinical setting in which it was used or the particular intervention related characteristics. Ischaemic conditioning may reduce the rates of some secondary outcomes including stroke (18 trials; 5995 participants; 149 events; risk ratio 0.72, 0.52 to 1.00; P=0.048; very low quality evidence) and acute kidney injury (36 trials; 8493 participants; 1443 events; risk ratio 0.83, 0.71 to 0.97; P=0.02; low quality evidence), although the benefits seem to be confined to non-surgical settings and to mild episodes of acute kidney injury only. CONCLUSIONS:  Ischaemic conditioning has no overall effect on the risk of death. Possible effects on stroke and acute kidney injury are uncertain given methodological concerns and low event rates. Adoption of ischaemic conditioning cannot be recommended for routine use unless further high quality and well powered evidence shows benefit.