David Naimark - Academia.edu (original) (raw)

Papers by David Naimark

Journal of the American Society of Nephrology, 2021

BackgroundThe Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clini... more BackgroundThe Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clinically measurable benefit with respect to risk of mortality or early complications with early dialysis initiation versus deferred dialysis start. After these findings, guidelines recommended an intent-to-defer approach to dialysis initiation, with the goal of deferring it until clinical symptoms arise.MethodsTo evaluate a four-component knowledge translation intervention aimed at promoting an intent-to-defer strategy for dialysis initiation, we conducted a cluster randomized trial in Canada between October 2014 and November 2015. We randomized 55 clinics, 27 to the intervention group and 28 to the control group. The educational intervention, using knowledge-translation tools, included telephone surveys from a knowledge-translation broker, a 1-year center-specific audit with feedback, delivery of a guidelines package, and an academic detailing visit. Participants included adults who had at...

Canadian Journal of Kidney Health and Disease, 2016

Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney f... more Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. Objective: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. Design: This study is a multicenter, 2-arm parallel, cluster randomized trial. Setting: The study involves 55 advanced chronic kidney disease clinics across Canada. Patients: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Measurements: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristic...

JAMA, 2011

Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by esti... more Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by estimated glomerular filtration rate (GFR) and albuminuria, but more accurate information regarding risk for progression to kidney failure is required for clinical decisions about testing, treatment, and referral. Objective To develop and validate predictive models for progression of CKD. Design, Setting, and Participants Development and validation of prediction models using demographic, clinical, and laboratory data from 2 independent Canadian cohorts of patients with CKD stages 3 to 5 (estimated GFR, 10-59 mL/min/1.73 m 2) who were referred to nephrologists between April 1, 2001, and December 31, 2008. Models were developed using Cox proportional hazards regression methods and evaluated using C statistics and integrated discrimination improvement for discrimination, calibration plots and Akaike Information Criterion for goodness of fit, and net reclassification improvement (NRI) at 1, 3, and 5 years. Main Outcome Measure Kidney failure, defined as need for dialysis or preemptive kidney transplantation. Results The development and validation cohorts included 3449 patients (386 with kidney failure [11%]) and 4942 patients (1177 with kidney failure [24%]), respectively. The most accurate model included age, sex, estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin (C statistic, 0.917; 95% confidence interval [CI], 0.901-0.933 in the development cohort and 0.841; 95% CI, 0.825-0.857 in the validation cohort). In the validation cohort, this model was more accurate than a simpler model that included age, sex, estimated GFR, and albuminuria (integrated discrimination improvement, 3.2%; 95% CI, 2.4%-4.2%; calibration [Nam and D'Agostino 2 statistic, 19 vs 32]; and reclassification for CKD stage 3 [NRI, 8.0%; 95% CI, 2.1%-13.9%] and for CKD stage 4 [NRI, 4.1%; 95% CI, −0.5% to 8.8%]). Conclusion A model using routinely obtained laboratory tests can accurately predict progression to kidney failure in patients with CKD stages 3 to 5.

Kidney International, 2018

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2015

Economic evaluations provide a unique opportunity to identify the optimal strategies for the diag... more Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-c...

American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 2, 2015

Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the ris... more Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Collaborative meta-analysis. 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants). Available eGFR, ACR, and 50 or more AKI events. Age, sex, race, eGFR, urine ACR, and interactions. Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.0...

Nephron Clinical Practice, 2011

Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of... more Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of patients with end-stage renal disease. PD technique failure has been cited as one of the reasons for this decline. The purpose of this study was to compare the factors that predict technique survival using artificial neural network (ANN) and logistic and Cox regression methods. We used high-quality, prospectively collected data from the United Kingdom Renal Registry and created both ANN and regression models to predict technique survival. Incident PD patients in the UK from 1999 to 2004 were included in the analysis. Technique failure was defined as a change in modality to hemodialysis for a period >30 days. Removal of dialysis center code had a significant effect on the fit and/or predictive performance of all three types of models. In contrast, the effect of demographic data, comorbidity, physical examination and laboratory data varied according to the type of model. PD center significantly impacts PD technique survival. Other putative predictive factors had marginal and/or variable effects. The presence of comorbid conditions and a high body mass index is not consistently associated with increased PD technique failure.

Nephrology Dialysis Transplantation, 2008

Background. Early technique failure has been a major limitation on the wider adoption of peritone... more Background. Early technique failure has been a major limitation on the wider adoption of peritoneal dialysis (PD). The objectives of this study were to use data from a large, multicentre, prospective database, the United Kingdom Renal Registry (UKRR), in order to determine the ability of an artificial neural network (ANN) model to predict early PD technique failure and to compare its performance with a logistic regression (LR)-based approach. Methods. The analysis included all incident PD patients enrolled in the UKRR from 1999 to 2004. The event of interest was technique failure. For both the ANN and LR analyses a bootstrap approach was used: the data were divided into 20 random training (75%) and validation (25%) sets. Models were derived on the latter and then used to make predictions on the former. Predictive accuracy was assessed by area under the ROC curve (AUROC). The 20 AUROC values and their standard errors were then averaged. Results. There were 3269 patients included in the analysis with a mean age of 59.9 years and a mean observation time of 430 days. Of the patients, 38.3% were female and 90.8% were Caucasian. 1458 patients (44.6%) suffered technique failure. The AUROC for the ANN model was 0.760 ± 0.0167 and the LR model was 0.709 and 0.0208. (P = 0.0164) Conclusions. Using UKRR data, both ANN and LR models predicted early PD technique failure with moderate accuracy. In this study, an ANN outperformed an LR-based approach. As the scope and the completeness of the UKRR increases, the question of whether more sophisticated ANN models will perform even better remains for further study.

Nephrology Dialysis Transplantation, 2006

Background. Dialysis centre effect has been suggested to influence survival in end-stage renal di... more Background. Dialysis centre effect has been suggested to influence survival in end-stage renal disease (ESRD) patients. Few studies over the past decade have commented on the existence of the centre effect using logistic regression models. Methods. We used high quality prospectively collected data from the UK Renal Registry (UKRR) and created an artificial neural network model to predict mortality within 1 year in this cohort. We used a multitude of demographic variables including co-morbodities as well as relevant laboratory data to create a prognostic model. Results. A highly efficient model for predicting 1 year mortality was created after restricting the model to use demographic and case-enriched data [area under the receiver operating characteristic curve (AUROC) ¼ 0.974]. The addition of the dialysis centre code and centre size as input variables did not add to the efficiency of the model (AUROC ¼ 0.962). Moreover, dialysis centre code or size alone was not predictive of mortality when applied to an artificial neuronal network architecture (AUROC ¼ 0.649 and 0.628). Conclusion. Residual effects in previous studies may have been due to the non-linear nature of the data and complex intervariable relationships. Centre size and other centre-related factors have no impact on survival on ESRD.

Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by esti... more Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by estimated glomerular filtration rate (GFR) and albuminuria, but more accurate information regarding risk for progression to kidney failure is required for clinical decisions about testing, treatment, and referral.

JAMA, 2012

Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low ... more Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

American Journal of Kidney Diseases, 2011

Journal of the American Society of Nephrology : JASN, Jan 11, 2015

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past... more eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 m...

Peritoneal Dialysis International, 2001

complications and have strikingly higher mortality rates than non-Tx patients. A previously faile... more complications and have strikingly higher mortality rates than non-Tx patients. A previously failed kidney transplant can be considered an adverse prognostic factor for patients commencing PD; these patients need to be closely monitored. Although this study was limited to PD patients, the same principles likely apply to fTx patients returning to any form of renal replacement therapy.

Journal of the American Society of Nephrology : JASN, Jan 11, 2015

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR i... more A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follo...

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 20, 2015

Chronic kidney disease (CKD) Stage 4 is on the path to kidney failure, but there is little inform... more Chronic kidney disease (CKD) Stage 4 is on the path to kidney failure, but there is little information on the risks associated with progression to Stage 4 per se. The objective of this study is to determine how progression from Stage 3 to Stage 4 CKD alters morbidity and mortality in a referred cohort of patients. We conducted a retrospective cohort study consisting of 1607 patients with estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m(2) referred to a nephrologist at a tertiary care center in Ontario, Canada, between January 2001 and December 2008. Interim progression from Stage 3 to Stage 4 chronic kidney disease was defined by two independent outpatient eGFR values <30 mL/min/1.73 m(2). Death, acute kidney injury (AKI) and all-cause hospitalizations subsequent to Stage 4 progression, but prior to the development of end-stage renal disease (ESRD), ascertained from administrative databases. The mean (standard deviation) baseline eGFR was 43 (8) mL/min/1.73 m(2)...

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2015

Economic evaluations provide a unique opportunity to identify the optimal strategies for the diag... more Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-c...

Circulation, Jan 5, 2014

Patients with chronic kidney disease stages 3 to 5 (glomerular filtration rate <60 mL/min/1.73... more Patients with chronic kidney disease stages 3 to 5 (glomerular filtration rate <60 mL/min/1.73m(2)) are at increased risk of cardiovascular (CV) disease when compared with patients with less severe chronic kidney disease. How CV events modify the subsequent risk of progression to end-stage-renal disease (ESRD) or all-cause mortality (ACM) before ESRD is not well known. This retrospective cohort study involved 2964 chronic kidney disease subjects referred between January 2001 and December 2008 to the nephrology clinic at Sunnybrook Health Sciences Center, Toronto, Ontario. Interim CV events (heart failure, myocardial infarction, and stroke), ESRD, and ACM were ascertained from administrative data. Over a median follow-up time of 2.76 years (interquartile range, 1.45-4.62), 447 (15%) subjects had a CV event. In the same time period, 318 (11%) developed ESRD, and 446 (15%) experienced ACM before ESRD (156 [5%] from a CV and 290 [10%] from a non-CV-related cause). When analyzed as a ...

Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2014

The relative influence of facilities and regions on the timing of dialysis initiation remains unk... more The relative influence of facilities and regions on the timing of dialysis initiation remains unknown. The purpose of the study is to determine the variation in eGFR at dialysis initiation across dialysis facilities and geographic regions in Canada after accounting for patient-level factors (case mix). In total, 33,263 dialysis patients with an eGFR measure at dialysis initiation between January of 2001 and December of 2010 representing 63 dialysis facilities and 14 geographic regions were included in the study. Multilevel models and intraclass correlation coefficients were used to evaluate the variation in timing of dialysis initiation by eGFR at the patient, facility, and geographic levels. The proportion initiating dialysis with an eGFR≥10.5 ml/min per 1.73 m(2) was 35.3%, varying from 20.1% to 57.2% across geographic regions and from 10% to 67% across facilities. In an unadjusted, intercept-only linear model, 90.7%, 6.6%, and 2.7% of the explained variability were attributable t...

Journal of the American Society of Nephrology, 2021

BackgroundThe Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clini... more BackgroundThe Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clinically measurable benefit with respect to risk of mortality or early complications with early dialysis initiation versus deferred dialysis start. After these findings, guidelines recommended an intent-to-defer approach to dialysis initiation, with the goal of deferring it until clinical symptoms arise.MethodsTo evaluate a four-component knowledge translation intervention aimed at promoting an intent-to-defer strategy for dialysis initiation, we conducted a cluster randomized trial in Canada between October 2014 and November 2015. We randomized 55 clinics, 27 to the intervention group and 28 to the control group. The educational intervention, using knowledge-translation tools, included telephone surveys from a knowledge-translation broker, a 1-year center-specific audit with feedback, delivery of a guidelines package, and an academic detailing visit. Participants included adults who had at...

Canadian Journal of Kidney Health and Disease, 2016

Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney f... more Background: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. Objective: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. Design: This study is a multicenter, 2-arm parallel, cluster randomized trial. Setting: The study involves 55 advanced chronic kidney disease clinics across Canada. Patients: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. Measurements: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristic...

JAMA, 2011

Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by esti... more Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by estimated glomerular filtration rate (GFR) and albuminuria, but more accurate information regarding risk for progression to kidney failure is required for clinical decisions about testing, treatment, and referral. Objective To develop and validate predictive models for progression of CKD. Design, Setting, and Participants Development and validation of prediction models using demographic, clinical, and laboratory data from 2 independent Canadian cohorts of patients with CKD stages 3 to 5 (estimated GFR, 10-59 mL/min/1.73 m 2) who were referred to nephrologists between April 1, 2001, and December 31, 2008. Models were developed using Cox proportional hazards regression methods and evaluated using C statistics and integrated discrimination improvement for discrimination, calibration plots and Akaike Information Criterion for goodness of fit, and net reclassification improvement (NRI) at 1, 3, and 5 years. Main Outcome Measure Kidney failure, defined as need for dialysis or preemptive kidney transplantation. Results The development and validation cohorts included 3449 patients (386 with kidney failure [11%]) and 4942 patients (1177 with kidney failure [24%]), respectively. The most accurate model included age, sex, estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin (C statistic, 0.917; 95% confidence interval [CI], 0.901-0.933 in the development cohort and 0.841; 95% CI, 0.825-0.857 in the validation cohort). In the validation cohort, this model was more accurate than a simpler model that included age, sex, estimated GFR, and albuminuria (integrated discrimination improvement, 3.2%; 95% CI, 2.4%-4.2%; calibration [Nam and D'Agostino 2 statistic, 19 vs 32]; and reclassification for CKD stage 3 [NRI, 8.0%; 95% CI, 2.1%-13.9%] and for CKD stage 4 [NRI, 4.1%; 95% CI, −0.5% to 8.8%]). Conclusion A model using routinely obtained laboratory tests can accurately predict progression to kidney failure in patients with CKD stages 3 to 5.

Kidney International, 2018

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2015

Economic evaluations provide a unique opportunity to identify the optimal strategies for the diag... more Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-c...

American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 2, 2015

Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the ris... more Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Collaborative meta-analysis. 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants). Available eGFR, ACR, and 50 or more AKI events. Age, sex, race, eGFR, urine ACR, and interactions. Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.0...

Nephron Clinical Practice, 2011

Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of... more Peritoneal dialysis (PD) rates continue to decline worldwide in spite of the increasing number of patients with end-stage renal disease. PD technique failure has been cited as one of the reasons for this decline. The purpose of this study was to compare the factors that predict technique survival using artificial neural network (ANN) and logistic and Cox regression methods. We used high-quality, prospectively collected data from the United Kingdom Renal Registry and created both ANN and regression models to predict technique survival. Incident PD patients in the UK from 1999 to 2004 were included in the analysis. Technique failure was defined as a change in modality to hemodialysis for a period &amp;amp;amp;amp;amp;amp;gt;30 days. Removal of dialysis center code had a significant effect on the fit and/or predictive performance of all three types of models. In contrast, the effect of demographic data, comorbidity, physical examination and laboratory data varied according to the type of model. PD center significantly impacts PD technique survival. Other putative predictive factors had marginal and/or variable effects. The presence of comorbid conditions and a high body mass index is not consistently associated with increased PD technique failure.

Nephrology Dialysis Transplantation, 2008

Background. Early technique failure has been a major limitation on the wider adoption of peritone... more Background. Early technique failure has been a major limitation on the wider adoption of peritoneal dialysis (PD). The objectives of this study were to use data from a large, multicentre, prospective database, the United Kingdom Renal Registry (UKRR), in order to determine the ability of an artificial neural network (ANN) model to predict early PD technique failure and to compare its performance with a logistic regression (LR)-based approach. Methods. The analysis included all incident PD patients enrolled in the UKRR from 1999 to 2004. The event of interest was technique failure. For both the ANN and LR analyses a bootstrap approach was used: the data were divided into 20 random training (75%) and validation (25%) sets. Models were derived on the latter and then used to make predictions on the former. Predictive accuracy was assessed by area under the ROC curve (AUROC). The 20 AUROC values and their standard errors were then averaged. Results. There were 3269 patients included in the analysis with a mean age of 59.9 years and a mean observation time of 430 days. Of the patients, 38.3% were female and 90.8% were Caucasian. 1458 patients (44.6%) suffered technique failure. The AUROC for the ANN model was 0.760 ± 0.0167 and the LR model was 0.709 and 0.0208. (P = 0.0164) Conclusions. Using UKRR data, both ANN and LR models predicted early PD technique failure with moderate accuracy. In this study, an ANN outperformed an LR-based approach. As the scope and the completeness of the UKRR increases, the question of whether more sophisticated ANN models will perform even better remains for further study.

Nephrology Dialysis Transplantation, 2006

Background. Dialysis centre effect has been suggested to influence survival in end-stage renal di... more Background. Dialysis centre effect has been suggested to influence survival in end-stage renal disease (ESRD) patients. Few studies over the past decade have commented on the existence of the centre effect using logistic regression models. Methods. We used high quality prospectively collected data from the UK Renal Registry (UKRR) and created an artificial neural network model to predict mortality within 1 year in this cohort. We used a multitude of demographic variables including co-morbodities as well as relevant laboratory data to create a prognostic model. Results. A highly efficient model for predicting 1 year mortality was created after restricting the model to use demographic and case-enriched data [area under the receiver operating characteristic curve (AUROC) ¼ 0.974]. The addition of the dialysis centre code and centre size as input variables did not add to the efficiency of the model (AUROC ¼ 0.962). Moreover, dialysis centre code or size alone was not predictive of mortality when applied to an artificial neuronal network architecture (AUROC ¼ 0.649 and 0.628). Conclusion. Residual effects in previous studies may have been due to the non-linear nature of the data and complex intervariable relationships. Centre size and other centre-related factors have no impact on survival on ESRD.

Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by esti... more Context Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by estimated glomerular filtration rate (GFR) and albuminuria, but more accurate information regarding risk for progression to kidney failure is required for clinical decisions about testing, treatment, and referral.

JAMA, 2012

Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low ... more Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

American Journal of Kidney Diseases, 2011

Journal of the American Society of Nephrology : JASN, Jan 11, 2015

eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past... more eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 m...

Peritoneal Dialysis International, 2001

complications and have strikingly higher mortality rates than non-Tx patients. A previously faile... more complications and have strikingly higher mortality rates than non-Tx patients. A previously failed kidney transplant can be considered an adverse prognostic factor for patients commencing PD; these patients need to be closely monitored. Although this study was limited to PD patients, the same principles likely apply to fTx patients returning to any form of renal replacement therapy.

Journal of the American Society of Nephrology : JASN, Jan 11, 2015

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR i... more A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follo...

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Jan 20, 2015

Chronic kidney disease (CKD) Stage 4 is on the path to kidney failure, but there is little inform... more Chronic kidney disease (CKD) Stage 4 is on the path to kidney failure, but there is little information on the risks associated with progression to Stage 4 per se. The objective of this study is to determine how progression from Stage 3 to Stage 4 CKD alters morbidity and mortality in a referred cohort of patients. We conducted a retrospective cohort study consisting of 1607 patients with estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m(2) referred to a nephrologist at a tertiary care center in Ontario, Canada, between January 2001 and December 2008. Interim progression from Stage 3 to Stage 4 chronic kidney disease was defined by two independent outpatient eGFR values <30 mL/min/1.73 m(2). Death, acute kidney injury (AKI) and all-cause hospitalizations subsequent to Stage 4 progression, but prior to the development of end-stage renal disease (ESRD), ascertained from administrative databases. The mean (standard deviation) baseline eGFR was 43 (8) mL/min/1.73 m(2)...

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research, 2015

Economic evaluations provide a unique opportunity to identify the optimal strategies for the diag... more Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-c...

Circulation, Jan 5, 2014

Patients with chronic kidney disease stages 3 to 5 (glomerular filtration rate <60 mL/min/1.73... more Patients with chronic kidney disease stages 3 to 5 (glomerular filtration rate <60 mL/min/1.73m(2)) are at increased risk of cardiovascular (CV) disease when compared with patients with less severe chronic kidney disease. How CV events modify the subsequent risk of progression to end-stage-renal disease (ESRD) or all-cause mortality (ACM) before ESRD is not well known. This retrospective cohort study involved 2964 chronic kidney disease subjects referred between January 2001 and December 2008 to the nephrology clinic at Sunnybrook Health Sciences Center, Toronto, Ontario. Interim CV events (heart failure, myocardial infarction, and stroke), ESRD, and ACM were ascertained from administrative data. Over a median follow-up time of 2.76 years (interquartile range, 1.45-4.62), 447 (15%) subjects had a CV event. In the same time period, 318 (11%) developed ESRD, and 446 (15%) experienced ACM before ESRD (156 [5%] from a CV and 290 [10%] from a non-CV-related cause). When analyzed as a ...

Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2014

The relative influence of facilities and regions on the timing of dialysis initiation remains unk... more The relative influence of facilities and regions on the timing of dialysis initiation remains unknown. The purpose of the study is to determine the variation in eGFR at dialysis initiation across dialysis facilities and geographic regions in Canada after accounting for patient-level factors (case mix). In total, 33,263 dialysis patients with an eGFR measure at dialysis initiation between January of 2001 and December of 2010 representing 63 dialysis facilities and 14 geographic regions were included in the study. Multilevel models and intraclass correlation coefficients were used to evaluate the variation in timing of dialysis initiation by eGFR at the patient, facility, and geographic levels. The proportion initiating dialysis with an eGFR≥10.5 ml/min per 1.73 m(2) was 35.3%, varying from 20.1% to 57.2% across geographic regions and from 10% to 67% across facilities. In an unadjusted, intercept-only linear model, 90.7%, 6.6%, and 2.7% of the explained variability were attributable t...