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GFR at initiation of dialysis and mortality in CKD: a meta-analysis.

ABSTRACT: The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality.A meta-analysis of cohort studies and trials.Patients with advanced CKD.We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis therapy initiation and mortality.Estimated or calculated GFR at dialysis therapy initiation.Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.16 cohort studies and 1 randomized controlled trial were identified (n = 1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR at dialysis therapy initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was significant heterogeneity (I(2) = 97%; P < 0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001; residual I(2) = 97%). The highest mortality risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P < 0.001), whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I(2) = 98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05; P < 0.001; residual I(2) = 97%).Paucity of randomized controlled trials, different methods for determining GFR, and substantial heterogeneity.Higher estimated rather than calculated GFR at dialysis therapy initiation is associated with a higher mortality risk in patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.

SUBMITTER: Susantitaphong P

PROVIDER: S-EPMC3395227 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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GFR at initiation of dialysis and mortality in CKD: a meta-analysis.

Susantitaphong Paweena P Altamimi Sarah S Ashkar Motaz M Balk Ethan M EM Stel Vianda S VS Wright Seth S Jaber Bertrand L BL

American journal of kidney diseases : the official journal of the National Kidney Foundation 20120401 6

<h4>Background</h4>The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality.<h4>Study design</h4>A meta-analysis of cohort studies and trials.<h4>Setting & population</h4>Patients with advanced CKD.<h4>Selection criteria for studies</h4>We performed a systematic literature search in MEDLINE, Coch ...[more]

PMID: 22465328

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Project description:Rationale & objectivesDue to unmeasured confounding, observational studies have limitations when assessing whether dialysis initiation reduces mortality compared with conservative therapy among adults with advanced chronic kidney disease (CKD). We addressed this issue in this meta-analysis.Study designMeta-analysis with bias analysis for unmeasured confounding.Setting & study populationAdults with stage 4 or 5 CKD who had initiated dialysis or conservative treatment.Selection criteria for studiesProspective or retrospective cohort studies comparing survival of dialysis versus conservatively managed patients were searched on MEDLINE and Embase from January 2009 to March 20, 2019.Data extractionHRs of all-cause mortality associated with dialysis initiation compared with conservative treatment.Analytical approachWe pooled HRs using a random-effects model. We estimated the percentage of effect sizes more protective than HRs of 0.80 and severity of unmeasured confounding that could reduce this percentage to only 10%. Subgroup analysis was performed for studies with only older patients (aged ≥ 65 years).Results12 studies were included that involved 16,609 dialysis patients and 3,691 conservatively managed patients. A random-effects model suggested that dialysis initiation was associated with a mean mortality HR of 0.47 (95% CI, 0.34-0.64), in which 92% (95% CI, 50%-100%) of the true effects were more protective than HRs of 0.80. To reduce the percentage of HRs < 0.80 to 10%, unmeasured confounder(s) would need to be associated with both dialysis initiation and mortality by relative risks of 4.05 (95% CI, 2.39-4.15), which is equivalent to shifting each study's estimated HR by 2.31-fold (95% CI, 1.51-2.36). Restricting studies to include only older patients did not modify the results.LimitationsLimited number of studies and evidence on the absence of publication bias.ConclusionsOur findings suggest that dialysis initiation considerably reduces mortality among adults with advanced CKD. Future bias-adjusted meta-analyses need to assess outcomes beyond mortality.

Project description:Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias.Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2)).Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart.Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation?10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying.Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009.The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11).Interpolated eGFR, moderate sample size, and likely unmeasured confounders.In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.

Project description:Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown.Observational study.17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years.Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ?160mmHg in 10-mmHg increments) and 5 (<60 to ?90mmHg in 10-mmHg increments) categories, respectively, and as continuous measures.Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ?12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access.Mean predialysis SBP and DBP were 141.2±16.1 (SD) and 73.7±10.6mmHg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP<140mmHg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ?160 (vs 140-<150) mmHg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality.Results cannot be inferred to show causality and may not be generalizable to women or the general US population.Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.

Project description:BACKGROUND:Several reviews have recently detailed the beneficial effects of weight loss surgery for kidney function. However, these studies have a number of limitations, including small sample size, few done in chronic kidney disease (CKD) stages 3 and 4, and many not including the main bariatric surgery procedures used in the United States today. STUDY DESIGN:This was an observational retrospective cohort study comparing propensity score-matched bariatric surgery patients and nonsurgery control patients who were referred for, but did not have, surgery. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy were also compared using propensity matching. SETTING & PARTICIPANTS:Patients (714 surgery patients; 714 controls) were from a large integrated health care system, a mean of 58±8 (SD) years old, and mostly women (77%) and non-Hispanic whites (56%) and had diabetes mellitus (66%) and/or hypertension (91%). PREDICTOR:Predictors at the time of surgery or referral to surgery were age, sex, race/ethnicity, weight, and presence of diabetes and/or hypertension. OUTCOMES:The primary outcome for this study was change in estimated glomerular filtration rate (eGFR) from serum creatinine level over a median 3-year follow-up period. MEASUREMENTS:Serum creatinine was used to calculate eGFR using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. RESULTS:Surgery patients had 9.84 (95% CI, 8.05-11.62) mL/min/1.73m2 greater eGFRs than controls at a median 3 years' follow-up and RYGB patients had 6.60 (95% CI, 3.42-9.78) mL/min/1.73m2 greater eGFRs than sleeve gastrectomy patients during the same period. LIMITATIONS:This study is limited by its nonrandomized observational study design, estimation of GFR, and large changes in muscle mass, which may affect serum creatinine level independent of changes in kidney function. CONCLUSIONS:Bariatric surgery, especially the RYGB procedure, results in significant improvements for up to 3 years in eGFRs for patients with CKD stages 3 and 4.

Project description:Rationale & objectiveDetermining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease.Study designCross-sectional study with multiple collections over less than 4 weeks.Setting & participantsClinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g).ExposureRepeat measurements from serially collected samples across 3 study visits.OutcomesMeasurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β2-microglobulin (B2M), and beta trace protein (BTP).Analytical approachWe calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.ResultsMedian CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values.LimitationsSmall sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.ConclusionseGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.

Dataset Information

GFR at initiation of dialysis and mortality in CKD: a meta-analysis.

Publications

GFR at initiation of dialysis and mortality in CKD: a meta-analysis.

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