Background Red cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown ...that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients. Study Design Retrospective observational study using a large HD patient cohort. Setting & Participants 109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31, 2011. Predictor Baseline and time-varying RDW, grouped into 5 categories: <14.5%, 14.5% to <15.5%, 15.5% to <16.5%, 16.5% to <17.5%, and ≥17.5%. RDW of 15.5% to <16.5% was used as the reference category. Outcome All-cause mortality. Results Mean age of study participants was 63 ± 15 (SD) years and the study cohort was 44% women. In baseline and time-varying analyses, there was a graded association between higher RDW and incrementally higher mortality risk. Receiver operating characteristic, net reclassification analysis, and integrated discrimination improvement analyses demonstrated that RDW is a stronger predictor of mortality as compared with traditional markers of anemia, such as hemoglobin, ferritin, and iron saturation values. Limitations Lack of comprehensive data that may be associated with both RDW and HD patient outcomes, such as blood transfusion data, socioeconomic status, and other unknown confounders; therefore, the possibility of residual confounding could not be excluded. Also, lack of information for cause of death; thus, cardiovascular mortality outcomes could not be examined. Conclusions In HD patients, higher RDW is associated with incrementally higher mortality risk. RDW is also a stronger predictor of mortality than traditional laboratory markers of anemia. Further studies are needed to determine the mechanisms underlying the association between RDW and mortality.
The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no ...benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure.
Retrospective cohort study.
9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016).
eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m2).
Time to all-cause death.
Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level.
Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m2, eGFRs <5 and ≥12mL/min/1.73m2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (Pinteraction = 0.002).
Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation.
Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years.
There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) ...variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients.
Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011).
Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 interquartile range, 0.07-0.23 g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (
<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (
<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk.
Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.
Abstract
Background
Arteriovenous fistulas (AVFs) are the preferred vascular access type in most hemodialysis patients. However, the optimal vascular access type in octogenarians and older (≥80 ...years) hemodialysis patients remains widely debated given their limited life expectancy and lower AVF maturation rates.
Methods
Among incident hemodialysis patients receiving care in a large national dialysis organization during 2007–2011, we examined patterns of vascular access type conversion in 1 year following dialysis initiation in patients <80 versus ≥80 years of age. Among a subcohort of patients ≥80 years of age, we examined the association between vascular access type conversion and mortality using multivariable survival models.
Results
In the overall cohort of 100 804 patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular access type increased during the first year of hemodialysis, but plateaued thereafter. Among 8356 patients ≥80 years of age and treated for >1 year, those with initial AVF/AVG use and placement of AVF from a central venous catheter (CVC) had lower mortality compared with patients with persistent CVC use. When the reference group was changed to patients who had AVF placement from a CVC in the first year of dialysis, those with initial AVF use had similar mortality. A longer duration of CVC use was associated with incrementally worse survival.
Conclusions
Among incident hemodialysis patients ≥80 years of age, placement of an AVF from a CVC within the first year of dialysis had similar mortality compared with initial AVF use. Our data suggest that initial CVC use with later placement of an AVF may be an acceptable option among elderly hemodialysis patients.
Background 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. Study Design Observational study. Setting & Participants 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. Predictor Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160 mm Hg in 10−mm Hg increments) and 5 (<60 to ≥90 mm Hg in 10−mm Hg increments) categories, respectively, and as continuous measures. Outcomes & Measurements 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. Results Mean predialysis SBP and DBP were 141.2 ± 16.1 (SD) and 73.7 ± 10.6 mm Hg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP < 140 mm Hg. 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) mm Hg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. Limitations Results cannot be inferred to show causality and may not be generalizable to women or the general US population. Conclusions 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.
In patients with advanced (estimated glomerular filtration rate <25 mL/min/1.73 m2) non-dialysis-dependent chronic kidney disease (CKD) the optimal transition of care to renal replacement therapy ...(RRT), i.e. dialysis or transplantation, is not known. Mortality and hospitalization risk are extremely high upon transition and in the first months following the transition to dialysis. Major knowledge gaps persist pertaining to differential or individualized transitions across different demographics and clinical measures during the 'prelude' period prior to the transition, particularly in several key areas: (i) the best timing for RRT transition; (ii) the optimal RRT type (dialysis versus transplant), and in the case of dialysis, the best modality (hemodialysis versus peritoneal dialysis), format (in-center versus home), frequency (infrequent versus thrice-weekly versus more frequent) and vascular access preparation; (iii) the post-RRT impact of pre-RRT prelude conditions and events such as blood pressure and glycemic control, acute kidney injury episodes, and management of CKD-specific conditions such as anemia and mineral disorders; and (iv) the impact of the above prelude conditions on end-of-life care and RRT decision-making versus conservative management of CKD. Given the enormous changes occurring in the global CKD healthcare landscape, as well as the high costs of transitioning to dialysis therapy with persistently poor outcomes, there is an urgent need to answer these important questions. This review describes the key concepts and questions related to the emerging field of 'Transition of Care in CKD', systematically defines six main categories of CKD transition, and reviews approaches to data linkage and novel prelude analyses along with clinical applications of these studies.
Background In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with ...higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. Study Design We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. Setting & Participants 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. Predictor Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4 mg/dL). Outcome All-cause mortality. Results 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0 mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4 mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0 mg/dL were 1.39 (95% CI, 1.23-1.58; P < 0.001) and 1.20 (95% CI, 1.06-1.36; P = 0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5 g/dL) and magnesium level < 2.0 mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P = 0.004), whereas patients with high serum albumin levels (≥3.5 g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 P ≤ 0.001 for magnesium < 2.0 and ≥2.0 mg/dL, respectively; reference: albumin < 3.5 g/dL and magnesium ≥ 2.0 mg/dL). Limitations Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. Conclusions Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously suggested as oncologic prognostication markers. These are associated with malnutrition and ...inflammation, and hence, may provide benefit in predicting mortality among hemodialysis patients.
Among 108,548 incident hemodialysis patients in a large U.S. dialysis organization (2007-2011), we compared the mortality predictability of NLR and PLR with baseline and time-varying covariate Cox models using the receiver operating characteristic curve (AUROC), net reclassification index (NRI), and adjusted R2.
During the median follow-up period of 1.4 years, 28,618 patients died. Median (IQR) NLR and PLR at baseline were 3.64 (2.68-5.00) and 179 (136-248) respectively. NLR was associated with higher mortality, which appeared stronger in the time-varying versus baseline model. PLR exhibited a J-shaped association with mortality in both models. NLR provided better mortality prediction in addition to demographics, comorbidities, and serum albumin; ΔAUROC and NRI for 1-year mortality (95% CI) were 0.010 (0.009-0.012) and 6.4% (5.5-7.3%) respectively. Additionally, adjusted R2 (95% CI) for the Cox model increased from 0.269 (0.262-0.276) to 0.283 (0.276-0.290) in the non-time-varying model and from 0.467 (0.461-0.472) to 0.505 (0.500-0.512) in the time-varying model. There was little to no benefit of adding PLR to predict mortality.
High NLR in incident hemodialysis patients predicted mortality, especially in the short-term period. NLR, but not PLR, added modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostication approaches.
Background Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among ...patients with advanced chronic kidney disease and mortality following their transition to dialysis. Study Design Observational study. Setting & Participants 32,348 US veterans who transitioned to dialysis during 2007 to 2011. Predictors Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. Outcomes Post–dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Results Mean age of the cohort was 72 ± 11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC > 80%, there were 14,006 deaths (mortality rate, 283 95% CI, 278-288/1,000 patient-years); among patients with PDC > 60% to 80%, there were 3,882 deaths (mortality rate, 294 95% CI, 285-304/1,000 patient-years); among patients with PDC ≤ 60%, there were 720 deaths (mortality rate, 291 95% CI, 271-313/1,000 patient-years). Compared with patients with PDC > 80%, the adjusted HR for post–dialysis therapy initiation all-cause mortality for patients with PDC > 60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC ≤ 60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post–dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Limitations Large number of missing values; results may not be generalizable to women or the general US population. Conclusions Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.
Background Prior studies have shown the association of low serum magnesium levels with adverse health outcomes in patients undergoing hemodialysis. There is a paucity of such studies in patients ...undergoing peritoneal dialysis (PD). Study Design Cohort study. Setting & Participants 10,692 patients treated with PD from January 1, 2007, through December 31, 2011, in facilities operated by a single large dialysis organization in the United States. Predictor Baseline serum magnesium levels, examined as 5 categories (<1.8, 1.8-<2.0, 2.0-<2.2 reference, 2.2-<2.4, and ≥2.4 mg/dL). Outcomes Time to first hospitalization and time to death using competing-risks regression models. Results The distribution of baseline serum magnesium levels in the cohort was <1.8 mg/dL, 1,928 (18%); 1.8 to <2.0 mg/dL, 2,204 (21%); 2.0 to <2.2 mg/dL, 2,765 (26%); 2.2 to <2.4 mg/dL, 1,765 (16%); and ≥2.4 mg/dL, 2,030 (19%). Of 10,692 patients, 6,465 (60%) were hospitalized at least once and 1,392 (13%) died during follow-up (median, 13; IQR, 7-23 months). Baseline serum magnesium level < 1.8 mg/dL was associated with higher risk for hospitalization and all-cause mortality after adjustment for demographic and clinical characteristics (adjusted HRs of 1.23 95% CI, 1.14-1.33 and 1.21 95% CI, 1.03-1.42, respectively). The higher risk for hospitalization persisted upon adjustment for laboratory variables, whereas that for all-cause mortality was attenuated to a nonsignificant level. The greatest risk for hospitalization was in patients with low serum albumin levels (<3.5 g/dL; P for interaction < 0.001). Limitations Possibility of residual confounding by unmeasured variables cannot be excluded. Conclusions Lower serum magnesium levels may be associated with higher risk for hospitalization in incident PD patients, particularly those with hypoalbuminemia. Additional studies are needed to confirm these findings and investigate whether correction of hypomagnesemia reduces these risks.
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