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BackgroundAlthough hemoglobin A1c (HbA1c) has been widely used as a clinical assessment tool for outcome analyses related to glycemic control, the relationship between HbA1c and average blood glucose (BG) specific to peritoneal dialysis (PD) patients with diabetes has not been characterized. We sought to develop HbA1c-BG equation models for PD patients.MethodsWe examined associations between HbA1c and random serum BG values over time in a contemporary 5-year (2001-2006) cohort of DaVita PD patients with diabetes. We identified 850 patients (mean age: 58 ± 13 years, 56% male) with 4,566 paired measurements of HbA1c and BG. The bootstrapping method was used to estimate average BG and corresponding HbA1c.ResultsLinear regression analyses yielded the following HbA1c-BG equations: (1) BG (mg/dl) = 24.1 + 28.6 × HbA1c - 12.2 × albumin [adjusted R(2) (R(2)adj = 0.454)], (2) BG = 55.3 + 28.8 × HbA1c - 10.2 × albumin - 3.3 × Hb (R(2)adj = 0.457), and (3) BG = 69.5 + 28.7 × HbA1c - 10.1 × albumin - 3.7 × Hb - 0.1 × age + race/ethnicity (-10.1 African Americans, -5.4 other race/ethnicities; R(2)adj = 0.457). All models showed greater explanatory power of BG variation than previously established HbA1c-BG equation models defined within non-PD cohorts [R(2)adj = 0.446 for both the Diabetes Control and Complications Trial (DCCT) and the A1c-Derived Average Glucose (ADAG) equations].ConclusionsThe association between HbA1c and BG in PD patients is different than that of patients with normal kidney function. Our analysis suggests that equations incorporating serum albumin and/or Hb values better estimate the HbA1c-BG relationship in PD patients compared to equations using HbA1c alone.

BackgroundAfrican Americans are at greater risk to reach end-stage renal disease and this risk may carry over in a kidney transplant recipient after kidney transplantation.MethodsLinking the five-yr patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 13 692 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function risks were estimated by Cox's regression (hazard ratio [HR] and 95% confidence interval) and logistic regression, respectively.ResultsPatients were 48 ± 14 yr old and included 39% women and 26% patients with diabetes. After adjusting for several relevant clinical and transplant-related variables, African American donor race was associated with higher all-cause mortality, with HR of 1.39 (1.09-1.78) for all-cause mortality, 1.80 (1.17-2.76) for cardiovascular mortality, 1.30 (1.03-1.64) for death-censored graft loss and 1.31 (1.10-1.57) for combined outcome over the six-yr observation period. In the non-African American recipient subcohort, but not in the African American recipient subcohort, African American donor race was associated with higher risk of death-censored graft loss (2.24 [1.44-3.49]) in our fully adjusted model.ConclusionsAfrican American donor race was associated with increased all-cause and cardiovascular mortality and graft loss.

PurposeThe Charlson comorbidity index (CCI) is a commonly used scale for assessing morbidity, but its role in assessing mortality in hemodialysis patients is not clear. Age, a component of CCI, is a strong risk factor for morbidity and mortality in chronic diseases and correlates with comorbidities. We hypothesized that the Charlson comorbidity index without age is a strong predictor of mortality in hemodialysis patients.MethodsA 6-year cohort of 893 hemodialysis patients was examined for an association between a modified CCI (without age and kidney disease) (mCCI) and mortality.ResultsPatients were 53±15 years old (mean±SD), had a median mCCI score of 2, and included 47% women, 31% African Americans and 55% diabetics. After adjusting for case-mix and nutritional and inflammatory markers including C-reactive protein and interleukin-6, 2nd (mCCI: 1-2), 3rd (mCCI=3), and 4th (mCCI: 4-9) quartiles compared to 1st (mCCI=0) quartiles showed death hazard ratios (95% confidence intervals) of 1.43 (0.92-2.23), 1.70 (1.06-2.72), and 2.33 (1.43-3.78), respectively. The mCCI-death association was robust in non-African Americans. The CCI-death association linearity was verified in cubic splines. Each 1 unit higher mCCI score was associated with a death hazard ratio of 1.16 (1.07-1.27).ConclusionsCCI independent of age is a robust and linear predictor of mortality in hemodialysis patients, in particular in non-African Americans.

Background and objectivesMineral and bone disorders (MBDs) are common in long-term dialysis patients and are risk factors for unfavorable outcomes. The associations between pretransplant levels of MBD surrogates and outcomes after kidney transplantation are not clear.Design, setting, participants, & measurementsData from the Scientific Registry of Transplant Recipients up to June 2007 were linked to the 5-year (July 2001-June 2006) cohort of a large dialysis organization in the United States. All dialysis patients who received a kidney transplant during this period were identified and divided into groups according to increments of pretransplant MBD markers. Unadjusted and multivariate adjusted predictors of transplant outcomes were examined.ResultsThe 11,776 patients were aged 47 ± 14 years and 39% were women. Compared with recipients with pretransplant time-averaged serum alkaline phosphatase of 80-120 U/L, recipients with pretransplant serum alkaline phosphatase of 120-160 and ≥160 U/L had 49% and 64% higher graft failure censored all-cause mortality in multivariable adjusted models. There was no significant association between time-averaged serum alkaline phosphatase categories and risk of death censored graft failure, delayed graft function (DGF), or acute rejection (AR). Compared with recipients with pretransplant time-averaged serum parathyroid hormone (PTH) levels of 150-300 pg/ml, there was no significant association with graft censored death among recipients with pretransplant serum PTH ≥800 pg/ml. In addition, the risk of graft failure, DGF, and AR did not show any association with time-averaged serum intact PTH level. There was no significant association between time-averaged serum calcium categories and risk of graft failure censored death, DGF, and AR.ConclusionsIn this cohort, hemodialysis patients with pretransplant serum alkaline phosphatase >120 U/L have unfavorable post-transplant mortality, whereas there was no association between serum PTH and serum calcium levels and post-transplant outcomes.

PurposeSeveral observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses.MethodsWe examined mortality-predictability of low (>1 but

BackgroundWhether peritoneal dialysis (PD) treatment leads to greater weight gain than with hemodialysis (HD) and if this limits access of obese end-stage renal disease patients to renal transplantation has not been examined. We undertook this study to determine the interrelationship between body size and initial dialysis modality on transplantation, mortality and weight gain.MethodsTime to transplantation, time to death and weight gain were estimated in a 1:1 propensity score-matched cohort of incident HD and PD patients treated in facilities owned by DaVita Inc. between 1 July 2001 through 30 June 2006 followed through 30 June 2007 (4008 pairs) in four strata of body mass index (BMI) (18.5 kg/m(2), including with BMI ≥ 30 kg/m(2) (aHR 1.45, 95% CI 1.11-1.89). PD patients had significantly lower all-cause mortality for patients with BMI 18.50-29.99 kg/m(2). Both these findings were confirmed on analyses of the entire unmatched incident cohort (PD 4008; HD 58 471). The effect of dialysis modality on weight gain was tested in 687 propensity score-matched pairs; the odds of >2, >5 or >10% weight gain were significantly lower in PD patients.ConclusionTreatment with PD is less likely to be associated with a significant weight gain and does not limit the access of obese patients to renal transplantation.

BackgroundDelayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF.MethodsLinking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF.ResultsPatients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34).ConclusionsPre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.

Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments 13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration > 13 exhibits increased mortality.

Diabetes mellitus (DM) is the most common cause of end-stage kidney disease and a major risk of morbidity and mortality. It is not clear whether medical management of DM has any significant beneficial effect on clinical outcomes at the end-stage of diabetic nephropathy with full-blown micro- and macro-angiopathic complications. Both loss of kidney function and dialysis treatment interfere with glucose homeostasis and confound glycemic control. Given the unique nature of uremic milieu and dialysis therapy related alterations, there have been some debates about reliance on the conventional measures of glycemic control, in particular the clinical relevance of hemoglobin A1c and its recommended target range of

Background and objectivesUnlike hemodialysis (HD), peritoneal dialysis (PD) is a continuous therapy and does not induce myocardial stunning. Yet, the death risk in HD and PD patients is similar. This study tested the hypothesis that serum potassium abnormalities contribute more to the death risk in PD patients than in HD patients.Design, setting, participants, & measurementsData from patients treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD patients; n=111,651 HD patients) were used to determine association of serum potassium with mortality.ResultsPD patients were significantly more likely to have serum potassium < 4 mEq/L, with an adjusted odds ratio of 3.30 (95% confidence interval [95% CI], 3.05, 3.56). There was a U-shaped relationship between time-averaged serum potassium and all-cause and cardiovascular mortality of PD patients, with adjusted hazards ratios of 1.51 for all-cause mortality for potassium < 3.5 mEq/L (95% CI, 1.29, 1.76) and 1.52 for potassium ≥ 5.5 mEq/L (95% CI, 1.32, 1.75). The population-attributable risks for all-cause mortality for serum potassium < 4.0 and ≥ 5.5 mEq/L were 3.6% and 1.9%, respectively, in PD patients, and 0.8% and 1.5%, respectively, in HD patients.ConclusionsAbnormalities in serum potassium contribute disproportionately to the high death risk in PD patients. This may, in part, account for the equivalent cardiac risk seen with the two therapies.

BackgroundThe role of pre-transplant erythropoiesis-stimulating agent (ESA) responsiveness in affecting post-transplant outcomes is not clear.MethodsLinking the 5-year patient data of a large dialysis organization to the 'Scientific Registry of Transplant Recipients', we identified 8795 hemodialyzed patients who underwent first kidney transplantation. Mortality or graft failure, delayed graft function (DGF) and acute rejection risks were estimated by Cox regression [hazard ratio (HR)] and logistic regression, respectively.ResultsPatients were 48 ± 14 years old and included 38% women and 36% diabetics. Compared to renal allograft recipients who were in the first quartile of pre-transplant ESA responsiveness index (ERI), i.e. ESA dose divided by hemoglobin and weight, recipients in second, third and fourth quartiles had higher adjusted graft-censored death HR (and 95% confidence intervals) of 1.7 (1.0-2.7), 1.8 (1.1-2.9) and 2.3 (1.4-3.9) and higher death-censored graft failure HR of 1.6 (1.0-2.5), 2.0 (1.2-3.1) and 1.6 (0.9-2.6), respectively. No significant association between pre-transplant ERI and post-transplant DGF or acute rejection was detected.ConclusionsHigher pre-transplant ERI during the hemodialysis treatment period was associated with worse post-transplant long-term outcomes including increased all-cause death and higher risk of graft failure.

BackgroundRecent observational studies and a controlled trial suggest more favorable outcomes upon later dialysis initiation in chronic kidney disease. The role of estimated glomerular filtration rate (eGFR) in predicting outcome at reinitiation of dialysis in failed kidney transplant recipients is unclear.MethodsFive-year data in a large dialysis organization was linked to the 'Scientific Registry of Transplant Recipients' to identify 747 failed kidney transplant patients with CKD Stage 5, who had restarted dialysis therapy. A propensity score for early (eGFR>10.5 mL/min/1.73 m2) versus late reinitiation of dialysis was fit by logistic regression. The mortality hazard ratio (HR) was estimated across tertiles of the fitted score.ResultsPatients were 44±14 years old and included 42% women. Male gender {odds ratio (OR), [95% confidence interval (CI)]: 1.82 (1.22-2.73)}, diabetes mellitus [OR: 1.75 (1.14-2.68)] and peripheral vascular disease [OR: 3.55 (1.17-10.77)] were associated with higher odds of early dialysis reinitiation. Each mL/min/1.73 m2 higher eGFR was associated with 6% higher death risk in unadjusted model [HR: 1.06 (1.01-1.11)], and although not significant in fully adjusted models [HR: 1.02 (0.96-1.07)], it was significant in some subgroups including women and younger patients. The death HR of higher eGFR across lowest to highest tertiles of propensity score of early dialysis initiation (corresponding healthiest to sickest patients) were 1.10 (0.98-1.24), 1.00 (0.91-1.10) and 0.99 (0.92-1.07), respectively (P for trend

BackgroundMaintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential.MethodsSurvival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients.ResultsPKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

BackgroundRecent studies show a survival advantage with kidney transplant in elderly patients compared with those on dialysis therapy.Study designIn our present study, we examined and compared the association of expanded criteria donor (ECD) kidney and living kidney donation with the outcome of kidney transplant across different ages, including elderly recipients.Setting & participantsUsing the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplant patients. Mortality and death-censored transplant failure risks were estimated by Cox proportional regression analyses during follow-up with a median of 3.9 years.PredictorsECD kidney and living kidney donation and age compared with others.OutcomesMortality and death-censored transplant failure risk.ResultsPatients were aged 45 ± 16 years and included 40% women and 19% patients with diabetes. Compared with transplant recipients 55 to younger than 65 years, the fully adjusted death-censored transplant failure risk was higher in patients 75 years and older (HR, 1.30; 95% CI, 1.09-1.56), 35 to younger than 55 years (HR, 1.13; 95% CI, 1.08-1.17), and 18 to younger than 35 years (HR, 1.64; 95% CI, 1.57-1.71). Compared with non-ECD kidneys, ECD kidneys were significant predictors of mortality in nonelderly patients (18-

ObjectiveLipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram-negative bacteria. Subclinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis (HD) patients. Endotoxin level and clinical effect are determined by its soluble receptor sCD14 and high-density lipoprotein. We examine the hypothesis that endotoxin level correlates with mortality.MethodsIn this cohort study, endotoxin levels were measured in 306 long-term HD patients who were then followed up for a maximum of 42 months. Soluble CD14 and cytokines levels were also measured.ResultsThe mean (±SD) endotoxin level was 2.31 ± 3.10 EU/mL (minimum: 0.26 EU/mL, maximum: 22.94 EU/mL, interquartile range: 1.33 EU/mL, median: 1.27 EU/mL). Endotoxin correlated with C-reactive protein (r = 0.11, P < .04). On multivariate logistic regression analysis, high body mass index and low high-density lipoprotein (HDL) cholesterol levels were associated with higher endotoxemia (endotoxin below or above of median). In multivariate Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the third quartile versus first quartile were associated with a trend toward increased hazard ratio for death (hazard ratio: 1.83, 95% confidence interval: 0.93 to 3.6, P = .08).ConclusionsIn this HD cohort, we found associations between endotoxemia and C-reactive protein, body composition, and HDL. Moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to assess the effect of endotoxemia on mortality in dialysis population.

In hemodialysis patients, lower body mass index and weight loss have been associated with higher mortality rates, a phenomenon sometimes called the obesity paradox. This apparent paradox might be explained by loss of muscle mass. The authors thus examined the relation to mortality of changes in dry weight and changes in serum creatinine levels (a muscle-mass surrogate) in a cohort of 121,762 hemodialysis patients who were followed for up to 5 years (2001-2006). In addition to conventional regression analyses, the authors conducted a ranking analysis of joint effects in which the sums and differences of the percentiles of change for the 2 measures in each patient were used as the regressors. Concordant with previous body mass index observations, lower body mass, lower muscle mass, weight loss, and serum creatinine decline were associated with higher death rates. Among patients with a discordant change, persons whose weight declined but whose serum creatinine levels increased had lower death rates than did those whose weight increased but whose serum creatinine level declined. A decline in serum creatinine appeared to be a stronger predictor of mortality than did weight loss. Assuming residual selection bias and confounding were not large, the present results suggest that a considerable proportion of the obesity paradox in dialysis patients might be explained by the amount of decline in muscle mass.

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and ≥10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and ≤5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175-199, 200-249, 250-299, and ≥300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk.

BackgroundHyponatremia is common in patients with conditions such as congestive heart failure and is associated with increased mortality in hospitalized patients. Congestive heart failure is common in patients with chronic kidney disease, but the association of serum sodium concentration with mortality in such patients is not well characterized.Methods and resultsWe examined the association of serum sodium concentration with all-cause mortality in a nationally representative cohort of 655 493 US veterans with non-dialysis-dependent chronic kidney disease (95 961 [15%] of them with congestive heart failure). Associations were examined in time-dependent Cox models with adjustment for potential confounders. During a median follow-up of 5.5 years, a total of 193 956 patients died (mortality rate, 62.5/1000 patient-years; 95% confidence interval, 62.2-62.8). The association of serum sodium level with mortality was U-shaped, with the lowest mortality seen in patients with sodium level of 140 mEq/L and with both lower and higher levels showing significant associations with increased mortality. Patients with serum sodium levels of

Background and objectivesThe influence of pretransplant dialysis modality on post-transplant outcomes is not clear. This study examined associations of pretransplant dialysis modality with post-transplant outcomes in a large national cohort of kidney transplant recipients.Design, setting, participants, & measurementsLinking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092 peritoneal dialysis patients who underwent first kidney transplantation were identified. Mortality or graft failure and delayed graft function risks were estimated by Cox regression (hazard ratio) and logistic regression (odds ratio), respectively.ResultsRecipients treated with peritoneal dialysis pretransplantation had lower (21.9/1000 patient-years [95% confidence interval: 18.1-26.5]) crude all-cause mortality rate than those recipients treated with hemodialysis (32.8/1000 patient-years [30.8-35.0]). Pretransplant peritoneal dialysis use was associated with 43% lower adjusted all-cause and 66% lower cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was associated with 17% and 36% lower unadjusted death-censored graft failure and delayed graft function risk, respectively. However, after additional adjustment for relevant covariates, pretransplant peritoneal dialysis modality was not a significant predictor of death-censored graft failure delayed graft function, respectively. Similar trends were noted on analyses using a propensity score matched cohort of 2092 pairs of patients.ConclusionsCompared with hemodialysis, patients treated with peritoneal dialysis before transplantation had lower mortality but similar graft loss or delayed graft function. Confounding by residual selection bias cannot be ruled out.

BackgroundSeveral studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients.MethodsWe compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models.ResultsPoisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5-3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000-5,999, 6,000-8,999 and ≥9,000 U/week (reference

ObjectiveObservational studies have yielded inconsistent findings regarding the association of hemoglobin A(1c) (HbA(1c)) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear.Research design and methodsLinking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively.ResultsPatients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure-censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA(1c) categories of 7 to

Background and objectivesConventional lipid profiles usually cannot predict cardiovascular outcomes in chronic disease states. We hypothesized that novel lipoprotein subfraction concentrations and LDL particle size measurements better predict mortality in maintenance hemodialysis (MHD) patients.Design, setting, participants, & measurementsMortality-predictability of LDL particle diameter and lipoprotein subfraction concentrations, measured by novel ion mobility, was examined in a cohort of 235 hemodialysis patients who were followed for up to 6 years using Cox models with adjustment for important covariables.ResultsPatients were 54 ± 14 years old (mean ± SD) and included 45% women with total, LDL and HDL cholesterol levels of 143 ± 42, 76 ± 29, and 37 ± 12 mg/dl, respectively. Over 6 years, 71 patients (31%) died. Conventional lipid profile was not associated with mortality. The death hazard ratio (HR, 95% confidence interval) of the highest versus lowest quartiles of very small and large LDL particle concentrations were 2.43 (1.03 to 5.72) and 0.38 (0.15 to 0.96), respectively. Across increasing quartiles of LDL particle diameter, death HRs were 1.00, 0.93 (0.46 to 1.87), 0.43 (0.21 to 0.89), and 0.45 (0.31 to 1.00), respectively.ConclusionsWhereas conventional lipid profile cannot predict mortality in MHD patients, larger novel LDL particle diameter or higher large LDL particle concentrations appear predictive of greater survival, whereas higher very small LDL particle concentration is associated with higher death risk. Examining lipoprotein subfraction modulation in chronic diseases is indicated.

Background and objectivesPosttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients.Design, setting, participants, & measurementsWe collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 ± 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk.ResultsDuring the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 ± 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR(1SD increase) 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR(1SD increase) 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups.ConclusionsIn this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.

Background and objectivesSerum phosphorus levels are associated with mortality, cardiovascular disease, and renal function loss in individuals with and without chronic kidney disease. The association of pretransplant serum phosphorus levels with transplant outcomes is not clear.Design, setting, participants, & measurementsData of the Scientific Registry of Transplant Recipients (SRTR) up to June 2007 were linked to the database (2001 through 2006) of one of the U.S.-based large dialysis organizations (DaVita). The selected 9384 primary kidney recipients were divided into five groups according to pretransplant serum phosphorus levels (mg/dl): 9.5 and ≥9.5, respectively. No significant association with delayed graft function was found.ConclusionsPretransplant phosphorus levels 7.5 to

BackgroundIn maintenance hemodialysis (HD) patients, overweight and obesity are associated with survival advantages. Given the greater survival of maintenance HD patients who are minorities, we hypothesized that increased body mass index (BMI) is associated more strongly with lower mortality in blacks and Hispanics relative to non-Hispanic whites.Study designRetrospective cohort study.Setting & participantsWe examined a 6-year (2001-2007) cohort of 109,605 maintenance HD patients including 39,090 blacks, 17,417 Hispanics, and 53,098 non-Hispanic white maintenance HD outpatients from DaVita dialysis clinics. Cox proportional hazards models examined the association between BMI and survival.PredictorsRace and BMI.OutcomesAll-cause mortality.ResultsPatients had a mean age of 62 ± 15 (standard deviation) years and included 45% women and 45% patients with diabetes. Across 10 a priori-selected BMI categories (

BackgroundIt is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD).ObjectivesWe hypothesized that ESRD patients with relative thrombocytosis (platelet count >300 × 10(3)/μL) have a higher mortality rate and that this association may be related to malnutrition-inflammation cachexia syndrome (MICS).DesignWe examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001-2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis.ResultsThe patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 ± 78 × 10(3)/μL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 × 10(3)/μL (reference), the all-cause (and cardiovascular) mortality rate with platelet counts between 300 and

Background and objectivesInterventional trials and some observational studies show target hemoglobin >13 g/dl to be associated with higher mortality in erythropoiesis-stimulating agent-treated (ESA-treated) hemodialysis patients; data for peritoneal dialysis (PD) patients are limited.Design, setting, participants, & measurementsWe tested our hypothesis that higher and lower achieved hemoglobin levels are associated with increased mortality in 9269 ESA-treated PD patients from all DaVita dialysis clinics during the time period July 2001 through June 2006 followed through June 2007 using a time-dependent analysis.ResultsLower hemoglobin was associated with significantly higher all-cause mortality in ESA-treated PD patients: with hemoglobin of 11.0 to

Background and objectivesThe association between pretransplant body composition and posttransplant outcomes in renal transplant recipients is unclear. It was hypothesized that in hemodialysis patients higher muscle mass (represented by higher pretransplant serum creatinine level) and larger body size (represented by higher pretransplant body mass index [BMI]) are associated with better posttransplant outcomes.Design, setting, participants, & measurementsLinking 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, 10,090 hemodialysis patients were identified who underwent kidney transplantation from July 2001 to June 2007. Cox regression hazard ratios and 95% confidence intervals of death and/or graft failure were estimated.ResultsPatients were 49 ± 13 years old and included 49% women, 45% diabetics, and 27% African Americans. In Cox models adjusted for case-mix, nutrition-inflammation complex, and transplant-related covariates, the 3-month-averaged postdialysis weight-based pretransplant BMI of 20 to

BackgroundObservational studies indicate greater survival in African American and Hispanic maintenance hemodialysis patients compared with their non-Hispanic white counterparts, although African Americans have shorter life expectancy than whites in the general population. We hypothesized that this apparent survival advantage is due to a more favorable nutritional/inflammatory profile in minority hemodialysis patients.Study designWe examined the association between race/ethnicity and 5-year survival before and after adjustment for case-mix and surrogates of the malnutrition-inflammation complex syndrome (MICS) using Cox regression with or without matched sampling in a large cohort of adult hemodialysis patients.Setting & participants124,029 adult hemodialysis patients, including 16% Hispanics, 49% non-Hispanic whites, and 35% African Americans.PredictorsRace/ethnicity before and after adjustment for MICS, including values for body mass index, serum albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, white blood cell count, lymphocyte percentage, hemoglobin, and protein intake.Outcomes5-year (July 2001 to June 2006) survival.ResultsIn dialysis patients, blacks and Hispanics had lower mortality overall than non-Hispanic whites after traditional case-mix adjustment. However, after additional control for MICS, Hispanics had mortality similar to non-Hispanic whites, and African Americans had even higher mortality. Unadjusted, case-mix-, and MICS-adjusted HRs for African Americans versus whites were 0.68 (95% CI, 0.66-0.69), 0.89 (95% CI, 0.86-0.91), and 1.06 (95% CI, 1.03-1.09) in the unmatched cohort and, 0.95 (95% CI, 0.90-0.99), 0.89 (95% CI, 0.84-0.94), and 1.16 (95% CI, 1.07-1.26) in the matched cohort, and for Hispanics versus whites, 0.66 (95% CI, 0.64-0.69), 0.84 (95% CI, 0.81-0.87), and 0.97 (95% CI, 0.94-1.00) in the unmatched cohort and 0.89 (95% CI, 0.84-0.95), 0.88 (95% CI, 0.83-0.95), and 0.98 (95% CI, 0.91-1.06) in the matched cohort, respectively.LimitationsAdjustment cannot be made for unmeasured confounders.ConclusionsSurvival advantages of African American and Hispanic hemodialysis patients may be related to differences in nutritional and inflammatory status. Further studies are required to explore these differences.

Background and objectivesThe optimal target for glycemic control has not been established for diabetic peritoneal dialysis (PD) patients.Design, setting, participants, & measurementsWe examined mortality-predictability of hemoglobin A1c random serum glucose in a contemporary cohort of diabetic PD patients treated in DaVita dialysis clinics July 2001 through June 2006 with follow-up through June 2007.ResultsWe identified 2798 diabetic PD patients with A1c data. Serum glucose correlated with A1C (r=0.51). Adjusted all-cause death hazard ratio and 95% confidence interval for baseline A1c increments of 7.0 to 7.9%, 8.0 to 8.9%, 9.0 to 9.9%, and ≥10%, compared with 6.0 to 6.9% (reference), were 1.13 (0.97 to 1.32), 1.05 (0.88 to 1.27), 1.06 (0.84 to 1.34), and 1.48 (1.18 to 1.86); and for time-averaged A1c values were 1.10 (0.96 to 1.27), 1.28 (1.07 to 1.53), 1.34 (1.05 to 1.70), and 1.81 (1.33 to 2.46), respectively. The A1c-mortality association was modified by hemoglobin level such that higher all-cause mortality was evident only in nonanemic patients. Similar but non-significant trends in cardiovascular death risk was found across A1c increments. Adjusted all-cause death HR for time-averaged blood glucose 150 to 199, 200 to 249, 250 to 299, and ≥300 mg/dl, compared with 60 to 99 mg/dl (reference), were 1.02 (0.70 to 1.47), 1.12 (0.77 to 1.63), 1.45 (0.97 to 2.18), and 2.10 (1.37 to 3.20), respectively.ConclusionsPoor glycemic control appears associated incrementally with higher mortality in PD patients. Moderate to severe hyperglycemia is associated with higher death risk especially in certain subgroups.

Background and objectivesMaintenance hemodialysis (MHD) patients often have protein-energy wasting, poor health-related quality of life (QoL), and high premature death rates, whereas African-American MHD patients have greater survival than non-African-American patients. We hypothesized that poor QoL scores and their nutritional correlates have a bearing on racial survival disparities of MHD patients.Design, setting, participants, & measurementsWe examined associations between baseline self-administered SF36 questionnaire-derived QoL scores with nutritional markers by multivariate linear regression and with survival by Cox models and cubic splines in the 6-year cohort of 705 MHD patients, including 223 African Americans.ResultsWorse SF36 mental and physical health scores were associated with lower serum albumin and creatinine levels but higher total body fat percentage. Spline analyses confirmed mortality predictability of worse QoL, with an almost strictly linear association for mental health score in African Americans, although the race-QoL interaction was not statistically significant. In fully adjusted analyses, the mental health score showed a more robust and linear association with mortality than the physical health score in all MHD patients and both races: death hazard ratios for (95% confidence interval) each 10 unit lower mental health score were 1.12 (1.05-1.19) and 1.10 (1.03-1.18) for all and African American patients, respectively.ConclusionsMHD patients with higher percentage body fat or lower serum albumin or creatinine concentration perceive a poorer QoL. Poor mental health in all and poor physical health in non-African American patients correlate with mortality. Improving QoL by interventions that can improve the nutritional status without increasing body fat warrants clinical trials.

The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

BackgroundRacial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities.MethodsIn a 6-year (2001-2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines.ResultsIn age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (-2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3-3.8) and 4.1-fold (2.2-7.2) higher death risk in Blacks and Whites, respectively.ConclusionsSignificant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI.

BackgroundChronic protein-energy wasting, termed malnutrition-inflammation complex syndrome, is frequent in patients with chronic kidney disease and is associated with anemia, morbidity, and mortality in patients on maintenance dialysis therapy. The Malnutrition-Inflammation Score (MIS) recently has been developed and validated in dialysis patients.Study designObservational cross-sectional study.Setting & participants993 prevalent kidney transplant recipients.PredictorMIS computed from change in body weight, dietary intake, gastrointestinal symptoms, functional capacity, comorbid conditions, decreased fat store/Systemic Global Assessment, signs of muscle wasting/Systemic Global Assessment, body mass index, serum albumin level, and serum transferrin level.OutcomesMarkers of inflammation and malnutrition, including serum C-reactive protein, interleukin 6, tumor necrosis factor alpha, serum leptin, prealbumin, body mass index, and abdominal circumference. The relationship was modeled by using structural equation models.ResultsMean age was 51 +/- 13 years, 57% were men, and 21% had diabetes. Median time from transplant was 72 months. MIS significantly correlated with abdominal circumference (r = -0.144), serum C-reactive protein level (r = 0.094), serum interleukin 6 level (r = 0.231), and serum tumor necrosis factor alpha level (r = 0.102; P < 0.01 for all). A structural equation model with 2 latent variables (malnutrition and inflammation factor) showed good fit to the observed data.LimitationsSingle-center study, lack of information about vascular access, presence of nonfunctioning kidney transplant, relatively high refusal rate.ConclusionsOur results confirm that MIS reflects both energy-protein wasting and inflammation in kidney transplant recipients. This simple instrument appears to be a useful tool to assess the presence of protein-energy wasting in this patient population.

Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas-areas active during the execution and the observation of an action-previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.