Search

Background and Objectives: Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements., Design, Setting, Participants, & Measurements: The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018., Results: Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally., Conclusions: This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries., (Copyright © 2022 by the American Society of Nephrology.)

Background and Objectives: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis., Design, Setting, Participants, & Measurements: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities., Results: Patients were 72±11 years, 5% were women, 24% were black, and 10% ( n =7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models., Conclusions: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units., (Copyright © 2018 by the American Society of Nephrology.)

Background and Objectives: Albuminuria is a robust predictor of CKD progression. However, little is known about the associations of changes in albuminuria with the risk of kidney events outside the settings of clinical trials., Design, Setting, Participants, & Measurements: In a nationwide cohort of 56,946 United States veterans with an eGFR≥60 ml/min per 1.73 m 2 , we examined the associations of 1-year fold changes in albuminuria with subsequent incident CKD (>25% decrease in eGFR reaching <60 ml/min per 1.73 m 2 ) and rapid eGFR decline (eGFR slope <-5 ml/min per 1.73 m 2 per year) assessed using Cox models and logistic regression, respectively, with adjustment for confounders., Results: The mean age was 64 (SD, 10) years old; 97% were men, and 91% were diabetic. There was a nearly linear association between 1-year fold changes in albuminuria and incident CKD. The multivariable-adjusted hazard ratios (95% confidence intervals) of incident CKD associated with more than twofold decrease, 1.25- to twofold decrease, 1.25- to twofold increase, and more than twofold increase (versus <1.25-fold decrease to <1.25-fold increase) in albuminuria were 0.82 (95% confidence interval, 0.77 to 0.89), 0.93 (95% confidence interval, 0.86 to 1.00), 1.12 (95% confidence interval, 1.05 to 1.20), and 1.29 (95% confidence interval, 1.21 to 1.38), respectively. Qualitatively similar associations were present for rapid eGFR decline (adjusted odds ratios; 95% confidence intervals for corresponding albuminuria changes: adjusted odds ratio, 0.86; 95% confidence interval, 0.78 to 0.94; adjusted odds ratio, 0.98; 95% confidence interval, 0.89 to 1.07; adjusted odds ratio, 1.18; 95% confidence interval, 1.08 to 1.29; and adjusted odds ratio, 1.67; 95% confidence interval, 1.54 and 1.81, respectively)., Conclusions: Relative changes in albuminuria over a 1-year interval were linearly associated with subsequent risk of kidney outcomes. Additional studies are warranted to elucidate the underlying mechanisms of the observed associations and test whether active interventions to lower elevated albuminuria can improve kidney outcomes., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: Depression in patients with nondialysis-dependent CKD is often undiagnosed, empirically overlooked, and associated with higher risk of death, progression to ESRD, and hospitalization. However, there is a paucity of evidence on the association between the presence of depression in patients with advanced nondialysis-dependent CKD and post-ESRD mortality, particularly among those in the transition period from late-stage nondialysis-dependent CKD to maintenance dialysis., Design, Setting, Participants, & Measurements: From a nation-wide cohort of 45,076 United States veterans who transitioned to ESRD over 4 contemporary years (November of 2007 to September of 2011), we identified 10,454 (23%) patients with a depression diagnosis during the predialysis period. We examined the association of pre-ESRD depression with all-cause mortality after transition to dialysis using Cox proportional hazards models adjusted for sociodemographics, comorbidities, and medications., Results: Patients were 72±11 years old (mean±SD) and included 95% men, 66% patients with diabetes, and 23% blacks. The crude mortality rate was similar in patients with depression (289/1000 patient-years; 95% confidence interval, 282 to 297) versus patients without depression (286/1000 patient-years; 95% confidence interval, 282 to 290). Compared with patients without depression, patients with depression had a 6% higher all-cause mortality risk in the adjusted model (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.09). Similar results were found across all selected subgroups as well as in sensitivity analyses using alternate definitions of depression., Conclusion: Pre-ESRD depression has a weak association with post-ESRD mortality in veterans transitioning to dialysis., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: In the general population, there is increasing recognition of the effect of thyroid function on patient-centered outcomes, including health-related quality of life and depression. Although hypothyroidism is highly prevalent in hemodialysis patients, it is unknown whether thyroid status is a risk factor for impaired health-related quality of life or mental health in this population., Design, Setting, Participants, & Measurements: We examined the association of thyroid status, defined by serum thyrotropin, with health-related quality of life and depressive symptoms over time in a prospective cohort of 450 patients on hemodialysis from 17 outpatient dialysis facilities from May of 2013 to May of 2015 who underwent protocolized thyrotropin testing, Short-Form 36 surveys, and Beck Depression Inventory-II questionnaires every 6 months. We examined the association of baseline and time-dependent thyrotropin categorized as tertiles and continuous variables with eight Short-Form 36 domains and Beck Depression Inventory-II scores using expanded case mix plus laboratory adjusted linear mixed effects models., Results: In categorical analyses, the highest baseline thyrotropin tertile was associated with a five-point lower Short-Form 36 domain score for energy/fatigue ( P =0.04); the highest time-dependent tertile was associated with a five-point lower physical function score ( P =0.03; reference: lowest tertile). In continuous analyses, higher baseline serum thyrotropin levels (+ Δ 1 mIU/L) were associated with lower role limitations due to physical health ( β =-1.3; P =0.04), energy/fatigue ( β =-0.8; P =0.03), and pain scores ( β =-1.4; P =0.002), equivalent to five-, three-, and five-point lower scores, respectively, for every 1-SD higher thyrotropin. Higher time-dependent thyrotropin levels were associated with lower role limitations due to physical health scores ( β =-1.0; P =0.03), equivalent to a three-point decline for every 1-SD higher thyrotropin. Baseline and time-dependent thyrotropin were not associated with Beck Depression Inventory-II scores., Conclusions: In patients on hemodialysis, higher serum thyrotropin levels are associated with impaired health-related quality of life across energy/fatigue, physical function, and pain domains. Studies are needed to determine if thyroid-modulating therapy improves the health-related quality of life of hemodialysis patients with thyroid dysfunction., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality., Design, Setting, Participants, & Measurements: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m 2 ) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011., Results: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance ( P interaction =0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance ( i.e. , <1.5 ml/min per 1.73 m 2 ), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance ( i.e. , ≥1.5 ml/min per 1.73 m 2 ; P interaction <0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk ( P trend <0.001 for both) irrespective of residual renal urea clearance strata ( P interaction =0.34 and P interaction =0.53, respectively)., Conclusions: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: 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., Design, Setting, Participants, & Measurements: 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)., Results: 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 ( P trend <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 ( P trend <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., Conclusions: 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., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population., Design, Setting, Participants, & Measurements: We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy., Results: During the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups., Conclusions: Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: Hypertension is the most important treatable risk factor for cardiovascular outcomes. Many patients with CKD are elderly, but the ideal BP in these individuals is unknown., Design, Setting, Participants, & Measurements: From among 339,887 patients with incident eGFR<60 ml/min per 1.73 m(2), we examined associations of systolic BP (SBP) and diastolic BP (DBP) with all-cause mortality, incident coronary heart disease (CHD), ischemic strokes, and ESRD from the time of developing CKD until the end of follow-up (July 26, 2013, for mortality, CHD, and stroke, and December 31, 2011, for ESRD) in multivariable-adjusted survival models categorized by patients' age., Results: Of the total cohort, 300,424 (88%) had complete data for multivariable analysis. Both SBP and DBP showed a U-shaped association with mortality. SBP displayed a linear association with CHD, stroke, and ESRD, whereas DBP showed no consistent association with either. SBP>140 mmHg was associated with higher incidence of all examined outcomes, but with an incremental attenuation of the observed risk in older compared with younger patients (P<0.05 for interaction) The adjusted hazard ratios and 95% confidence intervals associated with SBP≥170 mmHg (compared with 130-139 mmHg) in patients <50, 50-59, 60-69, 70-79, and ≥80 years were 1.95 (1.34 to 2.84), 2.01 (1.75 to 2.30), 1.68 (1.49 to 1.89), 1.39 (1.25 to 1.54), and 1.30 (1.17 to 1.44), respectively. The risk of incident CHD, stroke, and ESRD was incrementally higher with higher SBP in patients aged <80 years but showed no consistent association in those aged ≥80 years (P<0.05 for interaction for all outcomes)., Conclusions: In veterans with incident CKD, SBP showed different associations in older versus younger patients. The association of higher SBP with adverse outcomes was present but markedly reduced in older individuals, especially in those aged ≥80 years. Elevated DBP showed no consistent association with vascular outcomes in patients with incident CKD., (Copyright © 2016 by the American Society of Nephrology.)

Background and Objectives: Pulse pressure has been shown as a risk factor for mortality in patients on maintenance hemodialysis (MHD). However, the effect of change in pulse pressure during hemodialysis on survival in a large cohort of patients on MHD has not been sufficiently investigated., Design, Setting, Participants, & Measurements: This study examined the association between time-varying Δ pulse pressure (postdialysis minus predialysis pulse pressure) and mortality in a cohort of 98,577 patients on MHD (July 2001-June 2006) using Cox proportional hazard models with restricted cubic splines., Results: The average patient age was 62 years old; among the patients, 33% were black and 59% had diabetes. During 134,814 patient-years of at-risk time, 16,054 (16%) patients died, with 6827 (43%) of the deaths caused by cardiovascular causes. In the models including adjustment for either predialysis systolic BP or mean arterial BP, there was a U-shaped association between change in pulse pressure during hemodialysis and all-cause mortality. In the systolic BP plus case mix plus malnutrition-inflammation complex syndrome-adjusted model, large declines in pulse pressure (>-25 mmHg) and increases in pulse pressure >5 mmHg were associated with higher all-cause mortality (reference: ≥-5 to <5 mmHg): hazard ratios (95% confidence intervals [95% CIs]) for change pulse pressures of <-25, ≥-25 to <-15, ≥-15 to <-5, 5 to <15, 15 to <25, and ≥25 mmHg were 1.21 (95% CI, 1.14 to 1.29), 1.03 (95% CI, 0.97 to 1.10), 1.01 (95% CI, 0.96 to 1.06), 1.06 (95% CI, 1.01 to 1.11), 1.17 (95% CI, 1.11 to 1.24), and 1.15 (95% CI, 1.08 to 1.23), respectively. The U-shaped association was observed with cardiovascular death., Conclusions: Modest reductions in pulse pressure after hemodialysis are associated with the greatest survival, whereas large declines or rises in pulse pressure are related to higher mortality. Trials determining how to modify pulse pressure response to improve survival in the hemodialysis population are indicated., (Copyright © 2015 by the American Society of Nephrology.)

Background and Objectives: Depression is common and is associated with higher mortality in patients with ESRD or CKD (stage 5). Less information is available on earlier stages of CKD. This study aimed to determine the prevalence of depression and any association with all-cause mortality in patients with varying severity of nondialysis-dependent CKD., Design, Setting, Participants, & Measurements: This is a retrospective study of a national cohort of 598,153 US veterans with nondialysis-dependent CKD stages 1-5 followed for a median of 4.7 years in the US Department of Veterans Affairs Health System. Diagnosis of depression was established as a result of systematic screening and administration of antidepressants. Association of depression with all-cause mortality overall and stratified by CKD stages were examined with the Kaplan-Meier method and in Cox models., Results: There were 179,441 patients (30%) with a diagnosis of depression. Over median follow-up of 4.7 years, depression was associated with significantly higher age-adjusted mortality overall (hazard ratio, 1.55; 95% confidence interval, 1.54-1.57; P<0.001). Sequential adjustments for sociodemographic characteristics and especially for comorbid conditions attenuated this association, which nevertheless remained significant (hazard ratio, 1.25; 95% confidence interval, 1.23-1.26)., Conclusions: In this large cohort of predominantly elderly male patients with CKD, prevalence of depression and antidepressant use is high (30%) and is associated with significantly higher all-cause mortality independent of comorbid conditions.

Background and Objectives: Mineral 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, & Measurements: Data 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., Results: The 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., Conclusions: In 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.

Background and Objectives: The 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, & Measurements: Linking 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., Results: Recipients 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., Conclusions: Compared 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.

Background and Objectives: Conventional 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, & Measurements: Mortality-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., Results: Patients 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., Conclusions: Whereas 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 Objectives: Posttransplant 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, & Measurements: We 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., Results: During 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., Conclusions: In this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.

Background and Objectives: Serum 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, & Measurements: Data 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): <3.5, 3.5 to <5.5 (reference group), 5.5 to <7.5, 7.5 to <9.5, and ≥9.5. Unadjusted and multivariate adjusted risks for transplant outcomes were compared., Results: Patients were 48 ± 14 years old and included 37% women and 27% African Americans. After multivariate adjustment, all-cause and cardiovascular death hazard ratios were 2.44 (95% confidence interval: 1.28 to 4.65) and 3.63 (1.13 to 11.64), respectively, in recipients in the ≥9.5 group; allograft loss hazard ratios were 1.42 (1.04 to 1.95) and 2.36 (1.33 to 4.17) in recipients with 7.5 to >9.5 and ≥9.5, respectively. No significant association with delayed graft function was found., Conclusions: Pretransplant phosphorus levels 7.5 to <9.5 mg/dl and ≥9.5 mg/dl were associated with increased risk of functional graft failure and increased risk of all-cause and cardiovascular deaths, respectively, when compared with 3.5 to <5.5 mg/dl. Additional studies are needed to examine whether more aggressive control of pretransplant serum phosphorus may improve posttransplant outcomes.

Background and Objectives: Interventional 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, & Measurements: We 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., Results: Lower hemoglobin was associated with significantly higher all-cause mortality in ESA-treated PD patients: with hemoglobin of 11.0 to <12.0 g/dl as reference, the time-dependent adjusted death hazard ratios for hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.12 (1.00 to 1.24), 1.30 (1.12 to 1.50), and 1.38 (1.14 to 1.67), respectively. The time-dependent adjusted hazard ratios for cardiovascular death with hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.11 (0.93 to 1.32), 1.37 (1.09 to 1.72), and 1.12 (0.79 to 1.57), respectively. The same trend for association of lower hemoglobin level with higher mortality was seen in African-American and non-African American men and women. In contrast, there was no association between higher achieved hemoglobin and all-cause or cardiovascular mortality in ESA-treated PD patients., Conclusions: Lower, but not higher, achieved hemoglobin is associated with higher mortality in ESA-treated PD patients. Randomized controlled trials are needed to examine the target hemoglobin level with lowest mortality in PD patients.

Background and Objectives: The 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, & Measurements: Linking 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., Results: Patients 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 <22 and < 20 kg/m(2), compared with 22 to <25 kg/m(2), showed a nonsignificant trend toward higher combined posttransplant mortality or graft failure, and even weaker associations existed for BMI ≥ 25 kg/m(2). Compared with pretransplant 3-month- averaged serum creatinine of 8 to <10 mg/dl, there was 2.2-fold higher risk of combined death or graft failure with serum creatinine <4 mg/dl, whereas creatinine ≥14 mg/dl exhibited 22% better graft and patient survival., Conclusions: Pretransplant obesity does not appear to be associated with poor posttransplant outcomes. Larger pretransplant muscle mass, reflected by higher pretransplant serum creatinine level, is associated with greater posttransplant graft and patient survival.

Background and Objectives: Maintenance 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, & Measurements: We 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., Results: Worse 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., Conclusions: MHD 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., (Copyright © 2011 by the American Society of Nephrology)

Background and Objectives: The optimal target for glycemic control has not been established for diabetic peritoneal dialysis (PD) patients., Design, Setting, Participants, & Measurements: We 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., Results: We 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., Conclusions: Poor 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., (Copyright © 2011 by the American Society of Nephrology)

Background and Objectives: Maintenance hemodialysis (MHD) patients with larger body or fat mass have greater survival than normal to low mass. We hypothesized that mid-arm muscle circumference (MAMC), a conveniently measured surrogate of lean body mass (LBM), has stronger association with clinical outcomes than triceps skinfold (TSF), a surrogate of fat mass., Design, Settings, Participants, & Measurements: The associations of TSF, MAMC, and serum creatinine, another LBM surrogate, with baseline short form 36 quality-of-life scores and 5-year survival were examined in 792 MHD patients. In a randomly selected subsample of 118 subjects, LBM was measured by dual-energy x-ray absorptiometry., Results: Dual-energy x-ray absorptiometry-assessed LBM correlated most strongly with MAMC and serum creatinine. Higher MAMC was associated with better short form 36 mental health scale and lower death hazard ratios (HRs) after adjustment for case-mix, malnutrition-inflammation-cachexia syndrome, and inflammatory markers. Adjusted death HRs were 1.00, 0.86, 0.69, and 0.63 for the first to fourth MAMC quartiles, respectively. Higher serum creatinine and TSF were also associated with lower death HRs, but these associations were mitigated after multivariate adjustments. Using median values of TSF and MAMC to dichotomize, combined high MAMC with either high or low TSF (compared with low MAMC/TSF) exhibited the greatest survival, i.e., death HRs of 0.52 and 0.59, respectively., Conclusions: Higher MAMC is a surrogate of larger LBM and an independent predictor of better mental health and greater survival in MHD patients. Sarcopenia-correcting interventions to improve clinical outcomes in this patient population warrant controlled trials.

Background and Objectives: Obesity is associated with increased parathyroid hormone (PTH) in the general population and in patients with chronic kidney disease (CKD). A direct effect of adipose tissue on bone turnover through leptin production has been suggested, but such an association has not been explored in kidney transplant recipients., Design, Setting, Participants, & Measurements: This study examined associations of serum leptin with PTH and with biomarkers of bone turnover (serum beta crosslaps [CTX, a marker of bone resorption] and osteocalcin [OC, a marker of bone formation]) in 978 kidney transplant recipients. Associations were examined in multivariable regression models. Path analyses were used to determine if the association of leptin with bone turnover is independent of PTH., Results: Higher leptin levels were associated with higher PTH and lower vitamin D levels, and adjustment for vitamin D attenuated the association between leptin and PTH. However, higher leptin was also significantly associated with lower levels of the bone turnover markers: 1 SD higher leptin was associated with 0.13 lower log-OC (-0.17, -0.08, P < 0.001) and 0.030 lower log-CTX (-0.045, -0.016, P < 0.001) after multivariable adjustments. Path analysis indicated that the association of leptin with PTH was mostly mediated through vitamin D, and that the association between leptin and bone turnover was independent of PTH and vitamin D., Conclusions: Elevated leptin level is associated with lower bone turnover independent of its effects on serum PTH in kidney transplant recipients.

The introduction of calcitriol followed by several of its analogs in the 1990s made vitamin D receptor activators (VDRA) the cornerstone of therapy for secondary hyperparathyroidism. The 2003 publication of the first major epidemiologic study describing the association of VDRAs with survival in ESRD has raised the awareness of the nephrology community about the potential impact of these agents on morbidity and mortality. This study was followed by numerous other epidemiologic studies which attempted to address the inherent shortcomings of observational studies by using sophisticated statistical methods. The complex nature of the statistical designs applied by some of these studies has led to some confusion about how to interpret the results, and how to use the results in a way that offers the most help for patients, but does not impede future scientific research. This report presents a discussion of relevant studies examining the association between VDRA and survival, with the goal to examine shortcomings that still exist in the knowledge on this subject. Special emphasis is placed on the discussion of studies with discrepant results to highlight remaining controversies and to emphasize areas in need of further research. Not withstanding all of the limitations of epidemiologic studies, the preponderance of evidence favors a survival benefit for ESRD patients treated with VDRA. This should provide a powerful impetus to investigate in clinical trials the risks and benefits of VDRA administration as a means to prolong survival.

Background and Objectives: Epidemiologic studies show an association between higher predialysis serum phosphorus and increased death risk in maintenance hemodialysis (MHD) patients. The hypothesis that higher dietary phosphorus intake and higher phosphorus content per gram of dietary protein intake are each associated with increased mortality in MHD patients was examined., Design, Setting, Participants, & Measurements: Food frequency questionnaires were used to conduct a cohort study to examine the survival predictability of dietary phosphorus and the ratio of phosphorus to protein intake. At the start of the cohort, Cox proportional hazard regression was used in 224 MHD patients, who were followed for up to 5 years (2001 to 2006)., Results: Both higher dietary phosphorus intake and a higher dietary phosphorus to protein ratio were associated with significantly increased death hazard ratios (HR) in the unadjusted models and after incremental adjustments for case-mix, diet, serum phosphorus, malnutrition-inflammation complex syndrome, and inflammatory markers. The HR of the highest (compared with lowest) dietary phosphorus intake tertile in the fully adjusted model was 2.37. Across categories of dietary phosphorus to protein ratios of <12, 12 to <14, 14 to <16, and > or =16 mg/g, death HRs were 1.13, 1.00 (reference value), 1.80, and 1.99, respectively. Cubic spline models of the survival analyses showed similar incremental associations., Conclusions: Higher dietary phosphorus intake and higher dietary phosphorus to protein ratios are each associated with increased death risk in MHD patients, even after adjustments for serum phosphorus, phosphate binders and their types, and dietary protein, energy, and potassium intakes.

In individuals with chronic kidney disease, high dietary phosphorus (P) burden may worsen hyperparathyroidism and renal osteodystrophy, promote vascular calcification and cardiovascular events, and increase mortality. In addition to the absolute amount of dietary P, its type (organic versus inorganic), source (animal versus plant derived), and ratio to dietary protein may be important. Organic P in such plant foods as seeds and legumes is less bioavailable because of limited gastrointestinal absorption of phytate-based P. Inorganic P is more readily absorbed by intestine, and its presence in processed, preserved, or enhanced foods or soft drinks that contain additives may be underreported and not distinguished from the less readily absorbed organic P in nutrient databases. Hence, P burden from food additives is disproportionately high relative to its dietary content as compared with natural sources that are derived from organic (animal and vegetable) food proteins. Observational and metabolic studies indicate nutritional and longevity benefits of higher protein intake in dialysis patients. This presents challenges to providing appropriate nutrition because protein and P intakes are closely correlated. During dietary counseling of patients with chronic kidney disease, the absolute dietary P content as well as the P-to-protein ratio in foods should be addressed. Foods with the least amount of inorganic P, low P-to-protein ratios, and adequate protein content that are consistent with acceptable palatability and enjoyment to the individual patient should be recommended along with appropriate prescription of P binders. Provision of in-center and monitored meals during hemodialysis treatment sessions in the dialysis clinic may facilitate the achievement of these goals.

Background and Objectives: Elevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes associated with low serum calcium are also not well-characterized., Design, Setting, Participants, & Measurements: We examined associations of baseline, time-varying, and time-averaged serum calcium with all-cause mortality in a historic prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox models., Results: The association of serum calcium with mortality varied according to the applied statistical models. Higher baseline calcium and time-averaged calcium were associated with higher mortality (multivariable adjusted hazard ratio (95% confidence interval): 1.31 (1.13, 1.53); P < 0.001 for a baseline calcium 1 mg/dl higher). However, in time-varying analyses, lower calcium levels were associated with increased mortality., Conclusions: Higher serum calcium is associated with increased long-term mortality (as reflected by the baseline and time-averaged models), and lower serum calcium is associated with increased short-term mortality (as reflected by the time-varying models) in patients with NDD CKD. Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in these patients.

Increasing confusion exists as to which vitamin D compounds are more appropriate for persons with chronic kidney disease (CKD). Some opinion-based guidelines recommend administration of such nutritional vitamin D agents as ergocalciferol or cholecalciferol as the first therapy in hyperparathyroidism associated with low circulating levels of 25-hydroxy vitamin D (<30 ng/ml) in nondialysis dependent CKD patients. Insufficient to deficient levels of 25-hydroxy vitamin D have been reported in the majority of individuals with CKD, including both nondialysis dependent and maintenance dialysis patients. Epidemiologic studies have almost consistently indicated the survival benefit of active vitamin D agents across all stages of CKD, including among dialysis patients with 25-hydroxy vitamin D deficiency. To date, no large observational or interventional studies have shown any survival advantage of nutritional vitamin D in CKD patients. Several recent (postguideline) small studies have yielded mixed results regarding the potential benefits of ergocalciferol in CKD, including satisfactory to inadequate lowering of PTH level to target ranges, improving response to erythropoietin stimulating agents, and salutary effects on glycemic controls. Compared with nutritional vitamin D agents, active vitamin D compounds appear to more effectively lower the circulating levels of alkaline phosphatase, a conveniently available biomarker associated with increased mortality and coronary artery calcification in CKD patients. The ideal vitamin D therapy for CKD patients should be the one that improves survival irrespective of suggested or imposed target ranges for arbitrary or opinion-based surrogate end points. Randomized controlled trials are needed to verify which agents offer superior survival advantages.

Background and Objectives: Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients., Design, Setting, Participants, & Measurements: We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured., Results: Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P = 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant., Conclusions: An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

Background and Objectives: Blacks are over-represented among dialysis patients, but they have better survival rates than whites. It is unclear if the over-representation of blacks on dialysis is due to faster loss of kidney function or greater survival (or both) in predialysis stages of chronic kidney disease (CKD)., Design, Setting, Participants & Measurements: We compared predialysis mortality, incidence of end stage renal disease (ESRD), and slopes of estimated GFR (eGFR) in 298 black versus 945 white male patients with moderate and advanced nondialysis-dependent CKD (NDD-CKD) from a single medical center. Mortality and ESRD incidence were compared in parametric survival models, and slopes of eGFR were assessed in mixed-effects models., Results: Blacks had lower crude mortality and higher crude ESRD incidence. The lower mortality in blacks was explained by differences in case mix, especially a lower prevalence of cardiovascular disease, and the higher incidence of ESRD was explained by differences in case mix and baseline kidney function. The slopes of eGFR were similar in blacks and whites., Conclusions: Lower mortality in black versus white patients is also observed in NDD-CKD and can be accounted for by differences in clinical characteristics. Higher mortality of black patients in earlier stages of CKD may result in the selection of a subgroup with fewer comorbidities and better survival in later stages of CKD. The higher crude ESRD rate in blacks appears to result from lower mortality in late stages of CKD, not faster progression of CKD.

Background and Objectives: Assessments of iron stores by serum iron saturation ratio (ISAT) and ferritin are used to direct anemia therapy in chronic kidney disease (CKD) and are associated with clinical outcomes in patients on dialysis. The association of ISAT and ferritin with outcomes in patients with nondialysis-dependent CKD (NDD-CKD) has not been studied., Design, Setting, Participants, & Measurements: All-cause mortality and progression of CKD [slopes of estimated GFR (eGFR)] were examined in 453 men with NDD-CKD. Mortality and the composite of mortality and ESRD were studied in Cox models. Slopes of eGFR were examined in mixed-effects models., Results: Lower ISAT was associated with higher mortality; adjusted hazard ratio [95% confidence interval (CI)] with ISAT of <12%, 13 to 17%, and >23% versus 18 to 23%; 1.40 (0.99 to 1.98), 1.20 (0.82 to 1.76), and 0.97 (0.67 to 1.41), P = 0.025 for trend. ISAT was also associated with steeper slopes of eGFR (one log-unit higher ISAT associated with a slope of -0.89 ml/min/1.73 m(2) /yr (95% CI: -1.75, -0.02, P = 0.044). Serum ferritin level showed no significant association with outcomes overall, but a trend for higher mortality was observed in patients with a serum ferritin level >250 ng/ml., Conclusions: Higher ISAT is associated with lower mortality and with more progressive CKD. Clinical trials are needed to examine if correction of low iron levels can improve mortality without affecting kidney function in NDD-CKD.

Background and Objectives: Several 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 (PTH), indicative of a more severe secondary hyperparathyroidism and higher death risk, are usually given higher VDRA dosages, which can lead to confounding by medical indication and attenuated survival advantage of high VDRA dosages. It was hypothesized that the ratio of the administered paricalcitol dosage to serum PTH level discloses better the underlying dosage-survival association., Design, Setting, Participants, & Measurements: The 3-yr mortality predictability of the administered paricalcitol during the first 3 mo of the cohort divided by averaged serum intact PTH during the same period was examined in 34,307 MHD patients from all DaVita dialysis clinics across the United States using Cox regression., Results: MHD patients were 60.8 +/- 15.4 yr of age and included 47% women, 34% black patients, and 47% patients with diabetes. Initially, the ratio of paricalcitol (mircrog/wk) to PTH (pg/ml) was divided into four groups: 0 (reference), 1 to <30, 30 to <60, and >60 x 10(-3). Unadjusted, case mix-adjusted (demographics, comorbidity, and Kt/V), and malnutrition-inflammation complex syndrome-adjusted models, the death rate ratio for the paricalcitol/PTH index groups, were 0.99, 0.95, and 0.92. Restricted cubic splines analyses were consistent with a linear relation., Conclusions: Higher weekly paricalcitol dosage per each unit of serum PTH seems to have an incremental association with greater survival in MHD patients. The observed dosage-response phenomenon needs to be confirmed in clinical trials.

Background: Serum ferritin, frequently used as a marker of iron status in individuals with chronic kidney disease, is also an inflammatory marker. The concurrent combination of high serum ferritin and low iron saturation ratio (ISAT) usually poses a diagnostic dilemma. We hypothesized that serum ferritin > or =500 ng/ml, especially in the seemingly paradoxical presence of ISAT level <25%, is more strongly associated with inflammation than with iron in maintenance hemodialysis (MHD) patients., Design, Setting, and Participants: In 789 MHD patients in the Los Angeles area, the association of serum ferritin > or =500 ng/ml with inflammatory markers, including IL-6 (IL-6) and C-reactive protein levels, and malnutrition-inflammation score (MIS) was examined., Results: After multivariate adjustment for case-mix and other measures of malnutrition-inflammation complex, MHD patients with serum ferritin > or =500 ng/ml and ISAT <25% had higher odds ratio for serum C-reactive protein > or =10 mg/L. The area under the receiver operating characteristic curves for the continuum of ISAT and IL-6 in detecting a serum ferritin > or =500 ng/ml were identical (0.57 versus 0.56, P = 0.7). The combination of IL-6 with ISAT yielded a higher area under the receiver operating characteristic curve (0.61) than either ISAT or IL-6 alone (P = 0.03 and P = 0.02, respectively)., Conclusion: In MHD patients, ferritin values above 500 ng/ml, especially in paradoxical conjunction with low ISAT, are associated with inflammation. Strategies to dissociate inflammation from iron metabolism to mitigate the confounding impact of inflammation on iron and to improve iron treatment responsiveness may improve anemia management in chronic kidney disease.

Renal osteodystrophy is a significant complication in chronic kidney disease. This condition is referred to as mineral and bone disorders in chronic kidney disease, mainly because of its wider ranging impact, including an association with increased mortality and non-bone-related morbidity. Because most of the abnormalities that characterize mineral and bone disorders in chronic kidney disease (e.g., hyperphosphatemia, secondary hyperparathyroidism) are amenable to therapeutic interventions, this field has also been in the cross-hairs of many pharmaceutical companies. The advent of a number of new therapeutic options for mineral and bone disorders in chronic kidney disease has broadened our armamentarium but has also resulted in an intense marketing battle between pharmaceutical companies. The paucity of randomized, controlled trials in this field has allowed the various companies to promote unilaterally data that fit their needs and to attempt to discredit data that support their competitors' products. Although this attitude is expected and regarded as acceptable in a consumer society, on a scientific level, it has resulted in a polarized and often confused audience: The practicing nephrologists. This article provides a historical overview of how the field of mineral and bone disorders in chronic kidney disease has evolved from a pharmaceutical standpoint, with a critical emphasis of the key moments that resulted in the current acrimonious climate. Also assessed is what the key unanswered questions are in this field, and practical solutions to the discussed issues are provided.

Background and Objectives: Controlling serum potassium is an important goal in maintenance hemodialysis patients. We examined the achievement of potassium balance through hemodialysis treatments and the associated fluctuations in serum potassium., Design, Setting, Participants, & Measurements: A 3-yr (July 2001 to June 2004) cohort of 81,013 maintenance hemodialysis patients from all DaVita dialysis clinics across the United States were studied. Nine quarterly-averaged serum potassium groups (< 4.0, > or = 6.3 mEq/L and seven increments in-between) and four dialysate potassium concentration groups were created in each of the 12 calendar quarters. The death risk associated with predialysis potassium level and dialysate potassium concentration was examined using unadjusted, case-mix adjusted, and malnutrition-inflammation-adjusted time-dependent survival models., Results: Serum potassium correlated with nutritional markers. Serum potassium between 4.6 and 5.3 mEq/L was associated with the greatest survival, whereas potassium < 4.0 or > or = 5.6 mEq/L was associated with increased mortality. The death risk of serum potassium > or = 5.6 mEq/L remained consistent after adjustments. Higher dialysate potassium concentration was associated with increased mortality in hyperkalemic patients with predialysis serum potassium > or = 5.0 mEq/L., Conclusions: A predialysis serum potassium of 4.6 to 5.3 mEq/L is associated with the greatest survival in maintenance hemodialysis patients. Hyperkalemic patients who undergo maintenance hemodialysis against lower dialysate bath may have better survival. Limitations of observational studies including confounding by indication should be considered when interpreting these results.

Background and Objectives: Obesity is associated with secondary hyperparathyroidism in the general population. The objective of this study is to explore whether the same association is present in patients with chronic kidney disease., Design, Setting, Participants & Measurements: Linear regression models were used to examine the association between intact parathyroid hormone level and body mass index in 496 male US veterans (age 69.4 +/- 10.2 yr, 22.8% black) who had chronic kidney disease stages 2 to 5 and were not yet on dialysis (estimated GFR 31.8 +/- 11.2 ml/min per 1.73 m2)., Results: Higher intact parathyroid hormone was associated with higher body mass index after adjustment for age, race, diabetes, and serum calcium and phosphorus levels. This association was independent of age, race, diabetes status, and serum calcium and phosphorus but was limited to patient groups with lower albumin (P = 0.005 for the interaction term) or higher white blood cell count (P = 0.026 for the interaction term)., Conclusions: Higher body mass index is associated with secondary hyperparathyroidism in patients who have chronic kidney disease and are not yet on dialysis, especially in patients with evidence of malnutrition and inflammation. Confirmation of these findings in other patient groups with chronic kidney disease and better characterization of the underlying mechanisms of action will be necessary before advocating weight loss as a means to treat secondary hyperparathyroidism in chronic kidney disease.

Abnormalities of mineral metabolism are associated with increased mortality in patients with ESRD, but their effects in predialysis chronic kidney disease (CKD) are less well characterized. In this study, the associations between levels of serum phosphorus, calcium, and calcium-phosphorus product and progression of CKD were examined. Historical data were collected on 985 male US veterans (age 67.4 +/- 10.9; 23.9% black) with CKD stages 1 through 5. Unadjusted and multivariable-adjusted relative risks for progressive CKD (defined as the composite of ESRD or doubling of serum creatinine) were calculated for categories of serum phosphorus, calcium, and calcium-phosphorus product using Cox proportional hazards models. Higher phosphorus was associated with a higher risk for the composite end point (adjusted hazard ratio [HR] [95% confidence interval (CI)] for phosphorus levels 3.3 to 3.8, 3.81 to 4.3, and >4.3 versus <3.3 mg/dl 0.83 [0.54 to 1.27], 1.24 [0.82 to 1.88], and 1.60 [1.06 to 2.41]; P = 0.001 for trend). A 1-mg/dl higher phosphorus level was associated with an adjusted HR (95% CI) of 1.29 (1.12 to 1.48; P < 0.001). Higher calcium-phosphorus product also was associated with higher risk for progressive CKD (adjusted HR [95% CI] for calcium-phosphorus products 30 to 35, 36 to 40, and >40 versus <30 mg2/dl2 0.58 [0.36 to 0.94], 0.87 [0.57 to 1.34], and 1.37 [0.91 to 2.07]; P = 0.002 for trend). A 10-mg2/dl2 higher calcium-phosphorus product was associated with an adjusted HR (95% CI) of 1.29 (1.11 to 1.51; P = 0.001). Lower serum calcium showed a trend toward higher risk for progressive CKD but without statistical significance. Higher serum phosphorus and higher calcium-phosphorus product are associated with progression of CKD.