Erythropoietin, iron depletion, and relative thrombocytosis: a possible explanation for hemoglobin-survival paradox in hemodialysis.

Background: High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels greater than 13 g/dL in patients with chronic kidney disease appear to be associated with increased mortality.

Study Design: We conducted logistic regression and survival analyses in a retrospective cohort of long-term hemodialysis patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose-associated hemoglobin level of 13 g/dL or greater and mortality.

Setting & Participants: The national database of a large dialysis organization (DaVita) with 40,787 long-term hemodialysis patients during July to December 2001 and their survival up to July 2004 were examined.

Ratio of paricalcitol dosage to serum parathyroid hormone level and survival in maintenance hemodialysis patients.

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.

Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients.

Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.

Association between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alkalotic?

The optimal acid-base status for survival in maintenance hemodialysis (MHD) patients remains controversial. According to recent reports, acidosis is associated with improved survival in MHD patients. It was hypothesized that this inverse association is due to a confounding effect of the malnutrition-inflammation complex syndrome (MICS).

Serum and dialysate potassium concentrations and survival in hemodialysis patients.

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.

Hepatitis C virus and death risk in hemodialysis patients.

In maintenance hemodialysis (MHD) patients, hepatitis C virus (HCV) infection is common and may be associated with poor clinical outcomes. It was hypothesized that HCV infection would be associated with high all-cause and cardiovascular mortality in these patients after controlling for demographic and clinical characteristics, including surrogates of malnutrition-inflammation complex syndrome. A national database of 13,664 MHD patients who underwent HCV antibody serology testing at least once during a 3-yr interval (July 2001 through June 2004) was analyzed.

A1C and survival in maintenance hemodialysis patients.

Objective: The optimal target for glycemic control has not been established in diabetic dialysis patients.

Research Design And Methods: To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures.

Results: Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once.

Association between serum lipids and survival in hemodialysis patients and impact of race.

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter.

Longitudinal associations between dietary protein intake and survival in hemodialysis patients.

Background: Decreased dietary protein intake may be associated with increased mortality risk in individuals with kidney failure undergoing maintenance hemodialysis (MHD). We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in MHD patients.

Methods: The relation between urea kinetic-based normalized protein nitrogen appearance (nPNA) and all-cause and cardiovascular mortality was examined in a 2-year (July 2001 to June 2003) cohort of 53,933 MHD patients from virtually all DaVita dialysis clinics in the United States, using both conventional and time-dependent (repeated-measure) Cox models to estimate death hazard ratios for quarterly averaged nPNA categories controlled for case-mix, comorbidity, dialysis dose (Kt/V), and available markers of malnutrition-inflammation complex syndrome (MICS).

Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients.

Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States.

Association of morbid obesity and weight change over time with cardiovascular survival in hemodialysis population.

Background: In maintenance hemodialysis (MHD) outpatients, a reverse epidemiology is described, ie, baseline obesity appears paradoxically associated with improved survival. However, the association between changes in weight over time and prospective mortality is not known.

Methods: Using time-dependent Cox models and adjusting for changes in laboratory values over time, the relation of quarterly-varying 3-month averaged body mass index (BMI) to all-cause and cardiovascular mortality was examined in a 2-year cohort of 54,535 MHD patients from virtually all DaVita dialysis clinics in the United States.

Time-dependent associations between iron and mortality in hemodialysis patients.

The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States.

Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

Background: Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different.

Clinical characteristics and mortality in hepatitis C-positive haemodialysis patients: a population based study.

Background: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood.

Methods: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001.

Results: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals.

Reverse epidemiology of hypertension and cardiovascular death in the hemodialysis population: the 58th annual fall conference and scientific sessions.

Maintenance hemodialysis patients in the United States have a high prevalence (approximately 80%) of systolic hypertension and a high mortality (approximately 20% per year). Some reports indicate a paradoxical association between hypertension and mortality in hemodialysis patients (ie, a normal to low blood pressure is associated with poor outcome), whereas high pressure confers survival advantages, a phenomenon referred to as "reverse epidemiology." We hypothesized that malnutrition-inflammation complex syndrome may be a cause of this paradoxical association.

Static intra-access pressure ratio does not correlate with access blood flow.

Background: Access flow (Qa) measurement is recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) as the preferred method for access surveillance. Static intra-access pressure ratio (SIAPR) measurement is the second surveillance method of choice. The purpose of this prospective multicenter study was to investigate the relationship between SIAPR and Qa and to examine the premise upon which SIAPR surveillance is based-namely, that high SIAPR is a surrogate for low Qa associated with hemodynamically significant stenosis.

Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.

Background: Malnutrition-inflammation complex syndrome, an outcome predictor in maintenance hemodialysis (MHD) patients, may be related to anorexia.

Objectives: We examined whether subjectively reported appetite is associated with adverse conditions and increased morbidity and mortality in MHD patients.

Design: A cohort of 331 MHD outpatients was asked to rate their recent appetite status on a scale from 1 to 4 (very good, good, fair, and poor appetite, respectively).

A low serum iron level is a predictor of poor outcome in hemodialysis patients.

Background: Iron administration has been implicated as a cause of poor clinical outcome in maintenance hemodialysis (MHD) patients. However, the role of low iron levels in the clinical outcome of MHD patients is not clear.

Methods: We examined the predicting value of baseline serum iron level on prospective mortality and hospitalization in a cohort of all 1,283 MHD patients from 10 DaVita dialysis facilities in Los Angeles County, CA.

A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients.

An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.

Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients.

Background: Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO).

Methods: The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition.

Results: A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.

Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with Kt/V greater than 1.20.

Objectives: Normalized protein nitrogen appearance (nPNA), also known as protein catabolic rate (nPCR), reflects the daily protein intake in maintenance hemodialysis (MHD) patients. Several studies indicate that nPNA and Kt/V correlate with clinical outcome and also with each other. Thus, the relationship between low nPNA and poor outcome could be due to uremia, low Kt/V or due to reported mathematical coupling between nPNA and Kt/V.