Design, setting, participants, & measurements: In a prospective cohort study of predialysis patients, patients who were on dialysis, and kidney transplant recipients, serum was collected and assayed for both B-type natriuretic peptide and its N-terminal fragment. Median levels were compared using nonparametric tests, and predictors of B-type natriuretic peptide were determined by linear regression. Survival analysis and Cox regression were performed to examine the association of levels of B-type natriuretic peptide with cardiovascular events and death.

Results: Levels of B-type natriuretic peptide were highest in patients who were on dialysis. Patients who were receiving dialysis and had known cardiovascular disease, were not on the waiting list for kidney transplantation, or had left ventricular systolic dysfunction on echocardiography had significantly higher levels of B-type natriuretic peptide than patients without these characteristics. Glomerular filtration rate was an important predictor of B-type natriuretic peptide levels for patients who were not on dialysis (predialysis and renal transplant recipients). Left ventricular systolic dysfunction predicted B-type natriuretic peptide levels in patients who were on dialysis. Both forms of B-type natriuretic peptide were associated with a two- to three-fold increased risk for death in patients who were on dialysis.

Conclusions: Levels of B-type natriuretic peptide are greatest in patients who are on dialysis and have cardiovascular comorbidities and are strong predictors of death.

Design, setting, participants, & measurements: This multidisciplinary study identified candidate best practices in dialysis through a staged process, including systematic review, cognitive interviews, and a national "virtual focus group" of dialysis providers. The resulting candidate practices were rank-ordered by perceived importance as determined by mean RAND Appropriateness Scores from a national survey of nephrologists, nurses, and opinion leaders.

Results: A total of 155 candidate best practices were identified. Among these, respondents believed dialysis outcomes are most strongly related to 1) characteristics of multidisciplinary care conferences, 2) technician proficiency in protecting vascular access, 3) training of nurses to provide education in fluid management, vascular access, and nutrition, 4) use of random and blinded audits of staff performance, and 5) communication and teamwork among staff. In contrast, there was wide disagreement about the importance of facility-based health maintenance practices, optimal staffing ratios, frequency of dialysis-based physician visits, and optimal frequency of multidisciplinary care.

Conclusions: This study provides a "conceptual map" of candidate dialysis best practices and highlights areas of general agreement and disagreement. These findings can help the dialysis community think critically about what may define "best practice" and provide targets for future research in quality improvement.

Design, setting, participants, & measurements: Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality.

Results: Erythropoietin responsiveness values ranged from –2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87).

Conclusion: Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.

Design, setting, participants, & measurements: A total of 1079 patients who had an ankle-brachial index and serum creatinine recorded within 90 d of each other in 1999 were studied retrospectively. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Patients were categorized into four groups: Chronic kidney disease and peripheral arterial disease, chronic kidney disease alone, peripheral arterial disease alone, or no chronic kidney disease or peripheral arterial disease.

Results: The overall 6-yr mortality rate was 28% (n = 284). Patients with both chronic kidney disease and peripheral arterial disease had the highest mortality rate (45%) compared with patients with chronic kidney disease alone (28%), peripheral arterial disease alone (26%), and neither condition (18%). After adjustment for clinical and demographic variables, the chronic kidney disease and peripheral arterial disease group had an increased odds for death when compared with the no chronic kidney disease or peripheral arterial disease group or the single disease groups.

Conclusions: These findings indicate that patients with both chronic kidney disease and peripheral arterial disease have a significantly higher risk for death than patients with either disease alone.

Design, setting, participants, & measurements: This analysis used United States Renal Data System registry data to study retrospectively Medicare-insured kidney transplant candidates (n = 51,504), recipients (n = 29,614), and recipients with allograft failure (n = 2954) in 1995 through 2002. New-onset cerebrovascular disease events including ischemic stroke, hemorrhagic stroke, and transient ischemic attacks were ascertained from billing records, and participants were followed until Medicare-end or December 31, 2002. Multivariable survival analysis was used to compare cerebrovascular disease event incidence and risk profiles among the study samples.

Results: The cumulative, 3-yr incidence of de novo cerebrovascular disease events after transplantation was 6.8% and was lower than adjusted 3-yr estimates of 11.8% on the waiting list and 11.2% after graft loss. In time-dependent regression, transplantation predicted a 34% reduction in subsequent, overall cerebrovascular disease events risk compared with remaining on the waiting list, whereas risk for cerebrovascular disease events increased >150% after graft failure. Similar relationships with transplantation and graft loss were observed for each type of cerebrovascular disease event. Smoking was a potentially preventable correlate of posttransplantation cerebrovascular disease events. Women were not protected. All forms of cerebrovascular disease event diagnoses after transplantation predicted increased mortality.

Conclusions: Along with known benefits for cardiac complications, transplantation with sustained graft function seems to reduce risk for vascular disease events involving the cerebral circulation.

Design, setting, participants, & measurements: We searched electronic databases (Medline, Embase, American College of Physicians Journal Club, Cochrane) and hand searched Cochrane renal group records. Clinical practice guidelines, case reports, narrative reviews, and pooled individual patient data meta-analyses were excluded. Methodologic quality was measured using a validated questionnaire (Overview Quality Assessment Questionnaire). For reviews of randomized trials, we also evaluated adherence to recommended reporting guidelines (Quality of Reporting of Meta-Analyses).

Results: Ninety renal systematic reviews were published in year 2005, 60 of which focused on therapy. Many systematic reviews (54%) had major methodologic flaws. The most common review flaws were failure to assess the methodologic quality of included primary studies and failure to minimize bias in study inclusion. Only 2% of reviews of randomized trials fully adhered to reporting guidelines. A minority of journals (four of 48) endorsed adherence to consensus guidelines for review reporting, and these journals published systematic reviews of higher methodologic quality (P < 0.001).

Conclusions: The majority of systematic reviews had major methodologic flaws. The majority of journals do not endorse consensus guidelines for review reporting in their instructions to authors; however, journals that recommended such adherence published systemic reviews of higher methodologic quality.

Design, setting, participants, & measurements: The USRDS data for Medicare beneficiaries transplanted in 1991 to 2004 with Part A&B benefits from dialysis initiation through transplantation were examined. Clinical traits defining "high" expected IHD risk were defined as diabetes, prior IHD, or ≥ 2 other coronary risk factors. Pretransplant CE were identified by billing claims for noninvasive stress tests and angiography. Patients were quantified with claims for coronary revascularization procedures between CE and transplant. Post-transplant acute myocardial infarction (AMI) events were abstracted from claims and death records.

Results: Among 27,786 eligible patients, 46.3% underwent CE before transplantation. Overall, 9.5% who received CE also received pretransplant revascularization, but only 0.3% of lower-risk patients undergoing CE had revascularization. The adjusted odds of transplant without CE increased sharply with younger age and shorter dialysis duration. Increased likelihood of transplant without CE also correlated with black race, female sex, and certain geographic regions. Among patients transplanted without CE, 3-yr incidence of post-transplant AMI was 3% in lower-risk and 10% in high-risk groups, and varied by individual traits within these groups. Among lower-risk patients transplanted without CE, blacks were higher risk for AMI than whites (adjusted hazards ratio 1.47, 95% CI 1.11–1.93).

Conclusions: Observed practices demonstrate infrequent use of pretransplant revascularization after CE but also raise concern for socio-demographic barriers to evaluation access.

Design, setting, participants, & measurements: A prospective cohort study of an outpatient hemodialysis unit was conducted. Serial surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus were collected from patients who were undergoing chronic hemodialysis.

Results: Nineteen (28%) of the 67 enrolled patients were colonized with one or more antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%), and three (5%) patients were colonized with multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Independent risk factors associated with harboring multidrug-resistant gram-negative bacteria at enrollment were residence in a long-term care facility and antibiotic exposure for ≥7 d in the previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and 13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Antibiotic exposure was the only independent risk factor for multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug-resistant gram-negative bacteria acquisition was detected among 69% of acquired multidrug-resistant gram-negative bacterial strains.

Conclusions: The prevalence and acquisition of multidrug-resistant gram-negative bacteria surpassed that of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Endogenous acquisition, as opposed to patient-to-patient spread, was the predominant mechanism of acquisition. Residence in a long-term care facility and antibiotic exposure may be important factors promoting the spread of multidrug-resistant gram-negative bacteria among this patient population.

Design, setting, participants, & measurements: This retrospective cohort study linked data on patients aged 12 to 18 yr in 1999 and 2000 from the Centers for Medicare and Medicaid Services’ End Stage Renal Disease Clinical Performance Measures Project with 4-yr hospitalization and mortality records in the United States Renal Data System. Albumin was categorized as <3.5/3.2, ≥3.5/3.2 and <4.0/3.7, and ≥4.0/3.7 g/dl.

Results: Of 675 adolescents, 557 were hospitalized and 50 died. Albumin ≥4.0/3.7 g/dl was associated with male gender, Hispanic ethnicity, and higher hemoglobin level. Those with albumin ≥4.0/3.7 g/dl had fewer deaths per 100 patient-years and fewer hospitalizations per time at risk. In multivariate analysis, patients with albumin ≥4.0/3.7 g/dl had 57% decreased risk for death. Poisson regression showed progressive decrease in hospitalization risk as albumin level increased; however, confidence intervals were similar between albumin ≥4.0/3.7 g/dl and albumin ≥3.5/3.2 and <4.0/3.7 g/dl.

Conclusions: This study demonstrates decreased mortality and hospitalization risk with albumin ≥3.5/3.2 g/dl and suggests that adolescent hemodialysis patients who are able to achieve serum albumin ≥4.0/3.7 g/dl may have the lowest mortality risk.

Design, setting, participants, & measurements: This retrospective cohort study, using data from the Australia and New Zealand Dialysis and Transplant registry, included all patients who were aged 35 to 84 yr and started long-term renal replacement therapy in Australia from 1971 through 2006.

Results: Of 31,654 incident renal replacement therapy patients, 10.2% had analgesic nephropathy. Incidence and prevalence of renal replacement therapy attributed to analgesic nephropathy decreased earlier and faster among younger (age <55 yr) patients. Prevalence of analgesic nephropathy among 75- to 84-yr-old renal replacement therapy patients is still increasing. Compared with control subjects without diabetes, comorbidities (coronary artery, cerebrovascular, peripheral vascular, and chronic lung diseases) were more prevalent among patients with analgesic nephropathy at renal replacement therapy start. All-cause, cardiovascular, infection, and cancer mortality were higher among patients who had analgesic nephropathy and were on renal replacement therapy. For both comorbidities and mortality, the associations were stronger in younger patients.

Conclusions: Trends in renal replacement therapy attributed to analgesic nephropathy differed by age. Patients with analgesic nephropathy have more comorbidities and poorer survival on renal replacement therapy, especially among younger patients.

Design, settings, participants, & measurements: A retrospective cohort of 34,963 Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin variability, absolute hemoglobin level, and temporal hemoglobin trend were measured over rolling 6-mo exposure windows. Their association with mortality was estimated using history-adjusted marginal structural analysis that adjusts for time-dependent confounding by applying weights to observations inversely related to the predictability of observed levels of hemoglobin.

Results: In the primary analysis, each g/dl increase in hemoglobin variability was associated with an adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing hemoglobin trend were significantly associated with mortality; adjusted HR (95% CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively.

Conclusions: Marginal structural analysis demonstrates that hemoglobin variability is associated with increased mortality among chronic hemodialysis patients, and that this effect is more pronounced than appreciated using standard statistical techniques that do not take time-dependent confounding into account.

Design, setting, participants, & measurements: Designed as a cross-sectional, epidemiologic study, the Insulin Resistance Atherosclerosis Study was conducted in four centers: San Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles (California). The Modification of Diet in Renal Disease equation was used to classify individuals without diabetes and with normoalbuminuria (n = 856; age 40 to 69 yr) by the presence or absence of low glomerular filtration rate (<60 ml/min per 1.73 m²). A direct marker of insulin resistance, the insulin sensitivity index, was measured by the frequently sampled intravenous glucose tolerance test.

Results: Low glomerular filtration rate was related to hypertension and the metabolic syndrome. Low glomerular filtration rate was associated with fasting insulin concentration and insulin sensitivity index. Low glomerular filtration rate was also associated with insulin concentration after adjustment for potential determinants of glomerular filtration rate but was not associated with insulin sensitivity index.

Conclusions: Low glomerular filtration rate is associated with increased insulin concentration in individuals without diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine whether insulin concentration (insulin resistance) precedes the deterioration of renal function.

Design, setting, participants, & measurements: We conducted a retrospective cohort study of the clinical database used in a Department of Defense (DOD) medical system. Beneficiaries studied were DOD-eligible beneficiaries with CKD stage 3 (n = 7729) and 4 (n = 589) using the modified Modification of Diet in Renal Disease (MDRD)-estimated GFR formula but requiring manual correction for Black race. Compliance with selected Kidney Disease Outcomes Quality Initiative (KDOQI) CKD recommended targets (monitoring of recommended laboratory data, prescription of recommended medications, and referral to nephrology) was assessed over a 12-mo period, stratified by CKD stage. Logistic regression analysis was used to assess whether race (White, Black, or other) was independently associated with provider compliance with targets, adjusted for demographic factors and burden of comorbid conditions.

Results: Among the targets, only monitoring of LDL cholesterol was significantly less common among Blacks. For all other measures, compliance was either not significantly different or significantly higher for Black compared with White beneficiaries. However, patients categorized as "Other" race were in general less likely to achieve targets than Whites, and at stage 3 CKD significantly less likely to achieve targets for monitoring of phosphorous, hemoglobin, and vitamin D.

Conclusions: In the DOD health system, provider compliance with selected CKD stage 3 and 4 targets was not significantly lower for Black beneficiaries than for Whites, with the exception of LDL cholesterol monitoring. Patients classified as Other race were generally less likely to achieve targets than Whites, in some patients significantly so.

Design, setting, participants, & measurements: The associations of cardiovascular disease risk factors, subclinical cardiovascular disease, and clinical coronary heart disease with the risk for development of acute renal failure were examined in older adults in the Cardiovascular Health Study, a prospective cohort study of community-dwelling older adults. Incident hospitalized cases of acute renal failure were identified through hospital discharge International Classification of Diseases, Ninth Revision codes and confirmed through physician diagnoses of acute renal failure in discharge summaries.

Results: Acute renal failure developed in 225 (3.9%) of the 5731 patients during a median follow-up period of 10.2 yr. In multivariate analyses, diabetes, current smoking, hypertension, C-reactive protein, and fibrinogen were associated with acute renal failure. Prevalent coronary heart disease was associated with incident acute renal failure, and among patients without prevalent coronary heart disease, subclinical vascular disease measures were also associated with acute renal failure: Low ankle-arm index (≤0.9), common carotid intima-media thickness, and internal carotid intima-media thickness.

Conclusions: In this large, population-based, prospective cohort study, cardiovascular risk factors and both subclinical and clinical vascular disease were associated with incident acute renal failure in the elderly.

Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration.

Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m², and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval –0.2 to –0.5) for every 5-ml/min per 1.73 m² decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m², the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m² decrease in glomerular filtration rate.

Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m². Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals.