Although increased blood pressure is associated with adverse outcomes in the general population, elevated blood pressure is associated with decreased mortality in patients with end-stage renal ...disease undergoing maintenance hemodialysis. Recent investigations in the general population have demonstrated the predictive utility of pulse pressure (systolic minus diastolic blood pressure), a measure reflecting the pulsatile nature of the cardiac cycle.
To estimate the relationship between pulse pressure and mortality in patients undergoing maintenance hemodialysis and to test our hypothesis that an increasing pulse pressure would be associated with increased risk of death up to 1 year despite the inverse relationship between conventional blood pressure measures and mortality in patients with end-stage renal disease.
Retrospective cohort investigation of patients with end-stage renal disease undergoing maintenance hemodialysis at 782 hemodialysis facilities throughout the United States. Of 44 069 eligible patients as of January 1, 1998, 37 069 with complete demographic data were included in the analyses of clinical and laboratory data collected from October 1 through December 31, 1997. Patients were followed up through December 31, 1998.
The primary study outcome was death at 1 year. A secondary outcome was the magnitude of the pulse pressure.
The final patient cohort was similar to national averages with respect to age, sex, race, and diabetic status. Mean (SD) pulse pressures before dialysis were 75.0 (15.0) mm Hg and 66.9 (13.9) mm Hg after dialysis. By the end of the 1-year follow-up, 5731 patients (18.4%) died. After adjusting for level of systolic blood pressure, multivariable Cox proportional hazards modeling showed a direct and consistent relationship between increasing pulse pressure and increasing death risk. Each incremental elevation of 10 mm Hg in postdialysis pulse pressure was associated with a 12% increase in the hazard for death (hazard ratio, 1.12; 95% confidence interval, 1.06-1.18). Postdialysis systolic blood pressure was inversely related to mortality with a 13% decreased hazard for death for each incremental elevation of 10 mm Hg (hazard ratio, 0.87; 95% confidence interval, 0.84-0.90). In a multivariable linear regression model, important variables directly associated with elevated pulse pressure included age, diabetes, white race, female sex, and number of years receiving dialysis (all P<.001).
Pulse pressure is associated with risk of death in a large, nationally representative sample of patients undergoing maintenance hemodialysis. The recognition of pulse pressure as an important correlate of mortality in patients receiving dialysis highlights the need to investigate the relationship between potential therapeutic implications of conduit vessel function and clinical outcomes in patients with end-stage renal disease.
Background. Regional differences in haemoglobin values and process care measures were examined using data from the Centers for Medicare & Medicaid Services' End‐Stage Renal Disease (ESRD) Clinical ...Performance Measures Project. It was posited that regional differences in haemoglobin values are consequent upon differences in components of clinical practice. Methods. A national random sample of 8336 adult, in‐centre haemodialysis patients, stratified by the 18 regional ESRD Networks, was drawn. Information was collected for October–December 1998. Multivariable stepwise linear and logistic regression analyses were performed to identify variables associated with haemoglobin. Linear regression analysis was used to identify variables associated with Epo/Hb index (mean weight‐adjusted treatment level erythropoietin (Epo) dose divided by mean haemoglobin). Results. The percentage of patients with haemoglobin concentration <11 g/dl ranged from 34 to 52% across ESRD Networks. In addition to haemoglobin there was significant, non‐random variation among ESRD Networks with regard to prescribed Epo dose and administration route, intravenous (IV) iron prescription and dialyser flux (high flux=KUf ≥20 ml/mmHg/h) (all P‐values <0.001). Higher haemoglobin was associated with older age, male gender, higher serum albumin, higher transferrin saturation, higher Kt/V, lower serum ferritin and lower prescribed Epo dose (all P‐values <0.01). Diabetes mellitus as cause of ESRD, high‐flux dialyser use, IV iron prescription or subcutaneous Epo prescription were not associated with haemoglobin. Male gender, diabetes as cause of ESRD, older age, higher transferrin saturation and higher albumin concentrations were associated with lower Epo/Hb index. Prescription of IV iron and IV Epo were associated with higher Epo/Hb index. Conclusions. Regional mean haemoglobin levels vary considerably across the US and the variation in haemoglobin is explained by both non‐modifiable factors and modifiable clinical practice‐derived variables.
Manufacturers of parenteral solutions adhere to European and US Pharmacopoeia standards to define safety and sterility. In response to excess cases of aseptic peritonitis in peritoneal dialysis ...patients using icodextrin-containing dialysate that met all pharmacopoeia standards, a global recall was issued in May, 2002. We aimed to establish the cause of aseptic peritonitis.
We analysed 186 reports of aseptic peritonitis between September, 2001, and January, 2003. Extensive physical, chemical, and microbiological investigations of recalled dialysate were done. We calculated dose-response curves for peptidoglycan-induced interleukin 6 elaboration in peripheral blood mononuclear cells (PBMCs) from healthy donors and for sterile peritonitis in rats.
Although its chemical constituents and concentrations of endotoxin were within pharmacopoeia specifications, the dialysis solution elicited an interlukin 6 response in vivo and in vitro. We identified peptidoglycan from thermophilic acidophilic bacteria (Alicyclobacillus acidocaldarius) as the contaminating proinflammatory substance. In the PBMC assay, strong dose-response relations were noted between peptidoglycan concentrations and interleukin 6. In rats injected with peptidoglycan, dose-dependent increases of intraperitoneal neutrophils and pyrogenic cytokines were recorded. We measured a positive relation between peptidoglycan concentrations in recalled dialysate and reports of aseptic peritonitis. After implementation of corrective actions, the rate of peritonitis returned to baseline.
Excess cases of aseptic peritonitis in peritoneal dialysis patients were due to peptidoglycan contamination of dialysate by Alicyclobacillus. This outbreak serves as an example of how contemporary parenteral products with microbial contaminants can be considered safe under current pharmacopoeia tests, but provoke adverse clinical effects.
Inappropriate chronic inflammation associated with progressive, chronic kidney disease (CKD) reflects sustained activation of immunocompetent cells, like monocytes/macrophages. Advanced glycation end ...products (AGE) accumulate in CKD, but it is unclear if they stimulate monocytes by binding with the receptor for AGE (RAGE). Posited was the notion that RAGE plays a contributory role to monocyte-mediated systemic inflammation of progressive CKD. Peripheral blood monocytes were isolated from 102 patients without diabetes with varying severity of CKD. RAGE expression on peripheral blood monocytes increased with worsening CKD (r2 = 0.73) and was strongly correlated with plasma levels of pentosidine, a marker for AGE (r = 0.71). Strongly positive statistical correlations were observed in patients with CKD between monocyte RAGE and plasma levels of tumor necrosis factor alpha (TNF-alpha) (r = 0.61), the monocyte activation marker, neopterin (r = 0.65), and the systemic acute phase reactant, C-reactive protein (r = 0.44). Monocytes obtained from patients with CKD showed a monotonic increase in the number and affinity of specific AGE binding sites and increased production of TNF-alpha under stimulation of AGE. All these upregulatory responses in uremic monocytes could be largely blocked by an anti-RAGE antibody. It was concluded that RAGE expression was upregulated on monocytes from patients with CKD. Enhanced RAGE may amplify AGE-induced monocytes perturbation and contribute to monocyte-mediated systemic inflammation in progressive CKD.
Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is ...also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review ...and meta-analysis of potential precision markers for GDM.
Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m
) with offspring macrosomia or large-for-gestational age (LGA).
A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies n = 28,763; odds ratio OR 2.65; 95% Confidence Interval CI 1.91, 3.68), and LGA (10 studies n = 20,070; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers.
Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.
The Centers for Medicare & Medicaid Service's (CMS), national End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project is a data collection initiative to identify opportunities for ...improvement of care to adult, Medicare maintenance dialysis beneficiaries. This analysis of 1999 CPM data characterizes the profile of hemodialysis vascular access in the United States and identifies determinants of vascular access type 2 yr after the translation of vascular access clinical practice guideline statements into national CPMs. CPM data were collected during October to December 1999 and stratified by the 18 regional ESRD networks. Univariate and multivariable analyses were conducted to examine associations of access type with demographic, laboratory, and geographic variables. Multivariable logistic regression analyses were performed to identify independent variables associated with access type. A total of 8154 hemodialysis patients were sampled; 17% (n = 1399) were incident. Twenty-eight percent were dialyzed through an autologous arteriovenous fistula (AVF), 49% through a prosthetic graft (AVG), and 23% through a percutaneous catheter. Independent predictors of having a catheter for hemodialysis were female gender, white race, incident to hemodialysis status, and lower hemoglobin and serum albumin. For patients with a fistula or AVG, female gender (odds ration OR, 2.46 2.18 to 2.78) and black race (OR, 1.70 1.50 to 1.93) were the strongest predictors of dialysis through an AVG. Other predictors of dialysis through an AVG were older age, increased body mass index (BMI), diabetes mellitus as the cause of ESRD, and lower serum albumin. Even in adjusted analyses, there was significant geographic variability with respect to hemodialysis access type. Despite translation of practice guidelines for hemodialysis vascular access into national CPMs, there is substantial geographic variability and gender and racial disparity in angioaccess allocation in the United States. Quality improvement strategies to improve the prevalence of fistulae should focus on selected regions and include physician education about their practice patterns and potential biases.
A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States.
The Kidney Disease Outcomes Quality Initiatives (K/DOQI) guidelines on bone ...metabolism and disease in chronic kidney disease were recently published. Despite limited evidence of clinical effectiveness and without detailed consideration of cost, these guidelines recommend the use of a nonmineral-containing phosphate binder (i.e., sevelamer) in several common clinical situations. The objective of this study is to use the example of sevelamer to outline the information that is needed to assist health care payers with the decision to fund a new and expensive therapy.
We assessed the clinical benefit of sevelamer by performing a systematic review of all randomized trials evaluating its use. To estimate the direct budget impact associated with implementation of the K/DOQI bone disease guidelines, we used laboratory and medication data available from two cohorts of dialysis patients (one treated in Canada and one in the United States) to determine the proportion of patients who meet the criteria for the use of sevelamer as described in the K/DOQI bone disease guidelines.
No randomized trials document the impact of sevelamer on survival, hospitalization, or quality of life. However, at least 51% and 64% of dialysis patients in the Canadian and American cohorts, respectively, would meet K/DOQI criteria for use of sevelamer. Extrapolating to the United States dialysis population, adoption of the K/DOQI bone guidelines would result in expenditures of approximately $781 million annually on sevelamer alone.
Given their potential budgetary impact, future nephrology clinical practice guidelines should consider resource use, in addition to clinical data.
Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of ...reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis.
We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration.
As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients.
Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.
The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Practice Guidelines established a widely accepted set of recommendations for high-quality dialysis care. To ...enhance the End-Stage Renal Disease Core Indicators Project, an ongoing effort to assess and improve dialysis care in the United States, the Centers for Medicare and Medicaid Services (CMS) commissioned a project to develop clinical performance measures (CPMs) based on the NKF-DOQI guidelines.
The CMS contracted with Qualis Health, a private nonprofit organization serving as a Medicare Quality Improvement Organization, to facilitate a 9-month project to develop dialysis CPMs with the participation of a broad range of stakeholders from the renal community. Work groups were established to develop CPMs addressing 4 areas: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access management, and anemia management. The NKF-DOQI guidelines were prioritized based on the strength of the evidence supporting the guidelines, the feasibility of developing performance measures, and the significance of the areas addressed to the quality of care delivered to dialysis patients. Expert panels developed data specifications, sampling approaches, data-collection tools, and analytic strategies.
Sixteen CPMs were developed based on 22 of 114 NKF-DOQI guidelines. After establishing reliability through field-testing of data-collection instruments, the CPMs were applied to a sample of 8,838 randomly selected hemodialysis patients and 1,650 randomly selected adult peritoneal dialysis patients in summer 1999.
The development of CPMs based on the NKF-DOQI Clinical Practice Guidelines for dialysis care was accomplished in a timely and effective manner by engaging a broad range of stakeholders and technical experts. The CPMs are important tools to assess and improve the quality of dialysis care in the United States. Few comparable efforts exist in other fields of medicine.
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