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Biomedical subjects

G M Chertow

Publications and source records attributed to G M Chertow.

At least 19 recordsLinked to original sources

Mortality and costs of acute renal failure associated with amphotericin B therapy.

To assess the mortality and resource utilization that results from acute renal failure associated with amphotericin B therapy, 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital. Main outcome measures were mortality, length of stay, and costs; we controlled for potential confounders, including age, sex, insurance status, baseline creatinine level, length of stay before beginning amphotericin B therapy, and severity of illness. Among 707 admissions, there were 212 episodes (30%) of acute renal failure. When renal failure developed, the mortality rate was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal failure occurred, the mean adjusted increase in length of stay was 8.2 days, and the adjusted total cost was $29,823. Although residual confounding exists despite adjustment, the increases in resource utilization that we found are large and the associated mortality is high when acute renal failure occurs following amphotericin B therapy.

Acute Kidney Injury↗

Suspected iron dextran-related adverse drug events in hemodialysis patients.

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

Humans↗

Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients.

BACKGROUND: Cross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown. METHODS: To explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases. RESULTS: The overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001). CONCLUSIONS: Proxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and "malnutrition."

Adult↗

Cardiac arrest and sudden death in dialysis units.

BACKGROUND: For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented. METHODS: To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort of> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities. RESULTS: The cardiac arrest rate was 400 out of 5,744,708, corresponding to a rate of 7 per 100,000 hemodialysis sessions. Cardiac arrest was more frequent during Monday dialysis sessions than on other days of the week. Case patients were nearly twice as likely to have been dialyzed against a 0 or 1.0 mEq/L potassium dialysate on the day of cardiac arrest (17.1 vs. 8.8%). Patients who suffered a cardiac arrest were on average older (66.3 +/- 12.9 vs. 60.2 +/- 15.4 years), more likely to have diabetes (61.8 vs. 46.8%), and more likely to use a catheter for vascular access (34.1 vs. 27.8%) than the general hemodialysis population. Sixteen percent of patients experienced a drop in systolic pressure of 30 mm Hg or more prior to the arrest. Thirty-seven percent of patients who suffered cardiac arrest had been hospitalized within the past 30 days. Sixty percent of patients died within 48 hours of the arrest, including 13% while in the dialysis unit. CONCLUSIONS: Cardiac arrest is a relatively infrequent but devastating complication of hemodialysis. To reduce the risk of adverse cardiac events on hemodialysis, the dialysate prescription should be evaluated and modified on an ongoing basis, especially following hospitalization in high-risk patients.

Aged↗

Validation of questionnaires to estimate physical activity and functioning in end-stage renal disease.

BACKGROUND: Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed. METHODS: We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results. RESULTS: Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures. CONCLUSIONS: These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.

Cross-Sectional Studies↗

beta(2)-Microglobulin modified with advanced glycation end products delays monocyte apoptosis.

BACKGROUND: A local inflammatory reaction to beta(2)-microglobulin (beta(2)m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of human monocytes. METHODS: Human peripheral blood monocytes were incubated with or without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days. RESULTS: AGE-modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-beta(2)m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of beta-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte--macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-beta(2)m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-beta(2)m. CONCLUSIONS: These findings support a novel role for AGE-modified proteins such as AGE-beta(2)m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA.

Antibodies↗

Mechanisms underlying renoprotection during renin-angiotensin system blockade.

Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U(pr)V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), values close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-beta1, MCP-1, and interleukin-1beta and renal injury at 24 wk. Cns and Ena are thus equally effective renoprotective agents in this model. During renin-angiotensin system inhibition, renoprotection is dependent on control of both SBP and UprV. Incomplete suppression of renal cytokine gene expression may also contribute to CRD progression.

Animals↗

Survival after acute myocardial infarction in patients with end-stage renal disease: results from the cooperative cardiovascular project.

Cardiovascular disease (CVD) is the most common cause of death in patients with end-stage renal disease (ESRD). The optimal management strategy in this population is unknown. We studied 640 patients with ESRD and acute myocardial infarction during 1994 to 1995 as part of the Health Care Financing Administration's Cooperative Cardiovascular Project. The majority of patients were treated with medical therapy alone, 46 patients (7%) were treated with percutaneous transluminal coronary angioplasty (PTCA), and 29 patients (5%) underwent coronary artery bypass grafting (CABG). Patient characteristics and comorbid conditions were similar among the three groups. The overall 1-year mortality rate was 53%. Advanced age, low or high body mass index, history of peripheral vascular disease or stroke, the inability to walk independently, and several indicators of cardiac dysfunction were associated with an increased relative risk (RR) for death. Survival curves differed significantly by treatment modality, with 1-year survival rates of 45%, 54%, and 69% in the medical therapy alone, PTCA, and CABG groups, respectively (P = 0.03). After adjustment for confounding variables, the RR for death was less (but not significantly so) in the CABG group (RR, 0.6; 95% confidence interval, 0.3 to 1.1). There are no randomized clinical trial data to guide therapy of CVD in patients with ESRD. On the basis of these and other available data, CABG may be the optimal therapy for CVD in ESRD. In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone, it may be premature to dismiss PTCA as a therapeutic option in this population.

Age Factors↗

Ochrobactrum anthropi bacteremia in a patient on hemodialysis.

Although newer tunneled dialysis catheters offer improved capacity for blood flow and efficiency of dialysis, catheter-associated bacteremia remains an extremely important complication of this access strategy. This is a report of a case of catheter-associated bacteremia with Ochrobactrum anthropi, a water-borne gram-negative rod with an unusual pattern of antibiotic resistance. Given the organism's hydrophilic property and the frequency of catheter use in debilitated individuals with end-stage renal disease, Ochrobactrum anthropi infection should be considered in the differential diagnosis of a hemodialysis patient with unexplained fever.

Aged↗

Issues in renal nutrition for persons from the former Soviet Union.

Dietary practices differ greatly among individuals by race and ethnicity. The importance of these differences is accentuated in patients with end-stage renal disease, a population for whom dietary restrictions are often prescribed. In addition to the known variation in dietary practices among US-born whites and African-Americans, persons of other ethnicities often present new and unique challenges to the dialysis-nutrition care team. The UCSF-Mt. Zion Dialysis Unit (San Francisco, CA) is a university-affiliated dialysis unit that serves an ethnically diverse population in San Francisco's Western Addition neighborhood. Ten percent to 15% of patients are recent immigrants from the former Soviet Union. This report highlights the dietary practices of this immigrant community and the need for ethnicity-specific renal nutrition recommendations in modern dialysis practice.

Aged↗

Physical activity levels in patients on hemodialysis and healthy sedentary controls.

BACKGROUND: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. METHODS: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. RESULTS: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). CONCLUSIONS: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

Adult↗

Predicting acute renal failure after coronary bypass surgery: cross-validation of two risk-stratification algorithms.

BACKGROUND: Acute renal failure (ARF) requiring dialysis after coronary artery bypass grafting (CABG) occurs in 1 to 5% of patients and is independently associated with postoperative mortality, even after case-mix adjustment. A risk-stratification algorithm that could reliably identify patients at increased risk of ARF could help improve outcomes. METHODS: To assess the validity and generalizability of a previously published preoperative renal risk-stratification algorithm, we analyzed data from the Quality Measurement and Management Initiative (QMMI)1 patient cohort. The QMMI includes all adult patients (N = 9498) who underwent CABG at 1 of 12 academic tertiary care hospitals from August 1993 to October 1995. ARF requiring dialysis was the outcome of interest. Cross-validation of a recursive partitioning algorithm developed from the VA Continuous Improvement in Cardiac Surgery Program (CICSP) was performed on the QMMI. An additive severity score derived from logistic regression was also cross-validated on the QMMI. RESULTS: The CICSP recursive partitioning algorithm discriminated well (ARF vs. no ARF) in QMMI patients, even though the QMMI cohort was more diverse. Rates of ARF were similar among risk subgroups in the CICSP tree, as was the overall ranking of subgroups by risk. Using logistic regression, independent predictors of ARF in the QMMI cohort were similar to those found in the CICSP. The CICSP additive severity score performed well in the QMMI cohort, successfully stratifying patients into low-, medium-, high-, and very high-risk groups. CONCLUSIONS: The CICSP preoperative renal-risk algorithms are valid and generalizable across diverse populations.

Acute Kidney Injury↗

Prealbumin is as important as albumin in the nutritional assessment of hemodialysis patients.

BACKGROUND: Although serum prealbumin is considered a valid indicator of nutritional status in hemodialysis patients, there is relatively little evidence that its determination is of major prognostic significance. In this study, we aimed to determine the independent association of serum prealbumin with survival in hemodialysis patients, after adjusting for serum albumin and other indicators of protein energy nutritional status. METHODS: Serum prealbumin was measured in more than 1600 maintenance hemodialysis patients. We determined the correlations among prealbumin and other indicators of nutritional status, including serum albumin, and bioimpedance-derived indicators of body composition. The relationship between serum prealbumin and survival was determined using proportional hazards regression. RESULTS: The serum albumin was directly correlated with the serum prealbumin (r = 0.47, P < 0.0001), but still explained <25% of the variability in prealbumin. Prealbumin was inversely related to mortality, with a relative risk reduction of 6% per 1 mg/dL increase in prealbumin, even after adjusting for case mix, serum albumin, and other nutritional indicators. The increase in risk with lower serum prealbumin concentrations was observed whether the serum albumin was high or low. CONCLUSION: In hemodialysis patients, the serum prealbumin provides prognostic value independent of the serum albumin and other established predictors of mortality in this population.

Aged↗

Vintage, nutritional status, and survival in hemodialysis patients.

BACKGROUND: The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintage and body composition in hemodialysis patients. METHODS: We explored the relationships among vintage, nutritional status, and survival in a 3009 patient cohort of prevalent hemodialysis patients. Body weight, total body water, body cell mass, and phase angle by bioelectrical impedance analysis were the body composition parameters of interest. We examined vintage as an explanatory variable in multiple linear regression analyses (adjusted for age, gender, race, and diabetes) using body composition parameters and biochemical indicators of nutritional status as dependent variables. Proportional hazards regression was used to evaluate the association of vintage and survival with and without adjustment for case mix and laboratory variables. RESULTS: Dialysis vintage was 3.8 +/- 3.7 (median 2.6) years. Body composition parameters tended to be lower after dialysis year 2. Linear estimates per year of vintage beyond year 2 include -0.66 kg body wt (P < 0.0001), -0.17 kg total body water (P = 0.0003), -0.14 kg body cell mass (P < 0.0001), and -0.07 degrees phase angle (P < 0.0001). In unadjusted analyses, vintage was not associated with survival, either as a linear or higher order term. The adjustment for case mix yielded a vintage term associated with an increased relative risk (RR) of death (RR 1.04 (95% CI, 1.01 to 1.07 per year). A further adjustment for laboratory data yielded a RR of 1.06 (95% CI, 1.03 to 1.09 per year). CONCLUSION: Dialysis vintage is related to nutritional status in hemodialysis patients, with vintage of more than years associated with a significant decline in all measured nutritional parameters. Cross-sectional analyses probably underestimate these effects. A year accrued on dialysis is associated with a 6% increase in the risk of death, all else equal. Longitudinal assessments of nutritional status, including body composition, are required to better understand the natural history of wasting with ESRD and its implications for long-term survival.

Adult↗

Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

Adult↗

Chronic renal confusion: insufficiency, failure, dysfunction, or disease.

The terms routinely used to describe states of reduced glomerular filtration rate (GFR) not requiring renal replacement therapy are poorly defined. With increasing interest in the epidemiology of chronic renal insufficiency and the timing of initiation of dialysis, terms such as "pre-ESRD" and "pre-dialysis" have been popularized, again without clear definition. Unambiguous terminology should be adopted. The authors favor using the term chronic renal insufficiency to describe states of reduced GFR not severe enough to require dialysis or transplantation. The authors propose classifying patients with GFR of 60 to 41 mL/min, 40 to 21 mL/min, and 20 mL/min or below as having mild, moderate, and advanced degrees of chronic renal insufficiency, respectively. The use of this terminology will facilitate communication among nephrologists and other physicians and provide a framework for comparison of populations across cohort studies and clinical trials.

Glomerular Filtration Rate↗