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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
PubMed1999

Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure.

BACKGROUND: Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. METHODS: We reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of >/=2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. RESULTS: ARD, defined as >/=25% increase in serum creatinine concentration to >/=2 mg/dL, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years; P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min; P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002). CONCLUSIONS: In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes.

Adult↗
PubMed1999

Evidence-based organ allocation.

BACKGROUND: There are not enough cadaveric kidneys to meet the demands of transplant candidates. The equity and efficiency of alternative organ allocation strategies have not been rigorously compared. METHODS: We developed a five-compartment Monte Carlo simulation model to compare alternative organ allocation strategies, accommodating dynamic changes in recipient and donor characteristics, patient and graft survival rates, and quality of life. The model simulated the operations of a single organ procurement organization and attempted to predict the evolution of the transplant waiting list for 10 years. Four allocation strategies were compared: a first-come first-transplanted system; a point system currently utilized by the United Network of Organ Sharing; an efficiency-based algorithm that incorporated correlates of patient and graft survival; and a distributive efficiency algorithm, which had an additional goal of promoting equitable allocation among African-American and other candidates. RESULTS: A 10-year computer simulation was performed. The distributive efficiency policy was associated with a 3.5%+/-0.8% (mean +/- SD) increase in quality-adjusted life expectancy (33.9 months vs 32.7 months), a decrease in the median waiting time to transplantation among those who were transplanted (6.6 months vs 16.3 months), and an increase in the overall likelihood of transplantation (61% vs 45%), compared with the United Network of Organ Sharing algorithm. Improved equity and efficiency were also seen by race (African-American vs other), sex, and age (<50 or > or =50 years). Sensitivity analyses did not appreciably change the qualitative results. CONCLUSION: Evidence-based organ allocation strategies in cadaveric kidney transplantation would yield improved equity and efficiency measures compared with existing algorithms.

Algorithms↗
PubMed1999

Modality-specific nutrition support in ESRD: weighing the evidence.

Protein-calorie malnutrition affects a large fraction of patients with end-stage renal disease (ESRD) and contributes significantly to the high rates of mortality and morbidity observed in this population. Observational studies of specific interventions, including intradialytic parenteral nutrition (IDPN), suggest that aggressive nutrition support may be of some benefit to some patients with ESRD. Due in part to lack of data derived from prospective, randomized clinical trials, and to the large expense associated with these therapies, Medicare and other payers have strongly discouraged the prescription of IDPN and other intermittent, dialysis-specific methods of nutrition support, such as intraperitoneal nutrition (IPN). The "burden of proof" has been placed on the dialysis community. In response, we must continue to emphasize the importance of securing nutritional health for all patients on or anticipating renal replacement therapy. Intradialytic parenteral nutrition should be reserved for patients who are taking in sufficient calories yet are unable to tolerate oral or enteral protein-rich foods or formulas designed to meet daily protein requirements (> or = 1.5 g/kg in some patients). Intradialytic parenteral nutrition should not be prescribed in place of total parenteral nutrition (TPN) if the latter is truly needed. Creative methods of nutrition support, including the use of dietary supplements at dialysis (intradialytic oral or enteral nutrition), should be explored. Prospective clinical trials investigating the effects of nutrition support on survival, hospitalization rates, health-related quality of life, and functional status, are urgently needed.

Humans↗
PubMed1999

The urea [clearance x dialysis time] product (Kt) as an outcome-based measure of hemodialysis dose.

BACKGROUND: The normalized treatment ratio [Kt/V = the ratio of the urea clearance x time product to total body water] and the urea reduction ratio (URR) have become widely accepted measures of dialysis dose. Both are related to and derived from pharmacokinetic models of blood urea concentration during the dialysis cycle. Theoretical reconsideration of the models revealed that the premise about V on which they rest (that is, that V is a passive diluent with no survival-associated properties of its own) is flawed if the intended use of the models is for profiling clinical outcome (for example, mortality) rather than estimating urea concentration. As a proxy for body mass, V has survival-associated properties of its own. Thus, indexing clearance x time to body size could create an offsetting combination whereby one measure favorably associated with survival (Kt) is divided by another (for example, V). Observed clinical paradoxes support that interpretation. For example, patients with a low body mass have both higher URR and higher mortality than heavier patients. Increasing mortality is often observed at high URR, suggesting the possibility of "over-dialysis." Black patients tend to be treated at lower URR than whites but enjoy better survival on dialysis. Therefore, clearance x time was evaluated as an outcome-based measure of dialysis dose, not indexed to V, and various body size estimates were evaluated as separate and distinct measures. METHODS: The retrospective sample included 17,141 black and white hemodialysis patients treated three times per week. Logistic regression analysis was used to evaluate death odds in age-, gender-, race-, and diabetes-adjusted models. Kt and five body size estimates (total body water or V, body weight, body weight adjusted for height, body surface area, and body mass index) were evaluated using two analytical strategies. First, all of the measures were treated as continuous variables to explore different statistical models. Second, Kt and the body size measures were divided into groups to construct risk profiles. RESULTS: All evaluations revealed improving death odds with increasing Kt (whether adjusted for the body size estimates or not) and also with increasing body size (whether adjusted for Kt or not) for each estimate of size. Significant statistical interactions of Kt with gender, but not Kt with race, were observed in all models. There were no statistical interactions, suggesting that higher Kt was routinely required with increasing body size. Separate risk profiles for males and females suggested a higher Kt threshold for males. CONCLUSIONS: The urea clearance x time is a valid outcome-based measure of dialysis dose and is not confounded by indexing it to an estimate of body size, which has outcome-associated properties of its own. Dialysis prescriptions for males and females should be regarded separately, but there appears no need to make a distinction between the races.

Adult↗
PubMed1999

A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients.

OBJECTIVE: We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients. PATIENTS AND METHODS: We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites. RESULTS: Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs. CONCLUSION: We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.

Calcium↗
PubMed1998

Dose of hemodialysis and survival: differences by race and sex.

CONTEXT: Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics. OBJECTIVE: To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex. DESIGN: Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients. PATIENTS: A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died. MAIN OUTCOME MEASURES: The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels. RESULTS: Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters. CONCLUSION: Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.

Black or African American↗
PubMed1998

Independent association between acute renal failure and mortality following cardiac surgery.

PURPOSE: To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery. PATIENTS AND METHODS: The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis. RESULTS: Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10). CONCLUSIONS: Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

Acute Kidney Injury↗
PubMed1998

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD.

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.

Cardiovascular Diseases↗
PubMed1998

Beta 2-microglobulin modified with advanced glycation end products modulates collagen synthesis by human fibroblasts.

Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for patients undergoing long-term dialysis. beta 2-microglobulin modified with advanced glycation end products (beta 2m-AGE) is a major component of the amyloid in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active role in the pathogenesis of A beta 2m, or if its presence is a secondary event of the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of beta 2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to beta 2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by beta 2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF.

Amyloidosis↗
PubMed1998

Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction.

STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.

AIDS-Related Opportunistic Infections↗
PubMed1998

Aminoguanidine inhibits advanced glycation end products formation on beta2-microglobulin.

Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE-beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In experimental diabetes mellitus, blocking the formation of AGE prevents AGE-mediated tissue damage. In this study, it is postulated that similar pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a nucleophilic hydrazine compound that prevents AGE formation on collagen, may have a similar effect on the advanced glycation of beta2M. To test this hypothesis, beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the presence and absence of incremental concentrations of aminoguanidine. On the basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)-(carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination showed that aminoguanidine also inhibited the formation of fluorescent AGE on beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore, aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified collagen. If aminoguanidine is similarly active in vivo, this compound may be of clinical utility for treating DRA in patients on maintenance dialysis.

Analysis of Variance↗
PubMed1998

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.

To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

Adult↗
PubMed1998

Olecranon bursitis caused by infection with Candida lusitaniae.

We describe a 59-year-old woman with diabetes and chronic asthma treated with prednisone and methotrexate who developed chronic olecranon bursitis caused by Candida lusitaniae. Infection, especially with unusual microbial pathogens, should be considered in cases of chronic bursitis in patients taking immunosuppressive medicine, even if the classic signs of septic bursitis are absent. Infection with C. lusitaniae, a component of the normal mycoflora, may be a marker of serious immunosuppression, as this patient ultimately died of a Pneumocystis carinii infection.

Asthma↗
PubMed1997

Nephrology.

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Angiotensin-Converting Enzyme Inhibitors↗