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Biomedical subjects

E G Lowrie

Publications and source records attributed to E G Lowrie.

At least 37 records · Page 2Linked to original sources
PubMed1998

Acute-phase inflammatory process contributes to malnutrition, anemia, and possibly other abnormalities in dialysis patients.

The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.

Acute-Phase Proteins↗
PubMed1998

C-reactive protein as an outcome predictor for maintenance hemodialysis patients.

BACKGROUND: The possible association between inflammatory processes and other outcome measures in ESRD patients led us to measure the blood C-reactive protein (CRP) concentration in a large sample of hemodialysis patients, and to evaluate its statistical relationship with other common laboratory measures and patient survival. This was performed in a prospective, observational analysis with mortality as the principal outcome measure. METHODS: One thousand fifty-four routine blood samples, collected from as many patients during June and July 1995 (one sample per patient), were randomly selected for measurement of CRP, prealbumin, and other routine laboratory measures. Six months after the initial blood tests, patient survival was determined: Logistic regression analysis was the primary statistical tool used to evaluate laboratory associations with odds of death. Bivariate regression and correlation analyses were performed using all available data. RESULTS: The distribution of CRP values was skewed; approximately 35% of the values exceeded the upper limit of the laboratory's reference range. Serum albumin and prealbumin concentrations both correlated with the serum creatinine concentration (r = 0.378 and r = 0.347, respectively; P's < 0.001), and were inversely associated with the CRP (r = -0.254 and r = -0.354, respectively; P's < 0.001). CRP was also inversely associated with blood hemoglobin concentrations (r = -0.235; P < 0.001). Using multiple regression analysis to further explore these relationships, the serum creatinine concentration was inversely associated with CRP (r = -0.140; P < 0.001). However, after adjustment for the linkage of the serum creatinine with the serum albumin concentration (r = -0.378; P < 0.001), no relationship with creatinine was observed. Before and after adjustment for serum albumin and prealbumin concentration, the ferritin concentration correlated directly with CRP (r = 0.148; P < 0.001). Ferritin was inversely and highly correlated with total iron binding capacity (r = -0.516; P < 0.001). Independent associations of hemoglobin with albumin (t = 7.16; P < 0.001), prealbumin (t = 2.39; P = 0.017), and CRP (t = -4.27; P < 0.001) were observed. Also, the dose of erythropoietin was directly associated with the CRP concentration, before (r = 0.081, P = 0.009) and after (t = 2.03, P = 0.042) adjustment for the serum albumin and iron concentrations. CRP correlated directly with neutrophil (r = 0.318; P < 0.001) and platelet counts (r = 0.180; P < 0.001), but was weakly and inversely correlated with the lymphocyte count (r = -0.071; P = 0.04). A logistic regression analysis performed using the laboratory variables revealed a strong, independent, and inverse relationships between the serum albumin and creatinine concentrations, total lymphocyte count, and the odds risk of death. In this model, no significant relationship was observed between the odds risk of death and CRP. CONCLUSIONS: The data presented herein suggest that: (1) strong predictable associations exist among laboratory proxies for malnutrition, anemia, and the acute phase reaction, and (2) the pathobiology implied by these laboratory abnormalities influence patients' mortal risk primarily through depletion of vital body proteins, not inflammation.

C-Reactive Protein↗
PubMed1998

Predicting hemodialysis access failure with color flow Doppler ultrasound.

Color flow doppler ultrasound examination of the hemodialysis access was conducted in 2,792 hemodialysis patients to evaluate its value in predicting hemodialysis access failure. After baseline assessment of vascular access function with clinical and laboratory tests including color flow doppler evaluation these patients were followed for a minimal of 6 months or until graft failure occurred (defined as surgery or angioplasty intervention, or graft loss). The patient demographics and vascular accesses were typical of a standard hemodialysis patient population. On the day of the color flow doppler examination systolic and diastolic blood pressure, hematocrit, urea reduction ratio, dialysis blood flow, venous line pressure at a dialysis blood flow of 250 ml/min, and access recirculation rate were measured. At the conclusion of the study 23.5% of the patients had access failure. Case mix predictors for access failure were determined using the Cox Model. Case mix predictors of access failure were race, non-white was higher than white (p < 0.005), younger accesses had a higher risk than older accesses (p < 0.025), accesses with prior thrombosis had a higher risk of failure (p=0.042), polytetrafluoroethylene (PTFE) grafts had a higher risk than native vein fistulae (p < 0.05), loop PTFE grafts had a higher risk than straight PTFE grafts (p < 0.025), and upper arm accesses had a higher risk than forearm accesses (p=0.033). Most significant, however, was decreased access blood flow as measured by color flow doppler (p < 0.0001). The relative risk of graft failure increased 40% when the blood flow in the graft decreased to less than 500 ml/min and the relative risk doubled when the blood flow was less than 300 ml/min. This study has shown that color flow doppler evaluation, quantifying blood flow in a prosthetic graft, can identify those grafts at risk for failure. In contrast, color doppler volume flow in native AV fistulae could not predict fistula survival. This technique is noninvasive, painless, portable, and reproducible. We believe that preemptory repair of an anatomical abnormality in vascular access grafts with decreased blood flow may decrease patient inconvenience, associated morbidity, and associated costs.

Arteriovenous Shunt, Surgical↗
PubMed1997

Development of a population-specific regression equation to estimate total body water in hemodialysis patients.

We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).

Adult↗
PubMed1997

Bioimpedance norms for the hemodialysis population.

More than 3,000 hemodialysis patients were examined with single-frequency bioelectrical impedance analysis (BIA). Distributions of resistance, reactance, phase angle (PA), and estimates of total body water (TBW) and body cell mass (BCM) by BIA were determined, and compared with traditional laboratory markers of nutritional status. Bioimpedance parameters and body composition estimates differed significantly by age, sex, race, and diabetic status. PA and BCM correlated directly with serum creatinine, albumin, and prealbumin concentrations. Population-based norms for bioimpedance parameters and estimates of body composition are provided.

Age Factors↗
PubMed1997

Anemia in hemodialysis patients: variables affecting this outcome predictor.

Despite the prevalent use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients. The goal of this study was to evaluate the impact of anemia on patient survival and characterize the determinants of hematopoiesis that may be amenable to therapeutic manipulation to enhance rhEPO responsiveness and reduce death risk. Patient characteristics and laboratory data were collected for 21,899 patients receiving hemodialysis three times per week in dialysis centers throughout the United States in 1993. Hemoglobin concentrations (Hb) < or =80 g/L were associated with a twofold increase in the odds of death (odds ratio = 2.01; P = 0.001) when compared with Hb 100 to 110 g/L. No improvement in the odds of death was afforded for Hb >110 g/L. Using multiple linear regression, variables of rhEPO administration (rhEPO dose and percentage of treatments that rhEPO was administered), variables of iron status (serum iron, transferrin saturation, and ferritin), variables of nutritional status (serum albumin and creatinine concentration), and the dose of dialysis (urea reduction ratio) were found to be significantly associated with hemoglobin concentration (P < 0.001). Age, race, and gender were also found to be significantly associated with hemoglobin concentrations (P < 0.001). From this report, the following conclusions may be made. (1) Anemia may be predictive of an increased risk of mortality in some hemodialysis patients. (2) Hemoglobin concentrations > 110 g/L are not associated with further improvements in the odds of death. (3) Laboratory surrogates of iron stores, nutritional status, and the delivered dose of dialysis are predictive of hemoglobin concentration. Whether manipulation of the factors that improve anemia will also enhance the survival of patients on hemodialysis is unknown and should be evaluated by prospective, interventional studies.

Adult↗
PubMed1996

Modeling mortality risk in hemodialysis patients using laboratory values as time-dependent covariates.

Proportional hazards analyses assume that the magnitude of mortality risk for a predictor variable remains proportional over time. In a time-dependent model, the explanatory variable violates this assumption, and repeat observations are required to accommodate the change in risk that occurs over time. Using a retrospective cohort design, we tested the following laboratory values for a time-by-covariate interaction: hematocrit (HCT), serum albumin (ALB), and serum creatinine (CR). A random sample of 4,083 hemodialysis patients whose specimens were analyzed in a central laboratory over a 3-year period served as the study group. Using the baseline observation, we discovered significant probability values for the interaction terms TIME*CR (P = 0.013) and TIME*ALB (P < 0.01). The beta coefficient for TIME*HCT was not significant, indicating that the proportional hazard assumption was not violated by this covariate. Based on these results, we fitted a multivariate regression model containing two time-dependent covariates (CR and ALB) using a data structure that incorporated repeat observations of these laboratory values. Patients with high ALB levels experienced the lowest mortality risk. Similarly, serum CR levels were higher in long-term survivors. This analysis verifies the clinical importance of monitoring ALB and CR levels over time and the hazard of using a single laboratory observation to make long-term projections. Additionally, the predictive values of the time-dependent covariates ALB and CR affirm the significance of nutritional approaches directed toward maintaining visceral and somatic protein content throughout renal replacement therapy.

Adult↗
PubMed1996

Thoughts about judging dialysis treatment: mathematics and measurements, mirrors in the mind.

This article considers the contributions of the urea kinetic parameters, , Kt/V and nPCR, to beliefs about judging dialysis treatment. The values calculated from any set of data depend on the model (eg, 1 pool, 2 pool, or so forth) and the mathematics used to derive the values. Yet, the medical community debates the value of Kt/V at which patients should be treated even as they debate the mathematics by which Kt/V should be calculated. The resulting ambiguities about proper targets and methods may actually frustrate large-scale clinical quality enhancement initiatives. The casual use of mathematical models can mislead unwary clinicians and compromise quality enhancement. For example, the observation that a high Kt/V is associated with a high nPCR leads to the widespread belief that improving Kt/V must substantially improve nutritional status. The association, however, results mainly, if not solely, from mathematical coupling rather than biological cause and effect. The misguided belief could contribute to ineffective treatment of malnourished patients. Complicated mathematical models are useful tools for describing and evaluating evolving concepts about the physical properties of dialysis and for estimating the effects of new therapies. However, the changing nature of concepts, and therefore the mathematical models designed to support them, makes clinical care ideas that attempt to shoehorn old concepts into new equations. It is the result of the dialysis treatment, not the mathematical path by which it is achieved, that is associated with improved patient health. Consequently, clinical care should be guided by simple measurements that reflect the outcome of the treatment, not by mathematical parameters.

Humans↗
PubMed1995

Death risk predictors among peritoneal dialysis and hemodialysis patients: a preliminary comparison.

Variables associated with survival among 1,522 peritoneal dialysis patients and 16,404 hemodialysis patients who received treatment during 1992 were evaluated. Analysis was performed separately for the treatment types and for the combined patient group. In general, the associates of survival appear similar among patients receiving peritoneal or hemodialysis. Important variables appear related to nutrition, acid-base status (which is related to nutrition), and age.

Acid-Base Equilibrium↗
PubMed1995

Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients.

Protein energy malnutrition is common among persons with ESRD and contributes substantially to morbidity and mortality. The usual methods of nutritional assessment, such as anthropometry, can be misleading because of altered tissue hydration. Bioelectrical impedance analysis (BIA) has been recommended by some as a practical nutritional assessment tool but has not been validated in patients with ESRD. Thirty-three stable patients on maintenance hemodialysis were evaluated in an ambulatory clinical research center with simultaneous BIA, dual-energy x-ray absorptiometry, and deuterium oxide (D2O) and sodium bromide (NaBr) isotope dilution studies. Standard determinations of total body water (TBW) and body cell mass (BCM) were obtained and compared with values estimated by BIA. Two separate outpatient BIA measurements were also obtained approximately 2 wk before and after the clinical research center evaluation. BCM estimated by BIA was directly correlated (r = 0.92, P < 0.0001) with BCM determined by DEXA and NaBr. TBW estimated by BIA was directly correlated (r = 0.96, P < 0.0001) with TBW determined by deuterium oxide dilution. The reactance to resistance ratio (Xc/R) derived from BIA was inversely correlated (r = -0.73, P < 0.0001) with the extracellular water/TBW ratio determined by NaBr/D2O. Bland-Altman analyses showed that for TBW, BIA was in excellent agreement with D2O dilution. BCM was modestly underestimated by BIA compared with the dual-energy x-ray absorptiometry/NaBr standard and was adjusted by linear regression. The coefficients of variation on repeated BIA measurements were below 4%, demonstrating test-retest reliability. BIA is a valid and reliable method of nutritional assessment in maintenance hemodialysis patients.

Absorptiometry, Photon↗
PubMed1994

Survival of hemodialysis patients in the United States is improved with a greater quantity of dialysis.

The mortality rate for hemodialysis patients in the United States is higher than in other industrialized countries. Some attribute this to insufficient quantities of prescribed and delivered dialysis. A multicenter study in Dallas dialysis centers (Dallas Nephrology Associates) was begun in 1989 to assess the impact of increasing the delivered quantity of dialysis on mortality in subsequent years. Dialysis dose was measured by urea kinetic modeling. Kt/V, reflecting the fractional volume of body water clearance of urea during a dialysis treatment, was purposefully increased from 1.18 starting in 1989 to 1.46 in 1992. Additionally, the dialysis dose measured by the urea reduction ratio, the fractional reduction of blood urea nitrogen concentration caused by a dialysis treatment, increased from 63.0% to 69.6% between 1990 and 1992. Outcome analytical methods included both crude and standardized mortality rates and mortality ratios standardized to large end-stage renal disease databases at the United States Renal Data System and at National Medical Care, Inc. Crude mortality rates at Dallas Nephrology Associates decreased from 22.5% in 1989 to 18.1% in 1992. In comparison, between 1990 and 1992 the urea reduction ration in National Medical Care facilities increased from 57.1% to 62.5%. During that time crude mortality rates decreased from 21.8% to 19.5%. Crude mortality in the United States remained essentially unchanged in the same time period. By 1992, Dallas Nephrology Associates and National Medical Care had standardized mortality ratios of 0.77 and 0.74, respectively, compared with the US dialysis population, indicating almost 30% fewer observed deaths than expected. Monitoring dialysis dose by urea kinetic modeling or urea reduction ratio are equally effective in predicting improvement in patient survival. Improved survival is possible in the US end-stage renal disease program with greater amounts of dialysis. This strategy can save an estimated 8,000 to 16,000 lives per year.

Age Factors↗
PubMed1994

Chronic dialysis treatment: clinical outcome and related processes of care.

The selection of primary clinical outcome by which to evaluate the success of a therapy is discussed. Outcome should be relevant to the treatment, important to the patient and to the public health, and easy to measure with little associated variance. The odds of death is chosen as the primary outcome by which to evaluate chronic dialysis treatment because the purpose of dialysis is to preserve life. The odds of death is then correlated with the processes of care, which themselves may be measurable and therefore viewed as outcome of other processes. A general model for outcome research using existing data and for evaluating the relationships among processes and outcome is discussed using a large patient cohort analysis as an example. The analysis suggests that two dimensions of the care process account for most of the explainable death odds difference among patients: a dialysis intensity-related dimension and a nutrition-related dimension. Experience has suggested that knowledge of these principles combined with simple measurements has, over time, led dialysis professionals to increase the intensity of the dialysis treatment they deliver. That was not the case for the nutrition-related dimension. We speculate that these professionals understand, from prior knowledge, how to control dialysis intensity but do not possess similar knowledge about nutritional therapeutics for dialysis patients. Therefore, a better understanding of nutritional therapeutics will be required to achieve maximum reduction of mortality rates.

Humans↗
PubMed1994

The association of intradialytic parenteral nutrition administration with survival in hemodialysis patients.

Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.

Creatinine↗
PubMed1993

The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.

Diabetes Mellitus↗
PubMed1992

Race and diabetes as death risk predictors in hemodialysis patients.

Case mix and laboratory predictors of death risk were evaluated in 17,185 hemodialysis patients. The laboratory variables most closely associated with the increased death risk borne by diabetic patients (relative to non-diabetics) and White patients (relative to non-Whites) were identified. The analyses of laboratory death risk predictors were similar to those previously reported. Serum albumin concentration is the most powerful death risk predictor among all of the variables, both case mix and laboratory. Statistical models including only case mix variables reveal both race (RRWhites = 1.42) and diabetes (RRdiabetes = 1.43) as significant predictors. Adding creatinine, albumin, and BUN concentrations to the model eliminated diabetes as a significant predictor. Creatinine and albumin accounted for most of the change. Adding only creatinine eliminated race. The data suggest that reduced visceral and somatic protein mass and/or metabolism may be important determinants of mortality in dialysis patients. Because differences in the concentrations of creatinine and albumin explain much of the risk associated with being White or diabetic, differences in nutritional status may explain the reduced survival observed in those groups. Therefore, clinicians should not simply accept without question the notion that diabetics and Whites are doomed to inferior survival.

Adult↗