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E F Vonesh

Publications and source records attributed to E F Vonesh.

At least 37 records · Page 2Linked to original sources

Net fluid absorption under membrane transport models of peritoneal dialysis.

The effect of oncotic pressure and lymphatic flow on intraperitoneal dialysate volumes in peritoneal dialysis is investigated under each of two membrane transport models: one assuming a homogeneous single-pore membrane and the other a heteroporous three-pore membrane. In both cases, solute and fluid removal are assumed to occur via a mass transport model in which the peritoneum acts like a synthetic membrane separating two well-mixed compartments (body and dialysate). The homoporous mass transport model of Pyle and Popovich and the three-pore model of Rippe et al., although conceptually different, are shown to be equivalent mathematically. This feature allows one to apply the analytical solutions of Vonesh et al. to either model. It also enables one to apply parameter estimates from one model to another; for example, one can apply the lumped sum reflection coefficients of the three-pore model to a homoporous membrane model. A comparison is made between the use of empirically estimated rejection coefficients computed under the homoporous membrane model of Pyle and Popovich versus lumped-sum reflection coefficients calculated in accordance with the three-pore model of Rippe et al. The two models predict similar drain volumes provided the exchange is conducted using glucose as the osmotic agent. However, one does see a significantly different contribution of protein oncotic pressure and lymphatic drainage to fluid absorption under the two sets of osmotic reflection coefficients. Moreover, for a simulated exchange employing an osmotic agent with a molecular weight of 20,000 daltons, the use of reflection coefficients calculated under the three-pore model yields net ultrafiltration values which are more consistent and physiological than results obtained using the empirically estimated rejection coefficients. Since estimates of 'lymphatic flow' will vary according to the quantity and quality of input parameter values (i.e., hydrostatic pressure, protein concentrations, osmotic reflection coefficients), it would be better to label these estimates as the sum of lymphatic and unmodeled net fluid absorption.

Ascitic Fluid↗

Mixed-effects nonlinear regression for unbalanced repeated measures.

Repeated measures data, such as clinical pharmacokinetic data, growth data, and dose-response data, are often inherently nonlinear with respect to a given response function and are frequently incomplete and/or unbalanced. Nonlinear random-effects models together with a variety of estimation procedures have been proposed for the analysis of such data. This paper is concerned with a straightforward procedure for estimating and comparing the parameters of a generalized mixed-effects nonlinear regression model. The asymptotic properties of the proposed estimators are given and large-sample tests of hypothesis provided. The results are applied to in vitro data on the water transport kinetics of hemodialyzers used in the treatment of patients with chronic renal failure.

Biological Transport, Active↗

Patient and technique survival among an urban population of peritoneal dialysis patients: an 8-year experience.

Estimates of patient and technique survival are given for 146 peritoneal dialysis (PD) patients who underwent dialysis between January 1, 1981 through December 31, 1989. In all, 33 patients died and 44 patients changed treatment. Patient survival was 92% at 1 year, 80% at 2 years, and 55% at 4 years, while technique survival was 85% at 1 year, 74% at 2 years, and 47% at 4 years. Cox's proportional hazards regression model was used to assess the effects of sex, age, diabetes, cardiovascular disease (CVD), education, and training time on both patient and technique survival. Both patient age (P = 0.001) and CVD (P = 0.03) had a significant impact on patient survival. On the average, for every 10 years' increase in age, the risk of death increased by a factor of 1.71. Patients with CVD had a risk of death 2.57 times higher than the risk of death among patients without CVD. With respect to technique or method survival, black patients had a risk of changing treatment 2.24 times higher than that for white patients. Our patient and technique survivals are similar to that reported in the national CAPD registry over a comparable period (1981 to 1988).

Adolescent↗

Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Adolescent↗

The effect of hematocrit on peritoneal transport.

Eight stable patients, from our institution, on continuous ambulatory peritoneal dialysis (CAPD) were entered into a multicenter, randomized, double-blind, placebo-controlled study with erythropoietin (EP]. To assess the effect of hematocrit on peritoneal solute transport, we performed peritoneal equilibration tests (PET) on each patient on a quarterly basis throughout the study. Patients on EPO had a significant increase in hematocrit at 3 (32% +/- 5%), 6 (32% +/- 2%), and 9 (38% +/- 3%) months compared with baseline (22% +/- 4%). The D/P creatinine (Cr) at 4 hours was also significantly reduced in the patients on EPO at 3 (.70 +/- .1), 6 (.66 +/- .12) months when compared with baseline (.76 +/- .11). No significant change in D/Do glucose at 4 hours or in the 4-hour ultrafiltrate (except at 9 months) was found. Based on mixed-effects regression analysis, the 4-hour D/P Cr, peritoneal Cr clearance, and Cr mass transfer area coefficient significantly decreased as hematocrit levels increased. The 4-hour D/Do glucose and the 4-hour ultrafiltrate both demonstrated a positive correlation with increasing hematocrit levels, but this did not reach statistical significance. Although larger studies are needed, it appears that increasing hematocrit levels may negatively affect peritoneal solute transport in CAPD patients as determined by PET.

Anemia↗

Kinetic modeling as a prescription aid in peritoneal dialysis.

Methods for calculating fluid and mass removal in peritoneal dialysis are presented in order to aid clinicians in their care and management of patients and to assist them in their understanding of the physiological mechanisms which govern peritoneal transport. These methods are based on the Pyle-Popovich peritoneal mass transport model which encompasses both diffuse and convective transport as well as lymphatic flow and residual renal function. Algebraic solutions to the mass balance equations governing solute transport are provided. Since these solutions are expressed explicitly as functions of time, they are easily programmed for use on a personal computer or calculator. This offers considerable advantage over the more computer-intensive numerical solutions which had been previously required since one can now calculate both mass removal and changes in blood concentration at the end of an exchange without requiring any intermediate calculations. This computational advantage and the ability to model changes in blood concentration are shown to be of particular importance when modeling more dynamic therapies such as CCPD or Tidal peritoneal dialysis. Finally, the model and solutions, when assessed clinically among 5 patients on two separate occasions, resulted in predicted fluid and mass removals which were in high concordance with measured fluid and mass removals (concordance correlation coefficients in excess of 0.97). Our findings suggest that kinetic modeling can provide the kind of analytical tools necessary to guide clinicians in their care and management of peritoneal dialysis patients.

Algorithms↗

A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis.

Four hundred and eighty CAPD and 373 HD patients started regular dialysis treatment between 1981 and 1987 in 6 dialysis centers. The CAPD patients were 6 years older, on average, than the HD patients and had more complicating conditions (43.3% with 3 or more coexisting risk factors versus 28.9% with coexisting complications). The 7-year patient survival rate was not significantly different. Cox's proportional hazards regression showed that age, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, diabetes, malignancy and multisystem disease had significant adverse effects on patient survival. After correcting for the influence of these factors, no significant differences in patient survival were seen. However, after 53.5 years of age, the increase in the risk of death was significantly higher in HD than in CAPD patients. Technique survival was significantly different in the 6 centers and was better for HD than for CAPD. There was no statistically significant difference between CAPD and HD technique survival when peritonitis was eliminated as a cause of failure. Based on this 7 year analysis, CAPD would appear to be an excellent alternative to HD.

Female↗

Modelling peritonitis rates and associated risk factors for individuals on continuous ambulatory peritoneal dialysis.

A mixed effects Poisson regression model is proposed for analysing potential risk factors associated with peritonitis, a bacterial infection of the peritoneum which is common among individuals on continuous ambulatory peritoneal dialysis (CAPD). The model incorporates a set of fixed effects corresponding to concomitant information collected across individuals as well as a random effect due to individuals. The method of maximum likelihood is used to estimate the unknown parameters. When applied to clinical data obtained on 81 CAPD patients from four centres, the mixed effects model demonstrated a much better fit than the corresponding fixed effects Poisson regression model.

Adult↗

Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients: a multicenter study.

Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.

Ascitic Fluid↗

Comparison of patient and technique survival in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis: a multicenter study.

Patient and technique survival were compared in adult patients new to continuous ambulatory peritoneal dialysis (CAPD) or (primarily) center hemodialysis (HD) in the time period 1981 to 1983, and followed-up in March 1985. Risk factors were identified at entrance into the study, and results were analyzed using Cox's proportional hazards model. For nondiabetic patients, the difference in survival which favored CAPD (relative risk = 0.62) was not significant at the 5% level (p = 0.08). Age was a significant risk factor in both groups. The average number of hospital visits was the same; however, CAPD showed a small but significant increase in average annual hospital days per year (10.14 vs. 9.18). For diabetic patients, there was no significant difference in survival between CAPD and HD. The CAPD group showed a significant increase in hospital visits (relative risk 1.81 vs. 1.40) and average hospital days per year (19.43 vs. 13.41). Both CAPD groups showed significantly higher treatment changeover rates.

Adult↗

Efficient inference for random-coefficient growth curve models with unbalanced data.

Growth and dose-response curve studies often result in incomplete or unbalanced data. Random-effects models together with a variety of computer-intensive iterative techniques have been suggested for the analysis of such data. This paper is concerned with a noniterative method for estimating and comparing location parameters in random-coefficient growth curve models. Consistent and asymptotically efficient estimators of the location parameters are obtained using estimated generalized least squares. Two criteria for testing multivariate general linear hypotheses are introduced and their asymptotic properties are investigated. The results are applied to clinical data obtained on the blood ultrafiltration performance of hemodialyzers used in the treatment of patients with end-stage renal disease.

Biometry↗

Sample sizes in the multivariate analysis of repeated measurements.

Determination of sample sizes for comparing two or more treatments in repeated measurements experiments is considered. Multivariate normality of the individual's vector of repeated measures is assumed. Particular emphasis is placed on applications wherein the error variance-covariance matrix is arbitrary positive-definite. Sample size determination is based on power considerations associated with Hotelling's T2 test and the desire to detect a specified difference between any pair of treatment means. Tabulated sample sizes are given in the case of an equal variance-unequal covariance structure. The utility of these sample sizes is also demonstrated for a more general variance-covariance structure. Applications of these sample sizes are illustrated with two examples.

Analysis of Variance↗

Non-linear models for the analysis of longitudinal data.

Given the importance of longitudinal studies in biomedical research, it is not surprising that considerable attention has been given to linear and generalized linear models for the analysis of longitudinal data. A great deal of attention has also been given to non-linear models for repeated measurements, particularly in the field of pharmacokinetics. In this article, a brief overview of non-linear models for the analysis of repeated measures is given. Particular emphasis is placed on mixed-effects non-linear models and on various estimation procedures proposed for such models. Several of these estimation procedures are compared via a simulation study. In addition, simulation is used to investigate the effects of model misspecification, particularly with respect to one's choice of random-effects. A relatively straightforward measure useful in selecting an appropriate set of random effects is investigated and found to perform reasonably well.

Humans↗

A multinational clinical validation study of PD ADEQUEST 2.0. PD ADEQUEST International Study Group.

OBJECTIVE: To clinically validate the use of the newly released kinetic modeling program, PD ADEQUEST 2.0 for Windows (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), by assessing the level of agreement between measured and modeled values of urea and creatinine clearances (CCr), glucose absorption, total drain volumes, and net ultrafiltration for all forms of peritoneal dialysis. DESIGN: A nonrandomized, multinational, prospective longitudinal study. PATIENTS: The study involved 104 adult patients [41 on continuous ambulatory peritoneal dialysis (CAPD), 63 on automated peritoneal dialysis (APD)] from 16 centers in 7 countries. All patients underwent a 4-hour peritoneal equilibration test (PET) but with varying percentage dextrose concentrations (1.5% or 2.5% dextrose) and varying fill volumes (range 1.5 - 2.5 L). Patients with a residual renal function greater than 10 mL/min were excluded, as were patients who had peritonitis within 6 weeks prior to baseline. MAIN OUTCOME MEASURES: Correlation coefficients and Bland-Altman limits of agreement were used to assess the level of agreement between measured and modeled values of weekly peritoneal urea Kt/V (pKt/V) and total Kt/V, weekly peritoneal creatinine clearance (pCCr, L/week/1.73 m2) and total CCr (L/week/1.73 m2), daily drain volume (L/day), net ultrafiltration (UF, L/day), daily peritoneal urea and creatinine mass removal (g/day), and daily peritoneal glucose absorption (g/day). Measured values were obtained from three repeat 24-hour urine and dialysate collections per patient, while modeled values were calculated using the Baxter PD ADEQUEST 2.0 program in conjunction with kinetic parameters estimated from a 4-hour PET and long-dwell exchange independent of the 24-hour collections. RESULTS: The results show there is excellent agreement between measured and modeled urea Kt/V and CCr with concordance correlation coefficients ranging from 0.83 to 0.97 among CAPD and APD patients. There was also excellent agreement between measured and modeled values of glucose absorption and total drain volumes (concordance correlations of 0.90 and 0.98, respectively). This level of agreement was further supported by a Bland-Altman analysis of individual differences, including differences between measured and modeled net UF (coefficient of clinical agreement ranged from 0.66 to 0.92). CONCLUSIONS: Data from a carefully performed PET and overnight exchange can, in combination with a scientifically and clinically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD and APD prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for quickly estimating approximate levels of clearance for a wide variety of alternative prescriptions. This, in turn, should speed up the process by which a physician can optimize the dose of dialysis suitable for a given patient and his/her lifestyle.

Absorption↗

Correlation between peritoneal equilibration test and dialysis adequacy and transport test, for peritoneal transport type characterization. Mexican Nephrology Collaborative Study Group.

OBJECTIVE: The aim of this study was to analyze the correlation between the peritoneal equilibration test (PET) and the dialysis adequacy and transport test (DATT) for peritoneal transport type characterization, and the degree of patients' acceptance for each test. DESIGN: Cross-sectional, observational multicenter study. SETTING: Five referral (tertiary) dialysis centers of institutional practice. PATIENTS: The study included 107 adult continuous ambulatory peritoneal dialysis (CAPD) patients with a prescription of four exchanges of 2 L per day, irrespective of age, gender, cause of end-stage renal disease, time on dialysis, nutritional status, or residual renal function. Patients on immunosuppressive therapy and those with cancer, hepatitis B, or HIV, and those having a peritonitis episode within the previous 30 days, or three or more episodes during the previous 12 months, were excluded. MAIN MEASURES: Peritoneal transport type as classified by creatinine and urea dialysis-to-plasma (D/P) ratios by PET and DATT. RESULTS: Correlation coefficients between D/P ratios for creatinine and urea, obtained for the PET and the DATT, were 0.73 for D/P creatinine and 0.96 for D/P urea. Patients were classified into high, high-average, low-average, and low transport categories according to the mean and standard deviation of D/P creatinine values obtained from the PET at 4 hours. These values showed excellent concordance with those generated from the DATT data (alpha = 0.82, 95% confidence interval 0.67 - 0.93). Nineteen percent of patients showed discordance in their category when classified according to the PET versus the DATT. Patients' acceptance was better for the DATT than for the PET, as evaluated with a questionnaire. CONCLUSION: The DATT is an easy, inexpensive, and reliable test to assess peritoneal transport type, and it also provides information about peritoneal clearance of solutes and ultrafiltration. The DATT has better patient acceptance than the PET. Since the DATT has only been validated for patients on a fixed CAPD daily schedule of 4 x 2 L, the results should be confined only to patients receiving such a prescription.

Adolescent↗

The influence of dialysis treatment modality on the decline of remaining renal function.

A retrospective investigation was undertaken in which the rate of decline of residual renal function (RRF), estimated from creatinine clearance, was compared in 55 continuous ambulatory peritoneal dialysis (CAPD) and 57 hemodialysis (HD) patients for whom a minimum of four (mean of 7.6) well-spaced historic measurements of residual clearance were available. Because of the intrinsic variability that attends such data, specialized nonlinear, growth curve statistical methods were employed. Residual function was found to decline exponentially after the onset of therapy in both cohorts. The rate of decline in the HD group was twice that of the CAPD group (5.8% +/- 0.4% per month for HD vs 2.9% +/- 0.3% per month for CAPD; difference significant at p less than 0.0001). This difference remained highly significant (p less than 0.01) when corrected for other potential risk factors such as age, gender, hypertensive status, and use of angiotensin converting enzyme inhibitors in patients with diabetic or other forms of glomerular nephropathy. Differences between cohorts were not significant for patients with other diagnoses (p greater than 0.1) although the size of some of these subsets was very small. The physiologic mechanism for the more rapid fall-off of RRF on HD remains speculative, but could be related to renal ischemia secondary to intratreatment hypovolemia and/or to nephrotoxic effects of the inflammatory mediators of extracorporeal circulation.

Female↗

Peritoneal dialysis kinetic modeling: validation in a multicenter clinical study.

OBJECTIVE: To clinically validate the use of a computer-based kinetic model for peritoneal dialysis (PD) by assessing the level of agreement between measured and modeled values of urea and creatinine clearances and ultrafiltration (UF). DESIGN: An open multicenter observational study. PATIENTS: There were 111 adult continuous ambulatory peritoneal dialysis (CAPD) patients (47 female, 64 male) in four centers. All patients underwent a four-hour peritoneal equilibration test (PET) using 2.5% dextrose but with variable fill volumes (range: 1-3 L). Patients with a residual renal function greater than 10 mL/min were excluded. MAIN OUTCOME MEASURES: Correlations and limits of agreement between measured and modeled values of total weekly urea KT/V, total weekly normalized creatinine clearance (L/week/1.73 m2), daily drain volume (L), net ultrafiltration (L), daily peritoneal urea clearance (L/day), and daily peritoneal creatinine clearance (L/day). Measured values were obtained from 24-hour urine and dialysate collections while modeled values were based on results from the PET in combination with the PD ADEQUEST kinetic program. RESULTS: The results show there is excellent agreement between measured and modeled urea KT/V and creatinine clearances, with concordance correlations of 0.94 and 0.92, respectively. Given the excessive variation and limited range in ultrafiltration values, the concordance correlation between measured and modeled UF was only 0.50. In terms of daily peritoneal clearances and ultrafiltration, the level of precision (i.e., standard deviation) in the differences between modeled and measured values is +/- 1.05 L/day for urea clearance +/- 1.03 L/day for creatinine clearance, and +/- 0.919 L/day for ultrafiltration. By contrast, the level of precision (i.e., standard deviation) in the differences between two measured values is estimated to be +/- 0.979 L/day for urea clearance, +/- 0.802 L/day for creatinine clearance, and +/- 0.707 L/day for ultrafiltration. Defining the limits of clinical agreement to be +/- 2 standard deviations of the differences between two clinically measured 24-hour clearances (or ultrafiltration), we find that 94% of the modeled urea clearances, 87% of the modeled creatinine clearances, and 86% of the modeled ultrafiltration values fall within the limits of clinical agreement. CONCLUSION: Data for a carefully performed PET and overnight exchange can, in combination with a scientifically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD dialysis prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for predicting clearances for various alternative prescriptions and perhaps also as a means for checking certain types of noncompliance.

Adult↗