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F A Gotch

Publications and source records attributed to F A Gotch.

At least 19 recordsLinked to original sources
PubMed2000

Design and statistical issues of the hemodialysis (HEMO) study.

The Hemodialysis Study is a multicenter clinical trial of hemodialysis prescriptions for patients with end stage renal disease. Participants from over 65 dialysis facilities associated with 15 clinical centers in the United States are randomized in a 2 x 2 factorial design to dialysis prescriptions targeted to a standard dose or a high dose, and to either low or high flux membranes. The primary outcome variable is mortality; major secondary outcomes are defined based on hospitalizations due to cardiovascular or infectious complications, and on the decline of serum albumin. The Outcome Committee, consisting of study investigators, uses a blinded review system to classify causes of death and hospitalizations related to the major secondary outcomes. The dialysis dose intervention is directed by the Data Coordinating Center using urea kinetic modeling programs that analyze results from dialysis treatments to monitor adherence to the study targets, adjust suggested dialysis prescriptions, and assist in trouble-shooting problems with the delivery of dialysis. The study design has adequate power to detect reductions in mortality rate equal to 25% of the projected baseline mortality rate for both of the interventions.

Humans↗
PubMed2000

Whither goest Kt/V?

Uremia is characterized by gross contamination of body water with a wide spectrum of retained solutes normally excreted by the kidney. The rationale for dialysis therapy is that these retained solutes have concentration-dependent toxicity, which can be ameliorated through removal by dialysis. Apart from the well-established clinical consequences of abnormalities in fluid, electrolyte, acid base metabolism, and retained beta 2-microglobulin (beta 2 m), there is very little understanding of solute-specific uremic toxicity. Evidence is reviewed to demonstrate the following: (1) Many aspects of the uremic syndrome are controlled by adequate dialysis of low molecular weight solutes. (2) Urea can serve as a generic molecule to quantitate the fractional clearance of body water by dialysis (Kt/V) of retained low molecular weight solutes. (3) Urea has no concentration-dependent toxicity, and the generation rate of putative toxic low molecular weight solutes is not proportional to urea generation. The major clinical consequences and controversies stemming from these interrelationships are reviewed. Kinetic approaches to determine Kt/V dose equivalency between intermittent and continuous dialysis therapy are reviewed. We conclude that Kt/V can and will be generalized to describe the kinetics of other solutes such as beta2m as our knowledge of uremic toxicity grows, and hence, it is predicted that it will goeth and goeth and goeth.

Dialysis Solutions↗
PubMed2000

Urea is the best molecule to target adequacy of peritoneal dialysis.

For hemodialysis, a large base of data shows the validity of modelling the dialysis dose and reliably estimating protein intake from equilibrated Kt/V urea (eKt/VU), the total dialyzer urea clearance provided during each treatment divided by the urea distribution volume. An eKt/VU of 1.05 thrice weekly is judged adequate, but is still under study. In continuous ambulatory peritoneal dialysis (CAPD), two dosage criteria are widely recognized: continuous ("standard") Kt/VU (stdKt/VU = 2.0 weekly), and total creatinine (Cr) clearance normalized to body surface area (KCrT = 70 L/week/1.73 m2). The CANUSA study concluded that a stdKt/VU of 2.1 and a KCrT of 70 L/week/1.73 m2 gave equivalent clinical outcomes. The Dialysis Outcomes Quality Initiative (DOQI) recommends values of 2.0 and 60 L/week/1.73 m2 respectively. An analysis of these two parameters for males and females over a wide range of body surface areas (BSAs) was done and the analysis showed: (1) The U and Cr dose criteria are incommensurable--that is, they can virtually never be achieved simultaneously in anephric patients. (2) The Cr criterion varies widely with the sex of the patient and with the BSA-dependent variation in stdKt/VU over a range of 2.1 to 3.0. (3) The U criterion always produces a KCrT < 60 L/week/1.73 m2 in females and 60-70 L/week/1.73 m2 in males. With respect to U and Cr, the CANUSA results were concluded to be valid in patients with substantial residual renal function, but probably not applicable to anephric patients where the doses are clearly incommensurable.

Creatinine↗
PubMed1999

Imprecision of the hemodialysis dose when measured directly from urea removal. Hemodialysis Study Group.

BACKGROUND: The postdialysis blood urea nitrogen (BUN; Ct) is a pivotal parameter for assessing hemodialysis adequacy by conventional blood-side methods, but Ct is relatively unstable because of hemodialysis-induced disequilibrium. The uncertainty associated with this method is potentially reduced or eliminated by measuring urea removed on the dialysate side, a more direct approach that can determine adequacy from the fraction of urea removed and by substituting an estimate of the equilibrated postdialysis BUN (Ceq) for Ct. For a patient with a known urea volume (V), Ceq, the equilibrated Kt/V (eKt/V), and the solute removal index (SRI) can be calculated from the predialysis BUN (C0), total urea nitrogen removed (A), and V from simple mass balance calculations (dialysate/volume method). However, a theoretical error analysis showed that relatively small errors in A, C0, or V are magnified when SRI or eKt/V is calculated using this method, especially at higher eKt/V values (for example, if eKt/V = 1.4 per dialysis, a 7% dialysate collection error causes a 20% error in eKt/V). METHODS: During three to four baseline dialyses in each of 39 patients enrolled in the pilot phase of the HEMO Study, "A" was measured using an instrument that sampled dialysate frequently (Biostat), and V was calculated from A, C0, and Ceq (median CV for V = 5.6%). The mean V was then applied to the dialysate/volume method to estimate eKt/V and SRI during two to five subsequent dialyses per patient (comparison dialyses). The accuracy and precision of these estimates were assessed by comparing them with eKt/V and SRI derived from a direct measurement of Ceq drawn 30 minutes after dialysis (reference method), from mathematical curve-fitting of sequential dialysate urea concentrations (dialysate curve-fit method), and from another blood-side method that estimates eKt/V from single pool Kt/V and the fractional rate of solute removal (rate method): eKt/V = spKt/V - 0.6.K/V + 0.03. RESULTS: During 128 comparison dialyses, median absolute errors for calculated eKt/V compared with the reference method were 0.169, 0.061, and 0.071 for the dialysate/volume method, the rate method, and the dialysate curve-fitting method, respectively. The corresponding correlation coefficients were 0.47, 0.88, and 0.81. For SRI, median absolute errors were 0.044, 0.018, and 0.027, and the correlation coefficients were 0.54, 0.85, and 0.74 for the three methods. CONCLUSIONS: The precision of eKt/V and SRI measurements was significantly lower for the dialysate/volume method compared with the blood-side methods. Inclusion of the dialysate curve analysis provided by the Biostat restored precision to the dialysate method to a level comparable to that of the blood-side methods. New techniques employing dialysate urea analysis should include a concentration profile to avoid these inherent methodological errors and assure the accuracy of eKt/V and SRI.

Female↗
PubMed1999

Peritoneal dialysis adequacy: a model to assess feasibility with various modalities.

BACKGROUND: The current standard of adequacy for peritoneal dialysis (PD) is to provide a weekly normalized urea clearance (Kt/V) of 2.0 or more and a creatinine clearance (CCr) of 60 liter/1.73 m2 or more. As native renal function is lost, it is important to determine the effectiveness of the available therapeutic modalities in achieving these goals. METHODS: A model to assess our ability to provide a weekly Kt/Vurea of 2.0 or more and a CCr of 60 liter/1.73 m2 or more to anuric patients undergoing continuous ambulatory PD (CAPD) and automated PD (PD Plus) was developed. The body surface area (BSA) distribution was obtained from 38,768 patients undergoing dialysis during January 1997. The distribution of peritoneal transport rates (PTRs) was obtained from 2531 peritoneal equilibration tests performed during 1996. The weekly Kpt/Vurea was calculated for the various PTR groups and the range of BSA with four PD prescriptions: CAPD 8 liters, CAPD 10 liters, PD Plus 12 liters, and PD Plus 15 liters, using a previously validated kinetic program (PackPD). RESULTS: The predicted percentage of patients capable of achieving the adequacy goals for Kt/V and CCr, respectively, were 24.8 and 11. 2 for CAPD 8 liters, 54.2 and 33.0 for CAPD 10 liters, 77.8 and 54.9 for PD Plus 12 liters, and 93.2 and 72.9 for PD Plus 15 liters. CONCLUSIONS: Most patients can attain the current adequacy standards of therapy with automated PD, but few (less than 25%) can do so with standard CAPD in the absence of residual renal function.

Anuria↗
PubMed1999

Relationship between apparent (single-pool) and true (double-pool) urea distribution volume.

BACKGROUND: The volume of urea distribution (V) is usually derived from single-pool variable volume urea kinetics. A theoretical analysis has shown that modeled single-pool V (Vsp) is overestimated when the urea reduction ratio (URR) is greater than 65 to 70% and is underestimated when the URR is less than 65%. The "true" volume derived from double-pool kinetics (Vdp) does not exhibit this effect. An equation has been derived to adjust Vsp to the expected Vdp. METHODS: To validate these theoretical predictions, we examined data from the Hemodialysis (HEMO) Study to assess the performance of Vdp as estimated from Vsp using the previously published prediction equation. For increased precision, both Vsp and Vdp were factored by anthropometric volume (Va). Patients were first dialyzed with a target equilibrated dialysis dose (eKt/V) of 1.45 during a baseline period and were then randomly assigned to eKt/V targets of either 1. 05 (a URR of approximately 67%) or 1.45 (a URR of approximately 75%). A blood sample was obtained one hour after starting dialysis during one dialysis in each patient. RESULTS: Vsp/Va was (mean +/- SD) 1.014 +/- 0.127 in 795 patients during the baseline period when the URR was approximately 1.45. During the first modeled dialysis after randomization, the Vsp/Va fell to 0.961 +/- 0.138 in the group with an eKt/V target of 1.05, but did not change significantly under the high eKt/V goal. The correction of Vsp to Vdp using the prediction equation resulted in a Vdp/Va ratio of 0.96 to 0.98 in all three circumstances without significant differences. When a blood sample was drawn one hour after starting dialysis, the apparent Vsp/Va ratio at one hour was much lower at 0.708 +/- 0.139. However, the mean Vdp/Va ratio, computed using the correction equation, was 0.968 +/- 0.322, which was similar to the Vdp/Va ratio calculated from the postdialysis blood urea nitrogen. CONCLUSIONS: These data suggest that the previously derived formula for adjusted Vsp is valid experimentally. The Vsp/Vdp correction should be useful for prescribing hemodialysis with either a very low Kt/V (for example, daily and early incremental dialysis) or a very high Kt/V.

Humans↗
PubMed1999

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group.

Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta2-microglobulin (beta2M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse.

Acetic Acid↗
PubMed1997

Clinical outcome relative to the dose of dialysis is not what you think: the fallacy of the mean.

Several recent retrospective studies of mortality relative to the dose of dialysis have been widely interpreted to indicate that adequate thrice-weekly hemodialysis requires a single pool Kt/V (spKt/V) of at least 1.4 to 1.6 and higher. In these studies, mortality rate has been correlated to the mean delivered spKt/V, (spKt/Vd)m, with coefficient of variation (CV) on the means ranging up to 45%. To evaluate these reported relationships, two large databases were analyzed using population constants to transform urea reduction ratio and spKt/Vd to equilibrated Kt/Vd (eKt/Vd), which expresses dose corrected for treatment time. The eKt/V dose (D) values were correlated to the reported relative risks (RR) of mortality to derive a RR/D function. The RR/D function, derived from these data with stepwise linear regression analysis, is nonlinear, with a steep linear increase in RR for eKt/Vd less than 1.05 and constant RR for eKt/Vd > or = 1.05. This RR/D function is mathematically expressed as RR = 1.96 - 1.03(eKt/Vd) (equation 1) when 0.50 < or = eKt/Vd < or = 1.05, and RR = 0.88 (equation 2) when eKt/V > or = 1.05. We show that regression of RR on (eKt/Vd)m with large CV results in overestimation of RR relative to eKt/Vd for individual patients because of extrapolation of the linear relationship beyond the threshold where the slope becomes zero (see equation 2 above). It is concluded that (1) current clinical data indicate that adequate dialysis is provided with eKt/Vd of 1.0 to 1.1 on a thrice-weekly schedule, (2) it is essential to assure that all patients achieve this level of therapy, which is best accomplished using urea kinetic modeling for both prescription and measurement of delivered eKt/Vd, and (3) the current HEMO study is well designed to determine whether higher levels of eKt/Vd will further improve clinical outcome.

Female↗
PubMed1997

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study.

The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean +/- SD eKt/V for patients randomized to these targets was 1.14 +/- 0.11 and 1.52 +/- 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 +/- 0.11 and 1.50 +/- 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling.

Blood Urea Nitrogen↗
PubMed1996

Computerized urea kinetic modeling to prescribe and monitor delivered Kt/V (pKt/V, dKt/V) in peritoneal dialysis. Fresenius Randomized Dialysis Prescriptions and Clinical Outcome Study (RDP/CO).

A computerized urea kinetic model of peritoneal urea transport (PACK-PD) has been developed and used to calculate prescription parameters which would result in the prescribed weekly peritoneal urea clearance (pKpt/V) required to achieve levels of weekly summed renal + peritoneal urea clearance (pKprt/ V) targeted at 1.75 and 2.16. Baseline kinetic data were obtained and analyzed with PACK-PD on 88 patients, and the program then used these data to calculate the required pKpt/V and subsequently the delivered Kpt/V (dKpt/V) from the dialysate collections. A total of 108 prescriptions were written and compared to dKpt/V measured over one to 24 months in the 88 patients. Both continuous ambulatory peritoneal dialysis and automated peritoneal dialysis (APD) were studied (APD consisted of PD+ with one or two diurnal and two to four nocturnal cycler exchanges). The correlation of dKpt/V to pKpt/V showed r = 0.93 with 95% confidence limits (CL) on agreement of +/-20% over a range of pKpt/V 0.52-2.55. The 95% CL on (dKpt/V-pKpt/V) were +/-0.30. We concluded: (1) that the prescription can be modeled as reliably in peritoneal dialysis as in hemodialysis (HD) where dKt/V and pKt/V agree to +/-25%, (2) that any individual weekly dKpt/V may vary as much as 0.3-0.4 from pKpt/V, and (3) that frequent measurement of dKpt/V and adjustment of pKpt/V as needed are required (as in HD) to control mean dKpt/V to within +/-10% of mean pKpt/V.

Capillary Permeability↗