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Simple Kt/V formulas based on urea mass balance theory

&NA; The ratio Kt/V (K is patient clearance, t dialysis time, V urea space) has become the standard measure of dialysis adequacy. In this article simple Kt/V equations are developed theoretically from the urea mass balance equation. Two approximations lead to the most precise equation: where R is the post to pre dialysis urea ratio, BW/V is the amount of fluid removed during dialysis (&Dgr;BW) expressed as a fraction of urea distribution space (V) at dry body weight (BW), and t is dialysis length in hours. A second equation arises with V approximated as 58% of BW. One further approximation leads to a simpler but slightly less precise Kt/V formula: These and earlier published equations were tested with two sets of data: 1) 49 sessions involving 17 patients on maintenance dialysis and 2) 540 computer simulations spanning all likely values of Kt/V (0.6‐1.6), protein catabolic rate (0.6‐1.6), interdialytic weight gain (0‐4% of BW per day) and dialysis session length (2‐4 hr). The most precise formula (upper equation above) had a maximum error of 0.031 and 0.035 Kt/V units for the clinical and simulated data, respectively, whereas the lower equation was slightly less accurate with maximum Kt/V errors of 0.079 and 0.081, respectively. The proposed Kt/V equations are considerably more accurate than previously published formulas. ASAIO Journal 1994; 40:997‐1004.

Optimal Hemodialysis—The Role of Quantification

Mathematical modeling of urea dynamics is the most common method currently used to measure and deliver the optimal dose of hemodialysis for each patient. The modeling concept was popularized by Gotch, Sargent, and coworkers (1, 2) in 1974 and became known as urea kinetic modeling (UKM). Since then, hundreds of papers have been published by a myriad of workers, but two landmarks stand out: the U.S. National Cooperative Dialysis Study (NCDS) published in 1983 (3, 4) and Gotch and Sargents proposal in 1985 (5) of KtIV as a measure of the quantity of dialysis delivered to each patient. Roughly a decade has passed since the final report of the NCDS and the formulation of KtIV, yet quantification of patient therapy is not universally practiced among dialysis centers. Whether and how to use UKM remain controversial. In 1994, we find ourselves at a promising crossroads in the field of dialysis quantification. Emerging technology for automated urea sensing and a shift from blood-based to dialysate-based measurements offer a realistic expectation of improved accuracy and less complexity. This article will review the application and limitations of classical UKM, and will include simplified methods for measuring KtIV and the patients protein catabolic rate from blood concentrations. It will then focus on methods based on measurement of urea in spent dialysate and explore current developments in urea sensing that offer the prospect of automated UKM.

Slow isolated ultrafiltration for the treatment of congestive heart failure

Abstract Slow isolated ultrafiltration (UF) was used to remove excess water and sodium in refractory congestive heart failure (CHF) patients. Fifty-two patients (40 men, 12 women; age, 63.8 ± 10.2 years) presenting with CHF (class IV, New York Heart Association (NYHA)) were included in the study. Forty-one patients had normal renal function, and 11 patients had various degrees of renal failure before the episode of cardiac decompensation. Cardiac disease caused by ischemia, hypertension, or a combination was present in the majority of patients (n = 28). UF was performed in all cases via a venovenous modality using a double-pump module (blood and UF pumps) and using highly permeable membrane (AN69; Hospal, Lyon, France). The weight loss achieved by UF to restore dry weight was 9.2 ± 5.0 kg over 9.0 ± 10.5 days with satisfactory hemodynamic tolerances. Outcome of the 52 patients was as follows: 13 patients (nonresponders) died during the course of treatment; 24 patients (responders) had both cardiac and renal temporary improvement for a short or long duration period; 15 patients (partial responders) had cardiac improvement and renal degradation leading to long-term treatment (intermittent UF or dialysis). Interestingly, diuresis returned in 24 of 39 responder patients. In conclusion, isolated UF offers a simple and effective means of escape from the cardio-renal vicious circle in refractory CHF patients. UF must be considered as an integral tool for the modern treatment of CHF.

Urea kinetic modeling for CRRT

Urea kinetic modeling (UKM) for dialysis quantification and prescription, although widely used in chronic renal failure (CRF), has been largely absent in the acute setting. A quantitative approach to prescription of continuous renal replacement therapies (CRRTs) for acute renal failure (ARF) based on UKM is presented. For patients with a relatively constant urea generation rate, G, who are receiving a fixed dose of CRRT, blood urea nitrogen (BUN) falls in an exponential fashion, approaching a plateau level after 3 to 4 days of continuous treatment. The CRRT clearance, K, necessary to achieve a desired plateau value of BUN, Cgoal, may be computed as G/Cgoal x K for all but predilutional CRRT modalities may be calculated as equal to the effluent (dialysate plus ultrafiltrate) flow rate from the filter. Urea mass balance equations are proposed for the determination of patient G value either during the pretreatment rise in BUN or during the decline in BUN with CRRT. In the absence of a reliable estimate of patient G, a reasonable CRRT starting prescription is to set the filter effluent rate in liters per hour (approximately K) to 1.2 times the patients body weight in kilograms divided by the desired Cgoal in milligrams per deciliter. This relationship assumes moderate hypercatabolism (normalized protein catabolic rate = 2.0 g/kg/d) and patient urea distribution volume equal to 60% of body weight. For Cgoal = 60 mg/dL, this reduces to an easily remembered formula for K (in L/hr) of twice the patients body weight divided by 100.

Simple equations for protein catabolic rate determination from pre dialysis and post dialysis blood urea nitrogen.

&NA; Several simple equations exist for Kt/V determination from pre dialysis (Cpre) and post dialysis (Cpost) blood urea. However, comparable equations have not been available for calculation of protein catabolic rate (PCR), an essential parameter for assessing patient status. Three simple formulas for PCR determination were developed from the urea mass balance equation for an anuric patient in protein steady state receiving thrice weekly dialysis. The simplest formula, PCR = 0.0076[Kt/V][Cpre + Cpost] + 0.17 relates PCR (in g protein/kg/day) to Kt/V and pre and post dialysis blood urea nitrogen measurements (in mg urea nitrogen/dl) for the midweek session. When tested for 540 simulated patients spanning a range of Kt/V (0.6‐1.6); PCR (0.6‐1.6 g/kg/day); dialysis duration t (2‐4 hrs) and interdialytic weight gain expressed as a percentage of dry body weight gained daily (0‐4%), this equation yielded a maximum error of less than ±5%, within the accuracy generally required for clinical needs. A more accurate formula, where Clm is the logarithmic mean of Cpre and Cpost, gave maximum errors in PCR estimation for the same 540 simulated patients of less than ±0.6%. Both formulas require a precise value of Kt/V. The equation below incorporates a very accurate simple Kt/V equation recently published by the authors, allowing PCR to be expressed in terms of Cpre, the ratio of Cpost to Cpre (R), the ratio of session ultrafiltration volume (&Dgr;BW) to urea distribution volume (V), and dialysis time (t, in min). This equation was accurate to within a maximum error of ±1% for the simulated patient group. These equations allow simple and accurate patient PCR determination, and should be used in conjunction with a simple formula for accurate Kt/V determination to guide end‐stage renal failure patient therapy. ASAIO Journal 1995;41:889‐895.

On-line dialysis quantification in acutely ill patients: preliminary clinical experience with a multipurpose urea sensor monitoring device.

Direct dialysis quantification offers several advantages compared with conventional blood urea kinetic modeling, and monitoring urea concentration in the effluent dialysate with an on-line urea sensor is a practical approach. Such a monitoring device seems desirable in the short-term dialysis setting to optimize and personalize both renal replacement therapy and nutritional support of acutely ill patients. We designed a urea monitoring device consisting of a urea sensor, a multichannel hydraulic circuit, and a PC microcomputer. The sensor determines urea from catalysis of its hydrolysis by urease in liquid solution during neutral conditions. Hydrolysis of urea produces NH4+, and creates an electrical potential difference between two electrodes. Each concentration determination of urea is the average value of 10 measurements; samples are diverted and measured every 7 min. Laboratory calibration of the urea sensor has demonstrated linearity over the range 2–35 mmol/L. Urea monitoring was performed throughout the treatment course, either on the effluent dialysate or ultrafiltrate in seven acutely ill patients treated by either hemofiltration (n = 5) or hemodiafiltration (n = 2). The slope of the concentration of urea in the effluent over time was used to calculate an index of the dialysis dose delivered (Kt/V), urea mass removal, and protein catabolic rate. In addition, samples of the effluent were drawn every 21 min, and sent to the central laboratory for measurement of urea concentrations using an autoanalyzer. Kt/V values also were calculated with Garreds equation using pre and post session concentrations of urea in blood. Concentrations of urea in the effluent determined by the urea sensor were found to be very close to those obtained from the central laboratory over a wide range of values (3 to 42 mmol/L). In addition, Kt/V values for both hemofiltration and hemodiafiltration, when calculated with concentrations of urea in the effluent obtained by the urea sensor, did not significantly differ from Kt/V values obtained from the laboratory concentrations of urea in the effluent. On-line urea sensor monitoring of the effluent suppresses the cumbersome task of total effluent collection, and the complexity of urea kinetic analysis. The multipurpose prototype described here represents a new, simple, and direct assessment of dialysis dose and protein nutritional status of acutely ill patients, and is suitable for various modalities. ASAIO Journal 1998; 44:184–190.

Urea kinetic modeling with a prototype urea sensor in the spent dialysate stream.

The authors have previously demonstrated the feasibility and accuracy of urea kinetic modeling (UKM) based on monitoring urea concentration in the spent dialysate stream (SDS) throughout the hemodialysis (HD) session. They describe here a prototype urea sensor for this purpose and initial experience with HD patients. The sensor is based on ammonium ion and reference electrodes housed in a cell through which the entire SDS passes. The two electrode tips are bathed in urease solution on one side of a dialysis membrane; the SDS flows along the adjacent side. Urea diffusing across the membrane from the SDS is converted by the urease into ammonium ion, which is measured by the electrode pair. For evaluation, the prototype flowthrough urea sensor was installed in the SDS of a Cobe Centry 3 HD machine for 36 HD sessions. Independent measurement demonstrated a linear relationship between mv output of the sensor and logarithm of SDS urea concentration. The use of SDS urea concentration time profiles obtained with this sensor to obtain accurate values of patient protein catabolic rate (PCR) and KT/V is illustrated. Incorporation of urea sensors such as this prototype into HD machines, will permit complete automation of UKM in the near future.