Malgorzata Debowska

Bimodal dialysis: theoretical and computational investigations of adequacy indices for combined use of peritoneal dialysis and hemodialysis.

A theoretically correct method for evaluating the adequacy of bimodal dialysis (BMD), a combination of peritoneal dialysis (PD) and hemodialysis (HD) in the same patient, is lacking. We therefore performed computer simulations using a variable- volume, two-compartment urea kinetic model for 1-week treatments with 1) HD with three sessions, HD3, 2) continuous ambulatory PD, CAPD, 3) 6 days of CAPD and 1 day with HD session, and 4) 5 days of CAPD and 2 days with HD. Four dialysis adequacy indices (KT/V, stdKT/V, fractional solute removal, FSR, and equivalent clearance, EKR) were analyzed using four different reference methods for normalization of urea amount and concentration: 1) peak value, 2) peak average value, 3) time average value, and 4) treatment time average value. The analyses show that a proposed simplified rule of adding one third of weekly FSR for HD3 for each dialysis session and one seventh of weekly FSR for CAPD for each PD day for prediction of weekly FSR for BMD provides a fair prediction, although some corrections may be necessary, depending on the chosen reference method. In particular, KT/V may be added using this rule. We conclude that theoretically correct adequacy indices for BMD may be defined and calculated by using numerical simulations.

Adequacy indices for dialysis in acute renal failure: kinetic modeling.

Many aspects of the management of renal replacement therapy in acute renal failure (ARF), including the appropriate assessment of dialysis adequacy, remain unresolved, because ARF patients often are not in a metabolic steady state. The aim of this study was to evaluate a system of adequacy indices for dialysis in ARF patients using urea and creatinine kinetic modeling. Kinetic modeling was performed for two different fictitious patients (A and B) with characteristics described by the average parameters for two patient groups and for two blood purification treatments: sustained low efficiency daily dialysis (SLEDD) in Patient A and continuous venovenous hemofiltration (CVVH) in Patient B, based on data from a clinical report. Urea and creatinine generation rates were estimated according to the clinical data on the solute concentrations in blood. Then, using estimated generation rates, two hypothetical treatments were simulated, CVVH in Patient A and SLEDD in Patient B. KT/V, fractional solute removal (FSR) and equivalent renal clearance (EKR) were calculated according to the definitions developed for metabolically unstable patients. CVVH appeared as being more effective than SLEDD because KT/V, FSR, and EKR were higher for CVVH than SLEDD in Patients A and B. Creatinine KT/V, FSR, and EKR were lower and well correlated to the respective indices for urea. Urea and creatinine generation rates were overestimated more than twice in Patient A and by 30-40% in Patient B if calculated assuming the metabolically stable state than if estimated by kinetic modeling. Adequacy indices and solute generation rates for ARF patients should be estimated using the definition for unsteady metabolic state. EKR and FSR were higher for urea and creatinine with CVVH than with SLEDD, because of higher K.T and minimized compartmental effects for CVVH.

Can the Diverse Family of Dialysis Adequacy Indices Be Understood as One Integrated System

Background: Dialysis adequacy indices are based on the amount of removed solute and systemized into two groups: (1) fractional solute removal (FSR, non-dimensional), and (2) equivalent continuous clearance (ECC, ml/min), which are expressed using appropriate reference method for solute concentration or mass such as: peak, peak average, time average, and treatment time average values. Methods: A review and critical analysis of the recent studies was performed. Results: The indices are mathematically interrelated and depend on kinetic parameters of the treatment, as device clearance, treatment time, solute distribution volume, dialysis frequency. In particular, KT/V and KT can be directly translated to FSR and ECC using the treatment time average reference method. Conclusion: The diverse family of dialysis adequacy indices can be understood as one integrated system and be useful when assessing both standard treatment modalities and newer schedules and modalities (frequent dialysis, hybrid dialysis, dialysis in acute renal failure) of renal replacement therapies.

Kinetic Modeling and Adequacy of Dialysis

The mathematical description of hemodialysis (HD) includes two parts: 1) explanation of the exchange between patient’s blood and dialysate fluid across a semipermeable membrane of the dialyzer, and 2) characterization of the solute removal from the patient. The solute transport across the dialyzer membrane depends on the difference in hydrostatic pressure and solute concentration gradients between both sides of the membrane and also on the permeability of the membrane to the solute. The local equations for solute and fluid transport through the membrane are based on a phenomenological (thermodynamic) description according to the Staverman-Kedem-Katchalsky-Spiegler approach (Staverman, 1951; Kedem & Katchalsky, 1958; Katchalsky & Curran, 1965; Spiegler & Kedem, 1966). The two compartment model describes the functioning of the patient – dialyzer system, assuming that body fluid is divided into two parts: one directly (extracellular compartment) and one indirectly (intracellular compartment) accessible for dialysis (Schneditz & Daugirdas, 2001). The one compartment model of the solute distribution volume assumes that the solute is distributed in a single, homogenous pool. Solute kinetic modeling is based on a set of ordinary differential equations describing the changes of solute mass, concentration and distribution volume in body compartments and in the dialyzer. Using solute kinetic modeling one is able to evaluate dialysis efficiency. The question concerning dialysis dosing has been debated and remains controversial since the beginning of the dialysis treatment era. Between 1976 and 1981, the National Cooperative Dialysis Study (NCDS) was performed in the United States to establish objective, quantitative criteria for the adequate dose of dialysis (Gotch & Sargent, 1985; Sargent & Gotch, 1989; Locatelli et al., 2005). The primary analysis showed that morbidity was less at lower levels of time average urea concentration. The secondary ‘mechanistic’ analysis of the NCDS data done by Gotch and Sargent launched the issue of urea KT/V (Gotch & Sargent, 1985). Single-pool KT/V overestimates the removed amount of urea because of the postdialysis urea rebound, i.e., a fast postdialysis increase in urea concentration in plasma, which is a compartmental effect; therefore, the equilibrated KT/V (eqKT/V), estimated by the Daugirdas formula, was introduced to clinical practice (Daugirdas et al., 2001). Equilibrated KT/V values can be also calculated using an alternative equation by Daugirdas and

Phosphate Kinetics in Hemodialysis: Application of Delayed Pseudo One-Compartment Model.

Background/Aims: Various body-regulating mechanisms try to counteract rapid changes in serum phosphate levels during hemodialysis (HD). Neither recently proposed nor other existing standard compartment models are able to capture clinically observed intradialytic serum phosphate rebound. Methods: Phosphate serum concentration was frequently measured during 75 HD sessions in 25 patients. Time delay was introduced into the standard pseudo one-compartment model in order to reflect the time needed for the body-regulating mechanism to affect serum phosphate level. Results: Measured serum phosphate concentration at the end of 4 h dialysis session was on average larger than 1 h earlier (p value = 0.015). The model with time delay reproduced successfully 19 out of 21 and 9 out of 10 sessions with and without recorded intradialytic rebound, respectively. Conclusion: The intradialytic serum phosphate rebound is associated with the time delay reflecting efficacy of body-regulating mechanisms, that is, the larger the delay the larger is the intradialytic rebound.

ULTRAFILTRATION AND DIALYSIS ADEQUACY WITH VARIOUS DAILY SCHEDULES OF DIALYSIS FLUIDS

Dialysis regimens for continuous ambulatory peritoneal dialysis (CAPD) patients vary with the need for fluid removal, but also because of concerns about the local and systemic consequences of high glucose exposure. The implications of various regimens for dialysis adequacy—that is, fluid and small-solute removal—are not always clear. We therefore analyzed ultrafiltration (UF) and adequacy indices for 4 different combinations of dialysis fluid. Collections of 24-hour dialysate and urine were carried out in 99 patients on CAPD. On 4 separate occasions, each patient performed 4 exchanges in 24 hours, including 3 daily exchanges with 1.36% glucose and 1 night exchange with either 1.36% glucose (G1 schedule), 2.27% glucose (G2 schedule), 3.86% glucose (G3 schedule), or icodextrin (Ico schedule). Weekly, total, and dialysis Kt/V and KT were calculated for both urea and creatinine. The mean values of urea Kt/V and KT were significantly lower for the G1 schedule than for the G3 and Ico schedules. The adequacy indices for overnight application of 3.86% glucose and icodextrin were similar. Using dialysis fluids with 1.36% and 2.27% glucose overnight reduces glucose exposure, but those schedules may provide inadequate UF and small-solute removal in some patients (UF < 1 L daily, Kt/V < 1.7).

Subject-specific pulse wave propagation modeling: Towards enhancement of cardiovascular assessment methods

Cardiovascular diseases are the leading cause of death worldwide. Pulse wave analysis (PWA) technique, which reconstructs and analyses aortic pressure waveform based on non-invasive peripheral pressure recording, became an important bioassay for cardiovascular assessment in a general population. The aim of our study was to establish a pulse wave propagation modeling framework capable of matching clinical PWA data from healthy individuals on a per-subject basis. Radial pressure profiles from 20 healthy individuals (10 males, 10 females), with mean age of 42 ± 10 years, were recorded using applanation tonometry (SphygmoCor, AtCor Medical, Australia) and used to estimate subject-specific parameters of mathematical model of blood flow in the system of fifty-five arteries. The model was able to describe recorded pressure profiles with high accuracy (mean absolute percentage error of 1.87 ± 0.75%) when estimating only 6 parameters for each subject. Cardiac output (CO) and stroke volume (SV) have been correctly identified by the model as lower in females than males (CO of 3.57 ± 0.54 vs. 4.18 ± 0.72 L/min with p-value < 0.05; SV of 49.5 ± 10.1 vs. 64.2 ± 16.8 ml with p-value = 0.076). Moreover, the model identified age related changes in the heart function, i.e. that the cardiac output at rest is maintained with age (r = 0.23; p-value = 0.32) despite the decreasing heart rate (r = −0.49; p-value < 0.05), because of the increase in stroke volume (r = 0.46; p-value < 0.05). Central PWA indices derived from recorded waveforms strongly correlated with those obtained using corresponding model-predicted radial waves (r > 0.99 and r > 0.97 for systolic (SP) and diastolic (DP) pressures, respectively; r > 0.77 for augmentation index (AI); all p—values < 0.01). Model-predicted central waveforms, however, had higher SP than those reconstructed by PWA using recorded radial waves (5.6 ± 3.3 mmHg on average). From all estimated subject-specific parameters only the time to the peak of heart ejection profile correlated with clinically measured AI. Our study suggests that the proposed model may serve as a tool to computationally investigate virtual patient scenarios mimicking different cardiovascular abnormalities. Such a framework can augment our understanding and help with the interpretation of PWA results.

Selection of Genetic and Phenotypic Features Associated with Inflammatory Status of Patients on Dialysis Using Relaxed Linear Separability Method

Identification of risk factors in patients with a particular disease can be analyzed in clinical data sets by using feature selection procedures of pattern recognition and data mining methods. The applicability of the relaxed linear separability (RLS) method of feature subset selection was checked for high-dimensional and mixed type (genetic and phenotypic) clinical data of patients with end-stage renal disease. The RLS method allowed for substantial reduction of the dimensionality through omitting redundant features while maintaining the linear separability of data sets of patients with high and low levels of an inflammatory biomarker. The synergy between genetic and phenotypic features in differentiation between these two subgroups was demonstrated.

Are dialysis adequacy indices independent of solute generation rate

KT/V is by definition independent of solute generation rate. Alternative dialysis adequacy indices (DAIs) such as equivalent renal clearance (EKR), standard KT/V (stdKT/V), and solute removal index (SRI) are estimated as the ratio of solute mass removed to an average solute mass in the body or solute concentration in blood; both nominator and denominator in these formulas depend on the solute generation rate. Our objective was to investigate whether and under which conditions the alternative DAIs are independent of solute generation rate. By using general compartment modeling, we show that for the metabolically stable patient (in whom the solute generated during the dialysis cycle, typically, 1 week, is equal to the solute removed from the body), DAIs estimated for the dialysis cycle are in general independent of the average solute generation rate (although they may depend on the pattern of oscillations in the generation rate). However, the alternative adequacy parameters (such as EKR, stdKT/V, and SRI) may depend on solute generation rate for metabolically unstable patients.

Contents Vol. 30, 2010

221 28th Annual Meeting of the International Society of Blood Purification (ISBP) September 24–26, 2010, Marina del Rey, Calif., USA Guest Editors: Victor Gura (Beverly Hills, Calif.); Robert Zietse (Rotterdam)