Objective The three-pore model of peritoneal transport is used extensively for modeling peritoneal fluid and solute transport, but the currently used versions include certain modifications of the transport parameters that have not been validated quantitatively versus detailed data on fluid and solute kinetics. The aim of this study was to evaluate different versions of the three-pore model. Method Detailed clinical peritoneal fluid and solute transport data were obtained from 40 peritoneal dwell studies in clinically stable continuous ambulatory peritoneal dialysis patients in whom the dialysate volume was measured using a macromolecular volume marker (RISA). Results Using a new version of the three-pore model with several adjusted transport parameters, good agreement between the measured and the simulated values of dialysate volume and concentrations of small solutes and RISA (but not of endogenous protein) versus dwell time was obtained; however, the predicted peritoneal absorption for longer than the investigated dwell time would be too high. Conclusion The three-pore model, with some adjustments proposed in this study, may be used for detailed description of peritoneal transport kinetics, but it should be pointed out that, even after these adjustments, it still does not provide the correct description of peritoneal fluid absorption and transport of macromolecules.

Background: Apart from KT/V, equivalent urea clearance (EKR) and fractional solute removal (FSR) can also be used to assess the dialysis adequacy. Our objective was to analyze the relationships between these indices for different dialysis modalities and schedules, using urea kinetic modeling. Methods: EKR and FSR were calculated for HD (three or six times per week), automatic nightly PD (ANPD) and CAPD using the following reference values of urea concentration and mass in the body: peak, peak average, time average and treatment time average. Results: The standard KT/V approach is related to the treatment time average, whereas the standard EKR is related to the time average reference values. In spite of KT/V = 3.5 (K meaning dialyzer clearance or peritoneal diffusive mass transport coefficient), EKR and FSR were lower for ANPD and CAPD than for HD. The ratio of EKR to FSR was essentially the same for the different treatment modalities (range 3.48–4.07 ml/min). This could be explained by the theoretical analysis which predicts the value of EKR/FSR = V/Tc, independent of the treatment modality and schedules (V is a solute distribution volume, Tc is the time of the full dialysis cycle). Conclusion: Whereas the index KT/V in its standard form cannot be used to compare different dialysis regimens, EKR and FSR provide very similar evaluation of different dialysis modalities and schedules, and may be considered as equivalent measures for comparative studies of dialysis adequacy.

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.

Background Two major types of permanent loss of ultrafiltration capacity (UFC) were previously distinguished among patients treated with CAPD: 1) type HDR with high diffusive peritoneal transport rate of small solutes and low osmotic conductance, but with normal fluid absorption rate, and 2) type HAR with high fluid absorption rate, but with normal diffusive peritoneal transport rate of small solutes and normal osmotic conductance. However, the detailed pattern of changes in peritoneal transport parameters in patients developing loss of ultrafiltration capacity is not known. Objective Analysis of solute and fluid transport parameters in the same patient before and after UFC loss. Patients Seven CAPD patients who had undergone repeated dwell studies, which were carried out before and/or after the onset of UFC loss. Methods Dialysis fluids (2 L) with glucose or a mixture of amino acids as osmotic agent at three basic tonicities were applied during 6 hour dwell studies. Fluid and solute transport parameters were previously shown not to be affected by these dialysis solutions (except by hypertonic amino acid-based solution). Intraperitoneal dialysate volume and fluid absorption rate were assessed using radiolabeled human serum albumin (RISA). Osmotic conductance (aOS) was estimated by a mathematical model as ultrafiltration rate induced by unit osmolality gradient. Diffusive mass transport coefficients, KBD, for glucose, urea, and creatinine were estimated using the modified Babb-Randerson-Farrell model. Results Five patients had increased KBD for small solutes after the onset of UFC loss, and three of them had decreased aOS, whereas two patients had normal aOS. In one of them, aOS decreased with time after the onset of UFC loss with concomitant normalization of glucose absorption. In all studies of these five patients the fluid absorption rate was within the normal range. Two other patients had increased fluid absorption rate (about 5 ml/min), and one of them also had increased KBD for small solutes, in two consecutive dwell studies in each patient with the second study being carried out at 1 and 7 months respectively after the first one. In all four studies in these two patients, the aOS was within the normal range. The sodium dip during dialysis with 3.86% glucose-based solution was lost, not only among most patients with UFC loss related to reduced osmotic conductance, but also in patients with increased KBD. Conclusions The occurrence of two major types of UFC loss was confirmed. However, a case of a mixed type of UFC loss with high fluid absorption rate and high KBD for small solutes, but normal osmotic conductance, and with normalization of initially high KBD for small solutes, linked with decreasing initially normal osmotic conductance, was also found. As a reduced sodium dip with hypertonic glucose solution is not only seen in patients with reduced osmotic conductance, it cannot reliably be used as a single measure of decreased aquaporin function. Permanent ultrafiltration capacity loss may be a dynamic phenomenon with a variety of alterations in peritoneal transport characteristics.

Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2-2-3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one-compartment model was applied to describe the profile of phosphate in blood serum during intra- and interdialytic periods of 1-week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (KM ) and the rate of phosphate mobilization (RM ), were correlated with the reduction of serum phosphate concentration during dialysis (Cpost /Cpre ) and with equivalent continuous clearance (ECC) for phosphate. KM correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between RM and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one-compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one-compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate.

HD adequacy monitoring for phosphate may be performed using ECC, but it is less predictable than similar indices for urea and creatinine. The values of ECC for phosphate are within the range expected for its molecular size compared with those for urea and creatinine.

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.

In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.