Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 females; age 60 (21–87) years; median time on PD 19 (3–100) months) underwent sequential peritoneal equilibration test. Dialysis vintage and patient age did not correlate. Estimation of parameters of the two-pore model of peritoneal transport was performed. The estimated fluid transport parameters, including hydraulic permeability (LpS), fraction of ultrasmall pores (αu), osmotic conductance for glucose (OCG), and peritoneal absorption, were generally independent of solute transport parameters (diffusive mass transport parameters). Fluid transport parameters correlated whereas transport parameters for small solutes and proteins did not correlate with dialysis vintage and patient age. Although LpS and OCG were lower for older patients and those with long dialysis vintage, αu was higher. Thus, fluid transport parameters—rather than solute transport parameters—are linked to dialysis vintage and patient age and should therefore be included when monitoring processes linked to ageing of the peritoneal membrane

Mathematical modelling of bicarbonate supplementation and acid-base chemistry in kidney failure patients on hemodialysis.

Acid-base regulation by the kidneys is largely missing in end-stage renal disease patients undergoing hemodialysis (HD). Bicarbonate is added to the dialysis fluid during HD to replenish the buffers in the body and neutralize interdialytic acid accumulation. Predicting HD outcomes with mathematical models can help select the optimal patient-specific dialysate composition, but the kinetics of bicarbonate are difficult to quantify, because of the many factors involved in the regulation of the bicarbonate buffer in bodily fluids. We implemented a mathematical model of dissolved CO2 and bicarbonate transport that describes the changes in acid-base equilibrium induced by HD to assess the kinetics of bicarbonate, dissolved CO2, and other buffers not only in plasma but also in erythrocytes, interstitial fluid, and tissue cells; the model also includes respiratory control over the partial pressures of CO2 and oxygen. Clinical data were used to fit the model and identify missing parameters used in theoretical simulations. Our results demonstrate the feasibility of the model in describing the changes to acid-base homeostasis typical of HD, and highlight the importance of respiratory regulation during HD

Modelling Transcapillary Transport of Fluid and Proteins in Hemodialysis Patients.

The kinetics of protein transport to and from the vascular compartment play a major role in the determination of fluid balance and plasma refilling during hemodialysis (HD) sessions. In this study we propose a whole-body mathematical model describing water and protein shifts across the capillary membrane during HD and compare its output to clinical data while evaluating the impact of choosing specific values for selected parameters.The model follows a two-compartment structure (vascular and interstitial space) and is based on balance equations of protein mass and water volume in each compartment. The capillary membrane was described according to the three-pore theory. Two transport parameters, the fractional contribution of large pores (αLP) and the total hydraulic conductivity (LpS) of the capillary membrane, were estimated from patient data. Changes in the intensity and direction of individual fluid and solute flows through each part of the transport system were analyzed in relation to the choice of different values of small pores radius and fractional conductivity, lymphatic sensitivity to hydraulic pressure, and steady-state interstitial-to-plasma protein concentration ratio.The estimated values of LpS and αLP were respectively 10.0 ± 8.4 mL/min/mmHg (mean ± standard deviation) and 0.062 ± 0.041. The model was able to predict with good accuracy the profiles of plasma volume and serum total protein concentration in most of the patients (average root-mean-square deviation < 2% of the measured value).The applied model provides a mechanistic interpretation of fluid transport processes induced by ultrafiltration during HD, using a minimum of tuned parameters and assumptions. The simulated values of individual flows through each kind of pore and lymphatic absorption rate yielded by the model may suggest answers to unsolved questions on the relative impact of these not-measurable quantities on total vascular refilling and fluid balance

Model of fluid and solute shifts during hemodialysis with active transport of sodium and potassium.

BackgroundMathematical models are useful tools to predict fluid shifts between body compartments in patients undergoing hemodialysis (HD). The ability of a model to accurately describe the transport of water between cells and interstitium (Jv,ISIC), and the consequent changes in intracellular volume (ICV), is important for a complete assessment of fluid distribution and plasma refilling. In this study, we propose a model describing transport of fluid in the three main body compartments (intracellular, interstitial and vascular), complemented by transport mechanisms for proteins and small solutes.MethodsThe model was applied to data from 23 patients who underwent standard HD. The substances described in the baseline model were: water, proteins, Na, K, and urea. Small solutes were described with two-compartment kinetics between intracellular and extracellular compartments. Solute transport across the cell membrane took place via passive diffusion and, for Na and K, through the ATPase pump, characterized by the maximum transport rate, JpMAX. From the data we estimated JpMAX and two other parameters linked to transcapillary transport of fluid and protein: the capillary filtration coefficient Lp and its large pores fraction αLP. In an Expanded model one more generic solute was included to evaluate the impact of the number of substances appearing in the equation describing Jv,ISIC.ResultsIn the baseline model, median values (interquartile range) of estimated parameters were: Lp: 11.63 (7.9, 14.2) mL/min/mmHg, αLP: 0.056 (0.050, 0.058), and JpMAX: 5.52 (3.75, 7.54) mmol/min. These values were significantly different from those obtained by the Expanded model: Lp: 8.14 (6.29, 10.01) mL/min/mmHg, αLP: 0.046 (0.038, 0.052), and JpMAX: 16.7 (11.9, 25.2) mmol/min. The relative RMSE (root mean squared error)averaged between all simulated quantities compared to data was 3.9 (3.1, 5.6) %.ConclusionsThe model was able to accurately reproduce most of the changes observed in HD by tuning only three parameters. While the drop in ICV was overestimated by the model, the difference between simulations and data was less than the measurement error. The biggest change in the estimated parameters in the Expanded model was a marked increase of JpMAX indicating that this parameter is highly sensitive to the number of species modeled, and that the value of JpMAX should be interpreted only in relation to this factor

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 females; age 60 (21-87) years; median time on PD 19 (3-100) months) underwent sequential peritoneal equilibration test. Dialysis vintage and patient age did not correlate. Estimation of parameters of the two-pore model of peritoneal transport was performed. The estimated fluid transport parameters, including hydraulic permeability (LpS), fraction of ultrasmall pores ( u ), osmotic conductance for glucose (OCG), and peritoneal absorption, were generally independent of solute transport parameters (diffusive mass transport parameters). Fluid transport parameters correlated whereas transport parameters for small solutes and proteins did not correlate with dialysis vintage and patient age. Although LpS and OCG were lower for older patients and those with long dialysis vintage, u was higher. Thus, fluid transport parameters-rather than solute transport parameters-are linked to dialysis vintage and patient age and should therefore be included when monitoring processes linked to ageing of the peritoneal membrane