Impact of the nature of the capillary wall on plasma refilling during hemodialysis.

OBJECTIVES: Our aim was to clarify the impact of the nature of the capillary wall, defined by the contribution of large (LP), small (SP), and ultrasmall (UP) pores, on plasma refilling in a hemodialysis session. METHODS: This study included data from 78 patients. The relative blood volume change (ΔBV%) was monitored using a Crit-Line monitor. A bioimpedance device was used to measure extracellular and intracellular fluid volumes, and the excess fluid mass (MExF) was calculated. We simulated blood volume change (sΔBV%) based on a three-pore model. Hydraulic permeability of the capillary wall (LpS) and fractional contribution of LP to LpS (αLP) were determined by fitting sΔBV to ΔBV. The total refilling volume (TVref) was calculated from the total ultrafiltration volume and total blood volume change. Values were standardized to a body surface area of 1.73 m2 and are denoted by the subscript BSA. RESULTS: LpS and αLP were 3.09 (2.32, 4.68) mL/mmHg/min and 0.069 (0.023, 0.109), respectively. The standardized regression coefficient (ß) of the ultrafiltration rate (UFRBSA) and initial excess fluid mass (MExF,BSA,0) by multiple linear regression analysis of TVref,BSA without (Model 1) and with (Model 2) αLP were as follows: UFRBSA, 0.714/<0.001 (ß/p); MExF,BSA,0, 0.247/<0.001 (Model 1); UFRBSA, 0.799/<0.001; MExF,BSA,0, 0.066/0.237; and αLP, -0.327/<0.001 (Model 2). CONCLUSIONS: The impact of volume overload (MExF,BSA,0) on plasma refilling became insignificant with the addition of αLP in the model, suggesting that the nature of the capillary wall described by inter-endothelial gaps (LP) may have a greater impact on plasma refilling than volume overload.

Association of bioimpedance-derived 50-kHz phase angle as marker of body composition with electrical parameters regarding the Cole-Cole model.

Our aim is to clarify the association of the bioelectrical impedance-derived 50-kHz phase angle (φ50 ) with electrical parameters regarding the Cole-Cole model and clinical parameters. A total of 440 sets of bioelectrical impedance data from pre- and post-hemodialysis from 157 patients were used. Resistance at infinite frequency (Rinf ), resistance at 0 frequency (R0 ), capacitance of the cell membrane (Cm), and a parameter for the distribution of the time constant (α) were examined as electrical parameters. Normally hydrated lean tissue mass as a percentage of the dry weight (PNHLT ), excess fluid mass as a percentage of the dry weight (PExF ), body mass index (BMI), age, and sex (Nsex , 0 for male, 1 for female) were examined as clinical parameters. φ50 increased with the decrease in Rinf /R0 and α and also with the increase in Cm (multiple regression coefficients [ß]: pre/post, -0.886/-0.936, -0.175/-0.212, and 0.167/0.141), which determined the ratio of intra- to extracellular fluid volume (ICV/ECV), tissue homogeneity, and total cell mass. φ50 increased with an increase in PNHLT and BMI and decrease in PExF , Nsex , and age (ß: pre/post, 0.654/0.581, 0.466/0.412, -0.483/-0.473, -0.216/-0.154, and -0.145/-0.127). The concordance correlation coefficient between φ50 for pre- and post-hemodialysis (ρ = 0.772) may be improved (ρ = 0.950) by adding a multiplication of 0.2 and PExF to φ50 for correction. φ50 may be used to estimate body composition through the association with ICV/ECV, tissue homogeneity, and total cell mass. The correction for excess fluid is essential in order to use φ50 as a marker of body composition related to nutrition.

Patient-Specific Relationship Between Hydraulic Permeability of Microvasculature and the Extent of Burden of Excess Fluid in Hemodialysis Patients.

We have reported a significant correlation between hydraulic permeability of microvasculature adjusted with ultrafiltration rate (AdjLpst) and excess fluid divided by dry weight (ExF/DW) in a cross-sectional study of hemodialysis patients. We aimed to study longitudinally whether a similar relationship between them exists in each patient. Twelve hemodialysis (HD) patients in whom AdjLpst and ExF/DW had been measured more than four times (total of 85 measurements) were enrolled. AdjLpst was calculated by monitoring blood volume during HD. ExF was calculated from the fluid volume measured via bioimpedance spectroscopy. The borders of overhydration were 1.66 mL/mm Hg per min for AdjLpst and a positive value for ExF/DW. There was a significant correlation between AdjLpst and ExF/DW (r = 0.517). When the 85 measurements were classified into four quadrants according to ExF/DW and AdjLpst, the evaluations of fluid status agreed in 66 measurements. In six patients, significant positive correlations were found. In nine patients, equal to or more than 80.0% of evaluations by AdjLpst and those by ExF/DW agreed. In only one patient was there neither significant correlation nor agreement. AdjLpst of two patients suffering from chronic heart failure and microscopic polyangiitis was reduced compared with that of others loaded with the same extent of excess fluid. We concluded that there was a significant correlation between AdjLpst and ExF/DW and high agreement between evaluation by AdjLpst and evaluation by ExF/DW in the majority of patients. However, the relationship between them was patient-specific to some extent.

Evaluation of a pseudo-one-compartment model for phosphorus kinetics by later-phase dialysate collection during blood purification.

PURPOSE: Phosphorus removal is a major issue to assess for physicians engaging in hemodialysis. A pseudo-one-compartment model was reported as a novel model for phosphorus kinetics. We aimed to evaluate the adequacy of this model from the standpoint of the total mass of removed phosphorus during prolonged treatment. METHODS: Dialysate was collected during 6-h hemodialysis and hemodiafiltration treatment in 5 patients. Later-phase (from 4 to 6 h) dialysate was collected separately. Mobilization clearance (K(m)) and dialyzer clearance (K) were calculated by simple arithmetic operations utilizing stable serum phosphorus concentrations in this later phase. Volume of the accessible compartment (V(0)) was estimated by a fitting method. Amounts of removed phosphorus were calculated with these parameters and compared with measured values. The best sampling time points during treatment were also assessed, when the parameters were determined by serial serum phosphorus concentrations alone. RESULTS: Pearson's correlation coefficient (R) between calculated and measured values of removed phosphorus was 0.991 and the concordance correlation coefficient (ρ) was 0.987. When K(m), K and V(0) were determined by serial serum concentrations alone, including those at 0, 1, 4, and 6 h, the calculated mass of removed phosphorus had high R (0.974-0.975) or ρ (0.966-0.972) with the measured values. CONCLUSIONS: We confirmed that a pseudo-one-compartment model is useful for the estimation of removed phosphorus mass during prolonged blood purification by collecting dialysate. When the parameters are determined by a fitting method using serial serum concentrations alone, sampling at 0, 1, 4, and 6 h seems to be adequate.

The evaluation of filtration coefficients of microvasculature for the assessment of fluid status in hemodialysis patients.

PURPOSE: Bioimpedance spectroscopy (BIS) is widely used to assess fluid status in hemodialysis (HD) patients. Our purpose is to evaluate filtration coefficients (Lpst) as an alternative test to assess fluid status by utilizing BIS as a reference test.
 METHODS: 106 HD patients (determined group) were divided into two groups with (EX group: 53) or without excess fluid mass (ExF). ExF calculated from extracellular water and intracellular water measured by BIS. Multiple linear regression equation of Lpst was made using ExF (ExF/DW) and ultrafiltration rate (UFR/DW) to adjust Lpst (AdjLpst). The cut-off values of the tests for detection of EX were determined by receiver-operator characteristic curve analysis. Lpst, AdjLpst, serum atrial natriuretic peptide concentration (ANP), ultrasonically measured inferior vena cava diameter (IVCe/BSA), and blood volume change (Δ BV/TUF/DW) were examined. The detection abilities of these tests were evaluated in the distinct 61 patients (evaluated group).
 RESULTS: Patients of the EX group numbered 29 in the evaluated group. The correlation between AdjLpst and ExF/DW was the highest. The sensitivity of AdjLpst and specificity of Lpst were the highest. The specificity of AdjLpst was equivalent to that of Lpst. Unadjusted and adjusted odds ratios of AdjLpst were the higher (20.80, 95% CI, 5.61-77.10, 16.06, 95% CI 4.00-64.59, respectively) than those of the other tests.
 CONCLUSIONS: AdjLpst can detect patients of the EX group more accurately than other tests. Because AdjLpst is related to plasma refilling, it may indicate removable fluid overload. AdjLpst in conjunction with BIS may contribute to more adequate fluid management.

Low density lipoprotein apheresis ameliorates interferon-γ production in patients with nephrotic syndrome.

Rapid amelioration of hypercholesterolemia in nephrotic syndrome (NS) using low density lipoprotein-apheresis (LDL-A) sometimes leads to NS remission, along with improvement of impaired biodefense system; however, the mechanism of how LDL-A affects NS is still unknown. We studied IFN-γ production under IL-12 stimulation for 24 h in whole blood from 30 NS patients, 31 non-NS patients, 35 healthy volunteers and another four persistent NS patients due to refractory focal segmental glomerulonephritis and minimal change type nephrotic syndrome. We compared IFN-γ production in whole blood and peripheral blood mononuclear cells (PBMC) from persistent NS patients before and after each of 14 LDL-A procedures. Finally, we studied the effect that persistent NS patients' serum before and after LDL-A had on IFN-γ production in healthy volunteers' PBMC. Whole blood IFN-γ production was significantly lower in NS patients compared with healthy volunteers or non-NS patients. In persistent NS, after LDL-A, IFN-γ production returned to normal levels. IFN-γ production in PBMC varied greatly among these patients and did not show consistent changes after LDL-A. Healthy volunteers PBMC incubated with persistent NS patients' serum obtained after LDLA showed higher IFN-γ production than before LDL-A. IFN-γ production in peripheral blood is impaired if a patient is in a nephrotic state. LDL-A might restore suppressed PBMC function in persistent NS patients, thereby ameliorating the nephrotic state, possibly through removing interfering serum factors.

Evaluation of estimated creatinine clearance before steady state in acute kidney injury by creatinine kinetics.

BACKGROUND: A simple method to calculate estimated creatinine clearance using two serum creatinine concentration (Cr) values in acute kidney injury (AKI) was developed (eCrCl-AKI). We aimed to evaluate its accuracy and to clarify its contribution to the classification of AKI. METHODS: We validated the errors in eCrCl-AKI in a simulation study after various reductions in creatinine clearance (CrCl) at various levels of chronic kidney disease (CKD). We compared the eCrCl-AKI-based classification of RIFLE criteria with the Cr-based classification or that proposed by Waikar and Bonventre. The regression equations of eCrCl-AKI on time were determined and Cr values were reconstructed by creatinine kinetics substituting CrCl with eCrCl-AKI in actual patients. RESULTS: Most errors in eCrCl-AKI were relatively small (from -13.6 to +7.9%) with the exception of two Cr values that straddled the changing trend of Cr. The classification according to RIFLE criteria based on Cr was unstable and did not enable adequate classification, especially in milder reductions of CrCl with advanced CKD. The classification based on eCrCl-AKI was stable and enabled adequate classification. There were good agreements between measured Cr and reconstructed Cr with eCrCl-AKI. The regression equations of eCrCl-AKI revealed changes of renal function that were unexpected only from fluctuations of Cr. CONCLUSIONS: eCrCl-AKI can provide relatively accurate estimates for fluctuating CrCl. eCrCl-AKI enables more stable and earlier classification of AKI than Cr, at least in the simulation study. The more widespread use of eCrCl-AKI in actual clinical settings of AKI is necessary to evaluate this formula.

Discrepancy between cystatin C and creatinine points leading to a diagnosis of postrenal acute kidney injury and its reversibility: three case reports.

We report on three patients with postrenal acute kidney injury (AKI) showing a remarkably low level of cystatin C (CysC) compared with that of creatinine (Cr). The levels of Cr and CysC (Cr/CysC) were respectively as follows: 12.16 mg/dl/1.26 mg/l, 17.92 mg/dl/0.95 mg/l and 18.94 mg/dl/0.55 mg/l. The causes of urinary tract obstruction were benign prostatic hypertrophy, urinary bladder carcinoma and urethral stenosis due to radiation therapy for bladder carcinoma. Renal function was promptly recovered after relief of the obstruction. It is considered that the discrepancy strongly indicated AKI because of urinary tract obstruction and encouraged relief of the obstruction in order to recover renal function. Although the precise mechanism for the discrepancy was not determined, the maintenance of glomerular filtration and proximal tubular reabsorption of CysC long after the cessation of Cr excretion because of urinary tract obstruction seemed to be involved. This finding may be beneficial for the diagnosis and reversal of postrenal AKI and provides new insight into the process of postrenal AKI.

Comparisons of cystatin C with creatinine for evaluation of renal function in chronic kidney disease.

BACKGROUND: Because of the limitations of creatinine (Cr) as a marker for the glomerular filtration rate (GFR), cystatin C (CysC) has been proposed as an alternative substance. The aim here was to clarify the characteristics of CysC compared with Cr. METHODS: CysC and Cr were measured in 199 patients with chronic kidney disease. Regression analysis between CysC and Cr and comparisons of the effect of gender, inflammation, prescription of prednisolone, smoking and diabetes mellitus (DM) on these markers were performed. Sensitivity and specificity of CysC and Cr to discriminate estimated GFR of less than 50 ml/min/1.73 m(2) were computed and evaluated by the receiver-operating characteristic curve (ROC). RESULTS: The correlation coefficient between natural logarithmic Cr [ln(Cr)] and ln(CysC) was higher than that between these variables per se (0.941 vs. 0.906). When Cr was lower than 1.10 mg/dl, CysC rose more sharply than Cr. CysC divided by Cr (CysC/Cr) was higher in females (1.35 +/- 0.33 vs. 1.16 +/- 0.30; p < 0.001), in patients with elevated CRP (1.33 +/- 0.40 vs. 1.21 +/- 0.29; p < 0.001) and in patients prescribed with prednisolone (1.42 +/- 0.33 vs. 1.20 +/- 0.30; p < 0.001). A stepwise multiple linear regression model indicated that ln(CysC) was positively correlated with ln(Cr), age, female gender, prednisolone prescription, elevated CRP and DM (R = 0.964, p < 0.001). The area under the ROC curve of Cr was 0.900 and that of CysC was 0.925. CONCLUSION: CysC is a promising marker for GFR because it was not gender- or age-related. However, inflammation, prednisolone and DM caused CysC to deviate higher than expected from GFR. CysC can rise sensitively in early renal dysfunction.

Evaluation of markers to estimate volume status in hemodialysis patients: atrial natriuretic peptide, inferior vena cava diameter, blood volume changes and filtration coefficients of microvasculature.

Relationships among five markers of volume status - cardio-thoracic ratio (CTR), atrial natriuretic peptide (ANP), inferior vena cava diameter at quiet expiration (IVCe), blood volume change (Delta BV/TUF) during ultrafiltration and filtration coefficients of microvasculature (Lpst) - were investigated. Fifty stable hemodialysis patients were enrolled. The CTR was measured before hemodialysis (HD), and ultrasonic measurement of IVCe and sample collection for ANP were performed shortly after HD. Lpst and Delta BV/TUF were calculated using a CRIT-LINE monitor. Overhydrated patients determined by each marker (OVERctr, OVERivc, OVERanp, OVERlp and OVERbv) were compared. The agreement of volume status determined by each marker was assessed by kappa value, and the sensitivity and specificity of each marker to distinguish overhydrated patients were analyzed by a receiver-operating characteristic (ROC) curve. IVCe, ANP, Delta BV/TUF and Lpst, significantly correlated with each other. The correlation coefficients of Lpst with IVCe, ANP and Delta BV/TUF were higher than the others. The kappa value between ANP and Lpst was the highest. OVERanp was the highest, then OVERlp, OVERivc and OVERbv, in this order. The OVERlp and OVERivc patients were completely included in OVERanp. All patients, except one OVERbv patient, were included in OVERlp. The relatively high distinguishing ability of Lpst was demonstrated by ROC analysis. These results suggest that the determination of overhydration solely by ANP was an overestimation and by Delta BV/TUF was an underestimation. The relatively high correlation coefficients of Lpst with other markers, as well as its distinguishing ability, suggest that Lpst fluctuates in close relation to other markers.

The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema.

BACKGROUND: Massive systemic edema is often observed in patients with severe nephrotic syndrome, including diabetic nephropathy. Although furosemide, a loop diuretic, is often administered to these patients, some patients do not respond to this treatment, still showing massive edema. METHODS: The efficacy of indapamide which has a thiazide-like effect on distal convoluted tubules in combination with furosemide, was evaluated in eight patients with massive edema, in regard to both Na+ excretion and diuresis. Indapamide 2 mg was administered once a day, in the morning, to patients in whom it was considered that furosemide treatment of 40-120 mg a day for 1 week was ineffective. RESULTS: Urinary Na+ excretion was markedly increased, from 83.7 +/- 82.2 mEq/day to 140.7 +/- 33.8 mEq/day after 1 week of the combination therapy compared with furosemide alone (P < 0.01); urine volume was also increased, from 1070 +/- 230 ml to 1359 +/- 296 ml after 1 week of the combination therapy (P < 0.05). In this context, body weight was significantly decreased, from 57.2 +/- 12.3 kg to 53.4 +/- 12.8 kg, after the combination therapy (P = 0.01). Indapamide in combination with furosemide was well tolerated, and no significant changes in serum levels of creatinine and potassium were observed. CONCLUSIONS: This combination therapy appears to be effective in patients with massive edema, as it increased diuresis, and achieved potent Na+ excretion.

Simulation of post-dialysis urea rebound using regional flow model.

BACKGROUND: A regional flow model (RFM) can establish the missing link between hemodynamics and solute removal. We tried to simulate post-dialysis urea rebound using a RFM for the purpose of evaluating the validity of this model. METHODS: Eight patients on maintenance hemodialysis with negligible renal function were investigated. The parameters of the RFM were estimated so as to fit the calculated values of urea nitrogen to the measured values during a dialysis session. The estimated parameters were total urea distribution volume (TUV), systemic blood flow (Qsys), flow fraction (fQH) and volume fraction (fVH) of the high-flow system. Thirteen types of parameter sets were used for the estimation. The urea rebound at 60 min after a dialysis session (Creb) and the rebound ratio (RR) were calculated using these estimated parameters. The accuracy of the calculated Creb and RR was assessed. RESULTS: The accuracy of Creb and RR determined using estimated TUV, by taking Qsys as systemic blood flow calculated from ultrasonic echo cardiogram (Qucg), fQH as 0.8, and fVH as 0.2, was insufficient (method 1a). The accuracy of these values was significantly increased by taking fQH as 0.85 (method 1b). The estimation of Qsys with TUV did not improve the accuracy of Creb and RR (methods 2a and 2b). The estimation of fQH, fVH, and TUV (method 8) increased the accuracy of Creb and RR significantly compared with method 1a, but not compared with method 1b. Even with method 1b or method 8, the percentage RR was less than 90% in two patients. CONCLUSIONS: By taking fQH as 0.85, an acceptably accurate simulation of urea rebound can be accomplished with the necessity to estimate only TUV. The simulation was not significantly improved by the estimation of Qsys, fQH, and fVH. The RFM is useful in practice, although it has some limitations.