1 Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan, 2 Nephrology-Dialysis Service, Center Hospital, Saint-Nazaire, France, 3 Nihon University Graduate School of Business, Tokyo, Japan and 4 Nephrology Department, INSERM U 507, Necker Hospital, Paris, France
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. Oxalate kinetics during daily haemodialysis was compared with that of standard haemodialysis (STD HD) and haemodiafiltration (HDF) using high flux dialysers (FB 170 H and FB 210 U, Transdial, Paris, France). All dialysis sessions lasted for 4 h. Blood was withdrawn and spent dialysate was collected in plastic bags every hour to evaluate mass removal. Oxalate concentration in plasma and in spent dialysate was determined by an enzymatic method. Oxalate generation, distribution volume and tissue deposition were calculated using single-pool models adapted from previous studies.
Results. Although no significant difference was found in mass removal per session between dialysis strategies and dialyser types, weekly mass removal with daily HD was about 2 times greater than with STD HD or HDF. Even when daily HD was performed, the oxalate generation ratemass removal ratio (G/R ratio) remained at a value of approximately 2.
Conclusion. Although daily HD sessions led to a substantial increase in weekly oxalate removal, all three types of renal replacement therapy were insufficient to compensate for estimated oxalate generation. To eliminate sufficient amounts of oxalate generated in PH1 patients, at least 8 h of daily dialysis with a high-flux membrane would probably be required. Renal replacement therapy for PH1 patients needs be improved further.
Keywords: daily dialysis; haemodiafiltration; haemodialysis; oxalate kinetics; primary hyperoxaluria type 1
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The purpose of this study was to evaluate oxalate mass removal by various modes of dialysis therapy, including daily haemodialysis (daily HD), in a PH1 patient using a direct dialysate quantification method. We also estimated tissue deposition and generation of oxalate acording to simple models. Oxalate kinetics during STD HD were compared with values obtained during daily HD and haemodiafiltration (HDF) using high flux dialysers.
![]() |
Patient and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
At the time of the investigation, the patient was 59 years old and weighed 59 kg for 160 cm height. Oral administration of pyridoxin and vitamin C was discontinued during the study to exclude their effects on oxalate generation, accumulation or both.
Sample handling and analysis
Blood was withdrawn at the start of dialysis (Ci), after every hour of dialysis, at the end of dialysis (Cf), and at one (Cf+1) and two (Cf+2) hours after the end of dialysis. Blood samples were placed on ice and were centrifuged at 1000xg for 10 min at 4°C. Spent dialysate was collected into plastic bags every hour to evaluate oxalate mass removal. Sodium azide (0.02%) was added as a preservative. In order to prevent calcium salt precipitation, the spent dialysate was maintained at pH 5 by adding an appropriate amount of HCl. Plasma samples and ultrafiltrates were harvested and stored at -20°C until analysis.
The oxalate concentration in plasma and spent dialysate was determined by an enzymatic method based on the oxidation of oxalate by oxalate oxidase followed by the measurement of hydrogen peroxide (H2O2) produced using a peroxidase-catalysed reaction. Oxalate in dialysate, as in urine, was determined according to the method of Hallson et al. [4]. The plasma oxalate concentration in normal healthy subjects determined in our biochemistry laboratory was 2040 µmol/l and daily urinary output was 100450 µmol/24 h. Laboratory quality control for oxalate determination in dialysate was based on the assay of a 164 µmol/l specimen providing a variation coefficient of 9.5%.
Dialysis strategies
To compare oxalate removal efficiency, five protocols were followed using either FB 170 H or FB 210 U dialysers (1.7 or 2.1 m2 triacetate membrane, Transdial, France). STD HDs were performed for 4 h during three sessions weekly in protocols I (with a dialyser FB 170 H) and II (with a dialyser FB 210 U). HDFs were performed for 4 h during three sessions weekly in protocol III (with a dialyser FB 210 U). Daily HDs were performed for 4 h during six sessions weekly in protocols IV (with a dialyser FB 170 H) and V (with a dialyser FB 210 U). Protocols I, IV, and V were performed for 1 week, while protocols II and III, were performed for 2 weeks. The blood flow rate was 250 ml/min and the dialysate flow rate was 500 ml/min. HDF was performed using post-dilution mode with an infusion rate of 50 ml/min.
Calculations
Oxalate generation, its volume of distribution, and its tissue deposition were calculated by single-pool models adapted from Marangella [5].
Oxalate distribution volume V (l) was calculated from the following formula:
|
Tissue deposition of oxalate TD (µmol/24 h) was calculated from:
|
Since the oxalate concentration in plasma increases linearly until it reaches the threshold of serum calcium oxalate supersaturation [5,6], the oxalate generation rate was estimated as follows:
|
The integrated clearance of oxalate, KI (ml/min), was calculated according to the following equation:
|
All values are expressed as the mean and the standard error of the mean (M±SEM). Statistical analysis was performed using Student's t-tests and P values <0.05 were considered to be significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Kinetic modeling of oxalate generation rate and tissue deposition
Plasma oxalate kinetics and hourly oxalate mass removal during protocols II and V, shown in Figures 1 and 2
, illustrate calculated rates of oxalate generation, equilibration times and tissue deposition areas on time-concentration graphs. The mean equilibration time in the five protocols (±SEM) was 8.2±0.6 h (7.09.9 h range).
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Our study patient developed end-stage renal disease at 51 years of age. This is rather uncommon because 28% to 50% of PH1 patients reach end-stage renal failure by 15 years of age and the median age at the start of renal replacement therapy is 25 years [8]. Oxalate generation by the liver and from bone stores is variable among individuals and may depend on age, residual enzyme activity, pyridoxin sensitivity, and other factors [9]. We estimated oxalate kinetics in the present PH1 patient not receiving pyridoxin during various dialysis therapy modes by using simple oxalate kinetic models.
Recently, Marangella et al. [5,6] reported that plasma concentrations of oxalate increased linearly and then reached a plateau in PH1 patients after HD, suggesting that tissue deposition of oxalate occurs when the plasma concentration exceeds the solubility coefficient of this compound. Oxalate generation rate, its volume of distribution, and its tissue deposition were estimated in the present study by using simple, single-pool models adapted from Marangella et al. [5,6]. Our PH1 patient produced 46 mmol of oxalate per day, and had a tissue deposition of 25 mmol and a mean volume of distribution of about 38% of dry body weight. These results are in fairly good agreement with most recent reports, and concurs especially well with the results of Watts et al. [10] who assessed oxalate generation rates using a radioisotope.
An adequate control of oxalate balance is necessary to prevent additional oxalate deposition in PH1 patients on HD. A previous report indicated that oxalate removal rate was higher during HDF than STD HD [11]. However, in the present study we found no significant difference in mass removal per session between STD HD and HDF using triacetate membranes. This discrepancy may be explained by the type of membrane since in the previous study [11] HD was performed with Cuprophan and HDF with AN 69, a high permeable membrane. This suggests that the dialysis removal rate of oxalate may be increased by the use of high-flux dialysers but not by HDF. Moreover, our study showed that a larger membrane surface area or HDF, which also involves convective mass transfer, did not improve oxalate removal. Daily dialysis was the most effective strategy indicating that oxalate removal by HD is time-dependent.
However, the oxalate generation rate in our patient was far higher than oxalate removal, even when daily HD was performed. The high G/R ratio demonstrated the difficulty in removing oxalate by any of the HD strategies. In order to eliminate the accumulation of oxalate in PH1 patients, at least 8 h of daily dialysis is needed using a high-flux membrane. Although 8 h of night-time dialysis could be performed per day, the burden on the patients would be very heavy.
In terms of compliance, it would be difficult for PH1 patients to achieve adequate oxalate removal by prolonged dialysis using current techniques. Combined liver and kidney transplantation may be the best way to eliminate oxalate generation, but it is far more difficult to perform this operation than isolated renal or liver transplantation [12]. Renal replacement therapy should be improved to eliminate hyperoxalaemia in PH1 patients.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|