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Technical Briefs |
1
Lab. for Anal. Chem., Inst. for Nuclear Sci., Univ. of Gent, Proeftuinstraat 86, Gent, Belgium;
2
Renal Div., Dept. of Med., Univ. Hosp., DePintelaan 185, B-9000 Gent, Belgium;
a author for
correspondence: fax 32 (0)9 2646699, e-mail Cornelis{at}inwchem.rug.ac.be
Renal replacement therapy is currently achieved by hemodialysis (HD), hemofiltration, hemodiafiltration (HDF), continuous ambulatory peritoneal dialysis (CAPD), or renal transplantation. The concentration of trace elements in serum of patients could be influenced by these treatments. A significant increase of As concentrations in serum of patients on HD treatment has been reported (1)(2). As concentrations higher than the reference value were also observed in serum of patients on HDF [3]. Although there are several studies describing the status of trace elements in serum, plasma, and dialysate in CAPD patients [4, 5], no data on As serum concentrations of CAPD patients are available. The aim of this work is to determine total As concentrations and to speciate As species in serum, urine, and dialysate of CAPD patients.
Fourteen CAPD patients were studied. Serum, urine, and dialysate samples were collected from the University Hospital. Patients gave their informed consent before blood sampling. To decrease the influence of As intake from the diet, patients were requested to refrain from ingesting seafood during the 3 days before blood and urine collection. The reagents and apparatus for the separation and measurement of As species and for the measurement of total As have been described (6). Briefly, two types of HPLC columns were used for the separation of anionic and cationic As species: an anion exchange column (Supelcosil LC-SAX, 250 x 4.6 mm; Supelco, Bellefonte, PA) and a cation exchange column [Dionex (Sunnyvale, CA) Ionpac® CS 10, 250 x 4 mm]. A Perkin-Elmer (Norwalk, CT) 3030 atomic absorption spectrometer was used throughout for the detection of As signals. Analysis of serum creatinine was performed according to the Jaffe method (7).
The accuracy of the total As measurements was tested by simultaneously analyzing a Certified Freeze-Dried Reference Serum (CRM) of the University of Gent, Belgium. The accuracy of the As speciation measurements was tested by analyzing a BCR candidate Reference Material CRM 526 tuna tissue, as no serum reference material is yet available for the As speciation study. No significant differences were established between the analytical results and the certified values. The precision (CV) of the method for 10 replicate analyses of aqueous solution of As species at a concentration of 10.0 µg/L was always better than 5% for each form of As. The 3-day run-to-run precision of measurement of 10.0 µg/L As species added to serum was better than 10%.
The mean total As concentration in the serum of 14 CAPD patients is
4.67 ± 5.41 µg/L, significantly higher (P <0.001)
than the reference values of 0.96 ± 1.52 µg/L in serum of
healthy subjects previously obtained in our laboratory
(8), indicative of an accumulation of As in serum of CAPD
patients. The main As species in the serum of these patients are
dimethylarsinic acid (DMA) and arsenobetaine (AsB), respectively
carrying 15.2% (0.71 ± 1.05 µg/L) and 76.2% (3.56 ±
4.27 µg/L) of total As. No significant differences were observed
between CAPD patients and previously reported nondialyzed uremic
patients (0.82 ± 1.05 µg/L DMA and 3.55 ± 4.58 µg/L
AsB) (6). The DMA concentrations of CAPD patients are,
however, significantly lower than those of HD patients (1.93 ±
1.51 µg/L, 29.8% of total As, P <0.001)
(6), although no significant difference of AsB
concentration was observed between these two groups (3.56 ± 4.27
vs 3.47 ± 2.89 µg/L, P = 0.5658). Fig. 1
(top) shows the comparison of As species concentration in the
serum of the three groups of patients (uremic nondialyzed, CAPD, and
HD). The AsB data imply that the main source of As accumulation in
serum of CAPD patients comes from the diet, as AsB is particularly
present in fish and seafood. Significantly lower DMA concentration in
CAPD patients than in HD patients indicates that the CAPD treatment is
probably more efficient in removing the toxic inorganic As species from
the blood and better avoids the in vivo methylation in the body since
this treatment is a continuous procedure compared with the intermittent
procedure of HD.
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The mean concentrations of DMA, AsB, and total As in urine of 10 CAPD patients with residual urine production are 2.24 ± 1.80, 9.09 ± 8.50, and 12.28 ± 10.66 µg/L, respectively. These concentrations are significantly higher than the serum values of these patients (P = 0.0191, 0.009, and 0.040, respectively). However, considering the relatively small amount of urine produced by these patients (mean 758 mL/24 h) vs the overall blood volume (estimated mean 5000 mL/per patient, mean hematocrit 34.1%) and the volume of drained dialysate (mean 8680 mL/24 h), the absolute urinary excretion of As is very low. The mean amounts ± SD in the total urine are: DMA 1.34 ± 0.98 µg, AsB 4.62 ± 2.57 µg, and total As 6.30 ± 3.37 µg, and represent only 10% of total As distributed in the four compartments (serum 23%, packed cells 14%, dialysate 53%). Calculation of the ratio of DMA/AsB showed no significant difference between urine and serum (P = 0.1456) or dialysate (P = 0.0845). This suggests nonselectivity of renal removal of DMA, a more toxic As species than AsB.
A very low As concentration was found in fresh dialysate (0.04 µg/L).
The mean concentrations are, however, increased to 3.98 ± 4.91
(total As), 0.59 ± 0.87 (DMA), and 3.06 ± 3.96 (AsB) µg/L
in 24-h dialysate. No significant differences in As concentrations were
found between serum and drained dialysate after 24-h dialysis
(P = 0.4482, 0.5984, and 0.5770 for total As, DMA, and
AsB, respectively), indicating a nonselective accumulation or removal
of different As species. These results can be easily understood because
CAPD means a slow equilibrium dialysis. The low-molecular-mass species
of AsB and DMA are easily transferable across the peritoneal membrane,
and equilibrium in concentrations is readily achieved. The As species
in dialysate are significantly lower than those in urine (P
<0.005 for each As species) because of the concentrating capacity of
the kidney. The analysis of total As and As species on each of the four
exchanges of CAPD dialysate showed no significant differences in
concentrations on 1 day for the same patient. Considering a mean volume
of 8680 ± 912 mL of drained dialysate per day, the mean amount of
total As is 35.1 ± 45.7 µg per patient/24 h. Fig. 1
(bottom)
compares the concentrations of total As and the As species in the three
different fluids (serum, dialysate, and urine).
Neither inorganic As species of As(III) and As(V) nor methylmalonic acid and AsC could be detected in serum, urine, and dialysate of the CAPD patients, with one exception. Patient 5 showed measurable concentrations of As(III) and As(V) in urine, but not in her 24-h dialysate. The possibility that the urine was contaminated with inorganic As species during collection cannot be excluded, although a very clean collector was used for the urine, and the patient was instructed about the collection. As this result was only observed in one specimen, more patients and urine samples are needed to confirm this finding.
By dividing the subjects into the groups according to the serum creatinine concentrations, we found that the group with significantly higher serum creatinine concentration has a significantly higher As concentration (P <0.05). The creatinine concentrations for the groups of healthy subjects and CAPD and HD patients were respectively 80 ± 25, 646 ± 244, and 914 ± 173 µmol/L, whereas the As concentrations in the three groups were respectively 0.96 ± 1.52, 4.67 ± 5.41, and 6.47 ± 4.28 µg/L. A similar conclusion was obtained previously when we studied the accumulation of As in the serum of uremic patients on conservative treatment and of patients on hemodialysis treatment (6)(9).
Acknowledgments
We thank M.C. Lambert for the assistance on the collection of the samples.
References
The following articles in journals at HighWire Press have cited this article:
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  X. Zhang, R. Cornelis, J. De Kimpe, L. Mees, and N. Lameire Study of arsenic–protein binding in serum of patients on continuous ambulatory peritoneal dialysis Clin. Chem., January 1, 1998; 44(1): 141 - 147. [Abstract] [Full Text] [PDF]
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