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Is peritoneal rest a treatment for ultrafiltration failure during continuous ambulatory peritoneal dialysis?
CURRENT THERAPEUTIC RESEARCH VOL. 52, NO. 1, JULY 1992
IS PERITONEAL REST A TREATMENT FOR ULTRAFILTRATION FAILURE DURING CONTINUOUS AMBULATORY PERITONEAL DIALYSIS? TOSIHARU IKUTAKA,1 MOTOYUKI ISHIGURO,1 SEIICHI SHIMABUKURO, 1 TAKAHIRO HIRANO, 1 AND MICHIO ARAKAWA2 1Dialysis Center, Hirano General Hospital, and 2Second Department of Internal Medicine, Gifu University School of Medicine, Gifu City, Japan
ABSTRACT D e t e r i o r a t i o n of t h e p e r i t o n e u m ' s u l t r a f i l t r a t i o n c a p a c i t y is a n import a n t f a c t o r for d e t e r m i n i n g w h e t h e r c o n t i n u o u s a m b u l a t o r y peritoneal d i a l y s i s (CAPD) should be c o n t i n u e d o r discontinued. W h y t h e ult r a f i l t r a t i o n c a p a c i t y d e t e r i o r a t e s is n o t c l e a r l y u n d e r s t o o d , a n d effective t r e a t m e n t for this p r o b l e m has not y e t been established. To e x a m i n e t h e effect o f d i s c o n t i n u i n g CAPD on the recovery o f u l t r a f i l t r a t i o n c a p a c i t y , we followed up one p a t i e n t who showed d e t e r i o r a t e d p e r i t o n e a l f u n c t i o n 4 y e a r s a f t e r the i n i t i a t i o n of CAPD for 6 m o n t h s w i t h o u t p e r f o r m i n g CAPD. A c a t h e t e r inserted into the p e r i t o n e a l c a v i t y was n o t removed d u r i n g t h e 6-month period o f p e r i t o n e a l rest. We f o u n d t h a t t h e a m o u n t of fluid removed a f t e r a 240-minute CAPD i n c r e a s e d s i g n i f i c a n t l y (from - 4 5 0 ml to 150 ml) a f t e r 6 m o n t h s o f p e r i t o n e a l rest. The p a t i e n t ' s glucose r e a b s o r p t i o n r a t e i m p r o v e d slightly, b u t t h e blood u r e a n i t r o g e n d i a l y s a t e / p l a s m a r a t i o did not show a n y change. The p h o s p h a t i d y l c h o l i n e c o n c e n t r a t i o n in the dialy s a t e i n c r e a s e d f r o m 0.71 mg/dl to 2.07 mg/dl a f t e r 6 m o n t h s of perit o n e a l rest. At the end o f t h e 6-month period, t h e p a t i e n t ' s u l t r a f i l t r a . t i o n c a p a c i t y improved, a n d he was able to r e s u m e CAPD t h e r a p y . W e conclude t h a t p e r i t o n e a l rest is a useful t r e a t m e n t for d e t e r i o r a t e d ultrafiltration capacity of the peritoneum. INTRODUCTION
Continuous ambulatory peritoneal dialysis (CAPD) is a form of dialysis using the peritoneum, a biologic membrane. The peritoneum's primary functions are removing solutes and ultrafiltration. Preserving peritoneal function is critical in long-term CAPD. Since long-term CAPD has become feasible, various problems have been raised about this procedure. In particular, deterioration of the ultrafiltration capacity of the peritoneal membrane is an important factor for determining whether CAPD should be Address correspondenceto: Toshiharu Ikutaka, C.E., Hirano General Hospital, 176 Kurono, Gifu 501-04, Japan. Received for publication on February 11, 1992. Printed in the U.S.A. Reproduction in whole or part is not permitted. 202
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continued or discontinued. ~'2 The cause of this deterioration is not clearly understood, and effective treatment has not yet been established. To examine whether the ultrafiltration capacity could be improved by peritoneal rest, we compared the time course of peritoneal function in a patient who showed deteriorated ultrafiltration capacity 4 years after the start of CAPD with that of patients who had a satisfactory ultrafiltration capacity. We also examined whether peritoneal rest could restore the impaired ultrafiltration capacity. PATIENTS AND METHODS
The patient was a 39-year-old man whose primary disease was chronic glomerulonephritis, which followed an episode of acute glomerulonephritis at age 16. In January 1981, he underwent hemodialysis because of renal failure from chronic glomerulonephritis. In May 1981, he received a kidney transplant from a living donor, which failed in March 1983, because of a rejection reaction. Hemodialysis was started again, and he was transferred to our hospital to undergo CAPD to allow him to return to work. The patient's clinical course during the 5 years after the start of CAPD is shown in Figure 1. From the start of CAPD on April 18, 1984, through August 1986, his clinical course was uneventful. However, the amount of fluid removed began to decrease gradually thereafter. In January 1987, the total amount of daily fluid removed became 0 ml or even a negative value. Although we instructed the patient to limit his body weight CTR
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Figure 1. Clinical course during 5 years of continuous ambulatory peritoneal dialysis. CTR = cardiothoracic ratio; HD = hemodialysis; ECUM = extracorporeal ultrafiltration method. 203
PERITONEAL
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FAILURE
IN CAPD
water intake and altered the composition of the irrigation fluid, edema began to develop in the lower extremities, accompanied by an increased cardiothoracic ratio. However, the solute-removing capacity was well maintained. In January 1988, we added the extracorporeal ultrafiltration method (ECUM) once a week and continued CAPD, which, however, failed to recover the fluid-removing capacity. Clinical laboratory tests revealed that hematocrit and albumin values began to decrease in June 1987 (Figure 2). Therefore, in March 1988, the patient, who provided informed consent, began a period of peritoneal rest to improve his ultrafiltration capacity. When the ultrafiltration capacity improved in October 1988, the patient resumed CAPD. Since then, his daily total fluid removal has been 500 to 700 ml, and water balance has been controlled by limiting water intake. During the 6 months of peritoneal rest, the peritoneal catheter for CAPD was left in place, and peritoneal irrigation was performed with 500 ml of irrigation fluid containing 1.5% Dianeal (Baxter Limited, Tokyo, Japan) through the catheter every morning and evening. In addition, the site of the spike was protected by a spike protector, and the patient remained bag free. This method prevented the catheter from becoming occluded with fibrin and kept the patient from developing complications, such as peritonitis, that can be caused by a peritoneal catheter. We used the peritoneal equilibration test (PET) described by Twar-
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T. IKUTAKAET AL.
dowski and colleagues 3 as an index of peritoneal function (Table I). We regarded six patients (patients 2 though 7 in Table II) who underwent CAPD in our hospital as those with a satisfactory ultra filtration capacity. Changes in peritoneal function were assessed from the values as follows: (1) changes in the amount of removed fluid; (2) glucose reabsorption rate (D/Do); (3) capacity of removing solute (BUN dialysate/plasma [D/P] ratio); and (4) concentration of phosphatidylcholine (PDC) in dialysate. RESULTS
Figure 3 shows the changes in the amount of fluid removed from patients with a satisfactory fluid-removing capacity (normal group) and from the study patient before peritoneal rest and at 3 and 6 months after peritoneal rest. The amount of fluid removed was calculated by measuring the weight of drained dialysate. In the normal group, as the time of retention of peritoneal dialysis irrigation fluid increased, the amount of removed fluid also increased. After 240 minutes of retention, the amount of removed fluid was about 286 -+ 150 ml. On the other hand, the study patient had a negative fluid balance after 60 minutes of retention before peritoneal rest. After 120 minutes of retention, the fluid balance moved rapidly to the negative side, reaching - 4 5 0 ml at 240 minutes after the start of retention. However, after a 3-month peritoneal rest, the amount of fluid removed after 180 minutes of retention was about 50 ml, although this was not a satisfactory volume. Six months after the start of peritoneal rest, fluid removed from the study patient after 120 minutes of retention finally reached 150 ml.
Glucose Reabsorption Rate In the normal group, the D/Do was 43.2 -+ 15.9% at 120 minutes and Table I. Peritoneal equilibration test (PET).
1. Obtaining Samples
PET
Time (min)
0 60 120 Collecting blood 1" t Obtaining dialysate 1" t 2. Condition of Dialysis Dialysate 2.5% Dianeal Volume of injected fluid 2,000 ml Retention time 240 rain Position of injection supine Position of drainage sitting Drainage time 20 min 3. Measuring Method Amount of fluid removed = weight of dialysate--weight of Dianeal D/P = concentration in dialysate drained/concentration in serum D/Do = concentration in dialysate drained/concentration at 0 hour Value of phosphatidylcholine = iatroscanning method
205
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Table II. Clinical characteristics of patients undergoing continuous ambulatory peritoneal dialysis.
Patient Number
Sex
Age (yr)
1
M
40
2 3 4 5 6 7
F M F F F F
47 27 76 63 58 70
Durationof CAPDTreatment (months) 49 6 29 15 7 1 1 1
Basic Disease
UF Volume (ml/day)
CGN
- 250 600 1,500 800 800 1,200 1,500 1,200
CGN VUR CGN CGN CGN CGN
CGN = chronic glomerulonephritis;VUR = vesico-ureteralreflux; UF = ultrafiltration.
27.9 -+ 13.2% at 240 minutes after starting fluid retention and D/P; the time plot showed a gentle curve. These results were classified as high average (Figure 4). 3 However, in the study patient before peritoneal rest, 80% of glucose was absorbed into the body 120 minutes after starting retention. The changes in the amount of fluid removed and the D/Do indicate a (ml)
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206
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Figure 4. Peritonealequilibrationtest (PET) curvesand assessmentof PET.
time lag between glucose absorption and fluid transportation in the study patient. Although the study patient's D/Do both before and after peritoneal rest was grouped into the high category of Twardowski's classification,3 it improved by 5% to 8% after 6 months of peritoneal rest (Figure 5).
Capacity of Removing Solute The capacity of removing solute was assessed using BUN D/P, and comparisons were made with Twardowski's classification. 3 Although the normal group and the study patient were placed in the high category of Twardowski's classification both before and after peritoneal rest, the study patient showed some improvement after 6 months of peritoneal rest (Figure 6).
Concentration of Phosphatidylcholine in Dialysate The value of PDC in the dialysate drained after 240 minutes of retention was 2.3 -+ 1.69 mg/dl in the normal group (Figure 7). In the study
207
PERITONEAL REST FOR ULTRAFILTRATION FAILURE IN CAPD
D/Do=( glucoseconcentrationin drained dialysate ) glucose concentration in dialysateat 0 hour normal(n= 6) --. Mean-----SD × . ~ before rest after 3 months of rest ~ 0 - - 0 after6 months of rest
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Figure 5. Changesin glucosereabsorption. patient, it was 0.71 mg/dl before peritoneal rest, 6.23 mg/dl after 3 months of peritoneal rest, and 2.07 mg/dl after 6 months of peritoneal rest, indicating that the value increased markedly after 3 months of rest, then decreased after 6 months of rest, but was still higher than the value before rest. DISCUSSION Since long-term CAPD has become feasible, possible deterioration of the peritoneum's ultrafiltration capacity has been suggested. Cantaluppi and associates 4 and Naganuma 5 reported that deterioration of the ultrafiltration capacity occurred in about 11% of patients during a 3-year period of CAPD. However, these authors did not clarify the mechanism involved in this phenomenon. Verger and associates6 and Dobbie and colleagues7 reported edema of the peritoneal mesothelial cells and deposition of collagen fiber beneath the mesothelial cells in patients with deteriorated ultrafiltration capacity. These histologic changes correlated highly with increased glucose absorption. The authors speculated that mesothelial cells play a crucial role in maintaining ultrafiltration capacity. 208
T. IKUTAKAET AL.
BUN concentration in drained dialysate / BUN concentration in serum / =---= -...-
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Figure 6. Changes in capacity of removing solute.
In our study patient, fluid-removing capacity rapidly deteriorated 4 years after the initiation of CAPD. We speculated that this deterioration did not result from edema or exfoliation of peritoneal mesothelial cells, but was caused by rapid glucose absorption, which in t u r n decreased the osmolar gradient between the peritoneal dialysis irrigation fluid and the circulating blood. Other substances suggested as causes of impaired fluidremoving capacity of peritoneal membrane include acetic acid used as a buffer in the peritoneal dialysis irrigation fluid, s endotoxin, 9 hyperosmolar peritoneal dialysis irrigation fluid, and interleukin-1 produced in response to chemical stimulation, lo However, because none of these factors can fully explain the mechanism, t r e a t m e n t of deteriorated fluid-removing capacity has not yet been established. As a countermeasure to impaired fluid-removing capacity, Bazzato and coworkers 11 proposed an intravenous injection of furosemide or maintenance of dry weight by ECUM. Grahame and colleagues 12 pointed out t h a t the surfactant PDC, which is composed of phospholipids, can be used to improve impaired fluid-removing capacity. When PDC comes in contact with the mesothelial cells of the visceral and parietal peritonea, it forms a
209
PERITONEAL
REST FOR ULTRAFILTRATION
FAILURE IN CAPD
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single layer of long-chain fatty acids that causes the mesothelial cells to become hydrophobic. They suggested that this reaction might affect ultrafiltration and solute transportation capacities. Dipaolo and colleagues1~ reported that the amount of fluid removed was increased by introducing 50 mg/L of PDC into the peritoneal cavity of six patients with deteriorated ultrafiltration capacity caused by peritonitis. Yamamoto and others 14 also reported the usefulness of PDC as an agent for improving deteriorated fluid-removing capacity. Mactier and coworkers~5 noted that this effect resulted from inhibited water reabsorption due to the hydrophobic changes of the lymph canal surface caused by PDC. However, only a transient increase in fluid removal is effected by adding PDC to the peritoneal cavity. Whether PDC can maintain long-term fluid-removing capacity or improve peritoneal function has not yet been demonstrated. Dobbie and associates 7 reported that peritoneal mesothelial cells were stem cells of blood vessels and that regeneration of these cells required about 7 to 8 days, occurring without limitation. Verger 16 and Bazzato and colleagues~ reported that discontinuation of CAPD would improve ultrafiltration capacity and that it would take more than 3 months for the peritoneum to return to an almost normal histologic condition. We found that peritoneal rest caused the amount of fluid removed 240 minutes after initiation of retention to increase from - 4 5 0 ml to 150 ml. Creatinine D/P and D/Do also improved with peritoneal rest. PDC in the dialysate rose after peritoneal rest, and the study patient could return to
210
T. IKUTAKAETAL.
CAPD. We speculated that these effects resulted from histologic improvement of the peritoneum. The behavior of PDC has not been clarified. Our patient showed increased PDC in the dialysate after 6 months of peritoneal rest. This finding suggests that regeneration of peritoneal mesothelial cells occurred during the peritoneal rest, thereby increasing PDC production and secreting PDC into dialysate. We speculate a tight association between PDC and peritoneal mesothelial cells. Based on our findings, we conclude that peritoneal rest is a useful treatment for deteriorated ultrafiltration capacity in CAPD patients. References:
1. Ikutaka T, Ishiguro M, Hirano T, et al. Peritoneal function in patient with deteriorated ultrafiltration on long-term CAPD: A study with measuring D/P ratio for BUN and phosphatidylcholine (PDC) concentration in dialysis fluid before and after peritoneal rest. J Dial Assoc 1989; 22:499-504. 2. Ikutaka T, Ishiguro M, Nasu H, et al. A case report of deteriorated ultrafiltration capacity, who returned to CAPD after peritoneal rest. Kidney Dial 1990; 28:827-832. 3. Twardowski ZJ, Nolph KD, Khanna R, et al. Peritoneal equilibration test. PeritDialBull 1987; 7:138-147. 4. Cantaluppi A, Castelnovo C, Moriggi M, Scalamogna A. Ultrafiltration failure in continuous ambulatory dialysis. Advances in continuous ambulatory peritoneal dialysis. Peritoneal Dialysis Bulletin, Inc., 1986:12-15. 5. Naganuma S. Peritoneal function with CAPD. Current topics on peritoneal dialysis. (Symposium) Baxter Japan COR, 1987; 5:93. 6. Verger C, Brunschveig O, Charpentier Y, et al. Peritoneal structural alteration on CAPD. Advances in peritoneal dialysis. Excerpta Medica, 1981:10-15. 7. Dobbie JW, Zaki M, Wilson L. Ultrastructure studies on the peritoneum with special reference to chronic ambulatory peritoneal dialysis. Scott Med J 1981; 26:213-223. 8. Nolph K, Ryan L, Moore H, et al. Continuous ambulatory peritoneal dialysis. Perit Dial Bull 1984; 4:137-142. 9. Stenlake JB. Pharmaceutical chemistry: Citenda secunda artem. Pharmaceut J 1975; 215:533-540. 10. Shaldon S, Koch KM, Qullhorst E, Dinarello CA. Pathogenesis of sclerosing peritonitis in CAPD. Trans Am Soc Artif Intern Organs 1984; 30:193-194. 11. Bazzato G, Goli U, Landini S, et al. Restoration of ultrafiltration capacity of peritoneal membrane in patients on CAPD. Int J Artif Organs 1984; 7:93-96. 12. Grahame GR, Torchia MG, Dankewich KA, Ferguson IA. Surface active material in peritoneal effluent of CAPD patients. Peritoneal Dial Bull 1985; 5:109. 13. Dipaolo N, Sacchi G, Capotondo L. Physiological role of phosphatidylcholine in peritoneal function. In: Wiching E, ed. Peritoneal dialysis. Milan: Editore, 1988:49-51. 211
PERITONEALRESTFORULTRAFILTRATIONFAILUREIN CAPD
14. Yamamoto Y, Kamata M, Matsumine H, et al. Fluid removal effect of phosphatidylcholine on CAPD cases. Proceedings of the 31st Meeting of the Japanese Nephrology Society, 1988:393. 15. Mactier RA, Khanna R, Moore H, et al. Reduction of lymphatic absorption from the peritoneal cavity with intraperitoneal neostigmine, phosphatidylcholine and other drugs. In: Wiching E, ed. Peritoneal dialysis. Milan: Editore, 1988:41-44. 16. Verger C. Relationship between peritoneal membrane structure and its permeability: Clinical implications. Advances in continuous ambulatory peritoneal dialysis. Perit Dial Bull 1985:87-95.
212
IS PERITONEAL REST A TREATMENT FOR ULTRAFILTRATION FAILURE DURING CONTINUOUS AMBULATORY PERITONEAL DIALYSIS? TOSIHARU IKUTAKA,1 MOTOYUKI ISHIGURO,1 SEIICHI SHIMABUKURO, 1 TAKAHIRO HIRANO, 1 AND MICHIO ARAKAWA2 1Dialysis Center, Hirano General Hospital, and 2Second Department of Internal Medicine, Gifu University School of Medicine, Gifu City, Japan
ABSTRACT D e t e r i o r a t i o n of t h e p e r i t o n e u m ' s u l t r a f i l t r a t i o n c a p a c i t y is a n import a n t f a c t o r for d e t e r m i n i n g w h e t h e r c o n t i n u o u s a m b u l a t o r y peritoneal d i a l y s i s (CAPD) should be c o n t i n u e d o r discontinued. W h y t h e ult r a f i l t r a t i o n c a p a c i t y d e t e r i o r a t e s is n o t c l e a r l y u n d e r s t o o d , a n d effective t r e a t m e n t for this p r o b l e m has not y e t been established. To e x a m i n e t h e effect o f d i s c o n t i n u i n g CAPD on the recovery o f u l t r a f i l t r a t i o n c a p a c i t y , we followed up one p a t i e n t who showed d e t e r i o r a t e d p e r i t o n e a l f u n c t i o n 4 y e a r s a f t e r the i n i t i a t i o n of CAPD for 6 m o n t h s w i t h o u t p e r f o r m i n g CAPD. A c a t h e t e r inserted into the p e r i t o n e a l c a v i t y was n o t removed d u r i n g t h e 6-month period o f p e r i t o n e a l rest. We f o u n d t h a t t h e a m o u n t of fluid removed a f t e r a 240-minute CAPD i n c r e a s e d s i g n i f i c a n t l y (from - 4 5 0 ml to 150 ml) a f t e r 6 m o n t h s o f p e r i t o n e a l rest. The p a t i e n t ' s glucose r e a b s o r p t i o n r a t e i m p r o v e d slightly, b u t t h e blood u r e a n i t r o g e n d i a l y s a t e / p l a s m a r a t i o did not show a n y change. The p h o s p h a t i d y l c h o l i n e c o n c e n t r a t i o n in the dialy s a t e i n c r e a s e d f r o m 0.71 mg/dl to 2.07 mg/dl a f t e r 6 m o n t h s of perit o n e a l rest. At the end o f t h e 6-month period, t h e p a t i e n t ' s u l t r a f i l t r a . t i o n c a p a c i t y improved, a n d he was able to r e s u m e CAPD t h e r a p y . W e conclude t h a t p e r i t o n e a l rest is a useful t r e a t m e n t for d e t e r i o r a t e d ultrafiltration capacity of the peritoneum. INTRODUCTION
Continuous ambulatory peritoneal dialysis (CAPD) is a form of dialysis using the peritoneum, a biologic membrane. The peritoneum's primary functions are removing solutes and ultrafiltration. Preserving peritoneal function is critical in long-term CAPD. Since long-term CAPD has become feasible, various problems have been raised about this procedure. In particular, deterioration of the ultrafiltration capacity of the peritoneal membrane is an important factor for determining whether CAPD should be Address correspondenceto: Toshiharu Ikutaka, C.E., Hirano General Hospital, 176 Kurono, Gifu 501-04, Japan. Received for publication on February 11, 1992. Printed in the U.S.A. Reproduction in whole or part is not permitted. 202
0011-393X/92/$3.50
T. IKUTAKA ET AL.
continued or discontinued. ~'2 The cause of this deterioration is not clearly understood, and effective treatment has not yet been established. To examine whether the ultrafiltration capacity could be improved by peritoneal rest, we compared the time course of peritoneal function in a patient who showed deteriorated ultrafiltration capacity 4 years after the start of CAPD with that of patients who had a satisfactory ultrafiltration capacity. We also examined whether peritoneal rest could restore the impaired ultrafiltration capacity. PATIENTS AND METHODS
The patient was a 39-year-old man whose primary disease was chronic glomerulonephritis, which followed an episode of acute glomerulonephritis at age 16. In January 1981, he underwent hemodialysis because of renal failure from chronic glomerulonephritis. In May 1981, he received a kidney transplant from a living donor, which failed in March 1983, because of a rejection reaction. Hemodialysis was started again, and he was transferred to our hospital to undergo CAPD to allow him to return to work. The patient's clinical course during the 5 years after the start of CAPD is shown in Figure 1. From the start of CAPD on April 18, 1984, through August 1986, his clinical course was uneventful. However, the amount of fluid removed began to decrease gradually thereafter. In January 1987, the total amount of daily fluid removed became 0 ml or even a negative value. Although we instructed the patient to limit his body weight CTR
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300
amount of glucose in Dianeal
250
I,1I
200
Peritonitis
Peritonitis
01|984 12 I~85 4 1~8~ 4 1987 121988 2 .... 4 6 8 10 5 8 18 12 6 8 10 12 2 4 6 8 10 3 4 5 5 7 8 9 I0 11 12 I 2 3
Figure 1. Clinical course during 5 years of continuous ambulatory peritoneal dialysis. CTR = cardiothoracic ratio; HD = hemodialysis; ECUM = extracorporeal ultrafiltration method. 203
PERITONEAL
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FAILURE
IN CAPD
water intake and altered the composition of the irrigation fluid, edema began to develop in the lower extremities, accompanied by an increased cardiothoracic ratio. However, the solute-removing capacity was well maintained. In January 1988, we added the extracorporeal ultrafiltration method (ECUM) once a week and continued CAPD, which, however, failed to recover the fluid-removing capacity. Clinical laboratory tests revealed that hematocrit and albumin values began to decrease in June 1987 (Figure 2). Therefore, in March 1988, the patient, who provided informed consent, began a period of peritoneal rest to improve his ultrafiltration capacity. When the ultrafiltration capacity improved in October 1988, the patient resumed CAPD. Since then, his daily total fluid removal has been 500 to 700 ml, and water balance has been controlled by limiting water intake. During the 6 months of peritoneal rest, the peritoneal catheter for CAPD was left in place, and peritoneal irrigation was performed with 500 ml of irrigation fluid containing 1.5% Dianeal (Baxter Limited, Tokyo, Japan) through the catheter every morning and evening. In addition, the site of the spike was protected by a spike protector, and the patient remained bag free. This method prevented the catheter from becoming occluded with fibrin and kept the patient from developing complications, such as peritonitis, that can be caused by a peritoneal catheter. We used the peritoneal equilibration test (PET) described by Twar-
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F i g u r e 2. C h a n g e s in clinical v a l u e s d u r i n g 5 y e a r s of c o n t i n u o u s a m b u l a t o r y p e r i t o n e a l dialysis. B U N = blood u r e a n i t r o g e n ; Cr = c r e a t i n i n e ; T P = t o t a l protein; alb = albumin; ECUM = extracorporeal ultrafiltration method; HD = hemodialysis; Ht = hematocrit. 204
T. IKUTAKAET AL.
dowski and colleagues 3 as an index of peritoneal function (Table I). We regarded six patients (patients 2 though 7 in Table II) who underwent CAPD in our hospital as those with a satisfactory ultra filtration capacity. Changes in peritoneal function were assessed from the values as follows: (1) changes in the amount of removed fluid; (2) glucose reabsorption rate (D/Do); (3) capacity of removing solute (BUN dialysate/plasma [D/P] ratio); and (4) concentration of phosphatidylcholine (PDC) in dialysate. RESULTS
Figure 3 shows the changes in the amount of fluid removed from patients with a satisfactory fluid-removing capacity (normal group) and from the study patient before peritoneal rest and at 3 and 6 months after peritoneal rest. The amount of fluid removed was calculated by measuring the weight of drained dialysate. In the normal group, as the time of retention of peritoneal dialysis irrigation fluid increased, the amount of removed fluid also increased. After 240 minutes of retention, the amount of removed fluid was about 286 -+ 150 ml. On the other hand, the study patient had a negative fluid balance after 60 minutes of retention before peritoneal rest. After 120 minutes of retention, the fluid balance moved rapidly to the negative side, reaching - 4 5 0 ml at 240 minutes after the start of retention. However, after a 3-month peritoneal rest, the amount of fluid removed after 180 minutes of retention was about 50 ml, although this was not a satisfactory volume. Six months after the start of peritoneal rest, fluid removed from the study patient after 120 minutes of retention finally reached 150 ml.
Glucose Reabsorption Rate In the normal group, the D/Do was 43.2 -+ 15.9% at 120 minutes and Table I. Peritoneal equilibration test (PET).
1. Obtaining Samples
PET
Time (min)
0 60 120 Collecting blood 1" t Obtaining dialysate 1" t 2. Condition of Dialysis Dialysate 2.5% Dianeal Volume of injected fluid 2,000 ml Retention time 240 rain Position of injection supine Position of drainage sitting Drainage time 20 min 3. Measuring Method Amount of fluid removed = weight of dialysate--weight of Dianeal D/P = concentration in dialysate drained/concentration in serum D/Do = concentration in dialysate drained/concentration at 0 hour Value of phosphatidylcholine = iatroscanning method
205
180
240
t t
t t
PERITONEALREST FOR ULTRAFILTRATIONFAILUREIN CAPD
Table II. Clinical characteristics of patients undergoing continuous ambulatory peritoneal dialysis.
Patient Number
Sex
Age (yr)
1
M
40
2 3 4 5 6 7
F M F F F F
47 27 76 63 58 70
Durationof CAPDTreatment (months) 49 6 29 15 7 1 1 1
Basic Disease
UF Volume (ml/day)
CGN
- 250 600 1,500 800 800 1,200 1,500 1,200
CGN VUR CGN CGN CGN CGN
CGN = chronic glomerulonephritis;VUR = vesico-ureteralreflux; UF = ultrafiltration.
27.9 -+ 13.2% at 240 minutes after starting fluid retention and D/P; the time plot showed a gentle curve. These results were classified as high average (Figure 4). 3 However, in the study patient before peritoneal rest, 80% of glucose was absorbed into the body 120 minutes after starting retention. The changes in the amount of fluid removed and the D/Do indicate a (ml)
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206
T. IKUTAKA ET AL.
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Figure 4. Peritonealequilibrationtest (PET) curvesand assessmentof PET.
time lag between glucose absorption and fluid transportation in the study patient. Although the study patient's D/Do both before and after peritoneal rest was grouped into the high category of Twardowski's classification,3 it improved by 5% to 8% after 6 months of peritoneal rest (Figure 5).
Capacity of Removing Solute The capacity of removing solute was assessed using BUN D/P, and comparisons were made with Twardowski's classification. 3 Although the normal group and the study patient were placed in the high category of Twardowski's classification both before and after peritoneal rest, the study patient showed some improvement after 6 months of peritoneal rest (Figure 6).
Concentration of Phosphatidylcholine in Dialysate The value of PDC in the dialysate drained after 240 minutes of retention was 2.3 -+ 1.69 mg/dl in the normal group (Figure 7). In the study
207
PERITONEAL REST FOR ULTRAFILTRATION FAILURE IN CAPD
D/Do=( glucoseconcentrationin drained dialysate ) glucose concentration in dialysateat 0 hour normal(n= 6) --. Mean-----SD × . ~ before rest after 3 months of rest ~ 0 - - 0 after6 months of rest
1.00
0.500.75
0.50
120 -
0.25
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Figure 5. Changesin glucosereabsorption. patient, it was 0.71 mg/dl before peritoneal rest, 6.23 mg/dl after 3 months of peritoneal rest, and 2.07 mg/dl after 6 months of peritoneal rest, indicating that the value increased markedly after 3 months of rest, then decreased after 6 months of rest, but was still higher than the value before rest. DISCUSSION Since long-term CAPD has become feasible, possible deterioration of the peritoneum's ultrafiltration capacity has been suggested. Cantaluppi and associates 4 and Naganuma 5 reported that deterioration of the ultrafiltration capacity occurred in about 11% of patients during a 3-year period of CAPD. However, these authors did not clarify the mechanism involved in this phenomenon. Verger and associates6 and Dobbie and colleagues7 reported edema of the peritoneal mesothelial cells and deposition of collagen fiber beneath the mesothelial cells in patients with deteriorated ultrafiltration capacity. These histologic changes correlated highly with increased glucose absorption. The authors speculated that mesothelial cells play a crucial role in maintaining ultrafiltration capacity. 208
T. IKUTAKAET AL.
BUN concentration in drained dialysate / BUN concentration in serum / =---= -...-
normal ( o = 6 ) Mean-+-SD
x........K before rest
after 3 months of rest
1.00 -
o---O after 6 months of rest
F
0.75
0.50
0.25
/
0.0
60
I
180
20 240 (min)
Figure 6. Changes in capacity of removing solute.
In our study patient, fluid-removing capacity rapidly deteriorated 4 years after the initiation of CAPD. We speculated that this deterioration did not result from edema or exfoliation of peritoneal mesothelial cells, but was caused by rapid glucose absorption, which in t u r n decreased the osmolar gradient between the peritoneal dialysis irrigation fluid and the circulating blood. Other substances suggested as causes of impaired fluidremoving capacity of peritoneal membrane include acetic acid used as a buffer in the peritoneal dialysis irrigation fluid, s endotoxin, 9 hyperosmolar peritoneal dialysis irrigation fluid, and interleukin-1 produced in response to chemical stimulation, lo However, because none of these factors can fully explain the mechanism, t r e a t m e n t of deteriorated fluid-removing capacity has not yet been established. As a countermeasure to impaired fluid-removing capacity, Bazzato and coworkers 11 proposed an intravenous injection of furosemide or maintenance of dry weight by ECUM. Grahame and colleagues 12 pointed out t h a t the surfactant PDC, which is composed of phospholipids, can be used to improve impaired fluid-removing capacity. When PDC comes in contact with the mesothelial cells of the visceral and parietal peritonea, it forms a
209
PERITONEAL
REST FOR ULTRAFILTRATION
FAILURE IN CAPD
,,g/d~ 6.0i 5.04.0-
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(n=6)
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Mean+_-SD
after after 3 months 6 months of rest of rest
Figure 7. Phosphatidylcholine concentration in drained dialysate after 240 minutes.
single layer of long-chain fatty acids that causes the mesothelial cells to become hydrophobic. They suggested that this reaction might affect ultrafiltration and solute transportation capacities. Dipaolo and colleagues1~ reported that the amount of fluid removed was increased by introducing 50 mg/L of PDC into the peritoneal cavity of six patients with deteriorated ultrafiltration capacity caused by peritonitis. Yamamoto and others 14 also reported the usefulness of PDC as an agent for improving deteriorated fluid-removing capacity. Mactier and coworkers~5 noted that this effect resulted from inhibited water reabsorption due to the hydrophobic changes of the lymph canal surface caused by PDC. However, only a transient increase in fluid removal is effected by adding PDC to the peritoneal cavity. Whether PDC can maintain long-term fluid-removing capacity or improve peritoneal function has not yet been demonstrated. Dobbie and associates 7 reported that peritoneal mesothelial cells were stem cells of blood vessels and that regeneration of these cells required about 7 to 8 days, occurring without limitation. Verger 16 and Bazzato and colleagues~ reported that discontinuation of CAPD would improve ultrafiltration capacity and that it would take more than 3 months for the peritoneum to return to an almost normal histologic condition. We found that peritoneal rest caused the amount of fluid removed 240 minutes after initiation of retention to increase from - 4 5 0 ml to 150 ml. Creatinine D/P and D/Do also improved with peritoneal rest. PDC in the dialysate rose after peritoneal rest, and the study patient could return to
210
T. IKUTAKAETAL.
CAPD. We speculated that these effects resulted from histologic improvement of the peritoneum. The behavior of PDC has not been clarified. Our patient showed increased PDC in the dialysate after 6 months of peritoneal rest. This finding suggests that regeneration of peritoneal mesothelial cells occurred during the peritoneal rest, thereby increasing PDC production and secreting PDC into dialysate. We speculate a tight association between PDC and peritoneal mesothelial cells. Based on our findings, we conclude that peritoneal rest is a useful treatment for deteriorated ultrafiltration capacity in CAPD patients. References:
1. Ikutaka T, Ishiguro M, Hirano T, et al. Peritoneal function in patient with deteriorated ultrafiltration on long-term CAPD: A study with measuring D/P ratio for BUN and phosphatidylcholine (PDC) concentration in dialysis fluid before and after peritoneal rest. J Dial Assoc 1989; 22:499-504. 2. Ikutaka T, Ishiguro M, Nasu H, et al. A case report of deteriorated ultrafiltration capacity, who returned to CAPD after peritoneal rest. Kidney Dial 1990; 28:827-832. 3. Twardowski ZJ, Nolph KD, Khanna R, et al. Peritoneal equilibration test. PeritDialBull 1987; 7:138-147. 4. Cantaluppi A, Castelnovo C, Moriggi M, Scalamogna A. Ultrafiltration failure in continuous ambulatory dialysis. Advances in continuous ambulatory peritoneal dialysis. Peritoneal Dialysis Bulletin, Inc., 1986:12-15. 5. Naganuma S. Peritoneal function with CAPD. Current topics on peritoneal dialysis. (Symposium) Baxter Japan COR, 1987; 5:93. 6. Verger C, Brunschveig O, Charpentier Y, et al. Peritoneal structural alteration on CAPD. Advances in peritoneal dialysis. Excerpta Medica, 1981:10-15. 7. Dobbie JW, Zaki M, Wilson L. Ultrastructure studies on the peritoneum with special reference to chronic ambulatory peritoneal dialysis. Scott Med J 1981; 26:213-223. 8. Nolph K, Ryan L, Moore H, et al. Continuous ambulatory peritoneal dialysis. Perit Dial Bull 1984; 4:137-142. 9. Stenlake JB. Pharmaceutical chemistry: Citenda secunda artem. Pharmaceut J 1975; 215:533-540. 10. Shaldon S, Koch KM, Qullhorst E, Dinarello CA. Pathogenesis of sclerosing peritonitis in CAPD. Trans Am Soc Artif Intern Organs 1984; 30:193-194. 11. Bazzato G, Goli U, Landini S, et al. Restoration of ultrafiltration capacity of peritoneal membrane in patients on CAPD. Int J Artif Organs 1984; 7:93-96. 12. Grahame GR, Torchia MG, Dankewich KA, Ferguson IA. Surface active material in peritoneal effluent of CAPD patients. Peritoneal Dial Bull 1985; 5:109. 13. Dipaolo N, Sacchi G, Capotondo L. Physiological role of phosphatidylcholine in peritoneal function. In: Wiching E, ed. Peritoneal dialysis. Milan: Editore, 1988:49-51. 211
PERITONEALRESTFORULTRAFILTRATIONFAILUREIN CAPD
14. Yamamoto Y, Kamata M, Matsumine H, et al. Fluid removal effect of phosphatidylcholine on CAPD cases. Proceedings of the 31st Meeting of the Japanese Nephrology Society, 1988:393. 15. Mactier RA, Khanna R, Moore H, et al. Reduction of lymphatic absorption from the peritoneal cavity with intraperitoneal neostigmine, phosphatidylcholine and other drugs. In: Wiching E, ed. Peritoneal dialysis. Milan: Editore, 1988:41-44. 16. Verger C. Relationship between peritoneal membrane structure and its permeability: Clinical implications. Advances in continuous ambulatory peritoneal dialysis. Perit Dial Bull 1985:87-95.
212