PERITONEAL DIALYSIS: GLOBAL UPDATE

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1 Proceedings of the ISPD '98 -The VIIIth Congress of the ISPD /99 $ August 23-26, 1998, Seoul, Korea 1999 International Society for Peritoneal Dialysis Peritoneal Dialysis Internatianal, Vol.19 (1999), Supplement 2 Printed in Canada. All rights reserved. PERITONEAL DIALYSIS: GLOBAL UPDATE Ram Gokal p Manchester RoyalInfirmary, Department of Renal Medicine, Manchester, England eritoneal dialysis has evolved considerably over the last three decades. The dramatic increase in its use was initially related to the introduction of CAPD in Since then, the use ofpd has shown a linear increase. Associated with this dramatic rise in the number of patients on PD have been developments in the associated technology and in understanding pathophysiological mechanisms and complications and the means to overcome them. The result has been an improvement in patient survival rates, now comparable to those for hemodialysis (1), and an improvement in technique survival rates, presently still below that for HD (2). Despite truly impressive technical modifications and improved outcomes, PD technique survival re mains low, and long-term technique survival on PD is limited to between 2% and 4% of patients beyond 5 to 8 years of therapy (3). CURRENT GLOBAL USE OF PERITONEAL DIALYSIS Industrial sources set the total number of patients on dialysis (both PD and HD) to 830,000 at the end of Of the total number, about 30% reside in North America, 21% in Japan, 18% in Europe, and the remainder elsewhere in the world. About 115,000 patients (almost 14% of the total) are managed on PD. The annual growth rate for PD over the last five years has been steady at about 7.5%. It is interesting to assess what percentage of dialysis patients in an individual country are being managed by PD. Fig ures 1 and 2 show the breakdown for various countries in the West and in Asia. The percentages range from below 1% to about 80%. This spread is interesting and does not reflect in any way the merits or demerits of the technique and its suitability (or other wise) for managing patients in end-stage renal dis ease (ESRD). Two recent articles by Nissenson et al (4,5) have clearly delineated non medical factors important in therapy selection. These factors include financial reimbursement policies, physician experience (or lack thereof) with both therapies, patient understanding of modality options, resource availability, social factors, and cultural habits, KEY WORDS: Global PD use; survival; technique failure; dialysis solutions; future developments, Correspondence to: R. Gokal, Consultant Nephrologist, Department of Renal Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL United Kingdom.

2 Concern over healthcare costs is now escalating greatly everywhere, grounded in changing economic factors. In the United States, the Health Care Finance Administration (HCFA) ESRD program undertook a demonstration project, with emphasis on cost containment and on managing the total cost of care for dialysis patients. Nissenson concludes that in a managed care environment, the ESRD modality that provides the most value (defined as quality/cost) is likely to be the one most utilized (5). In terms of cost, it is recognized that PD patients are substantially less expensive to care for than are HD patients. The difference is related to reduced outpatient costs (mostly owing to the lower cost of dialysis) and reduced inpatient cost (mainly resulting from fewer inpatient stays). The impact of public versus private sector funding has a major influence on the therapy used. For instance, in Europe, in the public sector, 23% of patients were treated by PD, whereas in the private sector the figure was only 3%. Similar figures can be shown for PD in Japan (public sector, 18%; private sector, 3%). SURVIVAL -PATIENT AND TECHNIQUE Various study reports have shown that survival on PD is equivalent to HD (6). However, a true comparison is not possible because no randomized controlled study has been undertaken, and such a study would be almost impossible to perform. Reliance on registry data is therefore necessary, and these data are outlined in Table 1, which shows patient survival at various time intervals. Most of the studies had confounding variables, especially those related to the United State Renal Data System (USRDS) database, which is shows higher death rates in PD patients than in HD patients in a cohort studied at the end of the 1980s (7). The Canadian Organ Replacement Registry (CORR), however, reported on a cohort of patients taken onto dialysis in the early 1990s, and that study quite clearly showed that death rates on HD were higher within all age groups and for both diabetic and non diabetic patients (1). The difference was statistically significant in all patients except diabetics over the age of 65. The low mortality rates for PD were observed even after adjusting for age, primary renal diagnosis, center size, and pre-dialysis comorbid conditions. The reduced mortality for PD appeared to be concentrated in the first two years after initiation of dialysis; survival at five years was not significantly different. These results are quite dramatic, were arrived at in statistically apt ways, and conclusively show that PD is, at a minimum, as good as HD and probably better. Fenton et al (1) concluded that PD is associated with decreased mortality relative to HD, the effect being greatest in the first two years offollow-up. Be cause PD is a more cost-efficient, yet less practiced form of renal replacement therapy, greater use of the therapy may increase access to dialysis by patients and hence save lives. What is still disconcerting is the lower retention rate on PD as compared to HD, which is related to the inherent problems of PD: peritonitis, access, inadequate dialysis, and psychosocial factors (3).

3 Nevertheless, important developments have occurred in these areas. The last decade has seen these landmark PD events: 1. Y-set Study (8), with worldwide introduction of the double bag disconnect systems in the early 1990s. The impact on peritonitis rates has been considerable, and now peritonitis rates of an episode every two to three years are the norm. However, the incidence of serious peritonitis (Staphylococcus aureus, Pseudomonas) has not declined and remains a threat to PD integrity (9). 2. Outcomes shown in the USRDS data (Bloembergen Study) (7) dampened the enthusiasm for PD, especially in the U.S., but now have been countered by data from the Canadian Organ Replacement Registry (CORR Analysis) (1). 3. The CANUSA Study (10) in 1996 initiated the debate for higher solute clearance targets to improve outcomes. It was followed by the National Kidney Foundation's Dialysis Outcomes Quality Initiative (DOQI) guidelines in 1997 (11), which again aimed to improve patient outcomes. 4. The impact of the DOQI guidelines has also spurred introduction and increase in the use of automated PD (APD), facilitated by a new generation of sophisticated, patient-friendly cyclers, introduced in the mid 1990s. OTHER PERITONEAL DIALYSIS DEVELOPMENTS Significant strides have also been made in understanding the pathophysiology of solute and fluid transport, changes in the peritoneal membrane with time, and the need for improved biocompatible solutions to enhance peritoneal membrane integrity. The better understanding of solute transport, based on the three-pore theory (12), now has anatomical counterparts: the aquaporin water transport channel has been identified in the peritoneal mesothelium and capillaries (13), corresponding to the ultra small pores. The peritoneal equilibration test (PET) and its further development, the standard permeability analysis (SPA), enable the identification of deficits in the transport of solutes and fluid (14) by identifying vascular surface area and aquaporin channel integrity. It is now clear that the factors that most greatly affect patient survival are peritoneal permeability, nutrition, and fluid status. In the analysis of the CANUSA data (15), high or high-average permeability was associated with higher death rates, and similar results have been shown in studies in the U.K. (16) These results partly imply that fluid control is poor in these patients, that they are regarded as being "chronically fluid overloaded" (17), and that the fluid overload may magnify the cardiovascular problems that these patients already have (18). Peritoneal membrane damage has been linked to the bioincompatible nature of the PD fluid (hyperosmolality, low ph, the use of glucose, and glucose degradation products) (19). Glucose has been shown to lead to deposition of advanced glycosylation endproduct (AGE) - related products in the peritoneal membrane, leading to increased permeability (20). In vitro studies quite clearly show that hyperosmolality and low ph affect cell function and peritoneal membrane viability (21). New biocompatible solutions are now becoming available with the use of bicarbonate (normal ph) (22), icodextrin (iso-osmolar) (23), and newer, double-chambered glucose solutions with a high ph (24). The use of these solutions has achieved extended time on therapy for patients who have lost ultrafiltration (25). These developments will indeed impact favorably on patient technique survival and longevity. Peritoneal access has been improved by a better catheter (Swan neck), better implantation techniques, and better care (26). The role of S. aureus nasal carriage in exit site infections is especially dramatic: prophylaxis (intranasally or at the exit site) has substantially decreased catheterrelated infections and peritonitis (27,28). FUTURE DEVELOPMENTS Future developments will certainly involve better solution modifications and a profile of solutions to meet individual needs in terms of solute removal, fluid control, blood-pressure control, and perhaps even additives to minimize cardiovascular risk. It is feasible that on-line preparation of PD fluids for home APD therapy will make this therapy cheaper. Early start has been advocated (DOQI guidelines) (11) to try to better preserve residual renal function, to delay the use of blood access sites, to better control salt and water, and to permit continued liberaliza tion of the diet to ensure nutritional rehabilitation. The guidelines would also make it easier to increase the dialysis dose to maintain combined renal and dialysis Kt/V targets and to accommodate incremental dialysis at lower costs. With the introduction of the long-dwell icodextrin solution, it may be possible to use one or two exchanges initially and to increase the number of glucose exchanges gradually as residual renal function declines. There is no doubt that nutritional status declines with declining glomerular filtration rate (GFR) and that the poorer the nutritional state, the worse the outcome. An early start may well be advantageous, but has to be evaluated in conjunction with the potential morbidity of peritoneal dialy

4 sis in patients who may be relatively asymptomatic at the start of dialysis. Another approach in the future may well be to start renal replacement therapy with PD and to shift to HD when the need arises. A preliminary report seems to show prolonged survival of ESRD patients using this approach (29). Future strategies will also focus on the problems ofhigh cardiovascular morbidity and mortality. Interventions likely to impact on these problems include better fluid and bloodpressure control, prevention of permeability changes, and control of lipid and metabolic abnormalities. Overall, the factors that will promote growth in peritoneal dialysis are enhanced survival, economic benefits, product innovations, prescription flexibility, and a shift towards a healthier initiation. The current data indicate that the results of good PD practices are as good or even better than those ofhd. PD has advantages as an initial renal replacement therapy in terms of preserving residual renal function, maintaining nutritional status, and better controlling blood pressure and fluid level. Patient independence and survival are also maintained. It seems that an integrated policy in which transplantation, HD, and PD are equally available -with perhaps the initial therapy in most patients being PD -can improve the survival ofesrd patients. Such a policy would reflect the recognition that well-practiced PD is very cost effective. REFERENCES 1. Fenton SSA, Schaubel DE, Desmeules M, Morrison HI, Mao Y, Copleston P, et al. Hemodialysis versus peritoneal dialysis: A comparison of adjusted mortality rates. Am J Kidney Dis. 1997; 30: Maiorca R, Cancarini G, Zubani R, Camerini C, Manili L, Brimori G, et al. CAPD viability: A long-term comparison with hemodialysis. Perit Dial Int. 1996; 16: Gokal R, Oreopoulos D. Is long term CAPD possible? 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