Peritoneal Dialysis in the 21st Century

One major development in the field of kidney diseases in the 21st century will be in prevention of end-stage renal disease (ESRD). Basic research has made inroads into the understanding of the mechanisms of progression of chronic renal failure, including the understanding of the functions of genes activated by renal damage. All this may well result in a major reduction in the incidence of ESRD. The second important development will be in transplantation, which will constitute the mainstay of ESRD treatment in the next century. The clinical introduction of xenotransplantation and the cloning of one’s own organs via one’s stem cells may well represent the major areas of replacement therapy. This will reduce dialysis as a method to support the main treatments. These predictions will take some time to come to fruition. The first few decades in this century will face an increase, rather than a decrease, in the number of ESRD patients needing dialysis. Peritoneal dialysis (PD) will feature strongly in meeting this need in at least the first two decades of this century. PD has come a long way since the introduction of continuous ambulatory PD (CAPD) as a form of renal replacement therapy (RRT) over the quarter of a century it has been in existence. There have been some dramatic improvements in outcomes in patients treated by PD, such that it is now accepted as an equivalent therapy to hemodialysis (HD). In the last 5 yr, CAPD has proven to be as effective a treatment as HD, and in some instances may offer advantages over HD. As we move into the new millennium, it is clear that PD will feature strongly in the care and management of patients in ESRD as advances in the understanding of the pathophysiologic mechanisms and means to combat the adverse effects of PD are put into practice. Currently, there are more than 130,000 patients on PD worldwide, representing approximately 15% of the total world population requiring dialysis. It is anticipated that this number will increase during the next decade, especially in developing countries. Current Outcomes Several analyses have been undertaken in comparing the outcomes on PD and HD. Nolph (1) analyzed the relative risk of death on PD as compared with HD and by and large found that mortality risk was equal for HD and PD in the various studies reported. After this analysis was the report of Bloembergen et al. (2), which was based on the US Renal Data Systems (USRDS) data on prevalent patients (1987, 1988, and 1989). This showed that PD subjects had a 19% higher risk of mortality as compared with patients who used HD. This was met with considerable consternation in the United States and probably did the therapy a major disservice. Analysis from the Canadian Organ Replacement Registry on patients starting RRT between 1990 and 1994 showed that for incident patients, the survival with PD was better in the first 2 yr of treatment compared with HD with subsequently no difference up to 4 yr (3). In addition, it showed that there was a significantly lower risk of death in PD patients across all ages, regardless of whether or not the patient had diabetes; for ages 0 to 64 yr, the relative risk of death was 0.54 for PD patients without diabetes (for HD, the relative risk was 1) and 0.73 for patients with diabetes. A further comparative analysis from 11 Canadian centers showed that the apparent survival advantage of PD patients was due to lower comorbidity and a lower burden of acute onset end-stage disease at the inception of dialysis; survival was otherwise equal (4). More recent analysis of the USRDS data shows similar results: 5-yr survival of the 1993 cohort of dialysis patients is identical for PD and HD patients (5). The analysis on Medicare patients in the United States by Collins et al. (6) on the cohort of patients 1994 to 1997 concluded that in the first 2 yr of therapy, short-term PD is associated with superior outcomes compared with HD at all ages except in elderly women with diabetes. A further analysis of 17,000 PD patients from the Canadian Organ Replacement Registry database (1981 to 1997) has shown significant decrease in mortality rates during this period (7). Long-term survival from single center analysis shows no difference at 15 yr between PD and HD patients (8). A reasonable conclusion from all this information is that mortality is the same for HD and PD when comparing identical types of patients, at least for the first 3 to 4 yr of RRT. Patient survival statistics from long-term studies in PD patients during the 1990s show a 50 to 70% 5-yr survival (5,8). It is likely that the results will continue to improve as the various developments outlined below are incorporated into routine practice. PD to date has proven its utility and has become established in certain areas of care of patients with ESRD. These aspects, which have to be maintained or even further improved in the future, are outlined in Table 1. Table 1: Positive points about peritoneal dialysis therapy that have been established beyond doubtaCurrent Problems Requiring Improvement Technique Failure and Long-Term PD If PD is going to achieve wider acceptance, then several outstanding problems that currently detract from greater acceptance need to be overcome. Two major issues are the higher technique failure in PD compared with HD (still related in a third of dropouts to HD to peritoneal infections) and the low rate of achieving long-term PD. The latter is to a large extent related to long-term changes in peritoneal membrane structure and function. In the analysis by Davies et al. (9), technique survival in the seven studies in the 1990s was 30 to 50% at 5 yr. The major causes of dropout derived from these analyses are shown in Figure 1. The nonachievement of long-term PD is to a large extent related to long-term changes in peritoneal membrane structure and function. Long-term (more than 10 yr) PD is limited to a small percentage of those who start PD (10), and single-center analysis shows that survival for those who use PD is 20% at 10 yr (8). The major cause of failure in long-term studies is ultrafiltration failure, inadequate solute clearance, and peritonitis (11). In data from Japan (12) long-term survival from a cohort of 242 patients was for a median of 5.8 yr, with patients’ failure to respond to this technique related to membrane problems. Figure 1. : Reasons for therapy change to hemodialysis in long-term peritoneal dialysis patients in the 1990s. Percentages are averaged from seven outcome studies (3 , 9 , 65 , 150 – 153).Peritoneal Infections Peritonitis remains a problem and a major source of transfer to HD (13,14), even though rates have improved dramatically with the advent of technologic improvements related to the disconnect systems (15). The problem lies in persistent unresolving peritonitis due to Pseudomonas, fungal, and to a lesser extent Staphylococcus aureus infection (16,17). At present, there appears no obvious means to prevent gram-negative and fungal infections, and the only option is to develop better therapeutic regimens to improve the outcome of these infections. For S. aureus infection, there is greater reason for optimism. Several studies have shown nasal carriage of S. aureus is related to increased exit site infection and peritonitis (18,19). Prophylaxis with intranasal mupirocin, exit-site mupirocin, or cyclical rifampicin can dramatically reduce not only S. aureus exit-site infection and peritonitis, but also infections from other organisms (20,21). Mupirocin routinely administered to exit sites is now advocated in published guidelines (22) and is likely to favorably affect infection rates and survival. Patient dropout after persistent peritonitis remains a problem, and those who require catheter removal for cure do not return to PD. More research needs to be done into techniques for safer catheter removal and reimplantation in the presence of persistent peritonitis to avoid interruption of PD. Prevention of adhesions, which are extensive in some patients with persistent peritonitis, is also important. Peritoneal Access Transfer of patients to HD for peritoneal access failure is now reduced to approximately 5 to 10% (Figure 1). Access-related dropout is low, and the improvement in catheter-related infections from mupirocin prophylaxis augur well for the continuing improvement in peritoneal infection. The type of catheter and method of implantation are probably less important than the meticulous care taken during implantation and subsequent care with immobilization and exit-site care; these aspects are reviewed in the catheter guidelines of the International Society of Peritoneal Dialysis (23). Adequacy of Solute Removal In spite of the original description by Popovich et al. (24) and the theoretical work of Teehan et al. (25) suggesting prescription formulations, CAPD has remained standardized to 4 with This is such a prescription be to patients of renal and peritoneal It is now clear that a prescription needs to take these into dialysis regimens need to be at by in the and of and the time of on for solute have now the of which has been the Outcomes guidelines The are a of and a of for CAPD and higher on PD These have been to lower the for in low to 50 in with the Canadian have a outcome These have been based on the which showed that the greater the solute at start of maintained over the of the the better the there is considerable the for such it is accepted that higher are and be at all A of and a of 50 are and all patients be In developing have not of to these results from that lesser total can outcomes The new will more studies and data from these to the needs of patients in of and PD One way of achieving increased dialysis is by the use of of is it is the of dialysis. is a major advantage in patients with a peritoneal membrane these patients are to on regimens and on The on can the of achieving of solute and is likely to favorably affect has also major advantages for the patient from the of and this is the reason for its In the there is a higher These the on and the of PD is to change with this increased on prescription to of in the various regimens to achieve these will of solute It be to these increased are going to affect exit and studies are the (1) renal peritoneal and the small solute via and is and solute the same or for patient such as patients with the and and Peritoneal and with Long-Term PD In the last yr, have been made in the understanding of peritoneal and its related in of solute and This understanding has to the development of PD and the way for better treatment of patients PD with improved outcomes and The peritoneal of the and the is a that and peritoneal and The as a it is in the of peritoneal in solute and in and and in the and of the and from the in the peritoneal to the peritoneal have to at least that can offer the the the and and ultrafiltration in two across these It is now that there are that the This small and large (3 to 5 the of but not These have been in the and the is effective as a in spite of its small of 2 to 3 as it at this 50% of ultrafiltration these at the of small to 50 have been the equivalent of the small large probably less than of total are in In addition, there is from the peritoneal and are the mechanisms for solute which is also of the structure of the various to the peritoneal of and it is to this as In the of low across this membrane to over the standardized This the of the patient from to low and has and important for the prescription The with the to the transfer which is a of the of the into the and the is well to have several that it an for PD for of and on the of peritoneal especially in long-term PD PD, changes do take is the These are important. The use of PD and of infection and to changes in the of the and and of the membrane in the and the membrane This to has been in long-term dialysis patients and this is related to in the from in the The results of the changes are peritonitis, which is The data to of patients with this the a incidence of to of ultrafiltration is the peritoneal in long-term PD The major causes of ultrafiltration failure are the presence of large peritoneal and decrease in to related to or decrease in the ultrafiltration of the in the Long-term PD a large and the may well affect function. from the effects and reduced to there are major issues related to the There are several for changes in the peritoneal These to be the (1) continuous to dialysis to be in that are important are a of low and and its via the and mechanisms such as and to changes of and of type in the of in peritoneal and the presence of during which and also the of the of is now as a significant in peritoneal membrane The for the is to to reduce patient to the total of and avoid the and and to the PD as well as lower are now in and offer a There is also a need to develop means for of membrane damage. research needs to be done to the of of of ultrafiltration changes and peritoneal in membrane and to whether new may prevent research in this the of of to the use of use of dialysis with and low prevention of in the peritoneal membrane by use of or and of areas of research the of administered by or a small percentage of patients on for more than yr as in HD, these patients show an increased mortality and can develop These are important for to achieve long-term PD. Patient is a significant of in the long-term management on PD. et al. found that patient and for about the total number that to HD in long-term PD This may in be related to the acceptance of elderly patients, comorbidity and is likely to increase with time on dialysis and will the of the dialysis on a There is a need to develop to patients to The use of care in patient such as the and the use of PD in reduce the incidence of patient Currently, some of these patients are in a an to patients with ESRD are to in the United with to 15% on PD The use of may be in some of these patients when are in dialysis. The development of or a may well prevent of The development of that are to than the be of in It is well that mortality is increased in these The are There are the the risk failure, and several related to the dialysis therapy For PD, the established risk to the development of a membrane clear is the of an to and and and The of PD patients is more than the of HD patients research studies on the effects of and of and in the prevention of are studies on the effects of dialysis and the and prevention of chronic in the of and The of of on the of cells in to have been found in patients, and these are of mortality is in to 10% of the PD patients, and have The be to prevent this which is a of research will need to on the between and small solute and the of chronic on the development of There is some that is associated with chronic and peritoneal solute but this has not found to be by research is to the between chronic and as is the of an between and PD patients are more to disease which is associated with and from its to A has been to increased mortality and which is in HD patients with the new These are new and there is a need to this in PD patients and the between the higher of on PD and and with Dialysis though have been for solute on patients with chronic renal failure are to to below these dialysis is It not to patients to below of and then have to increase dialysis to these accepted In addition, this has major renal failure to in addition, the the small solute the the at the time of of which to a outcome et al. the of of dialysis and that CAPD in a patient with peritoneal be maintained for approximately with a single and from to with 2 of The guidelines advocated starting therapy when the use of dialysis will achieve solute by for the renal as with This is by PD only during the or by an of which has ultrafiltration of start has been and reviewed in an The show that it is to start with but the do not to be and the for start with dialysis needs to be with a that as is the with solute the will to start patients and than is the in the that better outcomes will If this the then better patient and in will be for of as will the need for of PD as an in an RRT The survival results on PD are better than on HD in the of therapy and technique survival on long-term PD is It is to PD as an therapy If PD therapy for reason peritonitis, inadequate or then a from PD to HD be This is and has shown better outcome In a this in better survival in patients starting with PD than it showed that patient outcome is not by starting patients on PD, patients are in a when problems There are several advantages to PD as an therapy to better renal incidence of compared with HD of access sites better and less and better results after The of PD and transfer to HD at an time the failure to do can to outcome Table peritoneal dialysis as the therapy for patients with end-stage renal are considerable to this that are and The needs to be better on the outcomes and advances in PD. also affect of is important that are are more likely to on to HD and on it It is that there is of patient with chronic renal failure to a renal the patient will an in the United States that when patients of all treatment the percentage starting PD was higher than the The USRDS in 1997 reviewed the of HD patients this dialysis when the was patient of PD when it was for and when it was for In a patient is with a that for patient PD to be the first option (Figure This may well to be an in the new Figure : of the of peritoneal dialysis (PD) in an renal replacement therapy patients are and therapy on the of and patient are by PD. start may also be undertaken especially in patients with diabetes; this is also by a single of and by the number of as the renal and in PD As in more there is now a greater of the of especially in the peritoneal membrane to the This has been shown in in patients with ultrafiltration failure, total of of and has shown a return of ultrafiltration This only in outcomes in PD and the for a to the various Table A to peritoneal dialysis to needs and The development with the for on PD therapy is the introduction of This is to a for of to ultrafiltration of at least It is also to and shows less and use in patients with a membrane and of ultrafiltration has the time on PD by a of in patients who otherwise have to HD These are also the patients who by to patients need a or to solute is for this of 10 to There is that may be improved with and there may be less areas of clinical research with some of the use of as of start dialysis prescription use in patient with its use in with other to use and 2 in with The only from its use is which are for of in less than of patients as have been to the affect of the peritoneal One such is as the and are to be to the The introduction of into clinical was based on in studies in and systems have the of a Several studies have clinical with these as or as a of and is not that to patients in of peritoneal and peritoneal membrane patients who at of PD related to and have been in a to improve dramatically on and The currently are or a have been for more than yr as an the is due to the of significant in the PD may be used to this In addition, it will to two the advantage not be The effects of on have been by a number of show a when used in patients but this has not been found in other studies of is by a in and a of which is with the use of two can only be used in to two Current on use in PD, other than the appears to be in a source in is in such as peritonitis, and in There is no that its use the development of has been to about a reduction in the of which is during and which is PD all aspects of and be used for all in CAPD or therapy, are for at least of the dialysis The recent development of of from other to be at a lower than is in of the two results in a of the which in the of can a The has a of and is less In a PD similar to but of was significantly increased suggesting that to may be related to For of at lower than currently causes a reduction in of the including and to be are increased which appears to be in In and of are also significantly reduced in such no is of will for better and less effects in the and and and and and have all been in or in patients in a limited way In with these an One can a for CAPD of an of two of and an of This is but clinical are to its PD for the of and removal of and of has been on the to peritoneal membrane and improve long-term in addition, for reduction in use are will major clinical needs related to the of improvement in of peritoneal membrane and of of dialysis. may various peritoneal functions and will its with and the of systems to PD that have been to not only and but also and other clinical that may in the way to therapy that the cells as a site for the of that is now in and and other of as well as such as and will be to or with derived from These will be to the by the that to the for such as and The peritoneal catheter in this be used to for use by the One may then a that after in its be In addition, it may be that the of HD and PD will in such a way that a single will to therapy with dialysis that is on in to that use and first that for PD way to therapy that to the peritoneal have been These by which the use of is used to therapeutic that to or improve the of the peritoneal membrane in long-term PD. In studies on the have and of a in of a of and of a The to the peritoneal by and in that the is a This then be used to or the and of the membrane for long-term It also be used to for of renal to to to improve to prevent development of peritoneal and to There have been considerable advances in the of PD in a therapy, which now has not as compared with HD. advances the to dialysis solute and and the of to the peritoneal membrane less is to improve the outcome of of the peritoneal membrane is going to be a and the will the therapy the to improve the long-term of the peritoneal are the important of of PD, and it is anticipated that these will continue to the use of PD and of continue to the use of PD. also the PD and care the percentage of have the PD and are This is in spite of data from that show that PD is than is HD that the outcomes have shown to be equivalent to those of HD in of survival and of it is to that PD, in some has limited use In the future, and need to and such be a to the further use of that is in developing countries. There is no that the next will an in the dialysis in and patients will be accepted dialysis. It is that related to will the use of a therapy, which PD is to PD will continue to increase in but only its to improve without its over HD The for the and beyond is to develop PD therapy that it patient and outcomes and is the future, and we need to to this Currently, only 15% of the world population that dialysis is by PD. This may well increase as therapy will be in developing and the of dialysis will those who the to for more treatment