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Criteria for selection of ESRD treatment modalities
Kidney International, Vol. 57, Suppl. 74 (2000), pp. S-136–S-143
Criteria for selection of ESRD treatment modalities NELSON MAZZUCHI, JUAN M. FERNA´NDEZ-CEAN, and ENRIQUETA CARBONELL Instituto de Nefrologı´a y Urologı´a del Uruguay, Servicio de Asistencia Renal Integral, Montevideo, Uruguay
Criteria for selection of ESRD treatment modalities. The most important renal replacement therapies (RRT) for end-stage renal disease (ESRD) patients are hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT). Survival, morbidity and quality of life are the main factors to select the best RRT modality for a particular patient. The outcome comparison suggest that RT is a better overall treatment for ESRD patients. On the other hand, the studies that compared patient outcome for HD and PD have yielded conflicting results. Neither treatment modality is best suited for all patients. The choice should be analyzed for each particular patient considering his demographic and comorbid conditions. Diabetic patients, patients with cardiovascular disease and elderly patients are high risk populations and they are discussed independently. The frequency of treatment modalities in the different countries is not in accordance with the analysis of the advantages and disadvantages of each one. Non-medical reasons are important factors in dialysis modality selection. In our experience the expertise of the nephrologic team is the most important one. RT, HD and PD should not be seen as competing therapeutic options, rather, they are complementary methods of dealing with uremia. An integrated approach combining HD, PD and RT is necessary to devise an individualized treatment program permitting optimal long-term physical and psychological well being and adequate integration in the family and society.
Technological and immunological developments within the last two decades have evolved several renal replacement therapy (RRT) options. The most important of them in the treatment of end-stage renal disease (ESRD) patients are hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT). Each modality has advantages and disadvantages. The challenge for the nephrologist is to devise an individualized treatment program permitting optimal long-term physical and psychological well being and adequate integration in the family and society. These goals are most effectively achieved by an integrated approach combining HD, PD and RT. Survival, morbidity and quality of life are the most important factors to select the best RRT modality for a particular patient. The rational long-term management Key words: hemodialysis, peritoneal dialysis, renal transplant.
2000 by the International Society of Nephrology
strategy may be based, also, on clinical status, patient age, patient preference, psychological stability, etiology of ESRD, comorbidity, suitable living-related donor, economic factors and social circumstances. DIALYSIS VS. RENAL TRANSPLANT Patient survival after RT is markedly better than that seen with either HD or PD [1–4]. However, some of the benefits associated with transplantation are related to patient selection, since dialysis patients with the most serious comorbid conditions are not accepted for the transplant waiting list and hence remain in the dialysis group. Some comparative studies of dialysis vs. RT survival have considered that the transplant group is favored by inclusion of these high-risk patients in the dialysis group [2, 3, 5, 6]. We analyzed survival for ESRD patients on dialysis vs. after transplantation, adjusting for the variables that were significantly and independently related with mortality [7]. This analysis concluded that, when the outcome is adjusted to comorbid factors, there are no differences between RT recipients’ and HD patients’ survival in nondiabetic patients, while RT gives better survival than HD in diabetics patients. Overall survival was significantly higher in RT recipients than in HD patients (P , 0.0001). However, treatment modality did not show a significant relation with mortality when analyzed together with age, heart disease, cancer and smoking habit. In non-diabetic patients, survival adjusted for age, heart disease, cancer and smoking habit was similar in RT recipients and HD patients (RR 5 1.03, P 5 0.87). On the contrary, when only diabetic patients were considered, treatment modality was significantly and independently related to mortality. Five-year adjusted survival was 89.2% for RT recipients and 40.9% for HD patients (P 5 0.017). Relative risk is not the same over time, that is, it is not proportional. HD patients had better initial survival in the first year and the RT recipients had higher long-term survival [7]. We suggest that ESRD patients without comorbid risk factors at the start of dialysis provide an ideal population for survival comparisons among different centers or different treatment modalities [8]. When only this low risk
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group was used to compare survival, no differences were observed. Ten-year survival was 87.9% for HD patients (N 5 134) and 82.6% for RT recipients (N 5 289) (P 5 0.231) [7]. Our data agree with several studies [2, 3, 5, 6]. Vollmer et al [2] and Hutchinson et al [5] found a similar survival with dialysis and cadaveric transplantation, after controlling for pretreatment risk factors. Garcia-Garcia et al [6] found a markedly lower mortality risk among diabetic transplant recipients than diabetic dialysis patients, although their findings did not achieve statistical significance. Port et al [3] compared mortality risk among cadaveric RT recipients vs. transplant candidates on dialysis in the cyclosporine era. They used a time-dependent Cox analysis to eliminate the time-to-treatment bias. Their dialysis group had been limited to those patients who were accepted to the transplant waiting list, in order to reduce the bias related to patient selection. They observed a markedly lower long-term risk (RR 0.25) among diabetic RT recipients compared with diabetic wait-listed dialysis patients (P , 0.001) and no differences among patients with glomerulonephritis or hypertension as cause of ESRD. These data suggest that the survival differences observed with dialysis or RT in non-diabetic patients survival are not due to the relative efficacy of the treatments. The pretreatment clinical status of the patients would be the major factor determining the different outcomes. While, in diabetic patients, the different outcomes might be attributed to a higher benefit of RT. Quality of life is only beginning to be used in depth as an outcome measure, and much work is needed to standardize research methodology and thus move this area forward. Transplant recipients displayed a higher quality of life based on subjective measures such as life satisfaction and general well being. Successful cadaveric transplants were associated with a marked and significant improvement in psychosocial well being (P , 0.002) even though physical activity did not increase [9]. Life satisfaction was higher in transplanted patients than in dialysis patients; dialysis patients were more anxious (P , 0.05) and more depressed (P , 0.001) than transplanted patients [10]. It has been reported that patients with functioning transplants were more likely to be able to work (nearly 75%) than dialysis patients (25% to 59%) [11]. However, other studies suggested that RT recipients are economically not more productive than patients on dialysis [10]. These and other studies concluded that there is objective evidence of successful rehabilitation and better quality of life for RT recipients in comparison to HD and continuous ambulatory peritoneal dialysis (CAPD) patients. However, further comparisons are needed, considering that RT recipients have a better functional state at the outset.
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Survival and quality of life comparisons suggest that RT is a better overall treatment for ESRD patients. The benefits may be greater for diabetic patients than for non-diabetic patients, and this fact might be considered in cadaveric kidney allocation. However, we believe that the choice of treatment modality should be analyzed for each particular patient considering his demographic and comorbid conditions. HEMODIALYSIS VS. PERITONEAL DIALYSIS Many studies that compared patient survival for HD patients and patients on either CAPD or continuous cyclic peritoneal dialysis (CCPD) have yielded conflicting results (Table 1). The majority of the studies suggest that patient survival is comparable with these two modalities [12–15]. Fenton et al [16] compared mortality rates between HD and CAPD/CCPD patients using Poisson regression modeling for incident patients and controlling for age, primary renal diagnosis and predialysis comorbid conditions. The mortality rate ratio for CAPD/CCPD relative to HD was 0.73 (95% CI; range 0.67–0.78). Two studies that analyzed data from the United States Renal Data Systems (USRDS), using Poisson regression modeling and adjusting for demographic characteristics reported increased risk on PD relative to HD or no difference between both treatment. Bloembergen et al [17] compared mortality in prevalent patients and they reported increased adjusted mortality risk on PD relative to HD. Vonesh and Moran [18] found little or no difference between PD and HD, including both prevalent and incident populations (Table 1). To date, no randomized controlled trial of PD vs. HD therapy has been conducted. Conclusions resulting from different observational studies are contradictory due to the differences of the study population, sample size or available data on comorbid conditions. Study design must also be considered in the interpretation of results. The information offered by incident patient studies using an intention-to-treat analysis that assigns patients to the initial modality and does not consider changes in dialytic modality is ideal for advising new patients. A prevalent patient study should be interpreted for patients already on ESRD therapy and not for advising new ESRD patients [19]. Morbidity comparisons between HD patients and CAPD patients have also yielded contradictory data. Some studies do not show differences in the average days of hospitalization and others find that the time of hospitalization is higher in CAPD than in HD [13, 20]. Maiorca et al [21] found higher hospitalization time in CAPD patients (20.0 days per patient year) than patients on bicarbonate HD (12.4 days per patient year). The cause of higher hospitalization in CAPD patients was related to peritonitis episodes. After the Y system was
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Mazzuchi et al: ESRD treatment criteria Table 1. Hemodialysis versus peritoneal dialysis: Risk of death in each dialysis modality
Study
HD
CAPD/CCPD
P or (95% CI)
Wolfe RA et al 1990 Serkes KD et al 1990: Non-diabetics Maiorca R et al 1991 Held PJ et al 1994: Non-diabetics Bloembergen WE et al 1995: USRDS 1987–1989 Fenton SSA et al 1997: CORR 1990–1994 Vonesh EF, Moran J, 1999: USRDS 1987–1989 USRDS 1989–1991 USRDS 1990–1992 USRDS 1991–1993
1.0 1.0 1.0 1.0
0.98 0.62 1.34 0.84
NS NS NS NS
1.0
1.19
0.001
1.0
0.73
(0.67–0.78)
1.0 1.0 1.0 1.0
1.17 1.06 1.06 1.08
0.001 NS NS 0.043
introduced, the frequency of peritonitis has decreased. We can expect that technical improvements will allow prevention of this complication and minimize the differences. Data from quality of life comparisons between HD and CAPD are controversial. Some studies suggest that CAPD patients have an improved quality of life and superior psychosocial adaptation to their condition compared to in-center HD patients [22]. Other studies found that overall quality of life was almost equal between patients on HD and patients on PD [23]. In the absence of a randomized trial comparing PD with HD, more extensive studies including adjustment for disease severity, dose of dialysis, and nutritional status are needed to better ascertain if differences in outcome between patients treated with PD vs. HD truly exist [18]. DEMOGRAPHIC AND COMORBID FACTORS Demographic and comorbid conditions should be considered in choosing treatment modality. Diabetes, cardiovascular disease and older age are the most important factor of death risk in ESRD patients. Diabetic patients, patients who have cardiovascular disease, and elderly patients present particular characteristics and will be analyzed independently. Younger ages and absence of comorbidity are conditions that are best treated by early transplantation. Children should receive renal transplantation as soon as feasible. For patients with autonomic neuropathy who have frequent episodes of hypotension during HD sessions, CAPD/CCPD should be the preferred dialysis treatment. In our opinion, there are several clinical conditions where transplantation is contraindicated (Table 2). DIABETIC PATIENTS Mortality of patients on dialysis is higher in diabetic than in non-diabetic patients [1, 24, 25]. In our experience, the survival analysis of 531 patients on HD, ad-
Table 2. Renal transplantation contraindications Advanced age (.70-year-old) Malignancy (unless free of recurrence for several years) Severe chronic pulmonary disease Cardiac failure resistant to treatment Severe peripheral vascular disease Severe neuropathy with trophic ulcer Advanced liver disease Active infection Active vasculitis Active glomerulonephritis Uncorrectable lower urinary tract problems
justing for age and comorbidity, showed that diabetic patients had 2.39 greater risk of death than non-diabetic patients (P , 0.0001) [9]. On the other hand, survival after RT is, at present, similar in diabetic and non-diabetic patients [1, 26]. In the Uruguayan Registry at December 1997, 10-year survival after transplant was 74% for diabetic patients and 79% for non-diabetic patients, respectively. In diabetic patients RT is the best choice. However the patients should be selected considering the risk after transplantation. The most significant predictors of mortality are preexisting ischemic heart disease, stroke and peripheral vascular disease. Khauli et al [4] observed significantly lower survival among patients with ischemic heart disease before transplantation. One- and five-year survival was 76% and 19% for patients with and 94% and 40% for patients without this condition (P 5 0.0002). Adjusted survival showed no difference between type I and type II diabetic patients after RT. Differences observed are due to the different frequency of cardiovascular complications [27]. Type II diabetic patients who received a renal allograft had a higher survival rate compared with patients maintained on HD treatment [27]. Renal transplantation should be considered as the treatment of choice in diabetic patients without vascular complications. Clinical vascular evaluation and the study of arterio-
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sclerotic heart disease are mandatory before transplant [27]. Diabetic transplant candidates older than 35 years of age or with clinical evidence of arterial disease should undergo an extensive vascular assessment, including stress thallium myocardial imaging. Coronary arteriography should be carried out if clinical symptoms or study alterations are present. As discussed below, coronary revascularization should be strongly considered before RT in patients with coronary artery disease. It has been reported that patients with significant coronary disease have a trend to better survival after RT than when maintained on dialysis [4] and that coronary revascularization significantly decreases the number of cardiac events after RT [28]. Cardiac failure resistant to treatment; severe peripheral vascular disease and severe neuropathy are considered definitive contraindications for RT [29]. Combined pancreas-kidney transplantation (PKT) and particularly simultaneous pancreas and kidney transplantation performed from a single cadaveric donor, has become an important option in selected insulin-dependent diabetic patients because of its ability to offer superior glycemic control and improved quality of life with greater potential for rehabilitation. Neither patient mortality nor kidney graft survival is significantly altered by adding a pancreas to kidney transplantation [30, 31]. However, overall morbidity after the combined operation is greater than that after kidney transplantation alone. Greater morbidity in PKT patients included cardiovascular, sepsis and noninfectious urologic complications [31]. In addition to greater morbidity, a high mortality was observed associated with PKT in some reports [30]. For these reasons, most transplant centers have restricted PKT to young patients with few diabetic complications and no coronary artery disease [30]. Although RT is the preferred treatment for diabetic ESRD patients, most patients are placed on dialysis either while awaiting RT or as their only therapy. The question of which dialysis modality provides the best outcome remains unresolved. It had been noted that CAPD has several advantages. CAPD avoids vascular access problems. It also improves blood pressure control and volume extraction is slower and better tolerated. CAPD allows greater independence and offers the opportunity to treat many diabetics at home, even those in the high risk population because of age and/or cardiovascular instability. CAPD offers excellent control of blood glucose levels using the intraperitoneal route to administer insulin. Because of these observations, CAPD had been proposed as the first therapeutic option in ESRD diabetic patients. However, PD patient survival has not proved to be significantly higher than HD patient survival (Table 3). Data from the USRDS suggested better results on HD than on PD. Held et al [15] reported that mortality adjusted for comorbidity was higher in CAPD than HD, overall and particularly among older
Table 3. Risk of death on hemodialysis versus peritoneal dialysis for diabetic patients HD CAPD/CCPD P or (95% CI) Held PJ et al 1994: USRDS Marcelli D et al 1995: Lombardy Registry Bloembergen WE et al 1995: USRDS 1987–1989 Fenton SSA et al 1997: CORR 1990–1994 (age ,65) CORR 1990–1994 (age $65) Vonesh EF, Moran J, 1999: USRDS 1989–1991 USRDS 1990–1992 USRDS 1991–1993
1.0
1.26
0.03 NS
1.0
1.38
,0.001
1.0 1.0
0.73 0.88
(0.62–0.87) (0.73–1.06)
1.0 1.0 1.0
1.10 1.18 1.18
,0.001 ,0.001 ,0.001
diabetic patients. Bloembergen et al [17] reported for prevalent patients an increased death rate on PD relative to HD. Data from the Canadian Registry (CORR) showed better results in PD than HD. Fenton et al [16], controlling for comorbid conditions, reported a decreased mortality rate ratio for CAPD/CCPD relative to HD for incident patients younger than 65 years old. Data from the Lombardy Registry, after taking into account the main comorbid conditions, showed no differences between the treatments [32]. Diabetic patients show high mortality and poor quality of life, not only when they require dialysis treatment, but also in the predialysis phase. A high proportion of diabetic patients with renal failure dies before initiation of dialysis and cardiovascular disease is the most frequent cause of death [33]. Prevention of cardiovascular disease is the most important factor to increase diabetic patient survival. We believe that therapy, before dialysis, on dialysis and after kidney transplantation should be individualized to the patient’s specific medical circumstances. Attention to control of hypertension, obesity and hyperlipidemia may slow the course of macrovascular disease, particularly of the coronary arteries, which threatens long-term survival of ESRD diabetic patients. PATIENTS WITH CARDIOVASCULAR DISEASE Cardiovascular disease is common in patients on longterm dialysis, and it accounts for almost 50% of overall mortality in this group [1, 24, 25]. It is a strong predictor of mortality in patients with ESRD [34, 35]. Dialysis management of patients with a prior history of congestive heart failure, cardiomegaly, or ischemic heart disease is a difficult problem. In HD, the intradialytic hypotension may be associated with arrhythmias, myocardial ischemia, mesenteric ischemia and worsening of retinopathy [36]. It was reported that type II diabetic patients with frequent (2 or more) intradialytic hypotensive episodes (systolic blood pressure lower than 80 mm Hg)
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had 2.8 times greater risk of myocardial infarction death [33]. There are several reports of successful PD performance in subjects with severe heart failure [37, 38]. Tolerance of the procedure, fluid management, prevention of arrhythmias, and patient survival were satisfactory in these reports. Advantages of PD in patients with cardiovascular disease include better hemodynamic control, less acute hypokalemia (which could result in arrhythmia), and better control of anemia. It has been reported that left ventricular mass decreased after six months of treatment with CAPD but not with HD, and it has been suggested that CAPD is more appropriate to improve the cardiac function [39]. CAPD/CCPD or hemofiltration should be the selected treatment modality in patients with severe cardiovascular instability. If HD is indicated, bicarbonate dialysate buffer should be used. Anemia should be corrected with erythropoietin to achieve an hematocrit of near 35%. Cardiovascular performance can be enhanced in many HD patients by increasing the dialysate calcium concentration and using cool temperature dialysate, which can also increase vascular resistance. Sequential ultrafiltration and isovolemic dialysis, the use of a higher dialysate sodium concentration (.140 mEq/L) and intake of caffeine to blunt the effect of the endogenous vasodilator adenosine may also prevent episodic hypotension [40]. It is commonly accepted that the evaluation for arteriosclerotic heart disease is mandatory before RT and the correction of a coronary lesion should be strongly considered in patients with coronary artery disease. We believe that all patients on dialysis, even if they are not transplant candidates, must be evaluated with the same criteria as non-uremic subjects. The indications for percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) must take into account the reported results. CABG is considered the best treatment because the risk of cardiac events is higher following PTCA than after CABG [41, 42]. ELDERLY PATIENTS Demographic data demonstrate that the dialysis population is growing progressively older. In the United States, the fraction of ESRD incident patients older than 65 years reached 46% in 1996 [1]. The most frequent treatment modality in elderly ESRD is in-center HD. In the United States, 82% of elderly patients were on HD, 10% on CAPD and only 2.7% had a functioning transplant [43]. Despite complex medical and psychosocial conditions, survival, quality of life and rehabilitation are acceptable in the elderly dialysis patients [43]. The five-year survival rate for the 65–74 age group was 21% in the United States and 38% in Japan [1]. Data from the USRDS
indicated that the life expectancy of ESRD patients aged 65 is roughly one-fourth that of a patient of the same age without ESRD [1]. The impact of ESRD on life expectancy decreases with increasing age, and is smallest for the oldest age groups. An acceptable subjective quality of life and degree of rehabilitation have been noted in several reports [44, 45]. In contrast, other recent studies painted a much grimmer picture of the life of elderly dialysis patients [46, 47]. Outcomes observed support the policy that dialysis should not be denied to elderly patients if there is hope for prolongation of an enjoyable span of life. However, dialysis should not be used merely to prolong the dying process. There are elderly patients who should not be started on dialysis and the major absolute contraindications to dialysis are advanced malignancy, irreversible dementia, advanced liver disease, advanced chronic obstructive pulmonary disease or severe cardiomyopathy. When there is doubt about chances of recovery from a severe underlying disease, a “trial” of dialysis may be offered. Withdrawal of dialysis at a later time is preferable to withholding it from the beginning. Few specific studies have addressed comparative survival between HD and PD in the elderly. Most studies indicate that survival of elderly patients on CAPD and on HD is similar [22, 43]. Two Italian reports, adjusting for comorbid conditions, showed that mortality was higher among older patients treated with HD [14, 48]. While large studies in the United States have suggested that the benefit of HD in the elderly is most prominent in diabetic patients [49]. The technique failure is more frequent when CAPD/CCPD is used. It was reported that the switching at one year in elderly subjects was 12.5% from CAPD/CCPD to HD and 1.7% from HD to CAPD/CCPD [49]. Elderly patients have frequent vascular access difficulties that can contribute to decreased dialysis delivery. Many elderly people do not have suitable vessels for successful creation of an endogenous arteriovenous (AV) fistula and this is particularly true in patients with diabetes or hypertensive vascular disease. A polytetrafluoroethylene (PTFE) graft is recommended in these patients. However, every opportunity for the construction of an endogenous AV fistula should be taken. Recent data from the USRDS indicate that the risk of access failure in patients over age 65 with an AV fistula is 24% lower than in similar patients having a PTFE graft [50]. Elderly patients on HD experience more intradialytic complications, such as hypotension, nausea, and vomiting, than do younger patients. The treatment of hypotension is often associated with temporary cessation or early termination of HD therapy. As we considered before, the association with diabetes and cardiovascular disease may increase this problems and CAPD/CCPD
Mazzuchi et al: ESRD treatment criteria
may be a more satisfactory alternative treatment modality than HD. Renal transplantation is a relatively recent treatment option among the elderly ESRD. Success of transplantation in geriatric ESRD patients over the last decade is due to improved patient selection as well as the use of cyclosporine A and lower doses of corticosteroids. Oneyear patient and graft survival rates of 85% and 75%, respectively, have been reported [51]. A controlled survival comparison of transplantation and dialysis among elderly patients based on data from the CORR showed, after adjusting for other known prognostic factors, that patients who received a transplant experienced significantly greater survival probability than those who remained on dialysis. Five-year survival rates were 81% and 51% for the transplant and dialysis groups, respectively (RR 5 0.47, P , 0.0001) [52]. Although overall results are good, we believe that RT should not be offered indiscriminately to the elderly. Patients at risk for coronary arterial disease should be identified and candidates for RT should be selected. The management of transplantation in the elderly requires an understanding of pharmacology, immunology, and physiology peculiar to this age group. Since the elderly have a degree of immune incompetence, they require less aggressive immunotherapy. PATIENT PREFERENCE AND PSYCHOSOCIAL FACTORS Several patient factors may modify the choice of RRT modality. The most important are patient preference, psychological stability, availability of a living-related donor, social circumstances and economic factors. Patient participation plays a vital role in the outcome. The different options for RRT should be discussed with each patient and the patient preference should be considered. However, little is known about the reasons for chronic dialysis patients to choose to be listed or not listed for renal transplantation. Recently, these reasons have been investigated [53]. The most reported reason for electing transplantation was “hoping for a better quality of life” (86% of respondents). The reason “hoping it will make me live longer” was reported by 69% never-transplanted patients and by 25% patients with previous transplant. In never-transplanted patients, the reasons “doctor thought it would be good for me” and “family and/or friends thought it would be good for me” were 50% and 42%, respectively. Patient preference depends strongly on medical or nonmedical information. Although the patient’s preferences should be taken into consideration, the nephrologist has the responsibility to make recommendations. Motivated patients with available resources, no matter what their cause of ESRD, should be considered as excel-
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lent candidates for home HD. Several studies have shown that patients who use home HD have an increased survival and better quality of life when compared to those who use different dialysis modalities [54, 55]. Psychological stability is more necessary when CAPD or home HD are selected. Having a living-related donor is a condition to prefer transplantation. CAPD/CCPD or home HD are preferable in patients who live at long distance from the HD center or with unavailability of transportation. In-center HD is often the only dialysis option in single adults with no support system. NON-MEDICAL FACTORS THAT MODIFY THE CHOICE OF TREATMENT MODALITIES The frequency of the different treatment modalities in the different countries is not in accordance with the analysis of the advantages and disadvantages of each modality. Renal transplantation offers the best form of RRT for patients with ESRD. However, transplant rates vary worldwide. The transplant rate in United States, Spain, Norway, Germany and the Czech Republic was greater than 40 new transplant per million population in 1997. On the other hand, in Japan the transplant rate was very low. These wide variations of transplant activity are dependent on cultural, legal and socioeconomic factors. The economic status of a country could be a factor; but, even in industrialized nations there are marked differences. The most important limitation in renal transplant programs is the transplantable organ availability. However, cultural and religious attitudes also influence the choice of transplant as an option. Related to the choice of dialysis modality, and according to the previous medical analysis, most patients can be treated with either HD or CAPD/CCPD. However, in practice, most patients in the world are treated with HD; more than 80% of the dialysis population. It is also interesting to note the differences in the choice of dialysis modality from country to country. CAPD/ CCPD is very frequent in the UK, Australia, New Zealand, Canada and Mexico. The percentage of CAPD/ CCPD patients is very low in the rest of the world. Therefore, nonmedical reasons are the most important factors in dialysis modality selection. According to Nissenson et al [56], several nonmedical factors are critical in the relative use of various ESRD modalities: (a) financial/reimbursement (b) lack of training of nephrologists and nurses as well as poor education of patients about dialysis options (c) resource availability (d) social mores (e) cultural habits. In the authors’ opinion, the reimbursement differences of the physician or the facilities (for HD or CAPD/CCPD) are critical in the modality selection. We do not deny the significance of the financial factors, but in our experience the knowledge and training of the
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nephrologic team (physicians and nurses) is the most important factor in the selection. In center HD was developed earlier than CAPD/CCPD in most countries. Conversely when CAPD/CCPD became a mature RRT, many teams had already a good experience and practice in HD. In these centers, the first choice may continue to be HD. In those centers with good experience in all dialysis modalities (a minority), the medical and patient reasons will be the key factors to select the modality. In centers with partial experience (mostly in HD), the choice of dialysis modality will be highly influenced by nonmedical and “nonpatient” reasons. Obviously, an economic factor is also connected to this RRT history. Substantial capital investment was necessary in those countries where in center HD was first developed. In these centers and from a business perspective, to keep the HD facility as full as possible to offset high fixed costs is a very important objective. This economic factor may slow the patient transfer to CAPD/CCPD and can interfere with the medical decision. The team bias determined both by the training deficit and economic factors could be overcome in several ways. Centers involved in both dialysis (HD and CAPD/ CCPD) and transplantation are the best for an adequate management of ESRD patients. It may be that a unit is unable to provide the full range of services. In such a case, agreement among different centers to ensure that their patients can receive the optimum therapy at each moment, could be the best. Also, the nephrologist training must include all treatment modalities. The physician should be prepared to regularly review the status of the patient. In this way, he or she will be able to determine if current therapy is appropriate, or if some changes have to be made to ensure that the patient receives the best therapeutic option. HD and PD should not be seen as competing therapeutic options, rather, they are two complementary methods of dealing with uremia. Neither one is best suited for all patients. Each modality has its own unique advantages and disadvantages and at the same time it shares problems that exist across therapies. Adequate selection of treatment modality and optimization of each treatment modality will allow us to improve the outcome and to offer to ESRD patients higher survival, less morbidity and better quality of life. Reprint requests to Dr. Nelson Mazzuchi, Ramo´n y Cajal 2546, Montevideo 11600, C. Correo 16217, Montevideo, Uruguay. E-mail: [email protected]
REFERENCES 1. US Renal Data System: USRDS 1998 Annual Data Report. Bethesda, MD, National Institutes of Health National Institute of Diabetes, Digestive, and Kidney Diseases, 1998 2. Vollmer WM, Wahl PW, Blagg CR: Survival with dialysis and transplantation in patients with end-stage renal disease. N Engl J Med 308:1553–1558, 1983
3. Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K: Comparison of survival probabilities for dialysis patients vs cadaver renal transplant recipients. JAMA 270:1339–1343, 1993 4. Khauli RB, Steinmuller DR, Novick AC, Buszta C, Goormastic M, Nakamoto S, Vidt DG, Magnusson M, Paganini E, Schreiber MJ: A critical look at survival of diabetics with end-stage renal disease: Transplantation versus dialysis. Transplantation 41:598– 602, 1986 5. Hutchinson TA, Thomas DC, Lemieux JC, Harvey CE: Prognostically controlled comparison of dialysis and renal transplantation. Kidney Int 26:44–51, 1984 6. Garcia-Garcia G, Deddens JA, D’Achiardi-Rey R, First MR, Samuels SJ, Kant S, Pollak VE: Results of treatment in patients with end-stage renal disease: a multi-variate analysis of risk factors and survival in 341 successive patients. Am J Kidney Dis 5:10–18, 1985 7. Mazzuchi N, Gonza´lez-Martı´nez F, Carbonell E, Curi L, Ferna´ndez-Cean J, Orihuela S: Comparison of survival for hemodialysis patients vs renal transplant recipients treated in Uruguay. Nephrol Dial Transplant, in press 8. Mazzuchi N, Carbonell E, Ferna´ndez-Cean J: ESRD patients without co-morbid risk factors at the start of hemodialysis are ideal as survival comparison population. Nephrol Dial Transplant 14:1091–1096, 1999 9. Rodin G, Voshart K, Cattran D, Halloran P, Cardella C, Fenton S: Cadaveric renal transplant failure: the short-term sequelae. Int J Psychiatry Med 15:357–364, 1985–86 10. Waiser J, Budde K, Schreiber M, Peibst O, Koch U, Bohler T, Hoffken B, Hauser I, Neumayer HH: The quality of life in end stage renal disease care. Transplant Int 11(Suppl 1):S42–S45, 1998 11. Evans RW, Manninem DL, Garrison LP, Hart LG, Blagg CR, Gutman RA, Hull AR, Lowrie EG: The quality of life of patients with end stage renal disease. N Engl J Med 312:553–559, 1985 12. Wolfe RA, Port FK, Hawthorne VM, Guire KE: A comparison of survival among dialytic therapies of choice: in-center hemodialysis versus continuous ambulatory peritoneal dialysis at home. Am J Kidney Dis 15:433–440, 1990 13. Serkes KD, Blagg CR, Nolph KD, Vonesh EF, Shapiro F: Comparison of patient and technique survival in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis: a multicenter study. Perit Dial Int 10:15–19, 1990 14. Maiorca R, Vonesh EF, Cavalli PL, De Vecchi A, Giangrande A, La Greca G, Scarpioni L, Bragantini L, Cancarini GC, Cantaluppi A, Castelnovo C, Castiglioni A, Poisetti PG, Viglino GA: Multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis. Perit Dial Int 11:118–127, 1991 15. Held PJ, Port FK, Turenne MN, Gaylin DS, Hamburger RJ, Wolfe RA: Continuous ambulatory peritoneal dialysis and hemodialysis: Comparison of patient mortality with adjustment for comorbid conditions. Kidney Int 45:1163–1169, 1994 16. Fenton S, Schaubel DE, Desmeules M, Morrison HI, Mao Y, Copleston P, Jeffery JR, Kjellstrand CM: Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates. Am J Kidney Dis 30:334–342, 1997 17. Bloembergen WE, Port FK, Mauger EA, Wolfe RA: A comparison of mortality between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 6:177–183, 1995 18. Vonesh EF, Moran J: Mortality in end-stage renal disease: A reassessment of differences between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 10:354–365, 1999 19. Port FK, Wolfe RA, Bloembergen WE, Held PJ, Young EW: The study of outcomes for CAPD versus hemodialysis patients. Perit Dial Int 16:628–633, 1996 20. Burton PR, Walls J: A selection adjusted comparison of hospitalization on continuous ambulatory peritoneal dialysis and haemodialysis. J Clin Epidemiol 42:531–539, 1989 21. Maiorca R, Cancarini GC, Brunori G, Camerini C, Manili L: Morbidity and mortality of CAPD and hemodialysis. Kidney Int 43(Suppl. 40):S4–S15, 1993 22. Nissenson AR: Dialysis therapy in the elderly patient. Kidney Int 43(Suppl. 40):S51–S57, 1993
Mazzuchi et al: ESRD treatment criteria 23. Becker BN, Stone WJ: Options for renal replacement therapy: Special considerations. Semin Nephrol 17:176–187, 1997 24. Mazzuchi N, Schwedt E, Fernandez JM, Cusumano AM, Ancao MS, Poblete H, Saldan˜a-Arevalo M, Espinosa NR, Centurion C, Castillo H, Gonzalez F, Milanes CL, Infante M, Ariza M: Latin American Registry of dialysis and renal transplantation. 1993 Annual dialysis data report. Nephrol Dial Transplant 12:2521–2527, 1997 25. Disney A: Dialysis treatment in Australia. 1982 to 1988. Am J Kidney Dis 15:402–409, 1990 26. Ekberg H, Christensson A: Similar treatment success rate after renal transplantation in diabetic and non-diabetic patients due to improved short- and long-term diabetic patient survival. Transplant Int 9:557–564, 1996 27. Hirsch MM: Renal transplantation in patients with type 2 diabetes mellitus. Nephrol Dial Transplant 10(Suppl. 7):S58–S60, 1995 28. Manske CL, Wang Y, Rector T, Wilson RF, White CW: Coronary revascularization in type I diabetic patients with nephropathy. Lancet 340:998–1002, 1992 29. Brynger H: Transplantation of the diabetic in 1994. Nephrol Dial Transplant 10(Suppl. 7):S56–S57, 1995 30. Manske CL, Wang Y, Thomas W: Mortality of cadaveric kidney transplantation versus combined kidney-pancreas transplantation in diabetic patients. Lancet 346:1658–1662, 1995 31. Douzdjian V, Abecassis MM, Corry RJ, Hunsicker LG: Simultaneous pancreas-kidney versus kidney-alone transplants in diabetics: Increased risk of early cardiac death and acute rejection following pancreas transplants. Clin Transplant 8:246–251, 1994 32. Marcelli D, Spotti D, Conte F, Limido A, Lonati F, Malberti F, Locatelli F: Prognosis of diabetic patients on dialysis: analysis of Lombardy Registry data. Nephrol Dial Transplant 10:1895–1900, 1995 33. Ritz E, Lippert J, Keller C: Hypertension, cardiovascular complications and survival in diabetic patients on maintenance haemodialysis. Nephrol Dial Transplant 10(Suppl. 7):S43–S46, 1995 34. Ferna´ndez JM, Carbonell ME, Mazzuchi N, Petruccelli D: Simultaneous analysis of morbidity and mortality factors in chronic hemodialysis patients. Kidney Int 41:1029–1034, 1992 35. Herzog CA, Ma JZ, Collins AJ: Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 339:799–805, 1998 36. Kimura K, Tabei K, Asano J, Hosoda S: Cardiac arrhythmias in hemodialysis patients. A study of incidence and contributory factors. Nephron 53:201–207, 1989 37. Rubin J, Ball R: Continuous ambulatory peritoneal dialysis as a treatment of severe congestive heart failure in the face of chronic renal failure. Report of eight cases. Arch Intern Med 146:1533–1535, 1998 38. Stegmayr BG, Banga R, Lundberg L, Wikdahl AM, PlumWirell M: PD treatment for severe congestive heart failure. Perit Dial Int 16(Suppl. 1):S231–S235, 1996 39. Leenen FHH, Smiuth DL, Khanna R, Oreopoulos DG: Changes in left ventricular hypertrophy and function in hypertensive patients started on continuous ambulatory peritoneal dialysis. Am Heart J 10:102–105, 1985 40. Shinzato T, Miwa M, Nakai S, Morita H, Odani H, Inoue I,
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Criteria for selection of ESRD treatment modalities NELSON MAZZUCHI, JUAN M. FERNA´NDEZ-CEAN, and ENRIQUETA CARBONELL Instituto de Nefrologı´a y Urologı´a del Uruguay, Servicio de Asistencia Renal Integral, Montevideo, Uruguay
Criteria for selection of ESRD treatment modalities. The most important renal replacement therapies (RRT) for end-stage renal disease (ESRD) patients are hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT). Survival, morbidity and quality of life are the main factors to select the best RRT modality for a particular patient. The outcome comparison suggest that RT is a better overall treatment for ESRD patients. On the other hand, the studies that compared patient outcome for HD and PD have yielded conflicting results. Neither treatment modality is best suited for all patients. The choice should be analyzed for each particular patient considering his demographic and comorbid conditions. Diabetic patients, patients with cardiovascular disease and elderly patients are high risk populations and they are discussed independently. The frequency of treatment modalities in the different countries is not in accordance with the analysis of the advantages and disadvantages of each one. Non-medical reasons are important factors in dialysis modality selection. In our experience the expertise of the nephrologic team is the most important one. RT, HD and PD should not be seen as competing therapeutic options, rather, they are complementary methods of dealing with uremia. An integrated approach combining HD, PD and RT is necessary to devise an individualized treatment program permitting optimal long-term physical and psychological well being and adequate integration in the family and society.
Technological and immunological developments within the last two decades have evolved several renal replacement therapy (RRT) options. The most important of them in the treatment of end-stage renal disease (ESRD) patients are hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT). Each modality has advantages and disadvantages. The challenge for the nephrologist is to devise an individualized treatment program permitting optimal long-term physical and psychological well being and adequate integration in the family and society. These goals are most effectively achieved by an integrated approach combining HD, PD and RT. Survival, morbidity and quality of life are the most important factors to select the best RRT modality for a particular patient. The rational long-term management Key words: hemodialysis, peritoneal dialysis, renal transplant.
2000 by the International Society of Nephrology
strategy may be based, also, on clinical status, patient age, patient preference, psychological stability, etiology of ESRD, comorbidity, suitable living-related donor, economic factors and social circumstances. DIALYSIS VS. RENAL TRANSPLANT Patient survival after RT is markedly better than that seen with either HD or PD [1–4]. However, some of the benefits associated with transplantation are related to patient selection, since dialysis patients with the most serious comorbid conditions are not accepted for the transplant waiting list and hence remain in the dialysis group. Some comparative studies of dialysis vs. RT survival have considered that the transplant group is favored by inclusion of these high-risk patients in the dialysis group [2, 3, 5, 6]. We analyzed survival for ESRD patients on dialysis vs. after transplantation, adjusting for the variables that were significantly and independently related with mortality [7]. This analysis concluded that, when the outcome is adjusted to comorbid factors, there are no differences between RT recipients’ and HD patients’ survival in nondiabetic patients, while RT gives better survival than HD in diabetics patients. Overall survival was significantly higher in RT recipients than in HD patients (P , 0.0001). However, treatment modality did not show a significant relation with mortality when analyzed together with age, heart disease, cancer and smoking habit. In non-diabetic patients, survival adjusted for age, heart disease, cancer and smoking habit was similar in RT recipients and HD patients (RR 5 1.03, P 5 0.87). On the contrary, when only diabetic patients were considered, treatment modality was significantly and independently related to mortality. Five-year adjusted survival was 89.2% for RT recipients and 40.9% for HD patients (P 5 0.017). Relative risk is not the same over time, that is, it is not proportional. HD patients had better initial survival in the first year and the RT recipients had higher long-term survival [7]. We suggest that ESRD patients without comorbid risk factors at the start of dialysis provide an ideal population for survival comparisons among different centers or different treatment modalities [8]. When only this low risk
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group was used to compare survival, no differences were observed. Ten-year survival was 87.9% for HD patients (N 5 134) and 82.6% for RT recipients (N 5 289) (P 5 0.231) [7]. Our data agree with several studies [2, 3, 5, 6]. Vollmer et al [2] and Hutchinson et al [5] found a similar survival with dialysis and cadaveric transplantation, after controlling for pretreatment risk factors. Garcia-Garcia et al [6] found a markedly lower mortality risk among diabetic transplant recipients than diabetic dialysis patients, although their findings did not achieve statistical significance. Port et al [3] compared mortality risk among cadaveric RT recipients vs. transplant candidates on dialysis in the cyclosporine era. They used a time-dependent Cox analysis to eliminate the time-to-treatment bias. Their dialysis group had been limited to those patients who were accepted to the transplant waiting list, in order to reduce the bias related to patient selection. They observed a markedly lower long-term risk (RR 0.25) among diabetic RT recipients compared with diabetic wait-listed dialysis patients (P , 0.001) and no differences among patients with glomerulonephritis or hypertension as cause of ESRD. These data suggest that the survival differences observed with dialysis or RT in non-diabetic patients survival are not due to the relative efficacy of the treatments. The pretreatment clinical status of the patients would be the major factor determining the different outcomes. While, in diabetic patients, the different outcomes might be attributed to a higher benefit of RT. Quality of life is only beginning to be used in depth as an outcome measure, and much work is needed to standardize research methodology and thus move this area forward. Transplant recipients displayed a higher quality of life based on subjective measures such as life satisfaction and general well being. Successful cadaveric transplants were associated with a marked and significant improvement in psychosocial well being (P , 0.002) even though physical activity did not increase [9]. Life satisfaction was higher in transplanted patients than in dialysis patients; dialysis patients were more anxious (P , 0.05) and more depressed (P , 0.001) than transplanted patients [10]. It has been reported that patients with functioning transplants were more likely to be able to work (nearly 75%) than dialysis patients (25% to 59%) [11]. However, other studies suggested that RT recipients are economically not more productive than patients on dialysis [10]. These and other studies concluded that there is objective evidence of successful rehabilitation and better quality of life for RT recipients in comparison to HD and continuous ambulatory peritoneal dialysis (CAPD) patients. However, further comparisons are needed, considering that RT recipients have a better functional state at the outset.
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Survival and quality of life comparisons suggest that RT is a better overall treatment for ESRD patients. The benefits may be greater for diabetic patients than for non-diabetic patients, and this fact might be considered in cadaveric kidney allocation. However, we believe that the choice of treatment modality should be analyzed for each particular patient considering his demographic and comorbid conditions. HEMODIALYSIS VS. PERITONEAL DIALYSIS Many studies that compared patient survival for HD patients and patients on either CAPD or continuous cyclic peritoneal dialysis (CCPD) have yielded conflicting results (Table 1). The majority of the studies suggest that patient survival is comparable with these two modalities [12–15]. Fenton et al [16] compared mortality rates between HD and CAPD/CCPD patients using Poisson regression modeling for incident patients and controlling for age, primary renal diagnosis and predialysis comorbid conditions. The mortality rate ratio for CAPD/CCPD relative to HD was 0.73 (95% CI; range 0.67–0.78). Two studies that analyzed data from the United States Renal Data Systems (USRDS), using Poisson regression modeling and adjusting for demographic characteristics reported increased risk on PD relative to HD or no difference between both treatment. Bloembergen et al [17] compared mortality in prevalent patients and they reported increased adjusted mortality risk on PD relative to HD. Vonesh and Moran [18] found little or no difference between PD and HD, including both prevalent and incident populations (Table 1). To date, no randomized controlled trial of PD vs. HD therapy has been conducted. Conclusions resulting from different observational studies are contradictory due to the differences of the study population, sample size or available data on comorbid conditions. Study design must also be considered in the interpretation of results. The information offered by incident patient studies using an intention-to-treat analysis that assigns patients to the initial modality and does not consider changes in dialytic modality is ideal for advising new patients. A prevalent patient study should be interpreted for patients already on ESRD therapy and not for advising new ESRD patients [19]. Morbidity comparisons between HD patients and CAPD patients have also yielded contradictory data. Some studies do not show differences in the average days of hospitalization and others find that the time of hospitalization is higher in CAPD than in HD [13, 20]. Maiorca et al [21] found higher hospitalization time in CAPD patients (20.0 days per patient year) than patients on bicarbonate HD (12.4 days per patient year). The cause of higher hospitalization in CAPD patients was related to peritonitis episodes. After the Y system was
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Mazzuchi et al: ESRD treatment criteria Table 1. Hemodialysis versus peritoneal dialysis: Risk of death in each dialysis modality
Study
HD
CAPD/CCPD
P or (95% CI)
Wolfe RA et al 1990 Serkes KD et al 1990: Non-diabetics Maiorca R et al 1991 Held PJ et al 1994: Non-diabetics Bloembergen WE et al 1995: USRDS 1987–1989 Fenton SSA et al 1997: CORR 1990–1994 Vonesh EF, Moran J, 1999: USRDS 1987–1989 USRDS 1989–1991 USRDS 1990–1992 USRDS 1991–1993
1.0 1.0 1.0 1.0
0.98 0.62 1.34 0.84
NS NS NS NS
1.0
1.19
0.001
1.0
0.73
(0.67–0.78)
1.0 1.0 1.0 1.0
1.17 1.06 1.06 1.08
0.001 NS NS 0.043
introduced, the frequency of peritonitis has decreased. We can expect that technical improvements will allow prevention of this complication and minimize the differences. Data from quality of life comparisons between HD and CAPD are controversial. Some studies suggest that CAPD patients have an improved quality of life and superior psychosocial adaptation to their condition compared to in-center HD patients [22]. Other studies found that overall quality of life was almost equal between patients on HD and patients on PD [23]. In the absence of a randomized trial comparing PD with HD, more extensive studies including adjustment for disease severity, dose of dialysis, and nutritional status are needed to better ascertain if differences in outcome between patients treated with PD vs. HD truly exist [18]. DEMOGRAPHIC AND COMORBID FACTORS Demographic and comorbid conditions should be considered in choosing treatment modality. Diabetes, cardiovascular disease and older age are the most important factor of death risk in ESRD patients. Diabetic patients, patients who have cardiovascular disease, and elderly patients present particular characteristics and will be analyzed independently. Younger ages and absence of comorbidity are conditions that are best treated by early transplantation. Children should receive renal transplantation as soon as feasible. For patients with autonomic neuropathy who have frequent episodes of hypotension during HD sessions, CAPD/CCPD should be the preferred dialysis treatment. In our opinion, there are several clinical conditions where transplantation is contraindicated (Table 2). DIABETIC PATIENTS Mortality of patients on dialysis is higher in diabetic than in non-diabetic patients [1, 24, 25]. In our experience, the survival analysis of 531 patients on HD, ad-
Table 2. Renal transplantation contraindications Advanced age (.70-year-old) Malignancy (unless free of recurrence for several years) Severe chronic pulmonary disease Cardiac failure resistant to treatment Severe peripheral vascular disease Severe neuropathy with trophic ulcer Advanced liver disease Active infection Active vasculitis Active glomerulonephritis Uncorrectable lower urinary tract problems
justing for age and comorbidity, showed that diabetic patients had 2.39 greater risk of death than non-diabetic patients (P , 0.0001) [9]. On the other hand, survival after RT is, at present, similar in diabetic and non-diabetic patients [1, 26]. In the Uruguayan Registry at December 1997, 10-year survival after transplant was 74% for diabetic patients and 79% for non-diabetic patients, respectively. In diabetic patients RT is the best choice. However the patients should be selected considering the risk after transplantation. The most significant predictors of mortality are preexisting ischemic heart disease, stroke and peripheral vascular disease. Khauli et al [4] observed significantly lower survival among patients with ischemic heart disease before transplantation. One- and five-year survival was 76% and 19% for patients with and 94% and 40% for patients without this condition (P 5 0.0002). Adjusted survival showed no difference between type I and type II diabetic patients after RT. Differences observed are due to the different frequency of cardiovascular complications [27]. Type II diabetic patients who received a renal allograft had a higher survival rate compared with patients maintained on HD treatment [27]. Renal transplantation should be considered as the treatment of choice in diabetic patients without vascular complications. Clinical vascular evaluation and the study of arterio-
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sclerotic heart disease are mandatory before transplant [27]. Diabetic transplant candidates older than 35 years of age or with clinical evidence of arterial disease should undergo an extensive vascular assessment, including stress thallium myocardial imaging. Coronary arteriography should be carried out if clinical symptoms or study alterations are present. As discussed below, coronary revascularization should be strongly considered before RT in patients with coronary artery disease. It has been reported that patients with significant coronary disease have a trend to better survival after RT than when maintained on dialysis [4] and that coronary revascularization significantly decreases the number of cardiac events after RT [28]. Cardiac failure resistant to treatment; severe peripheral vascular disease and severe neuropathy are considered definitive contraindications for RT [29]. Combined pancreas-kidney transplantation (PKT) and particularly simultaneous pancreas and kidney transplantation performed from a single cadaveric donor, has become an important option in selected insulin-dependent diabetic patients because of its ability to offer superior glycemic control and improved quality of life with greater potential for rehabilitation. Neither patient mortality nor kidney graft survival is significantly altered by adding a pancreas to kidney transplantation [30, 31]. However, overall morbidity after the combined operation is greater than that after kidney transplantation alone. Greater morbidity in PKT patients included cardiovascular, sepsis and noninfectious urologic complications [31]. In addition to greater morbidity, a high mortality was observed associated with PKT in some reports [30]. For these reasons, most transplant centers have restricted PKT to young patients with few diabetic complications and no coronary artery disease [30]. Although RT is the preferred treatment for diabetic ESRD patients, most patients are placed on dialysis either while awaiting RT or as their only therapy. The question of which dialysis modality provides the best outcome remains unresolved. It had been noted that CAPD has several advantages. CAPD avoids vascular access problems. It also improves blood pressure control and volume extraction is slower and better tolerated. CAPD allows greater independence and offers the opportunity to treat many diabetics at home, even those in the high risk population because of age and/or cardiovascular instability. CAPD offers excellent control of blood glucose levels using the intraperitoneal route to administer insulin. Because of these observations, CAPD had been proposed as the first therapeutic option in ESRD diabetic patients. However, PD patient survival has not proved to be significantly higher than HD patient survival (Table 3). Data from the USRDS suggested better results on HD than on PD. Held et al [15] reported that mortality adjusted for comorbidity was higher in CAPD than HD, overall and particularly among older
Table 3. Risk of death on hemodialysis versus peritoneal dialysis for diabetic patients HD CAPD/CCPD P or (95% CI) Held PJ et al 1994: USRDS Marcelli D et al 1995: Lombardy Registry Bloembergen WE et al 1995: USRDS 1987–1989 Fenton SSA et al 1997: CORR 1990–1994 (age ,65) CORR 1990–1994 (age $65) Vonesh EF, Moran J, 1999: USRDS 1989–1991 USRDS 1990–1992 USRDS 1991–1993
1.0
1.26
0.03 NS
1.0
1.38
,0.001
1.0 1.0
0.73 0.88
(0.62–0.87) (0.73–1.06)
1.0 1.0 1.0
1.10 1.18 1.18
,0.001 ,0.001 ,0.001
diabetic patients. Bloembergen et al [17] reported for prevalent patients an increased death rate on PD relative to HD. Data from the Canadian Registry (CORR) showed better results in PD than HD. Fenton et al [16], controlling for comorbid conditions, reported a decreased mortality rate ratio for CAPD/CCPD relative to HD for incident patients younger than 65 years old. Data from the Lombardy Registry, after taking into account the main comorbid conditions, showed no differences between the treatments [32]. Diabetic patients show high mortality and poor quality of life, not only when they require dialysis treatment, but also in the predialysis phase. A high proportion of diabetic patients with renal failure dies before initiation of dialysis and cardiovascular disease is the most frequent cause of death [33]. Prevention of cardiovascular disease is the most important factor to increase diabetic patient survival. We believe that therapy, before dialysis, on dialysis and after kidney transplantation should be individualized to the patient’s specific medical circumstances. Attention to control of hypertension, obesity and hyperlipidemia may slow the course of macrovascular disease, particularly of the coronary arteries, which threatens long-term survival of ESRD diabetic patients. PATIENTS WITH CARDIOVASCULAR DISEASE Cardiovascular disease is common in patients on longterm dialysis, and it accounts for almost 50% of overall mortality in this group [1, 24, 25]. It is a strong predictor of mortality in patients with ESRD [34, 35]. Dialysis management of patients with a prior history of congestive heart failure, cardiomegaly, or ischemic heart disease is a difficult problem. In HD, the intradialytic hypotension may be associated with arrhythmias, myocardial ischemia, mesenteric ischemia and worsening of retinopathy [36]. It was reported that type II diabetic patients with frequent (2 or more) intradialytic hypotensive episodes (systolic blood pressure lower than 80 mm Hg)
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had 2.8 times greater risk of myocardial infarction death [33]. There are several reports of successful PD performance in subjects with severe heart failure [37, 38]. Tolerance of the procedure, fluid management, prevention of arrhythmias, and patient survival were satisfactory in these reports. Advantages of PD in patients with cardiovascular disease include better hemodynamic control, less acute hypokalemia (which could result in arrhythmia), and better control of anemia. It has been reported that left ventricular mass decreased after six months of treatment with CAPD but not with HD, and it has been suggested that CAPD is more appropriate to improve the cardiac function [39]. CAPD/CCPD or hemofiltration should be the selected treatment modality in patients with severe cardiovascular instability. If HD is indicated, bicarbonate dialysate buffer should be used. Anemia should be corrected with erythropoietin to achieve an hematocrit of near 35%. Cardiovascular performance can be enhanced in many HD patients by increasing the dialysate calcium concentration and using cool temperature dialysate, which can also increase vascular resistance. Sequential ultrafiltration and isovolemic dialysis, the use of a higher dialysate sodium concentration (.140 mEq/L) and intake of caffeine to blunt the effect of the endogenous vasodilator adenosine may also prevent episodic hypotension [40]. It is commonly accepted that the evaluation for arteriosclerotic heart disease is mandatory before RT and the correction of a coronary lesion should be strongly considered in patients with coronary artery disease. We believe that all patients on dialysis, even if they are not transplant candidates, must be evaluated with the same criteria as non-uremic subjects. The indications for percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) must take into account the reported results. CABG is considered the best treatment because the risk of cardiac events is higher following PTCA than after CABG [41, 42]. ELDERLY PATIENTS Demographic data demonstrate that the dialysis population is growing progressively older. In the United States, the fraction of ESRD incident patients older than 65 years reached 46% in 1996 [1]. The most frequent treatment modality in elderly ESRD is in-center HD. In the United States, 82% of elderly patients were on HD, 10% on CAPD and only 2.7% had a functioning transplant [43]. Despite complex medical and psychosocial conditions, survival, quality of life and rehabilitation are acceptable in the elderly dialysis patients [43]. The five-year survival rate for the 65–74 age group was 21% in the United States and 38% in Japan [1]. Data from the USRDS
indicated that the life expectancy of ESRD patients aged 65 is roughly one-fourth that of a patient of the same age without ESRD [1]. The impact of ESRD on life expectancy decreases with increasing age, and is smallest for the oldest age groups. An acceptable subjective quality of life and degree of rehabilitation have been noted in several reports [44, 45]. In contrast, other recent studies painted a much grimmer picture of the life of elderly dialysis patients [46, 47]. Outcomes observed support the policy that dialysis should not be denied to elderly patients if there is hope for prolongation of an enjoyable span of life. However, dialysis should not be used merely to prolong the dying process. There are elderly patients who should not be started on dialysis and the major absolute contraindications to dialysis are advanced malignancy, irreversible dementia, advanced liver disease, advanced chronic obstructive pulmonary disease or severe cardiomyopathy. When there is doubt about chances of recovery from a severe underlying disease, a “trial” of dialysis may be offered. Withdrawal of dialysis at a later time is preferable to withholding it from the beginning. Few specific studies have addressed comparative survival between HD and PD in the elderly. Most studies indicate that survival of elderly patients on CAPD and on HD is similar [22, 43]. Two Italian reports, adjusting for comorbid conditions, showed that mortality was higher among older patients treated with HD [14, 48]. While large studies in the United States have suggested that the benefit of HD in the elderly is most prominent in diabetic patients [49]. The technique failure is more frequent when CAPD/CCPD is used. It was reported that the switching at one year in elderly subjects was 12.5% from CAPD/CCPD to HD and 1.7% from HD to CAPD/CCPD [49]. Elderly patients have frequent vascular access difficulties that can contribute to decreased dialysis delivery. Many elderly people do not have suitable vessels for successful creation of an endogenous arteriovenous (AV) fistula and this is particularly true in patients with diabetes or hypertensive vascular disease. A polytetrafluoroethylene (PTFE) graft is recommended in these patients. However, every opportunity for the construction of an endogenous AV fistula should be taken. Recent data from the USRDS indicate that the risk of access failure in patients over age 65 with an AV fistula is 24% lower than in similar patients having a PTFE graft [50]. Elderly patients on HD experience more intradialytic complications, such as hypotension, nausea, and vomiting, than do younger patients. The treatment of hypotension is often associated with temporary cessation or early termination of HD therapy. As we considered before, the association with diabetes and cardiovascular disease may increase this problems and CAPD/CCPD
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may be a more satisfactory alternative treatment modality than HD. Renal transplantation is a relatively recent treatment option among the elderly ESRD. Success of transplantation in geriatric ESRD patients over the last decade is due to improved patient selection as well as the use of cyclosporine A and lower doses of corticosteroids. Oneyear patient and graft survival rates of 85% and 75%, respectively, have been reported [51]. A controlled survival comparison of transplantation and dialysis among elderly patients based on data from the CORR showed, after adjusting for other known prognostic factors, that patients who received a transplant experienced significantly greater survival probability than those who remained on dialysis. Five-year survival rates were 81% and 51% for the transplant and dialysis groups, respectively (RR 5 0.47, P , 0.0001) [52]. Although overall results are good, we believe that RT should not be offered indiscriminately to the elderly. Patients at risk for coronary arterial disease should be identified and candidates for RT should be selected. The management of transplantation in the elderly requires an understanding of pharmacology, immunology, and physiology peculiar to this age group. Since the elderly have a degree of immune incompetence, they require less aggressive immunotherapy. PATIENT PREFERENCE AND PSYCHOSOCIAL FACTORS Several patient factors may modify the choice of RRT modality. The most important are patient preference, psychological stability, availability of a living-related donor, social circumstances and economic factors. Patient participation plays a vital role in the outcome. The different options for RRT should be discussed with each patient and the patient preference should be considered. However, little is known about the reasons for chronic dialysis patients to choose to be listed or not listed for renal transplantation. Recently, these reasons have been investigated [53]. The most reported reason for electing transplantation was “hoping for a better quality of life” (86% of respondents). The reason “hoping it will make me live longer” was reported by 69% never-transplanted patients and by 25% patients with previous transplant. In never-transplanted patients, the reasons “doctor thought it would be good for me” and “family and/or friends thought it would be good for me” were 50% and 42%, respectively. Patient preference depends strongly on medical or nonmedical information. Although the patient’s preferences should be taken into consideration, the nephrologist has the responsibility to make recommendations. Motivated patients with available resources, no matter what their cause of ESRD, should be considered as excel-
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lent candidates for home HD. Several studies have shown that patients who use home HD have an increased survival and better quality of life when compared to those who use different dialysis modalities [54, 55]. Psychological stability is more necessary when CAPD or home HD are selected. Having a living-related donor is a condition to prefer transplantation. CAPD/CCPD or home HD are preferable in patients who live at long distance from the HD center or with unavailability of transportation. In-center HD is often the only dialysis option in single adults with no support system. NON-MEDICAL FACTORS THAT MODIFY THE CHOICE OF TREATMENT MODALITIES The frequency of the different treatment modalities in the different countries is not in accordance with the analysis of the advantages and disadvantages of each modality. Renal transplantation offers the best form of RRT for patients with ESRD. However, transplant rates vary worldwide. The transplant rate in United States, Spain, Norway, Germany and the Czech Republic was greater than 40 new transplant per million population in 1997. On the other hand, in Japan the transplant rate was very low. These wide variations of transplant activity are dependent on cultural, legal and socioeconomic factors. The economic status of a country could be a factor; but, even in industrialized nations there are marked differences. The most important limitation in renal transplant programs is the transplantable organ availability. However, cultural and religious attitudes also influence the choice of transplant as an option. Related to the choice of dialysis modality, and according to the previous medical analysis, most patients can be treated with either HD or CAPD/CCPD. However, in practice, most patients in the world are treated with HD; more than 80% of the dialysis population. It is also interesting to note the differences in the choice of dialysis modality from country to country. CAPD/ CCPD is very frequent in the UK, Australia, New Zealand, Canada and Mexico. The percentage of CAPD/ CCPD patients is very low in the rest of the world. Therefore, nonmedical reasons are the most important factors in dialysis modality selection. According to Nissenson et al [56], several nonmedical factors are critical in the relative use of various ESRD modalities: (a) financial/reimbursement (b) lack of training of nephrologists and nurses as well as poor education of patients about dialysis options (c) resource availability (d) social mores (e) cultural habits. In the authors’ opinion, the reimbursement differences of the physician or the facilities (for HD or CAPD/CCPD) are critical in the modality selection. We do not deny the significance of the financial factors, but in our experience the knowledge and training of the
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nephrologic team (physicians and nurses) is the most important factor in the selection. In center HD was developed earlier than CAPD/CCPD in most countries. Conversely when CAPD/CCPD became a mature RRT, many teams had already a good experience and practice in HD. In these centers, the first choice may continue to be HD. In those centers with good experience in all dialysis modalities (a minority), the medical and patient reasons will be the key factors to select the modality. In centers with partial experience (mostly in HD), the choice of dialysis modality will be highly influenced by nonmedical and “nonpatient” reasons. Obviously, an economic factor is also connected to this RRT history. Substantial capital investment was necessary in those countries where in center HD was first developed. In these centers and from a business perspective, to keep the HD facility as full as possible to offset high fixed costs is a very important objective. This economic factor may slow the patient transfer to CAPD/CCPD and can interfere with the medical decision. The team bias determined both by the training deficit and economic factors could be overcome in several ways. Centers involved in both dialysis (HD and CAPD/ CCPD) and transplantation are the best for an adequate management of ESRD patients. It may be that a unit is unable to provide the full range of services. In such a case, agreement among different centers to ensure that their patients can receive the optimum therapy at each moment, could be the best. Also, the nephrologist training must include all treatment modalities. The physician should be prepared to regularly review the status of the patient. In this way, he or she will be able to determine if current therapy is appropriate, or if some changes have to be made to ensure that the patient receives the best therapeutic option. HD and PD should not be seen as competing therapeutic options, rather, they are two complementary methods of dealing with uremia. Neither one is best suited for all patients. Each modality has its own unique advantages and disadvantages and at the same time it shares problems that exist across therapies. Adequate selection of treatment modality and optimization of each treatment modality will allow us to improve the outcome and to offer to ESRD patients higher survival, less morbidity and better quality of life. Reprint requests to Dr. Nelson Mazzuchi, Ramo´n y Cajal 2546, Montevideo 11600, C. Correo 16217, Montevideo, Uruguay. E-mail: [email protected]
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