Abstract
Frequency distribution of age at the start of peritoneal dialysis, for patients from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia.
Table 1 shows the patients’ median ages and the diseases present at the start of PD that are considered possible risk factors for patient survival. Comparing the first five-year period to the last, the median age increased from 59.3 years to 68.1 years. The prevalence of hypertension increased by 25%, ischemic cardiopathy by 26%, peripheral vascular disease by 106%, type 2 diabetes by 48%, cerebral vascular disease by 21%, and chronic respiratory infection by 500%. The prevalence of tuberculosis, type 1 diabetes, and malignant hypertension all decreased. The mean number of risk factors per patient increased from 2.59 to 3.05. These data make it clear that clinical status at the start of PD grew progressively worse with time.
Risk Factors Present in Patients a at the Start of Peritoneal Dialysis
All patients are from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia.
During the period 1979–2000, 24 patients used automated peritoneal dialysis (APD). Nine patients started on APD; 15 started on CAPD and later switched to APD. At the end of January 2000, 39 patients were using CAPD (63%) and 23 were using APD (37%). Because the number of APD patients was low, APD patients have been grouped with CAPD patients in the analyses that follow.
Pd Retention and Overall Outcome
Cumulative PD retention was computed by considering both death and change of modality as the final event. Mean PD retention time in this population—that is, the time at which 50% of patients are still on treatment—is 2.93 years (35.2 months).
The outcomes for all PD patients since the start of our program are: 62 (12%) still on PD (median age: 68 years); 130 (25%) shifted to HD (median age: 64 years); 44 (9%) received a kidney graft (median age: 43 years); 10 (2%) recovered their renal function (median age: 62 years); 10 (2%) transferred to another center (median age: 75 years); and 256 (50%) died (median age: 71 years).
A histogram (Figure 2) shows the distribution of time our patients spent on PD (mean: 37 ± 34 months; median: 26 months). Seventeen patients remained on PD for more than 10 years, and one patient is still on PD after 17.7 years.
Frequency distribution of time spent on peritoneal dialysis (PD), for patients from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia.
Patient Survival
Only death was considered as the final event for calculating a patient's probability of surviving. The mean time to death—that is, the time at which patient survival is 50%—was 4.48 years (54 months). Patient survival of 75% was attained at 2.17 years, and 25% at 7.35 years (Figure 3).
Patient survival, technique survival, and retention on peritoneal dialysis, for patients from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia. For calculation of patient survival, the final event was death; for technique survival, it was change of modality; for retention analysis, it was both death and change of modality.
The analyses of factors affecting patient survival— namely, associated diseases, center experience, and dialysis dose—were reported in our previous papers (1-4). In one, we compared the long-term outcomes of 297 CAPD and 281 HD patients from our center for the years 1981–1993 (3). PD patients were older than HD patients (62 ± 14 years vs 56 ± 17 years; p = 0.0001) and had more associated diseases at the beginning of dialysis (2.9 ± 1.6 versus 2.4 ± 1.5; p = 0.0001). The observed patient survival was 14.4% on PD and 34.6% on HD after ten years (p = 0.004). A Cox regression analysis found that the factors significantly affecting survival were: age, cerebral and peripheral vascular disease, ischemic cardiopathy, malignancy, chronic liver disease, tuberculosis, and malignant hypertension. The dialysis modality, PD or HD, did not play a significant role (p = 0.121).
The above analyses of our patients were updated by prolonging observation until the end of 1996, when new results confirmed our previous reports (5). Results from the period 1991–1996 were of particular interest, because the mean age and comorbidity of incident HD patients progressively increased, thus decreasing the gap versus PD patients observed in previous studies. The similarity in age and clinical features of PD and HD patients increased the reliability of our results, because the results were less conditioned by the limits of statistical methods used to adjust for case mix. Moreover, in that period of time, even PD benefited by dialysis dose prescription according to the indices of adequacy that had already been applied in HD since the second half of the 1980s.
Our new study reported data from 155 HD and 139 PD patients. The probability of survival for both modalities was 36% after 60 months. No statistical difference was found either with “observed” patient survival, or with the Cox analysis, whose adjustments were of minor effect. As a consequence, the corrected survival curves showed only marginal differences from the observed ones and confirmed the ability of PD to assure the same probability of survival as HD in comparable groups of patients (Figure 4).
Adjusted survival curves for hemodialysis (HD) and peritoneal dialysis (PD), for patients from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia. Figures are for patients who started dialysis during the years 1991–1996. Reprinted from (5).
Many studies have pointed out that an adequate dialysis dose assures greater probability of survival. Two studies (2,6) are frequently quoted and have become the basis for guidelines on dialysis prescription (7). Today, general agreement exists that the target dialysis dose should be a weekly Kt/V urea of about 2 and a weekly creatinine clearance (wCrCl) of 60 L/ 1.73 m2 body surface area (BSA) (7-10).
An intriguing point is the relationship between Kt/V urea and wCrCl, which is highly significant in a PD population, but which has no value for the individual patient (4). The main reasons for the discrepancy are: different calculations of residual renal function (underestimated by Kt/V), different normalizations (total body water for Kt/V, and body surface area for wCrCl), and effect of individual peritoneal permeability pattern (the higher the permeability, the lower the difference between Kt/V and wCrCl) (11). For this reason, the Dialysis Outcomes Quality Initiative (DOQI) guidelines recommend achieving both adequacy targets. Maiorca et al showed that the best breakpoint among patient survival curves was reached by a wCrCl of 70 L/1.73 m2 BSA (4). On the other hand, the CANUSA study showed a continuous increase in patient survival as wCrCl increased (6). On this basis, it seems that the value suggested by the DOQI guidelines (7), that is, 60 L/1.73 m2 BSA per week, is a compromise, owing to the difficulty of reaching higher values in many patients.
Other studies have faced the problem of an adequate dialysis dose from other points of view. They demonstrated that an increasing dialysis dose has beneficial effects on protein intake (12,13), nutritional status (14-16), and red-cell count (17). It is noteworthy that, in all these studies, the suggested Kt/V is about 2.0, thus confirming the target suggested by the survival analysis (2,6).
Pd Failure
“True” technique survival has definitely been demonstrated to be worse on PD than on HD (3): 3% of HD patients changed modality versus 18% of PD patients. However, the high PD drop-out rate did not falsely improve technique survival, because the adjusted survival curves of patients discontinuing PD were similar to those of patients continuing on that modality. Our more recent analysis (5) confirmed those results.
The present analysis of technique survival considers only change of modality as the final event in drawing technique survival curves, as in our previous papers (1-3). In patients starting PD from July 1979 to January 2000, the mean technique survival time was 8.79 years (Figure 3). The 130 patients who changed modality (77 males and 53 females) spent a mean of 34 ± 33 months (median: 24 months) on PD. The discrepancy between these data can be explained by the high number of patients on treatment during the first years, which acted to reduce the percentage of patients discontinuing the method.
The reasons for change in modality are shown in Table 2. Peritonitis was the prevalent cause, representing 35.4% of all changes. Peritonitis was significantly more prevalent in males (11% of all men left PD owing to peritonitis) than in females (6% of all women left; p < 0.05). The second most common cause was either patient or partner ability or choice to continue: 36 patients (27.7%) left for this reason, and no significant difference between males and females was found. Mechanical causes—hernia, leakage, peritoneal–pleural effusion, and other reasons related to the abdominal pressure exerted by the intraperitoneal fluid—accounted for 8.5% of the PD failures. Mechanical failures were more frequent in females (4% of all women versus 1% of all men; p < 0.02%) probably owing to previous pregnancies and less abdominal muscle mass.
Reasons for Modality Change from Peritoneal Dialysis to Hemodialysis
NS = non significant.
When more than one cause was present, the most important cause is shown.
Statistical significance was calculated by chi-square test applied to the number of patients who left peritoneal dialysis for a definite cause versus other PD patients.
Inadequate biochemical control and inadequate fluid control represent 7.7% and 3.8% of the reasons for discontinuing PD, respectively. It is noteworthy that inadequate clearance or insufficient ultrafiltration led to PD stoppage in just 15 patients of the 510 at risk (3%); but adequacy of PD dose has been paid great attention only in the 1990s, which could have led to its underestimation formerly. The figures for surgical causes leading to PD discontinuance—for example, aortic aneurysm and colon resection for intestinal malignancy—represent less than 5% among the reasons for technique failure.
Figure 5 shows change over time in the reasons for leaving PD. The great increase in patient or partner choice during the 1985–1989 and 1990–1994 periods was due partly to burn-out and partly to the need to increase the number of bags to reach adequacy targets (2,6). In the following years, greater attention was paid to avoiding PD in patients with the largest body size (> 85 kg). Also, to avoid the risks of possibly inadequate biochemical control, modality changes were suggested earlier, when appropriate. These actions possibly explain the increase in modality changes owing to inadequate clearance and the reduction in the changes owing to patient or partner choice during the last five years. Also, in the earliest years of PD, many changes of modality were due to low biochemical control, probably owing to lower confidence in and experience with the modality, and to a lack of bags with fluid volumes larger than 2 L.
Reasons for discontinuing peritoneal dialysis over time, for patients from the Division of Nephrology, University of Brescia and Spedali Civili, Brescia. UF = ultrafiltration; perit–pleural eff = peritoneal–pleural effusion; ESI = exit-site infection.
Mechanical reasons for drop-out have been quite stable over time at about 10%. Peritonitis has accounted for 30% – 40% of PD drop-out in all periods of time considered, with little variation. This result is somewhat surprising, considering the important improvements in connection systems made during the 1980s (18-20) and applied in a timely fashion in our center.
Forty-six patients (9% of all patients on PD) stopped PD owing to peritonitis. Of the 46 patients, 14 stopped owing to a high frequency of peritonitis during the overall experience or during the last months, and 32 stopped owing to peritonitis that was difficult to cure either because of the causative micro -organisms (above all, fungi and pseudomonas), or because of abdominal problems (diverticulosis, diverticulitis, or the need for abdominal surgery for peritonitis not improving with antibiotic therapy).
Age and comorbidity among our new PD patients increased with time, and both of these factors could have impaired host defense against micro-organisms. The ratio between the patients leaving PD owing to particular peritonitis micro-organisms and abdominal problems, and those leaving owing to a high incidence of peritonitis was 9:5, 9:5, 5:3, and 9:1 respectively in the series of five-year periods considered.
This observation suggests a need both for improving the biocompatibility of PD fluids (21-23), to impair peritoneal defense less, and for improving patient selection. Increased experience with PD has led to the awareness that a change of modality occurring too late has a negative effect on the patient's life: in other words, “late change, early death.” This problem seems to be quite similar to that of late referral, which is increasingly being faced by the current literature (24-26). These problems reinforce the need for continual, critical review of the clinical status of every PD patient, and for a timely switch to HD when PD is no longer the best treatment for a given patient.