Abstract
Background
The contribution of peritoneal small solute clearance per se to peritoneal dialysis (PD) patient outcomes remains uncertain. The aim of the present study was to determine whether baseline peritoneal small solute clearance predicted subsequent survival in Australian and New Zealand PD patients.
Methods
The study included all adult patients in Australia and New Zealand that commenced PD between 1 April 2002 and 31 December 2005 and had a peritoneal Kt/V (pKt/V) measurement performed within 6 months of PD commencement. Time to death and death-censored technique failure were examined by Kaplan–Meier analyses and both univariate and multivariate Cox proportional hazards models.
Results
pKt/V measurements were available in 2434 (63%) of the 3841 individuals that began PD treatment in Australia and New Zealand during the study period. These patients were divided into 4 groups according to their baseline pKt/V values: <1.45 (n = 599), 1.45 – 1.69 (n = 550), 1.70 – 2.00 (n = 607), and >2.00 (n = 678). Compared with the reference group (pKt/V 1.70 – 2.00), patient mortality was significantly increased in individuals with pKt/V <1.45 [adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.24 – 2.84; p = 0.003] and tended to be increased in those with pKt/V 1.45 – 1.69 (adjusted HR 1.46, 95% CI 0.96 – 2.21; p = 0.074). Importantly, higher pKt/V values (>2.00) also tended to be associated with higher mortality (adjusted HR 1.42, 95% CI 0.96 – 2.11; p = 0.079). The other independent predictors of death were lower residual renal function (RRF), older age, peripheral vascular disease, diabetes mellitus, late referral, higher peritoneal permeability, and untreated hypertension. No interaction was observed between pKt/V, RRF, and survival. Death-censored technique failure was demonstrated to be significantly worse in the pKt/V 1.45 – 1.69 group (adjusted HR 1.36, 95% CI 1.03 – 1.79; p = 0.028), older individuals, and individuals with Asian racial origin.
Conclusions
Initial peritoneal Kt/V significantly and independently influences patient survival in Australian and New Zealand PD patients. Overall survival appears to be optimal in the pKt/V range 1.70 – 2.00, with poorer outcomes observed above and below these values. In particular, survival is significantly worse when the achieved pKt/V is <1.45. In addition, RRF is an important independent predictor of patient survival in the Australian and New Zealand incident PD patient populations. The results of this study should therefore draw attention to the possible danger of not delivering adequate PD dose to patients with considerable RRF.
The contribution of peritoneal small solute clearance per se to peritoneal dialysis (PD) patient outcomes continues to fuel controversy and debate (1-4). Early observational cohort studies, such as the CANUSA study (5) and others (6-9), reported that total (renal + peritoneal) small solute clearance is an important predictor of PD patient survival. However, subsequent reanalysis of the CANUSA study demonstrated that peritoneal clearance had no independent relationship with the clinical outcomes of PD patients after adjustment for residual renal clearance (10), thereby suggesting that peritoneal and renal clearances were not equivalent. Other investigators have reported similar findings (4,11-15) although there are conflicting reports that peritoneal small solute clearance exerts a beneficial effect on clinical outcomes in both anuric patients (16,17) and patients with little residual renal function (RRF) (18). The largest randomized controlled trial of PD adequacy (ADEMEX) (4), involving 965 incident and prevalent PD patients, found that a mean increase in peritoneal Kt/V (pKt/V) from 1.62 to 2.13 had no effect on patient survival, although the study was not powered to exclude a mortality reduction benefit of less than 30%. A smaller study of PD in anuric patients from Hong Kong also found no benefit in augmenting peritoneal small solute clearances (19). However, all of these studies were generally limited by statistical power, inclusion of predominantly prevalent patients (thereby raising the possibility of ascertainment bias due to the recruitment of participants that are at a more advanced stage in their disease and PD career), and underrepresentation of patients treated by automated PD (APD). Given that peritoneal solute clearance can be modulated, it is important to establish whether or not this parameter influences clinical outcomes independently of RRF and whether there is a dose-threshold effect.
Many clinical practice guidelines, such as those of the International Society for Peritoneal Dialysis (20), have recently changed their guidelines from recommending higher Kt/V levels to a weekly total Kt/V value of >1.7. However, the applicability of these targets to different populations with respect to different background mortality and body size has been challenged (21).
The aim of the present study was to determine whether baseline pKt/V predicted subsequent patient and technique survival independently of residual renal clearance in a large cohort of Australian and New Zealand PD patients using clearance data obtained from the Australian and New Zealand Dialysis and Transplant Association (ANZDATA) Registry.
Subjects and Methods
Study Population
The present analysis included all patients in Australia and New Zealand that commenced PD between 1 April 2002 and 31 December 2005, were older than 18 years, and had pKt/V measured within the first 6 months of PD commencement. These patients were followed until cessation of PD, death, or 31 December 2005.
The available data consist of information about the underlying cause of end-stage renal disease (ESRD), demographic details, a limited range of comorbidities (the presence of coronary artery disease, peripheral vascular disease, cerebrovascular disease, chronic lung disease, hypertension, and smoking), the type and dose of dialysis treatment, details about renal transplantation and measurements of pKt/V, residual renal glomerular filtration rate (GFR), and dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4h).
Baseline pKt/V, residual GFR, and D/P Cr 4h were collected once at the same time for each patient within the first 6 months of PD commencement. Peritoneal Kt/V was calculated from a 24-hour dialysate collection as peritoneal urea clearance per week adjusted for urea distribution volume, as determined by the Watson formula (22). Peritoneal Kt/V was considered as both a continuous variable and a categorical variable according to four prespecified groupings (<1.45, 1.45 – 1.69, 1.70 – 2.00, >2.00). The D/P Cr 4h was measured by a standard peritoneal equilibration test and analyzed as a continuous variable. The pKt/V categories were chosen because they approximated population quartiles and because Kt/V cutoff points of 1.7 and 2.0 are prominent in previous and current clinical practice guideline recommendations. Residual GFR was calculated as the arithmetic mean of 24-hour urinary urea and creatinine clearances and analyzed as both a continuous variable and a categorical variable according to four prespecified groupings (0 L/week/1.73 m2, 0.1 – 24.9 L/week/1.73 m2, 25 – 49.9 L/week/1.73 m2, >50 L/week/1.73 m2). For potentially related comorbidities, “Suspected” was combined with “Yes” for analyses. Body mass index (BMI) was calculated from the height and dry weight (empty of dialysis fluid) at commencement of PD and analyzed as either a categorical variable according to WHO criteria (obese >30 kg/m2, overweight 25 – 30 kg/m2, normal weight 18.5 – 24.99 kg/m2, and underweight <18.5 kg/m2) or as a continuous variable where indicated.
Statistical Analysis
Results are expressed as mean ± SD for parametric continuous data, as median and interquartile range for non-parametric continuous data, and as frequencies and percentages for categorical data. Differences in pKt/V between PD patient subgroups were evaluated by unpaired t-test or analysis of variance (ANOVA). The distributions of categorical variables across each of the four pKt/V groups were compared using the chi-square test. The independent predictors of pKt/V were determined by multiple linear regressions. Survival curves, survival probabilities, and estimated mean survival times were generated according to the Kaplan–Meier method. Survival analyses were also performed using univariate and multivariate Cox proportional hazards models using backward stepwise elimination based on the likelihood ratio. The covariates included in the Cox models were weekly pKt/V, residual GFR, peritoneal transport category, age, gender, racial origin, smoking status, BMI category, late referral (i.e., referral <3 months prior to commencement of dialysis), and the presence or absence of hypertension, chronic lung disease, coronary artery disease, peripheral vascular disease, cerebrovascular disease, or diabetes mellitus. Supplementary univariate and multivariate Cox regression analyses with residual GFR as a categorical variable were undertaken using the same covariates as above. For the overall survival analyses, data were censored at the time of renal transplantation, 31 December 2005, or 60 days after transfer to hemodialysis. The death-censored technique analyses were censored at the time of renal transplantation, death, or 31 December 2005. Adjusted survival curves were estimated using the Cox average covariate method, which calculates predicted survival probabilities at the mean levels of the covariates. Proportional hazards assumptions were checked by Schoenfeld residuals and scaled Schoenfeld residuals and examined by formal hypothesis test and graphically. First-order interaction terms between the significant covariates were examined for all models. Data were analyzed using the software package SPSS 12.0 (SPSS Inc., North Sydney, Australia). Any p values less than 0.05 were considered statistically significant.
Results
Baseline Characteristics
Measurements of pKt/V were available in 2434 (63%) of the 3841 individuals that began PD treatment in Australia or New Zealand between 1 April 2002 and 31 December 2005. Compared with the 1407 patients that did not have a pKt/V measurement available for study, those that did had significantly higher BMIs and were less likely to be female or to have lung disease, coronary artery disease, peripheral vascular disease, or cerebrovascular disease (Table 1). Not having a pKt/V measurement available was a significant risk factor for technique failure [hazard ratio (HR) 2.97,95% confidence interval (CI) 2.70 – 3.28] and death (HR 4.41, 95% CI 3.77 – 5.18). Only those people with pKt/V measurements were considered for further analysis of the impact of baseline peritoneal pKt/V on PD outcomes. The total follow-up period was 3267 patient-years.
Comparison of Baseline Characteristics of Incident Australian and New Zealand Peritoneal Dialysis Patients That Did or Did Not Have Peritoneal Kt/V (pKt/V) Measurements Performed During the First Six Months of Dialysis Onset [Results are expressed as mean±SD, number (percentage), or median (interquartile range) for residual renal function.]
BMI = body mass index; D/P Cr 4h = dialysate-to-plasma ratio of creatinine at 4 hours.
Within 3 months of dialysis commencement.
The main baseline demographic and clinical characteristics of the study population are presented in Table 2. Continuous ambulatory PD was used in 60.9% of our patients and APD in 39.1% (data were missing for the remainder). Mean baseline pKt/V was 1.74 ± 0.43. Patients with higher pKt/V measurements had lower BMI and were more likely to be younger, female, nondiabetic, nonsmokers, free of coronary and peripheral vascular disease, and treated by APD (Table 2). Racial origin did not vary significantly between the pKt/V groups. Using multiple linear regression, the only independent predictors of higher measured baseline pKt/V were lower BMI (p < 0.001), lower residual GFR (p < 0.001), use of APD (p = 0.006), and smoking (p = 0.003). Residual GFR was inversely correlated with pKt/V, such that the pKt/V <1.45 group had markedly higher residual GFRs than the pKt/V >2.0 group (47.7 vs 19.1 L/week/1.73 m2, respectively). The same correlation was observed between urea distribution volume and pKt/V (Table 2).
Baseline Characteristics of the Study Population (n=2434) [Results are expressed as mean±SD, number (percentage), or median (interquartile range; residual renal function; RRF). Differences between peritoneal Kt/V (pKt/V) categories were assessed by chi-square test or ANOVA, depending on data type.]
TSI = Torres Strait Islanders; PI = Pacific Islanders; BMI = body mass index; D/P Cr 4h = dialysate-to-plasma ratio of creatinine at 4 hours; APD = automated peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis.
Urea distribution volume calculated by Watson formula.
On categorization of residual GFR according to the four predefined groups, patients with RRF 0.1 – 24.9 L/week/1.73 m2 had a significantly higher pKt/V than patients in the groups with higher residual GFR. Anuric patients had higher pKt/V compared to the group with RRF between 0.1 – 24.9 L/week/1.73 m2 (p < 0.001). In addition, anuric patients underwent a longer period of treatment for ESRD by other renal replacement therapy modalities before starting with PD (p < 0.001; Table 3).
Peritoneal Kt/V (pKt/V) and Time on Treatment for End-Stage Renal Disease (ESRD) by Other Modalities Before Initiation of Peritoneal Dialysis (PD) According to Categorized Residual Renal Function (RRF) (Differences between RRF categories were assessed by ANOVA. Values expressed as mean±SD.)
By the end of the study, 1570 (64.5%) patients were alive on PD, 472 (19.4%) had transferred to hemodialysis, 101 (4.1%) had been transplanted, 17 (0.7%) had spontaneously recovered renal function and ceased dialysis, 3 (0.12%) were lost to follow-up, and 271 (11.1%) had died.
Technique Survival and Death-Censored Technique Survival
On analysis of technique survival including death as a failure in a multivariate Cox proportional hazards model, patients with weekly pKt/V 1.70 – 1.99 experienced significantly better outcomes than those with a pKt/V <1.45 (adjusted HR 1.39, 95% CI 1.10 – 1.77; p = 0.006], 1.46 – 1.69 (adjusted HR 1.39, 95% CI 1.10 – 1.74; p = 0.005), or >2.0 (adjusted HR 1.30, 95% CI 1.04 – 1.61; p = 0.019). The other independent predictors of poorer technique survival were higher D/P Cr 4h (p = 0.046), lower residual GFR (p = 0.008), BMI 25 – 30 kg/m2 (p = 0.021), peripheral vascular disease, late referral (p = 0.019), and absence of treated hypertension (p = 0.021). No significant first-order interactions between pKt/V groups and other covariates (including BMI and RRF) were identified.
Median actuarial death-censored technique survival for the overall population was 3.45 years (95% CI 3.23 – 3.67 years). The causes of technique failure among the study cohort were reported as patient preference (24%), followed by inadequate solute clearance (11%), acute peritonitis (6%), recurrent peritonitis (5%), and inadequate fluid clearance (6%). Compared with the reference group (weekly pKt/V 1.70 – 1.99), all other pKt/V categories tended to be associated with poorer death-censored technique survival on multivariate Cox proportional hazards model analysis, although this reached statistical significance only for the 1.45 – 1.69 pKt/V group (adjusted HR 1.36, 95% CI 1.03 – 1.79) (Table 4). The other independent predictors of poorer death-censored technique survival were younger age and Asian racial origin. No significant first-order interactions were identified between pKt/V and other covariates (including BMI and RRF).
Predictors of Death-Censored Technique Survival in 2434 Incident Peritoneal Dialysis Patients in Australia and New Zealand, Based on the Results of Univariate and Multivariate Cox Regression Analyses
RRF = residual renal function; TSI = Torres Strait Islanders; PI = Pacific Islanders; BMI = body mass index; D/P Cr 4h = dialysate-to-plasma ratio of creatinine at 4 hours; APD = automated peritoneal dialysis; HR = hazard ratio.
Within 3 months of dialysis commencement.
Overall Survival
During the study period 271 (11.1%) patients died. The causes of death were cardiovascular disease (43.2%), withdrawal from dialysis (18.1%), infection (14.8%), malignancy (8.5%), cachexia (2.2%), perforated abdominal viscus (0.8%), and other (13.2%). Mean patient survival was 3.17 years (95% CI 3.10 – 3.23 years). Using multivariate Cox proportional hazards model analysis, weekly pKt/V was strongly and nonlinearly related to patient survival (Table 5; Figure 1). Compared with the reference group (pKt/V 1.70 – 2.00), mortality was significantly increased in individuals with pKt/V <1.45 (adjusted HR 1.87, 95% CI 1.24 – 2.84; p = 0.003) and tended to be decreased in those with pKt/V 1.45 – 1.69 (adjusted HR 1.46, 95% CI 0.96 – 2.21; p = 0.074). Higher pKt/V values (>2.00) also tended to be associated with poorer survival (adjusted HR 1.42, 95% CI 0.96 – 2.11; p = 0.079). The other independent predictors of poorer survival were lower RRF (Figure 2), older age, peripheral vascular disease, diabetes mellitus, chronic lung disease, late referral, higher D/P Cr 4h, and absence of treated hypertension. Including duration of ESRD before PD in the model did not significantly alter the association between pKt/V and mortality (pKt/V <1.45: adjusted HR 1.89, 95% CI 1.24 – 2.84; pKt/V 1.45 – 1.69: adjusted HR 1.48, 95% CI 0.97 – 2.24; pKt/V 1.70 – 2.00: reference; pKt/V >2.00: adjusted HR 1.44, 95% CI 0.90 – 2.13), although increasing duration of ESRD before PD was independently associated with an increased risk of death (adjusted HR 1.14, 95% CI 1.07 – 1.22; p < 0.001). No interaction was observed between pKt/V, RRF, and survival (p = 0.987) or between pKt/V, BMI, and survival (p = 0.544).
Multivariate Cox-adjusted patient survival curves for each of four peritoneal Kt/V (pKt/V) groups.
Multivariate Cox-adjusted patient survival curves for each of four residual renal function (RRF) groups.
Predictors of Survival in 2434 Incident Peritoneal Dialysis Patients in Australia and New Zealand, Based on the Results of Univariate and Multivariate Cox Regression Analyses
RRF = residual renal function; TSI = Torres Strait Islanders; PI = Pacific Islanders; BMI = body mass index; D/P Cr 4h = dialysate-to-plasma ratio of creatinine at 4 hours; APD = automated peritoneal dialysis; HR = hazard ratio.
Within 3 months of dialysis commencement.
Discussion
The present study demonstrated that, among patients with measured values, baseline pKt/V is a highly significant predictor of both patient and technique survival in the Australian and New Zealand incident PD patient populations. The predictive value of pKt/V was independent of RRF, demographic characteristics, BMI, comorbid clinical illnesses, and peritoneal transport status. Moreover, the survival benefit conferred by pKt/V appeared to be nonlinear, with optimal outcomes observed in the range 1.70 – 2.00. Peritoneal Kt/V values above or below this range tended to be associated with worse outcomes, which became statistically significant when pKt/V was <1.45.
Our study is by far the largest examination to date of the relationship between pKt/V and PD outcomes and the first to demonstrate a significant association between the two parameters in the presence of appreciable RRF. Its findings contrast somewhat with those of the ADEMEX trial (4), which found no difference in overall patient survival among 481 patients randomly allocated to an intensified PD prescription to achieve a peritoneal creatinine clearance >60 L/week/1.73 m2 (mean achieved weekly pKt/V 2.13) and 484 controls receiving four daily exchanges of 2 L standard PD solution (mean achieved weekly pKt/V 1.62). Part of the apparent disparity may be explained by the fact that, in our study, survival was greatest in the group with pKt/V values between 1.70 and 2.00 and tended to be worse above and below this range. It is conceivable therefore that, while a certain level of peritoneal small solute clearance confers benefit to PD patients, too high a level of pKt/V may be counterproductive. The reasons for this are uncertain but may potentially result from excessive peritoneal membrane and systemic exposure to harmful substances (e.g., glucose degradation products) and/or excessive dialysate losses of beneficial substances, such as proteins, amino acids, and other nutrients. Some observational cohort studies have suggested that the use of low glucose degradation product PD solutions may be associated with enhanced survival compared to conventional solutions (23), although this observation was not confirmed by several small randomized controlled trials (24,25). It is also possible that the results of our population-based study reflect the wishes of physicians to steer treatment not solely by pKt/V but by other parameters as well, such as a clinical status free of uremic symptoms, absence of fluid overload or congestive heart failure, and normalized biochemical parameters. These broader adequacy targets have not yet been addressed in larger randomized clinical trials but may explain the dissimilar results in our observational cohort study.
It should be emphasized that, because this study was observational and not randomized, its results are hypothesis-generating only and cannot definitively establish the presence of a causal U-shaped relationship between pKt/V and survival. The ADEMEX trial provides the best available evidence to date on this issue and has greater statistical power than our study by virtue of the higher death rate in its study population. Nevertheless, the observation in our study of optimal survival in the pKt/V range 1.70 to 2.00 does raise the possibility that a randomized controlled trial comparing an intervention group targeting a lower pKt/V in the range 1.70 to 2.00 versus a control group similar to that of the ADEMEX trial might potentially have a higher likelihood of demonstrating a survival difference between the two groups if such a difference did in fact exist. This possibility has been investigated to some extent by Lo et al. (19), who conducted an open-label randomized controlled trial of three different total weekly Kt/V targets (1.5 – 1.7 vs 1.7 – 2 vs >2) in 320 incident PD patients with renal Kt/V≤1.0. No significant differences were observed between the three groups with respect to patient survival (2-year survival 81.5% vs 86.1% vs 87.3%); however, the overall death rate was low (70 deaths in total) and so the study did not have sufficient statistical power to detect a clinically important difference in the primary outcome measure. Patients in the lowest total Kt/V target group were more likely than patients in other groups to be withdrawn from the trial by their physicians (15.4% vs 6.7% vs 5.4%), but this may have been influenced by a lack of physician blinding.
Similarly, the prospective, multicenter European Automated PD Outcome Study (EAPOS) found that pKt/V had no effect on overall or technique survival in 177 patients (12). However, the results may have been adversely affected by the preferential selection of anuric prevalent APD patients and by the relatively low number (n = 31) of deaths (thereby making a possible type 2 statistical error likely). Other negative studies (13-15,19,26) have likewise been limited by small sample sizes (≤320 patients), short follow-up times, low event rates, and restriction to single-center observations.
Whereas the major previous studies were ethnically homogenic, our study had a significant proportion of different ethnicities. Despite this diversity, achieved pKt/V and survival were similar in all ethnic groups.
Patients with higher BMI tended to have a higher mortality and had a lower pKt/V. However, the relation between higher pKt/V and mortality was not affected by increasing BMI in the analysis, nor was the relation between BMI and outcome affected by pKt/V.
In keeping with the findings of Szeto and associates (17,18), the present study demonstrated that low pKt/V values (especially <1.45) had statistically significant and clinically important detrimental associations with mortality. However, it is important to note that, in the predominantly prevalent populations examined by Szeto et al., one group was anuric (17) and the other had a mean measured residual renal clearance of only 10.8 L/week/1.73 m2 (18). In contrast, the levels of RRF were considerably higher in the Australian and New Zealand incident PD patient populations (29.5 L/week/1.73 m2), but pKt/V was still found to be significantly associated with outcomes in this context. Our finding that RRF was inversely correlated with pKt/V, such that the pKt/V <1.45 group had markedly higher residual GFRs (47.7 L/week/1.73 m2) than the pKt/V >2.0 group (19.1 L/week/1.73 m2) highlighted a significant difficulty in analyzing the independent effects of RRF and pKt/V on PD patient outcomes, since the two parameters are clearly not entirely independent of one other. Patients with substantial RRF are likely to receive less-intensive PD prescriptions, resulting in lower observed pKt/V values. Conversely, patients with low residual GFRs are more likely to be prescribed higher PD exchange volumes and/or frequencies, resulting in higher pKt/V measurements. Although we attempted to adjust for the potentially confounding effect of residual renal clearance, the possibility of residual confounding cannot be entirely excluded. In this respect, it is also important to note that, despite the observed inverse association between pKt/V and residual GFR, no interaction (effect modification) was observed between pKt/V, residual GFR, and survival. Interestingly, although anuric patients achieved significantly higher pKt/V values (1.88 ± 0.39) compared with other patients, this group had significantly worse overall survival [mean survival 2.92 (95% CI 2.78 – 3.06) years vs 3.25 (95% CI 3.18 – 3.32) years], suggesting that residual renal clearance is quantitatively a more important determinant of survival than peritoneal clearance. Other factors not analyzed but that may contribute to a higher rate of death per se can result in lower pKt/V and thereby induce reverse causality. Those factors could be abdominal adhesion due to surgery or bowel disease.
In addition, the possibility cannot be excluded that physicians’ prescriptions were influenced by other patient-related factors, leading to higher prescribed doses to seemingly more patients with subjective higher mortality risks and vice versa. Although we tried to minimize this effect in our multivariate analysis, confounding by indication cannot be ruled out and might be an explanation for the U-curved relationship between peritoneal Kt/V and survival in our study.
The strengths of this study include its very large sample size and the robustness of its findings across different statistical methodologies. Since we included all centers across both countries, the external validity of our findings was greatly enhanced. Moreover, our cohort consisted solely of incident patients, thereby avoiding the potentially confounding factor of survivor bias associated with prevalent population studies.
The use of Registry data in this paper also carried significant limitations. Because of the retrospective nature of the analysis and the fact that only 63% of the entire cohort had baseline pKt/V results, the potentials for both recall and selection biases were present. As shown in Table 1, patients with certain characteristics were more likely to have undergone a pKt/V measurement during the study period. Although these differences were statistically significant, the actual sizes of the differences were generally minor. It is nevertheless noteworthy that patients in whom a pKt/V measurement was available experienced significantly better survival than those individuals in whom such a measurement was not available. This result indicates that our overall findings may have been influenced by patient selection. Given that the study included only patients that had a measured pKt/V within the first 6 months following initiation of PD, there was the potential for survival bias since patients had to survive long enough to have their pKt/V measured. Censoring data at the time of transfer to hemodialysis or renal transplantation may also have introduced informative censoring bias. Furthermore, the strength of registry analyses with respect to their extent of coverage must be balanced against their main weakness, which is a limited depth of coverage. ANZDATA does not collect information on PD prescription (volume and type of fluid), peritoneal ultrafiltration, peritoneal sodium removal, patient compliance, individual unit management protocols, or the severity of comorbidities; therefore, residual confounding or unidentified associations could not be entirely excluded. Hence, it is possible that a low initial pKt/V is simply a marker for suboptimal PD management in general. Moreover, since serial changes in pKt/V measurements within individuals were not collected, only the influence of baseline pKt/V on subsequent survival could be evaluated in this analysis. It is unknown how those baseline pKt/V measurements were subsequently modified during the course of the study. In common with other registries, ANZDATA is a voluntary registry and there is no external audit of data accuracy.
In conclusion, residual renal function is a highly significant independent predictor of patient survival in the Australian and New Zealand incident PD patient populations. Initial peritoneal Kt/V is also significantly and independently associated with patient survival in these populations. Overall survival appears to be optimal in the pKt/V range 1.70 – 2.00, with poorer outcomes observed below and above these values. In particular, survival is significantly worse when the achieved pKt/V is <1.45. The results of our study should therefore draw attention to the possible danger of not delivering adequate peritoneal dialysis dose to patients with considerable residual renal function.
Footnotes
David Johnson is a consultant for Baxter Healthcare Pty Ltd and has previously received research funds from this company. He has also received speakers’ honoraria and research grants from Fresenius Medical Care. Stephen McDonald has received speaking honoraria from AMGEN Australia, Fresenius Australia, and Solvay Pharmaceuticals and travel grants from AMGEN Australia, Genzyme Australia, and Jansen–Cilag. Markus Rumpsfeld has received speaking honoraria from Baxter Healthcare Pty Ltd and Gambro and travel grants from AMGEN and Baxter Healthcare Pty Ltd.
Acknowledgments
The authors gratefully acknowledge the substantial contributions of the entire Australia and New Zealand nephrology community (physicians, surgeons, database managers, nurses, renal operators, and patients) in providing information for and maintaining the ANZDATA Registry database.