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Dialysis |
* Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, and VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania
Address correspondence to: Dr. Beth Piraino, 3504 5th Ave., Suite 200, Pittsburgh, PA 15213. Phone: 412-383-4899; Fax: 412-383-4898; E-mail: piraino{at}pitt.edu
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Abstract |
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90 d after start of HD was 0.44/yr, increased compared with overall rate of 0.16/yr (P < 0.004). HD catheters, used in 67% of patients who started HD, were associated with a strikingly increased rate of bacteremia. Peritonitis 90 d was 0.22/yr, no different from the overall rate. Modality was not an independent predictor of overall infections (PD versus HD: relative risk 1.30; 95% confidence interval 0.93 to 1.8; P = 0.12) using multivariate analysis. PD and HD patients had similar infection rates overall, but type of infection and risk over time varied. HD patients had an especially high risk for bacteremia in the first 90 d, whereas the risk for peritonitis for the PD cohort was not different over time. These results support the placement of permanent accesses (fistula or PD catheter) before the start of dialysis to avoid use of HD catheters. |
Introduction |
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The rates of hospital admissions for septicemia are higher in hemodialysis (HD) patients than peritoneal dialysis (PD) patients (2,3). HD compared with PD as an initial modality doubles the risk for hospitalization for septicemia (3). The hospitalization rates for septicemia in PD have remained relatively constant since 1997, whereas the rates for hospitalization in HD patients have doubled between 1991 and 2001, because of a striking increase in the admission rate for vascular access infection (2). However, the recorded rate of death for septicemia is higher for PD patients (29.3 per 1000 patient-years) than for HD patients (26.1 per 1000 patient-years) for the most current period for which data are available (1). These results seem inconsistent and confusing.
Most previous reports that used USRDS data did not include the critical initial period of time on dialysis, because USRDS collection of information does not begin until the 90th day of dialysis. This is a time when a high proportion of patients are using HD catheters, which are known to increase the risk for bacteremia (4,5). Excluding this period of time will underestimate the rate of infections.
The use of HD catheters has been shown repeatedly to be an independent predictor of death in HD patients (6–9). Data from elderly patients with preexistent Medicare, permitting tracking of information from day 1 of HD, indicate that 15.1% of patients with an HD catheter die in the first 90 d compared with 6.7% with a fistula, with a hazard ratio of death with an HD catheter of 2.15 (9). Therefore, the risk for bacteremia and death in HD are especially high in the first 3 mo of dialysis.
A common perception is that PD is associated with a higher risk for infection compared with HD. However, the impact of dialysis modality on the rate and particularly type of infection has not been well studied, especially during the first few months of dialysis. Using a dialysis registry that tracks patients from the first day of dialysis, we designed this study to compare the rates and type of infections in patients who were incident to either HD or PD, controlling for important variables.
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Materials and Methods |
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We excluded 63 patients who were on HD and 57 who were on PD and had any previous ESRD therapy, including failed renal transplants. This was done to focus on patients who initiated dialysis as a first ESRD therapy and to avoid confounding a potential impact of one therapy on another and the access related to that modality. Eight patients who were incident to ESRD during the period studied were excluded because all were started on HD (but not at our center) and transferred to PD at our center within 3 mo of initiation of dialysis (range 0.33 to 1.90 mo) and therefore were on two modalities. To evaluate any potential bias, we ran an additional analysis that included these eight patients in the PD group. Modality was defined as that started on the first day of dialysis and time at risk began at the outpatient dialysis treatment for HD and the first day of training for PD. The majority of time on PD was on automated PD (APD; 92%), with the remaining time on continuous ambulatory PD (CAPD).
Follow-up continued to September 1, 2005. Individuals were censored at transfer to another modality (three on HD and seven on PD), improvement in residual renal function that led to discontinuation of dialysis (two on HD and one on PD), transplantation (four on HD and 15 on PD), permanent transfer to another center on the same modality (five on HD and zero on PD), and death (33 on HD and seven on PD). Temporary transfers to another modality, transient cessation of dialysis as a result of partial recovery of renal function, no dialysis as a result of catheter malfunction, or time in a rehabilitation center were not reasons for censoring when the patient returned to the original modality in <1 mo (six each on HD and PD). However, the time off the dialysis therapy was excluded as were infections during this short period for both HD and PD because the focus of this article is on infections on one modality versus the other.
Prospective data that were collected included demographics, comorbid conditions at dialysis initiation, serum albumin at the start of dialysis, infection episodes, and hospitalizations as a result of infections. Comorbidity status at the start of dialysis was assessed using Charlson Comorbidity Index (CCI) (10), scored by an experienced physician assistant for HD and an experienced research nurse for PD. A careful review of the patient’s medical history and physical examination was used to determine the correct score. Diabetes was defined as elevated blood glucose and a history of diabetes on the basis of review of the history of the patient regardless of the use of insulin or hypoglycemic medications. The guide for scoring the CCI is in Appendix 1. Infections that were included in the registry were those related to the access regardless of whether hospital admission was required and all infections that required hospital admission.
Infections were classified as catheter infections, either exit site (defined as drainage, erythema, or exit-site pain) or tunnel infection (defined as swelling or pain/tenderness with or without erythema over the catheter tunnel) for both HD and PD. Pneumonia was defined as radiologic evidence of pneumonia in the clinical setting of pneumonia. Peritonitis was defined as cloudy effluent with 
100/µl white cells with 50% of these polymorphonuclear cells. Cellulitis was defined as infection of subcutaneous tissue that required hospitalization. Bacteremia and fungemia were defined by positive blood cultures. "Other infections" that required hospital admission included infected limb ulcers.
Infectious rates were calculated by dividing the total number of infections by total time at risk in the HD or PD cohorts and expressed as number of infections per dialysis year. We also expressed rates as the number of episodes per 1000 d at risk because this is the way it generally is expressed in HD. All hospitalizations as a result of infections were included in the analysis as well as all access-related infections. We also determined the rate of infection during the first 90 d of dialysis, both HD and PD.
Protocols to reduce the risk for infections were used in both the HD and PD programs. All patients with HD catheters had antibiotic cream placed at the exit site after cleansing of the site at the end of dialysis as part of routine HD catheter care, done by the staff. All HD patients with a catheter were asked to keep this dry and specifically to refrain from showers. All PD patients were instructed to wash the PD catheter exit site using antibacterial soap in the shower and then after the shower use a cotton swab to put antibiotic cream around the catheter at the exit site. PD patients were told to avoid tub baths.
Statistical Analyses
Variables (PD versus HD) were compared using t test, Mann-Whitney U test, or 
2 test, as appropriate. Poisson regression analysis was used to assess the impact of various factors on outcome of interest (total infections and infections that required hospitalization). Because age and diabetes are part of CCI, they were not analyzed as separate covariables. Two different models were used for multivariate Poisson regression to evaluate the impact of variables (one with age and diabetes and the other with CCI along with other variables) because age and diabetes are part of CCI. Interactions of dialysis modality with age, race, gender, diabetes, and CCI were tested. Because an interaction was found between modality and diabetes, separate models also were run in those with and without diabetes. Number Crunch Statistical System software (Dr. Jerry Hintze, Kaysville, UT) was used for statistical analysis.
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Results |
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Overall rates of catheter infection (exit site and tunnel) were similar for HD and PD patients (0.35 versus 0.41 per year; P = 0.20, respectively). S. aureus catheter infections for HD were 0.05 per year. This was comparable to 0.07 per year for PD (P = 0.30).
Rates of infection for CAPD versus APD were not different. There were no episodes of peritonitis on CAPD compared with 0.26 per year on APD (P = 0.14). Catheter infection rates were similar, 0.35 per year on CAPD and 0.42 per year on APD (P = 0.43).
Table 3 shows the results of the multivariate analysis. In the first model, CCI (which includes both age and diabetes) was used, whereas in the second model, age and diabetes were used in place of CCI. In both models, a decreased serum albumin at the start of dialysis was a strong predictor of subsequent infection. Black patients were at decreased risk for infection in both models. Dialysis modality (PD versus HD) was not an independent risk for infection; neither was gender. In the second model, which separates diabetes and age, younger age was a risk factor for infection as was the presence of diabetes.
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Interactions
There was not a significant interaction of modality with age, albumin, or CCI. However, significant interactions were seen with modality and diabetes (P = 0.02). In addition, there were important interactions in infection risk for modality and gender (P = 0.04).
The interaction between modality and diabetes for infection risk was explored further. Patients who had diabetes and were on PD had higher infection rates than patients who had diabetes and were on HD (1.28 versus 0.84/yr; P < 0.004). Conversely, patients without diabetes had a lower risk for infection on PD than on HD (0.51 versus 0.69/yr; P < 0.03). Separate models were run in patients with and without diabetes. Adjustment for albumin, age, race, gender, and dialysis modality was NS in individuals with diabetes (RR 1.13; 95% confidence interval [CI] 0.76 to 1.67; P = 0.55) or in individuals without diabetes (RR 0.67; 95% CI 0.37 to 1.21; P = 0.18).
The interaction between modality and gender (P = 0.04) for infection risk also was evaluated further. Men who were on PD had a significantly higher rate of infection than women who were on PD (1.07 versus 0.71/yr; P < 0.009). In contrast, infection rates were the same in men and women who were on HD. When stratified by gender and controlling for age, race, and diabetes, significant differences were seen in infection rate by modality for men (PD versus HD: RR 1.92; 95% CI 1.13 to 3.27; P = 0.02) and women (PD versus HD: RR 0.61; 95% CI 0.39 to 0.96; P = 0.03).
White patients had a similar infection rate on PD and HD (0.99 versus 0.97/yr). However, black patients had a lower rate of infections on PD than on HD (0.44 versus 0.68; P < 0.002). This held true with the multivariate analysis as well.
Hospitalization for Infections
The all-cause admission rate was 2.4 per dialysis year for HD and 1.4 per dialysis year for PD (P < 0.001). However, PD patients had a higher rate of infection-related hospitalization (0.42 versus 0.29 hospitalization per year at risk; P < 0.001). Two models were used for multivariate Poisson regression analysis for infections that required hospitalization, one with CCI, albumin, gender, race, and modality and a second model using age, diabetes, albumin, gender, race, and modality (Table 4). Albumin and modality were significant predictors in both models. CCI was significant in the first model as were age and diabetes in the second model. There were no significant interactions of race or diabetes with modality for the risk for hospitalization for infection. However, there was a trend for interaction of gender with mode for hospitalization for infection (P = 0.06). Men who were on PD had a higher admission rate for infection compared with men who were on HD (0.59 versus 0.32 per dialysis year), whereas women who were on PD had similar rates of infection as women who were on HD (0.29 versus 0.24 per dialysis year).
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Discussion |
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The risk for bacteremia in HD patients was strikingly increased during the first 90 d of dialysis. The early risk for bacteremia in HD patients very likely is related to the use of HD catheters as the initial access in 67% of our HD patients, similar to that reported in the CHOICE study (8). HD catheters are widely known to increase the risk for bacteremia (4,5). These results support the need for a fistula-first protocol so that all patients who want HD have a fistula placed before commencement of dialysis (5). If HD catheter use could be avoided with careful planning of dialysis initiation, then it is possible that the risk for infection actually may be lower for HD compared with PD. In some cases, this may require placing an HD graft if a primary fistula cannot be achieved in a timely manner. For patients who desire PD, a prudent approach would be to place a PD catheter in a timely manner and avoid a period on HD with an HD catheter. This approach is very likely to decrease the risk for bacteremia.
Our study refutes the common misconception that PD is associated with an overall higher rate of infection as compared with HD. In particular, we found bacteremia to be a complication almost solely of HD. These results are consistent with those of Abbott and Agodoa (11), who examined 327,993 patients who initiated dialysis between January 1992 and June 1997 for risk for hospitalization for bacterial endocarditis. HD patients had an RR of 17.86 (95% CI 6.62 to 48.90) compared with the general population in 1996. This was in contrast to PD patients, who had an insignificant increased risk compared with the general population (10.54; 95% CI 0.71 to 158.13).
When septicemia is examined, as opposed to endocarditis, the evidence is less clear. Powe et al. (12) examined data from the USRDS and found that 11.7% of HD patients and 9.4% of PD patients had during 7 yr at least one episode of septicemia. Part of the problem with examining septicemia from the USRDS is the lack of clarity regarding the definition of septicemia as pointed out recently by O’Seaghdha and Foley (13). Sepsis and septicemia may be confused with peritonitis by the coding doctors. The USRDS does not provide a definition of septicemia, and it is not clear that doctors are using this only for bacteremia. To study this further through the USRDS successfully will require abandoning the term "septicemia" and replacing it with more specific terms, such as bacteremia and peritonitis.
In a center with a low incidence of both bacteremia in HD patients and peritonitis in PD patients, the overall rate of infection was similar in the two cohorts. Our center rate for catheter-related bacteremia in HD of 1.2 per 1000 d (Figure 1) is well below recent published rates of 2.5 to 5.5 per 1000 patient days (14). Likewise, our center rate for peritonitis of 0.24 per patient year (one episode per 50 dialysis months) is a low rate but certainly achievable by other centers (15). The low rates of bacteremia and peritonitis at our center may be due to the close attention to infectious risk, patient and staff training, and prophylactic use of exit-site antibiotic cream to prevent exit-site infection in both HD and PD patients (16,17).
We found a low serum albumin at the start of dialysis, younger age, race, and the presence of diabetes to be the strongest risk factors for overall infections, regardless of modality and controlling for other comorbid conditions. Our findings are consistent with other studies showing the presence of diabetes, low serum albumin, and temporary vascular access to be risk factors for septicemia in HD patients (10,18,19). Hypoalbuminemia also has been shown to be a risk factor for subsequent peritonitis (20–22). This relationship between hypoalbuminemia and infection in dialysis patients is an association rather than a proven causal relationship. Precisely how a low serum albumin level increases the risk for infection in both HD and PD patients is uncertain.
We found a higher rate of admissions for infection in the PD patients compared with the HD patients. PD patients were likely to be admitted to the hospital for management of infections, especially limb ulcers and peritonitis. Vascular access may make it less likely to hospitalize HD patients for treatment of limb ulcers, because patients can receive intravenous antibiotics during dialysis. However, the overall hospitalization rate was lower among PD patients. Many dialysis-related infections are treated as outpatients. Studies that use only admissions for infections will not determine accurately the infection rates for the two modalities.
There were interesting interactions between infection risks on the two modalities and both race and diabetes. Black patients had a lower rate of infection on PD than on HD. Historically, in the United States, black patients are less likely to be placed on PD for somewhat unclear reasons, but some literature suggests a higher risk for infection on PD compared with other patients (23). Most of this literature is older; with new technology and the decrease in coagulase-negative infections, black patients may no longer have a higher risk for infection. Our results suggest that PD may be underused in black patients and that in regard to infection risk, PD is a good choice for this population. However, the total number of black patients who were on PD in our study is small, so further studies should confirm our finding.
Patients with diabetes seem to have a higher risk for infection on PD than on HD. This result was independent of serum albumin level at the start of dialysis. These results are consistent with the finding of Sarnak and Jaber (24), who found that patients who have diabetes and are on PD had a strikingly higher risk for death from "sepsis" than patients who did not have diabetes and were on PD. We also found a lower rate of infection on PD for individuals without diabetes. It is interesting to speculate as to whether this may explain the results of some observational studies showing a higher risk for death with increasing time on dialysis with PD compared with HD for patients with diabetes. More studies will be needed in this area.
There are limitations to this study. The study is based on a single center. Our unit is an academic dialysis unit, and our overall infection rate is low in both PD and HD compared with many other centers. As with all observational studies, there may be confounding by selection bias. We use exit-site antibiotic prophylaxis to decrease the rate of both peritonitis (PD) and bacteremia (HD), and this may be a different approach than in other programs. Our numbers limit the evaluation of the interactions between race and diabetes with infections on modalities. Whether our results could be generalized to other sites or units with higher infection rates is not known.
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Conclusion |
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Acknowledgments |
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B.P. and J.B. are consultants and on the Speakers Bureau for Baxter Healthcare Corporation. We do not believe that these represent a conflict of interest for the subject matter of this article.
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Footnotes |
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a N.A.'s current affiliation is Fatima Memorial Medical and Dental College, Lahore, Punjab Province, Pakistan. 
Received April 14, 2006. Accepted September 11, 2006.
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This article has been cited by other articles:
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  L. S. Dalrymple and A. S. Go Epidemiology of Acute Infections among Patients with Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1487 - 1493. [Abstract] [Full Text] [PDF]
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 T. Lobbedez, A. Lecouf, M. Ficheux, P. Henri, B. H. de Ligny, and J.-P. Ryckelynck Is rapid initiation of peritoneal dialysis feasible in unplanned dialysis patients? A single-centre experience Nephrol. Dial. Transplant., April 19, 2008; (2008) gfn213v1. [Abstract] [Full Text] [PDF]
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 A. Davenport Pyrexia of unknown origin in a haemodialysis patient NDT Plus, April 1, 2008; 1(2): 109 - 111. [Full Text] [PDF]
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O. Khawar, K. Kalantar-Zadeh, W. K. Lo, D. Johnson, and R. Mehrotra Is the Declining Use of Long-Term Peritoneal Dialysis Justified by Outcome Data? Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1317 - 1328. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
) and peritoneal dialysis (PD;
). Data are episodes per 1000 d at risk.