Outcome in patients with end-stage renal disease following heart or heart–lung transplantation receiving peritoneal dialysis

Shyama D. Jayasena, Ahmad Riaz, Christina M. Lewis, Guy H. Neild, F. Derek Thompson and Robin G. Woolfson

Department of Nephrology, Middlesex Hospital, UCLH Trust, London, UK



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. End-stage renal disease (ESRD) complicates 5–10% of heart and heart–lung transplant patients. We report our experience of peritoneal dialysis (PD) in 17 such patients.

Methods. Between March 1995 and February 1999, 13 heart transplant and four heart–lung transplant patients (11 male, 6 female) joined our PD programme (10 continuous ambulatory PD, seven automated PD). Median time from heart or heart–lung transplantation to ESRD was 9 years (range 1–13 years), and median age at introduction of renal replacement therapy was 51 years (range 23–66 years). The frequency of exit-site infections, peritonitis, and PD survival (including technique failure and death) in the transplant group (TxP) was calculated retrospectively. These were compared with two contemporary control groups: PD patients immunosuppressed for other indications (ISP, n=19) and, all other patients recruited onto the PD programme (NISP, n=132).

Results. Median follow-up was 10 months (range 2–27 months) for TxP, 7 months (range 2–29 months) for ISP, and 14 months (range 1–48 months) for NISP groups. The frequency of exit-site infections was similar in each group: 1 in 26 months for TxP; 1 in 30 months for ISP, and 1 in 27 months for NISP (P=NS). The frequency of peritonitis was greater in the TxP group at 1 in 15 months, compared with 1 in 20 months for ISP and 1 in 29 months for NISP (TxP vs NISP, P<0.05). PD failure following infection was 23.5% for TxP, 10.5% for ISP, and 12.9% for NISP. Actuarial PD survival at 24 months was only 25.2% in the TxP group compared with 79% in the NISP group. There were no deaths related to immediate complications of PD.

Conclusions. Increased risk of PD peritonitis and reduced PD survival is reported in this cohort of 17 heart and heart–lung recipients with ESRD. Nevertheless, for patients with severely impaired cardiac function, PD may still offer therapeutic advantage.

Keywords: cardiac function; end-stage renal disease; exit-site infection; heart; heart-lung transplantation; peritoneal dialysis; peritonitis



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The outcome from heart and heart–lung transplantation has improved considerably following the introduction of cyclosporin and, more recently, tacrolimus. Although patient survival now exceeds 50% at 10 years after heart transplantation [1], one consequence is an increasing number of patients who develop end-stage renal disease (ESRD) due to calcineurin inhibitor nephrotoxicity [2,3]. ESRD affects 10% of heart transplants after 10 years and 10% of heart–lung transplants after 5 years [2]. Review of the published literature indicates that most of these patients with ESRD have been treated with either haemodialysis or renal transplantation [4,5].

Peritoneal dialysis (PD) is a safe and effective alternative to haemodialysis in the treatment of ESRD and offers significant advantage to patients with co-morbidities, particularly those with impaired cardiac function. In addition, more prolonged preservation of residual renal function, less strict control of diet and fluid intake and increased independence makes this treatment more attractive in patients starting dialysis. Peritonitis and exit-site infections are the main complications of PD, although the introduction of disconnect and automated PD systems have reduced the frequency of peritonitis significantly. There are data to suggest that non-transplant immunosuppression predisposes to episodes of peritonitis and can adversely affect outcome [6], but the literature contains few reports regarding the use of PD to treat ESRD in patients immunosuppressed for continuing solid-organ transplantation. Heart and heart–lung transplant recipients commonly have significant cardiovascular co-morbidities, and PD is therefore an attractive therapeutic strategy for these patients. Since 1995 we have offered PD to this patient group and in this paper we report our clinical experience with 17 such patients.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
This is a retrospective study of heart and heart–lung transplant recipients who received outpatient PD treatment for ESRD attributed to cyclosporin or tacrolimus nephrotoxicity. All patients had previously undergone transplantation at the Cardiac Transplant unit, Harefield Hospital, and all PD was prescribed and managed by the PD Unit, Middlesex Hospital. Between 1 March 1995 and 28 February 1999, 17 heart or heart–lung transplant recipients (TxP) were treated with PD. Outcome data were compared with two other contemporary control groups. Firstly, a group of 19 patients requiring continuing immunosuppression for other indications, such as autoimmune disease and recent transplant failure (ISP), and secondly, 132 non-immunosuppressed patients (NISP) recruited onto the PD programme during that period.

In our PD Unit, all episodes of peritonitis and exit-site infection are prospectively recorded and these data were validated by checking both the patient's case notes and the records of the Microbiology Department. All patients were dialysed either by continuous ambulatory PD (Solo Disconnect System, Baxter Inc) or by automated PD (Home Choice System, Baxter Inc).

The outcome measures in this study were the frequencies of exit-site infection and peritonitis, and survival of PD.

Statistical methods
Comparisons between groups were performed using the chi squared test with two degrees of freedom. The criterion of statistical significance was taken as P<0.05.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Patient groups
TxP group
The clinical characteristics of the 17 TxP patients (median age 51 years, range 23–66 years, 11 males) are shown in Table 1Go. Patients 3, 16 and 17 were selected for treatment with PD because of poor cardiac status. Patients 16 and 17 started PD early because of diuretic-resistant fluid retention and remained hypotensive (systolic BP<100 mmHg) throughout. Patient 12 was offered PD because of lack of vascular access and poor cardiac status. The remaining patients chose PD as their preferred mode of treatment for ESRD.


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Table 1. Clinical characteristics of TxP group

 
After a median patient follow-up of 10 months (range 2–27 months), the incidence of exit-site infection and peritonitis, and the immunosuppressive regimen are presented in Table 2Go. The total number of exit-site infections was eight and there were 14 episodes of peritonitis. Of the 17 patients, three were immunosuppressed without prednisolone and eight were taking three immunosuppressive drugs concurrently.


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Table 2. Comparison of peritonitis and exit-site infection (ESI) rates in heart/heart–lung transplant recipients (TxP), immunosuppressed patients (ISP) and non-immunosuppressed patients (NISP) undergoing peritoneal dialysis

 

ISP group
Table 3Go shows the clinical data of the 19 ISP patients (median age 53 years, range 17–42 years, six males). After a median patient follow-up of 7 months (range 2–29 months), the incidence of exit-site infection and peritonitis, and immunosuppressive regimen are presented in Table 2Go. The total number of exit-site infections was six and there were nine episodes of peritonitis. All 19 patients in the ISP group were on prednisolone and only one patient in this group was taking three immunosuppressive drugs simultaneously.


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Table 3. Clinical characteristics of ISP group PD patients immunosuppressed for reasons other than heart or heart/lung transplantation

 

NISP group
The comparative group of NISP patients taken on to the PD programme during the period March 1995 to March 1999 consisted of 132 patients (84 male). The median age when starting PD was 52 years (range 17–83 years) with a median duration on PD of 14 months (range 1–48 months), see Table 2Go. The total number of exit-site infections was 75, with 70 episodes of peritonitis. Two patients were lost to follow-up as a result of transfer to other renal units.

Episodes of infection
Exit-site infections
Comparative data for exit-site infections are presented in Table 4Go and no difference in exit-site infection rate was observed between groups. The spectrum of responsible organisms was similar in all three groups although CNS and Gram-negative infections were more common in the immunosuppressed patients (i.e. TxP and ISP groups), compared to NISP group in whom 77% of exit-site infections were due to Staphylococcus aureus infections. All episodes of MRSA infection in the TxP group occurred in one patient.


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Table 4. Comparison of infective organisms responsible for exit-site infection and peritonitis in heart/heart–lung transplant recipients (TxP), immunosuppressed patients (ISP), and non-immunosuppressed patients (NISP) undergoing peritoneal dialysis

 

Peritonitis
Comparative data for episodes of peritonitis are presented in Table 4Go. These show that peritonitis rates were significantly higher in the TxP group compared with the NISP group (P<0.05, {chi}2 test), with an intermediate peritonitis rate for the ISP group. The spectrum of responsible organisms was similar in all three groups, although Gram-negative infection was over-represented in the ISP group.

Patient outcome data
The percentage of patients who stopped PD because of infection (two recurrent peritonitis, one TB peritonitis, and one persistent exit-site infection) appears higher for the TxP compared with either the ISP or NISP groups which had very similar results (see Table 5Go). The percentage of patients dying on PD was much higher in the TxP group compared with either the ISP or NISP groups (see Table 5Go). Of the six deaths on PD, five were due to heart or heart–lung transplant failure and one due to stroke (see Table 1Go); none of these deaths was due to infective complications of PD.


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Table 5. Patient outcome data for heart/heart–lung transplant recipients (TxP), immunosuppressed patients (ISP), and non-immunosuppressed patients (NISP) undergoing peritoneal dialysis

 
Actuarial survival of PD data is shown in Figure 1Go and includes transfer of patients to HD and death of patients on PD. For the two patients who underwent renal transplantation, the data is censored to the date of transplantation. The figure shows similar rates of attrition for ISP and NISP groups but with a steady and more rapid fall-off in the TxP group, although numbers are relatively small. In view of the small numbers, no subgroup analyses were undertaken for CAPD vs APD.



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Fig. 1. Actuarial PD survival including treatment failure and death for heart/heart–lung transplant recipients (TxP), immunosuppressed patients (ISP), and non-immunosuppressed patients (NISP) undergoing peritoneal dialysis.

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
We have described the incidence and type of infective complications of PD in 17 patients with ESRD following heart or heart–lung transplantation, and have compared this with contemporary data from other immunosuppressed and non-immunosuppressed patients receiving PD. Although we observed no significant increase in the rate of exit-site infection in these transplant recipients, the rate of peritonitis was significantly increased compared with non-immunosuppressed patients. This increased infection rate was responsible for the increased failure of PD with transfer to HD, but was not responsible for the increased mortality on PD in this patient group.

The peritonitis rate in the ISP group was intermediate between that of the TxP group and the NISP group but was not significantly different from either. In contrast, Andrews and his colleagues [6] reported a significantly increased peritonitis rate in 39 immunosuppressed patients (mean age 44 years), including 24 failed renal-transplant recipients, six patients with vasculitis and four with SLE, when compared with 146 non-immunosuppressed patients. The difference in results may reflect our smaller sample size; however, their peritonitis rates were greater than those reported in our study with one episode of peritonitis per 7 patient months for immunosuppressed patients and one episode per 18 patient months for non-immunosuppressed patients. No data for exit-site infections were given in their study.

The spectrum of organisms responsible for infective episodes was similar in all three groups, although the rates of coagulase-negative staphylococcal and Gram-negative exit-site infection and peritonitis due to Gram-negative infection were higher in immunosuppressed patients. These patterns contrast with those reported by Andrews et al. [6] who noted an increased frequency of peritonitis due to Staph. aureus, Gram-negative, and fungal infection. Differences in levels of immunosuppression in their study compared with ours may account for these different patterns of infection. In our study, the levels of immunosuppression appeared to be similar in the TxP and ISP groups although no patients in the ISP group received triple therapy.

Mortality on PD for the TxP group exceeded that for the ISP and NISP groups, despite similar median age at initiation of dialysis. Most deaths in the TxP group were due to failure of the heart or heart–lung transplant and therefore reflect the greater cardiovascular co-morbidity of these patients, which is already present by the time they reach ESRD. The development of ESRD is well known to prejudice significantly the survival of heart-transplant recipients. Goldstein et al. [7] reported a 25% mortality at 12 months after the initiation of HD compared with an 8% mortality for patients who did not require dialysis. There are few published survival data for PD in these high-risk patients. Bernadini et al. [8] described 12 patients with ESRD following heart transplantation, of whom eight were initially treated with PD. Their overall survival, independent of subsequent dialysis modality, was 81% at 12 months and 44% at 24 months. The survival of PD patients was worse than for HD patients, a finding that the authors attributed to more severe co-morbidities. These outcome data are comparable to our findings and emphasize the very much worse prognosis compared with other immunosuppressed and non-immunosuppressed PD patients. In our study, no patient in the TxP group died as a result of complications of PD therapy, and most deaths in this patient cohort were due to cardiac failure. It is our clinical view that transplant patients with impaired cardiac function are relatively better managed by PD compared with HD.

In conclusion, we have shown that PD can be used safely to treat ESRD in immunosuppressed heart and heart–lung transplant recipients. However, the peritonitis rate in this group is significantly increased and is responsible for the increased rate of PD failure. Despite this, PD may still offer a therapeutic advantage, particularly in patients with impaired cardiac function.



   Notes
 
Correspondence and offprint requests to: Dr R. G. Woolfson, Department of Nephrology, Middlesex Hospital, Mortimer Street, London W1N 8AA, UK. Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. van Gelder T, Balk AHMM, Zietse R, Hesse C, Mochtar B, Weimar W. Renal insufficiency after heart transplantation: a case-control study. Nephrol Dial Transplant 1998; 13: 2322–2326[Abstract]
  2. Woolfson RG, Neild GH. Cyclosporin nephrotoxicity following cardiac transplantation. Nephrol Dial Transplant 1997; 12: 2054–2056[Free Full Text]
  3. Herlitz H, Lindelow B. Renal failure following cardiac transplantation. Nephrol Dial Transplant 2000; 15: 311–314[Free Full Text]
  4. Kuo PC, Luikart H, Busse-Henry S et al. Clinical outcomes of interval cadaveric renal transplantation in cardiac allograft recipients. Clin Transplant 1995; 9: 292–297
  5. Frimat L, Villemot J-P, Cormier L et al. Treatment of end-stage renal failure after heart transplantation. Nephrol Dial Transplant 1998; 13: 2905–2908[Abstract]
  6. Andrews PA, Warr KJ, Hicks JA, Cameron JS. Impaired outcome of continuous ambulatory peritoneal dialysis in immunosuppressed patients. Nephrol Dial Transplant 1996; 11: 1104–1108[Abstract]
  7. Goldstein DJ, Zuech N, Sehgal V, Weinberg AD, Drusin R, Cohen D. Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression. Transplantation 1997; 63: 664–668[ISI][Medline]
  8. Bernadini J, Piraino B, Kormos RL. Patient survival with renal replacement therapy in heart transplant patients. ASAIO J. 1998; 44: M546–548[ISI][Medline]
Received for publication: 27.12.00
Revision received 27. 3.01.