Posttransplant Outcomes of Peritoneal Dialysis Versus Hemodialysis Patients

Posttransplant Outcomes of Peritoneal Dialysis Versus Hemodialysis Patients C. Freitas, M. Fructuoso, L.S. Martins, M. Almeida, S. Pedroso, L. Dias, A.C. Henriques, and A. Cabrita ABSTRACT The impact of dialysis modality on posttransplant outcomes remains controversial. The authors have compared primary failure, delayed graft function (DGF), acute rejection episodes as well as patient and allograft survivals among patients undergoing renal transplantation between 2004 and 2009, according to the modality of hemodialysis (HD) versus peritoneal dialysis (PD). We studied 306 patients (268 HD and 38 PD) with a mean follow-up of 29 ⫾ 16 months. The PD cohort included a predominance of females (68.4% vs 36.2%; P ⫽ .001), lower age at transplantation (38 ⫾ 14 vs 46 ⫾ 12 years; P ⫽ .004), shorter time on dialysis (33 ⫾ 49 vs 59 ⫾ 157 months; P ⫽ .043), and higher rate of living donor grafts (PD 31.6% vs HD 13.1%; P ⫽ .003). Donor age (PD 43 ⫾ 13 vs HD 45 ⫾ 14 years; P ⫽ .30), human leukocyte antigen mismatch (P ⫽ .17), panel reactive antibody values (HD 11 ⫾ 22 vs PD 13 ⫾ 26; P ⫽ .55), and hyperimunized patients (HD 3.73%; PD 7.89%; P ⫽ .23) were not different. Primary graft failure (3.4% vs 0%; P ⫽ .025) and DGF (37.1% vs 13.1%; P ⫽ .037) were more frequent among HD patients, but incidences of acute rejection episodes were similar (HD 10.5% vs PD 5.3%; P ⫽ 0.19). Neither recipient survival at 1 (97% in PD and HD) or 3 years (HD 90% vs PD 94%; P ⫽ .657) nor allograft survival at 1 year (HD 94% vs PD 95%; P ⫽ .80) or 3 years: (HD 70%, vs PD 81%; P ⫽ .73) were different. Graft function was similar at 1 (HD 64.2 ⫾ 25 vs PD 56.4 ⫾ 24 mL/min; P ⫽ .17) and 3 years (HD 62.3 ⫾ 21 vs PD 46 ⫾ 23 mL/min; P ⫽ .16). In our study, HD patients showed an higher incidence of DGF and primary allograft failure, but there was no difference in acute rejection episodes, long-term survivals, or renal function. OR SUITABLE patients with end-stage renal disease (ESRD), kidney transplantation is superior to dialysis in terms of mortality risk and quality of life.1–3 Preemptive renal transplantation is the best option because it reduces the incidence of acute rejection episodes and prolongs graft and patient survivals.4,18 Unfortunately, most patients do not have a potential living donor and the usual waiting period for a deceased donor organ remains long.5 The use of pretransplant dialysis becomes essential. Hemodialysis (HD) and peritoneal dialysis (PD) are alternative options for ESRD patients.5 The impact of pretransplantation dialysis modality on transplant outcomes has been a matter of interest for a long time.7 Increased time on dialysis pretransplantation has been associated with negative graft and recipient outcomes,6 but studies about the impact of dialysis modality on posttransplant outcomes have shown conflicting results.5,8 To institute prophylactic measures, it is essential to understand whether a given dialysis modality is associated with a particular posttrans-

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© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 43, 113–116 (2011)

plantation complication.5 The authors studied the effect of pretransplantation dialysis modality (HD or PD) on posttransplant outcomes among kidney transplant recipients, focusing on short-term events, including primary failure, delayed graft function (DGF) and acute rejection episodes, as well as long-term patient and allograft survivals. PATIENTS AND METHODS We retrospectively studied 306 consecutive adult patients undergoing renal transplantation between January 2004 and June 2009 in a single transplant center. All patients were either on HD (n ⫽ 268) From the Department of Nephrology (C.F., M.F., L.S.M., M.A., S.P., L.D., A.C.H., A.C.), and the Department of Transplantation (L.S.M., M.A., S.P., L.D., A.C.H.), Santo António Hospital, Porto, Portugal. Address reprint requests to Cristina Freitas, Largo do Professor Abel Salazar, 4099-001 Porto, Portugal. E-mail: crislmf@ yahoo.com.br 0041-1345/–see front matter doi:10.1016/j.transproceed.2010.12.008 113

114 or PD (n ⫽ 38) before transplantation. We excluded preemptive patients. The majority of patients (100% on PD, 99% on HD) were treated with a calcineurin inhibitor-based regimen as well as monoclonal or polyclonal antibody induction therapy in 271 patients. The mean follow-up was 29 ⫾ 16 months. We gathered clinical data of recipient age and gender, ESRD cause, dialysis duration, dialysis modality before transplantation, last panel reactive antibody (PRA), donor age, human leukocyte antigen (HLA) mismatch, delayed graft function (DGF; characterized as the need for dialysis in the first week posttransplantation), acute rejection episodes (confirmed by biopsy), and renal function at 12, 24, and 36 months. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) study equation, based on serum creatinine, age, gender and race. The statistical analysis was performed with SPSS 15.0 for Windows (SPSS, Inc., Chicago, Ill). Univariate analysis used chi-square or Student’s t-test for categorial or continuous data, respectively. P ⬍ .05 was considered significant.

RESULTS

Among the 306 patients who underwent transplantation, 183 (59.8%) were males. The overall mean age at transplantation was 44.8 ⫾ 12.6 years (range, 16 –74). Before transplantation, 268 patients (87.6%) were on HD and 38 (14.4%) on PD. The median time on dialysis was 58.1 ⫾ 69.0 months (range, 3– 404). Patients were divided into 2 groups, according to the pretransplantation dialysis modality: HD versus PD. Donor, recipient, and transplant characteristics are summarized in Table 1. The number of diabetics (DP 2.6%; HD 8.2%; P ⫽ .22) was similar among the groups, but PD patients were predominantly females (68.4% vs 36.2%; P ⫽ .001), showed a lower mean age at transplantation (P ⫽ .004), and had less time on dialysis before transplantation (P ⫽ .043). Donor age, number of HLA mismatches, PRA values, and number of hyperimunized patients (PRA ⬎ 20%) were not different between groups, but the PD group included more living donor transplantations (31.6% vs 13.1%; P ⫽ .003). In both groups, most patients were immunosuppressed with antithymocyte globulin (ATG) or Daclizumab in combination with mofetil mycophenolate (MMF), tacrolimus (FK), and prednisolone (P). More primary graft failure was observed among HD patients (3.4% vs 0%; P ⫽ .025); it was secondary to allograft vein thrombosis (n ⫽ 6) or acute rejection episodes (n ⫽ 3). DGF was also more frequent among HD patients (37.1% vs 13.1%; P ⫽ .037), but the rate of acute rejection episodes was similar between the groups (P ⫽ .19). When comparing HD with PD, neither patient nor graft survivals at 1 or 3 years were significantly different (Table 1). The most frequent causes of graft loss were death with a functioning graft (HD 41.2% vs PD 50%; P ⫽ .81) and allograft venous thrombosis (HD 35.3% vs PD 50%; P ⫽ .68). Allograft function was similar among both groups at 1 (P ⫽ .17) and 3 (P ⫽ .16) years posttransplantation.

FREITAS, FRUCTUOSO, MARTINS ET AL Table 1. Donor, Recipient, and Transplant Characteristics Characteristics

Donor gender (male/female) Donor age (y) ESRD etiology Diabetic nephropathy Glomerular Other Time on dialysis (mo) Number of allografts (1/⬎1) Living/deceased donor Donor age (y) HLA identities (mean) HLA mismatch 0/1–6 PRA ⬎20%/⬍20% Primary failure DGF Acute rejection Recipient survival (y) 1 2 3 Allograft survival (y) 1 2 3 Allograft function (mL/min) eGRF year 1 eGRF year 2 eGRF year 3

HD Patients (n ⫽ 268)

171/97

PD Patients (n ⫽ 38)

P

12/26

.001

45.8 ⫾ 12.1

38.2 ⫾ 14.1

.004

18 129 121 33.0 ⫾ 49.6 222/46 35/233 44.8 ⫾ 14.2 2⫾1 6/262 49/219 9/259 96/163 28/240

1 14 23 59.5 ⫾ 157.3 33/5 12/26 42.3 ⫾ 13.2 3⫾2 3/35 8/30 0 5/33 2/36

.33 .19 .08 .043 .54 .03 .30 .17 .06 .55 .025 .037 .19

97.0% 93.9% 90.3%

97.4% 96.2% 93.7%

.90 .65 .16

93.7% 88.5% 70%

94.7% 88.5% 81.2%

.80 .99 .73

64.2 ⫾ 25.1 61.6 ⫾ 21.3 62.3 ⫾ 21.5

56.3 ⫾ 24.8 55.9 ⫾ 22.9 46.5 ⫾ 22.6

.17 .18 .16

eGRF, estimated graft renal function.

DISCUSSION

In this study, PD patients were mostly women, showed a younger mean age than HD patients, and has time on dialysis before transplantation and received more living donor organs. Recipient age8 is a predictive factor for graft and patient survival.8 Each year of life increases the risk of graft failure by 1%8 and the risk of recipient death by 4%.8 Whether recipient gender influences short-term graft outcomes is controversial; some authors have associated DGF with female gender,9 but others have reported no relation.10 Longer time on dialysis before transplantation has been6,7,11 negatively associated with short-term allograft outcomes7 and recipient survival.6 The risk of graft failure increases by 2%8 and patient death by 4%–5%8 for each year that the patient stays on PD or HD.8 Living donation is associated with a lower risk of graft failure,8,12 of DGF,13 and of recipient death.8 The studies on the influence of dialysis modality on posttransplant outcomes have shown conflicting results.5,8 Some authors14,15 have described a protective effect of PD on graft and recipient survivals8; others have reported, that especially in older and diabetic subjects16 PD is associated with higher rates of early and long-term death-censored graft failure16,17;

POSTTRANSPLANT OUTCOMES

whereas other workers did not observe graft or patient survivals to be affected by dialysis modality.15,18 Our results showed an higher incidence of DGF and primary allograft failure among HD patients, but no relation was found with acute rejection episodes, with allograft and patient survivals, or with allograft function at 12, 24, or 36 months. DGF shows a negative impact on recipient and graft survivals19,20 as well as renal function.9,19,21 It is associated with nearly a 3 time higher risk of death and death-censored graft failure17 as well as a 38% increased risk of an acute rejection episode19,21 and a higher mean serum creatinine value at 3.5 years follow-up.19 As in our study, HD as the dialysis modality has been associated with a greater incidence of DGF after renal transplantation.14 –17,22,23 The mechanism is not completely clear.8,15 Residual renal function that may be better preserved in PD patients15 could be responsible for a more physiologic water balance15 posttransplantation thereby contributing to better preservation of graft function.7,14,15 Other factors, particularly living donation,13 donor age, ischemia times, HLA match, PRA status, and recipient body weight24 can affect immediate kidney function. In our study, living donation was less common among HD patients, who experienced a greater rate of DGF, but no relation was established with donor age, ischemia times, HLA matches, or PRA status. HD patients experienced an higher rate of primary graft failure, mostly owing to graft vascular thrombosis. The literature, contrary to our results suggests that renal thrombosis is the major cause of graft lost among PD patients within the first year posttransplantation8,23,25; it was nearly 10-fold higher26 than that in HD patients. The mechanism is not known, but some authors have hypothesized that it may be explained because hypercoagulable states are not detected as readily in PD as in HD patients.8 Early graft venous thrombosis is usually associated with an acute rejection episode or a surgical complication.27,28 In our study, no difference was noted in the acute rejection episodes between patients on PD and HD. However, HD patients were older and on dialysis for longer times. Dialysis patients have a 5- to 6-fold increased risk of cardiovascular disease29; peripheral vasculopathy is known to be associated with longer times on dialysis.30 We may hypothesize that our HD patients have more atherosclerotic disease predisposing to surgical complications and graft thrombosis. Although we observed a relation between HD as the pretransplant dialysis modality and greater rates of DGF and primary graft failure, there was no relation to long-term outcomes of graft and patient survivals. The small number of patients on PD when compared with HD impaired the statistical power of the study; a false-negative result may be present. Furthermore, differences in recipient age, time on dialysis, and living donation may act as confounding factors. Therefore, it is not possible to confirm a relation between prior HD and inferior short-time posttransplant outcomes. In conclusion, our study supported the concept that dialysis modality may influence short-term posttransplant

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outcomes such as primary failure and DGF. Pretransplant dialysis modality did not influence long-term results among our patients. REFERENCES 1. Papalois VE, Moss A, Gillingham KJ, et al: Pre-emptive transplants for patients with renal failure: an argument against waiting until dyalisis. Transplantation 70:625, 2000 2. Asderakis A, Agustine T, Dyler P, et al: Pre-emptive kidney transplantation: the attractive alternative. Nephrol Dial Transplant 13:1799, 1998 3. Wolfe RA, Ashby VB, Milford EL, et al: Comparison of mortality in all patients on dialysis, patients on dialysis waiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341:1725, 1999 4. Kasiske BL, Snyder JJ, Matas AJ, et al: Preemptive kidney transplantation: the advantage and advantaged. J Am Soc Nephrol 13:1358, 2002 5. Helal I, Abdereahim E, Hamida B, et al: Impact of dialysis modality on posttransplantation results in kidney transplantation. Transplant Proc 39:2547, 2009 6. Cosio FG, Alamir A, Yim S, et al: Patients survival after renal tranplantation: The impact of dialysis pre-transplant. Kidney Int 53:767, 1998 7. Bleyer AJ, Burkart JM, Russell GB, et al: Dialysis modality and delayed graft function after cadaveric renal transplantation. J Am Soc Nephrol 10:154, 1999 8. Goldfarb-Rumyantzev AS, Hurdle JF, Scandling JD, et al: The role of pretransplantation renal replacement therapy modality in kidney allograft and recipient survival. Kidney Int 3:537, 2005 9. Junhinskis J, Trushkov S, Bicans J, et al: Risk factors for development of delayed graft function in deceased donor renal transplants. Transplant Proc 41:746, 2009 10. Jung GO, Yoon MR, Kim SJ, et al: The risk of delayed graft function and comparison of clinical outcomes after deceased donor kidney transplantation: single-center study. Transplant Proc 42: 705, 2010 11. Resende L, Guerra J, Santana C, et al: Influence of dialysis duration and modality on kidney transplant outcomes. Transplant Proc 41:837, 2009 12. Port FK, Dyktra DM, Merion RM, et al: Trends and results for organ donation and transplantation in United States. Am J Transplant 5:843, 2005 13. Sharma AK, Tolani SL, Rathi GL, et al: Evaluation of factors causing delayed graft function in live related donor renal transplantation. Saudi J Kidney Dis Transplant 21:242, 2010 14. Vanholder R, Heering P, Loo AV, et al: Reduced incidence of acute renal failure in patients treated with peritoneal dialysis compared with hemodialysis. Am J Kidney Dis 33:934, 1999 15. Caliskan Y, Yazici H, Gorgulu N, et al: Effect of pretransplant dialysis modality on kidney transplantation outocome. Perit Dial Int 29(Suppl 2):S117, 2009 16. Joseph JT, Jindal RM: Influence of dialysis on posttransplant events. Clin Transplant 16:18, 2002 17. Snyder JJ, Kasiske BL, Gilbertson DT, et al: A comparison of transplant outocomes in peritoneal and hemodialysis patients. Kidney Int 62:1423, 2002 18. Yang Q, Zhao S, Chen W, et al: Influence of dialysis modality on renal transplant complications and outcomes. Clin Nephrol 72:62, 2009 19. Yarlagadda SG, Coca SG, Formica RN Jr, et al: Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant 24:1039, 2009 20. Quiroga I, McShane P, Koo DD, et al: Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant 21:1689, 2006

116 21. Boom H, Mallat MJ, de Fijter JW, et al: Delayed graft function influences renal function but not survival. Kidney Int 58:859, 2000 22. Van Bissen W, Vanholder R, Van Loo A, et al: Peritoneal dialysis favourably influences early graft function after renal transplantation compared to hemodialysis. Transplantation 69:508, 2000 23. Ojo AO, Hanson JA, Wolfe RA, et al: Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients. Kidney Int 55:1952, 1999 24. Meurisse M, Albert A, Defraigne JO, et al: Multiple risk factor analysis of non-immunological delayed graft function after kidney transplantation. Clin Transplant 3:312, 1988 25. Palomar R, Morales P, Rodrigo E, et al: Venous graft thrombosis in patients on peritoneal dialysis before transplantation. Transplant Proc 39:2128, 2007

FREITAS, FRUCTUOSO, MARTINS ET AL 26. Murphy BG, Hill CM, Middleton D, et al: Increased renal allograft thrombosis in CAPD patients. Nephrol Dial Transplant 9:1166, 1994 27. Bakir N, Sluiter WJ, Ploeg RJ, et al: Primary renal graft thrombosis. Nephrol Dial Transplant 11:140, 1996 28. Aschwander M, Thalhammer C, Schaub S, et al: Renal thrombosis after renal transplantation - early diagnosis by duplex sonography prevented fatal outcome. Nephrol Dial Transplant 21:825, 2006 29. Xue JL, Frazier ET, Herzog CA, et al: Association of heart disease with diabetes and hypertension in patients with ESRD. Am J Kidney Dis 45:316, 2005 30. O’Hare AM, Hsu CY, Bacchetti P, et al: Peripheral vascular disease risk factors among patients undergoing hemodialysis. J Am Soc Nephrol 13:497, 2002