Patient outcomes after kidney allograft loss

doi:10.1016/j.trre.2007.09.005

Transplantation Reviews

Volume 22, Issue 1, January 2008, Pages 62-72

https://doi.org/10.1016/j.trre.2007.09.005 Get rights and content

Abstract

Despite considerable advances in immunosuppression and in short-term graft survival, little improvement has been observed in long-term survival rates. About 30% of patients lose their graft in the first 5 years, and this percentage increases up to 50% at 10 years. Graft losses, due to causes other than death with functioning graft, are an important cause of end-stage renal disease. Patients with failed graft account for 4% to 10% of those admitted yearly for dialysis therapy. There is no evidence about the superiority of hemodialysis or peritoneal dialysis in the treatment of these patients. Graft failure seems to be an important risk factor associated with morbidity and mortality, mostly in the first months after restarting dialysis. The causes of these high morbidity and mortality rates are not very well known. However, a poor control of the chronic kidney disease complications, the persistence of a chronic inflammatory state due to the failed graft, and the lack of a protective effect of the functioning graft could play an important role. This inflammatory state could be mediated by the presence of the rejected graft, and nephrectomy has been recommended. A variable number of patients with failed graft are relisted for a new transplant, thus increasing the shortage of organs. Graft survival of repeat transplantation with the new immunosuppressive regimens is very close to that of first-graft survival. Moreover, retransplantation increases patient survival rates in some series when compared with patients on dialysis. Complications during the first transplant such as BK virus nephropathy or lymphoproliferative diseases do not necessarily recur after the repeat transplant.

Introduction

Kidney transplantation has been considered as the most cost-effective therapy for end-stage renal disease. However, such improvements in morbidity and mortality attributed to transplantation could be due to a positive selection of patients. Kidney graft recipients are younger and have fewer morbid conditions than those remaining in dialysis. Comparison of patient survival between patients undergoing transplantation and those in the waiting list, with similar characteristics, has shown that transplant recipients have a lower risk of death than dialysis patients on the waiting list, even in long-term follow-up. Moreover, the benefits are larger among 20- to 39-year-old patients, white patients, and younger patients with diabetes [1], [2]. Further studies have confirmed these findings in countries outside the United States and Canada [3], [4] and in selected groups of high-risk patients [5]. Furthermore, they also have a better quality of life [6], [7], [8], [9] and consume fewer health care resources [10], [11]. Despite considerable advances in recipient care, in immunosuppression, and in the rate of short-term outcomes, long-term graft survival has experienced little improvement [12], [13]; and a single transplant is unlikely to meet the need of lifelong renal replacement therapy for many patients, particularly the youngest.

However, there are few reports dealing with the outcome and the management of patients who have lost their grafts and have returned to dialysis, particularly when we compare the amount of literature concerning the incidence of graft rejection, chronic allograft nephropathy, new immunosuppressive regimens and graft, and patient outcomes. There is no mention in the American [14] or European [15], [16] guidelines for renal transplantation about the care of patients who have lost their grafts. Moreover, in a recent conference in Lisbon about the care of renal transplant recipient in which kidney transplantation specialists from 3 continents took part, although most of the topics about the care of transplanted patients were debated, the aspects related with graft failure patients were obviated [17]. The purpose of the present article is to review (1) the impact of failed graft on dialysis programs, (2) the management of the graft loss patient, (3) the patient survival after graft loss, and (4) the effect of retransplantation on patient outcome.

Section snippets

Incidence and causes of graft loss

One-year graft survival reported by the Organ Procurement and Transplantation Network/United Network of Organ Sharing renal transplant registry is up to 90%. However, after a 5-year follow-up, around 30% of transplanted patients have lost their graft or have died with a functioning kidney [18]. The major causes of early graft failure, defined as occurring in the first 6 months after transplantation, are acute rejection, technical problems, and a nonviable kidney [19], [20]. After the first

Starting time

Patients with a failed kidney graft have some common characteristics. First, most of them have experienced an episode of great freedom and increased quality of life during their renal transplant period compared with the previous period when they were on dialysis. Second, they might have an increased morbidity due to a longer period of renal failure and to the effects of immunosuppressive therapy for variable, but many times, long periods. Finally, failed-graft patients are well known to

Patient outcome

It has been known for many years that death rates, when compared with those in patients with functioning kidney, are increased after graft loss [74], and the causes of death are similar to that observed in patients with functioning grafts (Table 3). Several other single-center studies, including our own institution (Fig. 1), reported similar results [75], [76], [77]. However, most of the data available in the literature about patient outcome are from the United States Renal Data System (USRDS).

Incidence

According to the data from single centers [21], [75], [76], [77], [84] and from the American registry [78], 40% to 70% of the patients who lose the graft and are treated with dialysis are included in the transplant waiting list for retransplantation, 20% to 30% are not included in the waiting list because of medical complication or because they do not want a second transplant, 10% to 30% die in the first years after graft loss (Table 4), and even 14% die during the first year [78]. Among the

Summary

Kidney graft loss is an important cause of end-stage renal disease. Graft failure increases patient mortality when compared with transplant with functioning grafts and even with never-transplanted dialysis patients in the waiting list. Cardiovascular diseases and infection seem to be the most important cause of the increased mortality after graft failure. This could be attributed, at least in part, to the increased incidence of some cardiovascular diseases such as acute coronary syndromes when

References (114)

A. Laupacis et al.
A study of the quality of life and cost-utility of renal transplantation
Kidney Int
(1996)
R. Jofre et al.
Changes in quality of life after renal transplantation
Am J Kidney Dis
(1998)
J. Whiting et al.
Cost-effectiveness of organ donation: evaluating investment into donor action and other donor initiatives
Am J Transplant
(2004)
H.-U. Meier-Kriesche et al.
Long-term allograft survival: have we made significant progress or is it time to rethink our analytical and therapeutic strategies?
Am J Transplant
(2004)
R. Marcén et al.
Renal transplant recipients outcome after losing the first graft
Transplant Proc
(2003)
S. Hariharan
Long-term kidney transplant survival
Am J Kidney Dis
(2001)
S. Coupel et al.
Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months
Kidney Int
(2003)
M. Arias et al.
Return to dialysis after renal transplantation. Which would be the best way?
Kidney Int
(2002)
J.S. Gill et al.
Opportunities to improve the care of patients with kidney transplant failure
Kidney Int
(2002)
R. Marcén et al.
Chronic kidney disease in renal transplant recipients
Transplant Proc
(2005)

G. Fernández-Fresnedo et al.

Relevance of chronic kidney disease classification (K/DOQI) in renal transplant patients

Transplant Proc

(2006)

D. Ansell et al.

Chronic renal failure in kidney transplant recipients. Do they receive optimum care?: data from the UK renal registry

Am J Transplant

(2007)

S.S. Khan et al.

Does predialysis nephrology care influence patient survival after initiation of dialysis?

Kidney Int

(2005)

S.V. Jassal et al.

Continued transplant immunosuppression may prolong survival after return to peritoneal analysis

Am J Kidney Dis

(2002)

F.P. Secin et al.

Cumulative incidence, indications, morbidity and mortality of transplant nephrectomy and the most appropriate time for graft removal: only nonfunctioning transplants that cause intractable complications should be excised

J Urol

(2003)

P. Delgado et al.

Intolerance syndrome in failed renal allografts: incidents and efficacy of percutaneous embolization

Am J Kidney Dis

(2005)

M.A. Zargar et al.

Reasons for transplant nephrectomy: a retrospective study of 60 cases

Transplant Proc

(2001)

A.K. Khakhar et al.

The impact of allograft nephrectomy on percent panel reactive antibody and clinical outcome

Transplant Proc

(2003)

V. Lorenzo et al.

Ablation of irreversibly rejected renal allograft by embolization with absolute ethanol: a new clinical application

Am J Kidney Dis

(1993)

F. Cofan et al.

Efficacy of renal vascular embolization versus surgical nephrectomy in the treatment of nonfunctioning renal allograft

Transplant Proc

(1999)

D. Hom et al.

Complete renal embolization as an alternative to nephrectomy

J Urol

(1999)

O.A. Adeyi et al.

Serum analysis after transplant nephrectomy reveals restricted antibody specificity against structurally defined HLA class I mismatches

Transpl Immunol

(2005)

R.J. Howard et al.

What happens to renal transplant recipients who lose their graft?

Am J Kidney Dis

(2001)

J.S. Gill et al.

Mortality after kidney transplant failure: the impact of non-immunologic factors

Kidney Int

(2002)

B. Kaplan et al.

Death after graft loss: an important late study endpoint in kidney transplantation

Am J Transplant

(2002)

P. Rao et al.

Survival on dialysis post-kidney transplant failure: results from the Scientific Registry of Transplant Recipients

Am J Transplant

(2007)

J.C. Magee et al.

Repeat organ transplantation in the United States, 1996–2005

Am J Transplant

(2007)

P.I. Terasaki

Humoral theory of transplantation

Am J Transplant

(2003)

M.C. Yagmurdur et al.

The effect of graft nephrectomy on long-term graft function and survival in kidney retransplantation

Transplant Proc

(2005)

R.R. Denny et al.

Survival on hemodialysis versus renal transplantation following primary renal allograft failure

Transplant Proc

(1997)

R. Wolfe et al.

Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant

N Engl J Med

(1999)

C.G. Rabbat et al.

Comparison of mortality risk for dialysis patients and first renal transplant recipients in Ontario Canada

J Am Soc Nephrol

(2000)

P. Schnuelle et al.

Impact or renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up

J Am Soc Nephrol

(1998)

S.P. McDonald et al.

Survival of cadaveric kidney transplant compared with those receiving dialysis treatment in Australia and New Zealand

Nephrol Dial Transplant

(2002)

A.O. Ojo et al.

Survival of marginal cadaveric donors compared with other recipients and wait-listed transplant candidates

J Am Soc Nephrol

(2001)

C.W. Pinson et al.

Health-related quality of life after different types of solid organ transplantation

Ann Surg

(2000)

A.J. Lee et al.

Characterisation and comparison of health related quality of life for patients with renal failure

Curr Med Res Opin

(2005)

F. Berthoux et al.

Epidemiological data of treated end-stage renal failure in the European Union (EU) during the year 1995: report of the European Renal Association Registry and the National Registries

Nephrol Dial Transplant

(1999)

R. Marcén et al.

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine

Transplantation

(2001)

B.L. Kasiske et al.

Recommendations for the outpatients surveillance of renal transplant recipients

J Am Soc Nephrol

(2000)

The EBPG expert group on renal transplantation. European best practice guidelines for renal transplantation (Part 1)....

The EBPG expert group on renal transplantation. European best practice guidelines for renal transplantation (Part 2)....

M. Abbud-Filho et al.

A report of the Lisbon conference on the care of the kidney transplant recipient

Transplantation

(2007)

J.M. Cecka

The OPTN/UNOS renal transplant registry

W.C.J. Amend et al.

The first three postransplant months

S. Prommool et al.

Time dependency of factors affecting renal allograft survival

J Am Soc Nephrol

(2000)

Excerpts from the United States renal data base. 2006 annual data report: atlas of chronic kidney disease & end-stage renal disease in the United States. 7

Transplantation Am J Kidney Dis

(2007)

K.L. Womer et al.

Chronic allograft dysfunction: mechanism and new approaches to therapy

Semin Nephrol

(2000)

I. Ledebo et al.

Initiation of dialysis-opinions from an international survey: report on the dialysis opinion symposium at the ERA-EDTA congress, 18 September 2000 Nice

Nephrol Dial Transplant

(2001)

European best practice guidelines for peritoneal dialysis. 2 The initiation of dialysis

Nephrol Dial Transplant

(2005)

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