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Volume: 15 Issue: 1 February 2017 - Supplement - 1

FULL TEXT

Outcome of Renal Transplant in Recipients

Objectives: End-stage renal disease develops in a high percentage of patients with vasculitis, in whom kidney transplant has become a therapeutic option. However, limited data are available on the prognosis and outcomes after kidney transplant in these patients.

We aimed to compare the long-term graft survival and graft function in 8 renal transplant recipients with vasculitis (granulomatosis with polyangiitis, microscopic pol­yangiitis, Goodpasture syndrome, and Henoch-Schönlein purpura) with the other kidney recipients at a single center.

Materials and Methods: We conducted a retrospective study of patients followed for chronic renal failure associated with vasculitis before renal transplant.

We excluded patients with no biopsy-proven neph­ropathy.

Results: There was no difference in the occurrence of metabolic and cardiovascular complications in our case group compared with the other graft recipients. Infections were frequent and included cytomegalo­virus and urinary tract infection. The rates of bacterial and viral infection were equivalent in our population. The incidence of allograft loss was estimated at 1.8%, less than that seen in our entire transplant population. The presence of vasculitis was not significantly related to renal failure (P = .07). Extrarenal relapse occurred in 1 patient with microscopic polyangiitis. Antineutrophil cytoplasmic antibody levels in patients with granulo­matosis with polyangiitis and microscopic polyangiitis did not seem to influence the renal outcome (P = .08). Circulating antineutrophil cytoplasmic antibodies were associated with the development of vascular lesions in the graft but were not significantly cor­related with graft survival (P = .07).

Conclusions: This study supports the theory that renal transplant is an effective treatment option for patients with end-stage renal disease secondary to vasculitis. These patients fare similarly to, if not better than, other patients.


Key words : Antibodies, Antiglomerular basement membrane disease, Antineutrophil cytoplasmic, Prognosis, Purpura, Schoenlein-Henoch

Introduction

Renal vasculitis results in end-stage renal disease in 20% to 40% of patients.1-3 Data from small case series indicate that recurrence of vasculitis after transplant is infrequent and is rarely associated with graft loss,4-6 whereas relapse rates are below those reported in the entire transplant population.7 We aimed to highlight the outcome of renal transplant (RT) in a case series of 8 patients with renal vasculitis followed at a single transplant unit.

Materials and Methods

Our cohort of 8 patients included 3 patients diag­nosed with granulomatosis with polyangiitis (GPA), 1 with microscopic polyangiitis (MPA), 2 with Goodpasture syndrome, and 2 with Henoch-Schönlein purpura (HSP). All patients were treated between 1986 and 2015, and all relevant data were gathered using patient record review. We compared vasculitis patients with all other patients who underwent RT at our center to determine the correlation between vasculitis and the occurrence of metabolic, cardiovascular, infectious, and immu­nologic complications. The study was approved by the Ethical Review Committee of the Institute. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration.

Clinical data
We sought to obtain data on the following variables: patient age, sex, date of diagnosis, date of remission induction, date of transplant, type of vasculitis, and graft outcomes. We collected information on the antineutrophil cytoplasmic antibody (ANCA) status at the time of transplant and at intervals for the first posttransplant year. We also evaluated antimyelo­peroxidase and antiproteinase-3 results at the time of transplant, anti-glomerular basement membrane (GBM) antibody status, evidence of recurrent vasculitis, and the results of all graft biopsies.

Definitions
For ANCA vasculitis, remission was defined by the absence of clinical evidence of active ongoing vasculitis, with a Birmingham Vasculitis Activity Score of 0 to 1.8

Statistical analyses
The probability of an event over time was determined using Kaplan-Meier life-table analysis, and comparisons between factors were performed with log-rank tests. Patient and graft survival data were calculated by defining the date of transplant as time zero. Hazard ratios were generated using Cox regression. Statistical analyses were performed using software (StatView, SAS Institute, Cary, NC, USA). A P value of < .05 was considered to indicate statistical significance, and all tests were 2-tailed.

Results

The incidence of vasculitis at our transplant center was 1.1% (8 patients of a total of 693 who underwent RT). The mean age of the vasculitis patients at the time of transplant was 27.3 years (range, 12-32 years), and the male-to-female ratio was 3. The mean serum creatinine level at diagnosis was 480.25 μmol/L (range, 289-690 μmol/L). The median delay between diagnosis and the onset of ESRD was 21 ± 6 months. All patients underwent hemodialysis before RT. The mean duration of hemodialysis before RT was 66.7 months. Seven of 8 patients experienced remission during dialysis; a single GPA patient experienced an extrarenal relapse. The median interval between dialysis and RT was 58.37 ± 20 months. Half of the recipients received organs from living donors. All patients were negative for ANCA and anti-GBM antibodies before transplant. The demographic and clinical characteristics of the 8 patients are illustrated in Table 1.

No posttransplant relapse was observed in patients with GPA, although a single patient with MPA had an extrarenal relapse. Four patients were tested for ANCA by immunofluorescence every 6 months; only a single patient with MPA was positive for antimyeloperoxidase antibodies by enzyme-linked immunosorbent assay, 9 months after RT; this result coincided with clinical relapse. The ANCA levels in patients with GPA and MPA did not seem to influence renal outcomes (P = .08). The immuno­suppression regimens and major clinical outcomes are summarized in Table 1.

All patients received intravenous methylpred­nisolone (500, 250, 125, and 90 mg on postoperative days 1 through 4) and intravenous induction therapy with antithymocyte globulin (1.5 mg/kg daily for a total of 4-6 doses). Oral immunosuppression consisted of prednisone 60 mg daily, tapered to 5 to 10 mg daily by 3 months, and various combinations of the following agents: mycophenolate mofetil (500 mg twice daily), tacrolimus adjusted to a target trough blood level of 10 to 15 ng/mL for 3 months and 6 to 10 ng/mL thereafter, and cyclosporine adjusted to a target trough blood level of 200 to 250 ng/mL for 3 months and 150 to 200 ng/mL thereafter. The oral immunosuppressive regimens of tacrolimus + mycophenolate mofetil and cyclosporine + myco­phenolate mofetil were used in an equivalent manner. The median posttransplant follow-up was 57 ± 18 months. The mean glomerular filtration rate was 92 mL/min (range, 88-112 mL/min), indicating excellent graft function. A pretransplant diagnosis of vasculitis was not significantly related to renal failure (P = .07). Circulating ANCA was associated with the deve­lopment of vascular lesions in the graft but was not significantly correlated with graft survival (P = .07). No graft loss or death occurred (Table 2). The post­transplant complications are summarized in Table 2.

Discussion

None of the patients in our series experienced recurrence of their initial nephropathy. According to the literature, RT should be offered to patients with vasculitis because they have better graft and patient survival than other kidney transplant recipients.9 There are a number of published reports indicating that RT is an excellent option for treating patients with ANCA-associated vasculitis who develop ESRD.10 In our series, we observed 3 patients with GPA who had a good graft outcome and good patient survival rates. Five years after transplant, reported patient survival rates in ANCA vasculitis are as high as 86% to 93%.11

A large retrospective analysis of 59 patients with ANCA vasculitis and ESRD from a single transplant center showed better survival in patients who underwent RT than in those who remained on dialysis.12 None of our 3 patients experienced a relapse; however, an extrarenal relapse occurred in a patient with MPA. Reports of relapse rates and the severity of ANCA vasculitis following RT have varied widely.4,13-16 However, the total number of ANCA vasculitis exacerbations after transplant described in the literature is low, and no prospective trials have been reported. We perform routine ANCA screening, and our data indicate that ANCA positivity is not uncommon following RT for ANCA vasculitis, but this status does not seem to be useful as a predictor of disease relapse. This is consistent with the literature, which agrees that ANCA status is not significantly associated with graft failure.17,18 However, in our patient with MPA, ANCA positivity was a marker of disease activity and renal relapse.

There are no clear guidelines on RT in patients with ANCA-positive vasculitis. We observed 2 patients with Goodpasture syndrome who had a good clinical course. We evaluated anti-GBM antibodies before transplant in these 2 patients, as it is optimal to delay RT until anti-GBM antibodies are undetectable in the serum for 12 months and the disease has been in remission for at least 6 months without the use of cytotoxic agents.19 Recurrent Goodpasture syndrome after RT is rare, but it can occur at any time and should be considered when late graft dysfunction is present.20 Reportedly, many patients develop linear IgG deposits along the glomeruli of the renal allograft, but this development does not cause histologic or functional damage to the graft.21

Transplant is the best option for HSP nephritis, despite a documented risk for recurrence. The risk for recurrence and graft loss is reportedly as high as 35% and 11% at 5 years posttransplant.22 An aggressive form of the original disease, with crescents at initial biopsy, and a rapid progression to ESRD may predict a higher rate of recurrence.23 However, neither of our 2 patients experienced recurrence, despite the presence of crescents on biopsy of the native kidneys.

We acknowledge the limitations of this study. It is a retrospective study with a relatively limited number of patients, and no systematic graft biopsies were performed. There are limited data on the number of patients with vasculitis receiving RT, even though RT is the treatment of choice for ESRD in this population. Our results support the existing data that transplanted vasculitis patients exhibit a renal survival equal to or superior than patients with other renal disease, and very few grafts are lost due to vasculitis recurrence.


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Volume : 15
Issue : 1
Pages : 93 - 96
DOI : 10.6002/ect.mesot2016.O74


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From the 1Department of Nephrology, the 2Laboratory of Renal Pathology (LR00S001), and the 3Laboratory of Kidney Transplantation Immunology and Immunopathology (LR03SP01), Charles Nicolle Hospital, Tunis, Tunisia
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Meriam Hajji, Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
Phone: +216 21 578 566
E-mail: meriam.hajjiwm@hotmail.fr