Transplant failure risk higher for AAV kidney patients, study finds
Researchers advise tailored management for AAV-GN transplant patients
People with ANCA-associated vasculitis (AAV) affecting the kidneys who receive kidney transplants face higher long-term risks of transplant failure and death compared with those who undergo transplants for other reasons.
That’s according to a study from France, which also found that the presence of ANCAs — self-reactive antibodies that play a key role in driving AAV — may help predict how well a transplant will perform.
The researchers also advised against using azathioprine, an immune-suppressing drug commonly used to prevent organ rejection, as maintenance therapy for patients with AAV-related glomerulonephritis (AAV-GN). The condition is a severe form of inflammation that affects the glomeruli (the filtering units of the kidneys).
“These findings highlight the need for tailored post-transplant management in AAV-GN patients,” the researchers wrote.
The study, “Outcomes after kidney transplantation in ANCA-associated renal vasculitis,” was published in Kidney International Reports.
Have treatment advances improved things for AAV transplant recipients?
AAV is typically caused by ANCAs, autoantibodies that bind to and over-activate neutrophils, a type of immune cell. This leads to inflammation of small blood vessels (vasculitis) in various organs. The kidneys are commonly affected, often resulting in reduced kidney function that can progress to kidney failure. In such cases, patients may require regular dialysis or a kidney transplant.
However, ”it remains unclear whether advances in vasculitis treatment and transplant care over the past decade have improved patient and [transplant] outcomes after kidney transplantation in AAV,” the researchers wrote.
To know more, they conducted a retrospective study on transplant outcomes in adults with kidney failure caused by AAV-GN at 12 transplant centers in France.
Participants were diagnosed between 1980 and 2020, at a mean age of 52. Two-thirds were men (67%). The majority had ANCA antibodies (98%), most of which (73%) were against the myeloperoxidase (MPO) protein. These patients received kidney transplants at a mean age of 59, usually from a deceased donor (90%).
Each AAV-GN patient was matched by age and sex to two transplanted patients from the same center with kidney failure due to causes other than AAV-GN. A lower proportion of AAV-GN patients had diabetes (11% vs. 22%) and received preventive transplantation (7.3% vs. 13%) than controls, and they more commonly underwent a kidney biopsy (93% vs. 32%).
Delayed function of the transplanted kidney (graft) — defined as the need for at least one dialysis session within seven days after kidney transplantation before the new organ begins to function — occurred in 18% of patients with AAV-GN, a rate similar to that seen in the control group. No differences were seen between the two groups in terms of kidney function or graft failure, which refers to the transplanted kidney losing its ability to work properly.
Further analysis showed that among AAV patients, a longer cold ischemia time — the period during which the donated kidney is kept cold and bloodless between removal and transplantation — was associated with a 7% increased risk of delayed graft function. Patients who had experienced a previous AAV relapse had a 77% lower risk of developing delayed graft function.
AAV-GN patients showed a trend toward poorer graft survival (a 55% higher risk of graft failure) and significantly lower overall survival (48%) than controls. Patients’ and donors’ ages at the time of the transplant, use of corticosteroids or azathioprine, delayed graft function, disease relapse after the transplant, and transplant rejection were significantly associated with graft survival in people with AAV-GN. Despite these, “there was no difference in graft survival regarding ANCA status at [kidney transplant],” the researchers wrote.
Overall, 15 patients with AAV-GN had a disease relapse after their kidney transplant. Relapse was defined by signs of glomerulonephritis on biopsy, markers of kidney damage, or symptoms in other organs. Relapses occurred, on average, about 3.4 years after transplantation. Most of the patients who relapsed were ANCA-positive at the time of transplant, and all had detectable ANCAs at the time of relapse.
Patients who experienced a disease relapse were more likely to experience graft failure (60% vs. 11%) and acute kidney rejection (40% vs. 17%) than those who did not relapse.
Further analysis indicated that relapses increased the risk for graft failure by about 3.5 times. While ANCA positivity at transplant tended to be associated with a higher relapse risk (4.17 times greater), it was also linked to a 69% lower risk of transplant rejection. Azathioprine maintenance therapy was associated with a higher risk of both transplant rejection and graft failure.
“Short-term outcomes (including delayed graft function, kidney function recovery, and acute rejection) were similar between groups,” the researchers wrote. “In contrast, long-term outcomes were poorer in AAV-GN patients, with higher rates of graft failure and overall mortality.”
Doctors managing these patients, the researchers wrote, should consider “the burden of pre-transplant treatment and events, and their impact on post-transplant outcomes.”
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