One thousand and twenty-six (1026) patients underwent KTx at our center between February 2006 and January 2022. Nine patients met the inclusion criteria. Six of the nine patients were granulomatosis with polyangiitis (GPA) proteinase 3 (PR3)-ANCA positive. Three patients were microscopic polyangiitis (MPA) myeloperoxidase (MPO)-ANCA positive. The patients’ pre-transplant characteristics are presented in Table 1.

At diagnosis, 8 patients were treated with methylprednisolone pulses (500–1000 mg daily for 3 days) and intravenous cyclophosphamide (15 mg/kg) every 2–3 weeks for 3–6 months, plus prednisone at the initial dose of 1 mg/kg per day tapered to 5–10 mg/day. As maintenance therapy, azathioprine: (range 2 mg–0.5 mg/kg/day) or oral cyclophosphamide (2 mg/kg/day) were added to the low prednisone dose for 12–18 months. The cumulative dose of cyclophosphamide is reported in Table 1. Three patients were also treated with plasmapheresis. One patient did not receive any treatment because of rapidly progressive glomerulonephritis leading to renal failure requiring immediate dialysis. Before transplantation, 4 of 9 (44.4%) patients experienced a relapse with lung involvement and were treated with corticosteroids and cyclophosphamide (Table 1).

At transplantation, the mean age was 55 ± 10.5 years, 4 patients were male. Seven patients (77.8%) received a deceased donor transplant and two received a living donor kidney: one was a pre-emptive transplant. Median time on dialysis was 74.6 [161–24] months. At the time of transplantation, all patients were in clinical remission, ANCAs were positive in 4 of them (44.4%).

Induction therapy included basiliximab (20 mg day 0–4) and methylprednisolone (500 mg on day 0, 125 mg day 1–2) according to our internal protocol in all patients. Maintenance therapy was mycophenolate mofetil (2 g per day tapered to 1 at the end of the first year), prednisone (20 mg per day tapered to 5 mg per day at day 60), and tacrolimus (0.1 mg/kg bid) in 8 patients (88.9%). Cyclosporine (3 mg/kg per day tapered to 1.5 mg per day at month 2), prednisone, and everolimus (1 mg bid) were used in one patient. In two patients, mycophenolate mofetil was withdrawn; it was replaced with Azathioprine in one patient because of a pregnancy plan 31 months after transplant, while in the second patient, no other drug was introduced because of an Epstein-Barr virus infection (Table 2).

During follow-up no AAV relapse with renal involvement was observed. One patient with granulomatosis with polyangiitis had a biopsy-confirmed extrarenal recurrence 53 months after transplantation (relapse rate 0.011 per patient per year). The recurrence affected the paranasal sinuses (biopsied), and the eyes, causing visual acuity reduction and exophthalmos. ANCA was negative throughout the relapse. The patient was treated with methylprednisolone pulses: 500 mg/day for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. Two Rituximab doses of 1 g each were also administered 15 days apart after the methylprednisolone pulses, while azathioprine was suspended. The patient showed rapid improvement in symptoms and achieved complete remission.

The mean follow-up period was 132 ± 61.1 months.

One patient died 127 months after transplantation of metastatic squamous cell carcinoma.

During the observation period, no significant variation in creatinine or proteinuria was detected: mean serum creatinine 1.38 ± 0.4 mg/dl (at month 12), and mean creatinine at the end of the observation period was 1.29 ± 0.5 mg/dl. Mean proteinuria was 0.261 ± 0.3 g/L (at month 12) and 0.318 ± 0.4 mg/L at the end of follow-up. No patient experienced acute rejection episodes. Two patients underwent kidney biopsy for rapid and progressive worsening of renal function. In one patient who had an almost doubling of creatinine (1.5 to 2.6 mg/dl) without significant proteinuria, negative urinary sediment, and negative ANCA, the renal biopsy result was consistent with calcineurin inhibitor toxicity. Tacrolimus dosage was reduced, and creatinine levels returned to baseline values. In the second patient, because of persistent, incomplete renal recovery (creatinine 2.39 mg/dl at month 6), a renal biopsy was performed and showed diffuse interstitial fibrosis and diffuse arteriosclerotic damage attributable to the donor (Table 3).

Finally, we carried out a narrative comparison between a previous series published by our group (Table 4) including patients transplanted between December 1987 and January 2006 (cohort 1: 1225 patients) [9] and the most recent cohort including patients transplanted between February 2006 and January 2022 (cohort 2: 1026 patients). In the first cohort, 7 relapses in 19 patients were observed: relapse rate: 0.076 per patient per year. After relapse, 4 patients experienced an acute rejection episode, and three of them developed rapidly progressive renal insufficiency. In the present cohort, only one extrarenal relapse in 9 patients was observed (relapse rate of 0.011 per patient per year), and no acute rejection episodes were diagnosed. Forty-seven percent of cohort 1 patients were treated with cyclosporine-based maintenance immunosuppression, whereas tacrolimus-based immunosuppression was used in 89% of cohort 2 patients.

The most relevant complications during follow-up were infections, cardiovascular complications, and cancer.

The cumulative incidence of infection was 55%. Two patients had cytomegalovirus infection. One patient became infected (D + /R–) 5 months after transplantation following the prophylactic treatment period. The second patient experienced cytomegalovirus reactivation (D + /R +) 17 days after transplantation. Another patient had Epstein– Barr virus infection that was treated with a reduction in immunosuppressive therapy (mycophenolate mofetil withdrawal) and became DNA negative.

During follow-up, two patients were hospitalized: one for SARS-CoV-2 pneumonia and the other for community-acquired pneumonia, both of which resolved without any sequelae.

No major cardiovascular events were observed during follow-up; 88.9% of patients were hypertensive and on treatment with at least two drugs. One patient initiated oral anticoagulant treatment for atrial arrhythmia, and one patient (11.1%) developed insulin-dependent diabetes.

Interestingly, seven patients were diagnosed with cancer (cumulative incidence 77.8%). Two patients had squamous cell carcinoma, one had basal cell carcinoma, and one had both. Two patients had renal cell carcinoma (RCC) of the native kidneys. One patient had both undifferentiated squamous-cell carcinoma and RCC, and died of metastatic skin cancer. The curve for the cumulative risk of cancer is shown in Fig. 1.

Curve for the cumulative risk of cancer