MONITORING KIDNEY AND PANCREAS ALLOGRAFT BIOPSIES IN SIMULTANEOUS
PANCREAS KIDNEY RECIPIENTS WITH TACROLIMUS-EVEROLIMUS-PREDNISONE
MAINTENANCE THERAPY
J. N. Petroni, P. D. Uva, D. Curcio, L. Reniero, R. Pilotti, E. Chuluyan, D. Casadei
J. Goldberg
Instituto de Nefrología Buenos Aires, Nephrology S.A. Buenos Aires, Argentina
(a) Objectives: Protocol allograft biopsies in simultaneous pancreas-kidney (SPK) transplant
recipients is controversial. We performed surveillance protocol biopsies in 19 SPK transplants in a
series of patients with a maintenance immunosupression with tacrolimus, everolimus and steroids.
(b) Methods: we performed 65 SPK transplants. Induction therapy consisted of Thymoglobulin (1.5
mg/kg for five days) and Solumedrol and patients were maintained on a triple immunosuppression
protocol (FK506 target level, 10-12 ng/ml, predisone tapered to 4 mg/day and sodic-mycophenolate
1440 mg/day). After the first month of transplant patients who did not experienced rejection or did
not have active infections or other complications switched sodic-mycophenolate to everolimus
(target 3-5 ng/ml) and FK506 target was decreased. These patients were offered laparoscopic
protocol biopsies at 3-6 month and 12-18 months post-transplant. 24 patients were swiched and 19
patients consented and had at least one biopsy performed. The biopsies samples were fixed (10%
buffered Formalin), frozen and routinely stained. In some cases immunoperoxidase for Insulin and/
or Glucagon were analyzed by a pathologist and classified using Banff criteria. Additionally, C4d
staining was performed in all biopsies. Also, DSA were determined at the same time of biopsies. All
biopsies were done with no clinical signs of graft dysfunction. Systemic portal drainage was
performed in all pancreas transplant patients, while exocrine secretion were enteric (6) or bladder
(13) drained. Rejections were treated with methylprednisolone and/or thymoglobulin.
(c) Results: At 3-6 months, we observed the following results: i) 12 patient had mild ATN in kidney
biopsies and normal pancreas biopsies specimens; ii) one patient had kidney toxicity with normal
pancreas biopsies, iii) one patient had mild ATN in kidney and mild pancreas chronic rejection iv) two
patients showed mild ATN in kidney with pancreas undetermined rejection; v) two patient had
kidney borderline rejection and normal pancreas specimen vi) one patient had kidney borderline
rejection with simultaneous pancreas undetermined rejection. C4d stainings were negative in all
pancreas and kidney specimens analyzed. DSA testing was negative in all 19 patients at this time.
Four patients received treatment (1 patient with both undeterminded pancreas and borderline
kidney received Solumedrol pulses and Thymoglobulin and three patients with undetermined
pancreas, borderline kidney and ACR Banff 1A kidney received Solumedrol pulses) and one did not (1
undetermined pancreas). At one year three patients refused to have a second biopsy done and
another patient had lost both grafts due to graft Tuberculosis (a patient with treated borderline
kidney rejection at 3mo). Pancreas biopsies were normal in 11 patients (including all 3 treated
patients and the patient with mild chronic rejection at 3mo), 1 had mild chronic rejection (a type 2
DM now on Metformin) and 3 results are pending. Kidney biopsies had mild ATN in 10 patients
(including the Banff 1A rejection at 3mo), 1 had borderline rejection (with previous treated pancreas
undetermined and kidney borderline rejection), 1 had ACR Banff 1A (previous normal biopsies) and 3
reports are pending. Both patients with abnormalities were treated with Solumedrol pulses. 17
patients continue with protocol therapy (tacrolimus-everolimus-prednisone) and 1 patient had
discontinued the everolimus and changed back to sodic micophenolate.
(d) Conclusions: Our data, show that 5 patients (20%) had subclinical immunological findings at 3
months and 2 patients at 1 year that conducted to early anti-rejection treatment that allowed good
results. We also observed different findings in both organs, and renal allograft rejection is a poor
surrogate for pancreas allograft status.