Gianluca Leonardi

Assessment of cardiovascular risk in waiting-listed renal transplant patients: a single center experience in 558 cases

Abstract:  Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole‐stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high‐cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high‐risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended.

No recurrence of Kaposi's sarcoma in a case of renal retransplantation under a calcineurin inhibitor free immunosuppressive regimen: first report

Retransplantation in recipients with a previous history of post-transplant Kaposi’s sarcoma remains matter of debate. Even if a recent unique report suggests that retransplantation without recurrence is possible, the majority of authors emphasizes the high risk of relapse and therefore advices this kind of patients against retransplantation. Here we report a case of uneventful kidney retransplantation in a 31-year-old woman whose first kidney graft failed after reduction of the immunosuppressive regimen because of the onset of cutaneous and visceral Kaposi’s sarcoma. In this case, to our knowledge the first to be reported with this protocol, we adopted as immunosuppressive strategy a triple therapy with Sirolimus, Mycophenolate mofetil and steroid, with Basiliximab at induction. After 20 months the kidney function is excellent (creatinine clerance 89.3 ml/min) without evidence of Kaposi’s sarcoma recurrence. Kaposi’s sarcoma (KS) is 400-fold more frequent in kidney graft recipients than in general population with an incidence ranging from 0.5% of all renal transplants performed in Western and Northern countries to nearly 5% in the Mediterranean area. Complete remission of the cutaneous form of KS is generally achievable with reduction/discontinuation of immunosuppression with variable risk of graft failure. Indeed, if immunosuppression is reintroduced or also minimally maintained, KS generally recurs [1,2] and retransplantation is not recommended [3]. Here, we report the case of an Italian patient that lost the first kidney transplant as a consequence of the discontinuation of immunosuppression because of the onset of visceral and cutaneous KS and that has been retransplanted in our centre without recurrence of KS under an immunosuppressive regimen based on Sirolimus (SRL), Mycophenolate mofetil (MMF) and low dose of steroid. On May 1994, a 20-year-old Italian woman received a living related (father) kidney transplant for end stage renal disease caused by chronic glomerulonephritis. The initial immunosuppression consisted of Cyclosporin A (CsA) and steroid. The graft functioned immediately and attained normal serum creatinine level within 4 weeks. Thirteen months after transplantation, a biopsy of a laterocervical lymphoadenomegaly revealed the presence of KS. Endoscopy showed multiple gastric lesions as well of KS. Serology for Human Immunodeficiency Virus (HIV) type 1 and 2 and thoraco-abdominal computed tomography scan were negative. We are lacking information about Human Herpesvirus 8 (HHV8) state of both the donor and the recipient. CsA was stopped, Azathioprine was added and steroid was maintained at a lower dosage. Three months later, the graft failed for an intractable rejection. KS disappeared within 2 months from the beginning of dialysis. On February 2005, she underwent retransplantation in our centre from a HHV8 negative and CMV negative deceased donor. During the pre-transplant period (since 2000), at the moment of the surgery and after transplantation, recipient’s IgG anti-HHV8 were always positive whereas HHV8 DNA Polymerase Chain Reaction was negative. Initial immunosuppression consisted of Basiliximab, SRL 10 mg/day for 3 days tapered off on the bases of plasma levels (target plasma level 15–20 ng/ ml), MMF 1 g twice a day and prednisone 25 mg/day. Postoperative course was uneventful and renal function excellent. In the early follow up a sacral Herpes Zoster successfully treated with Acyclovir has been observed. At month 2 prednisone was tapered to 5 mg/day. From month 7, the SRL target level was 8–12 ng/ml (mean: 11.9 ± 0.5 ng/ml) and MMF was reduced to 1 g/day. At the end of follow up the regimen is SRL 2 mg/day, MMF 500 mg twice a day, and prednisone 5 mg/day. The kidney function is excellent (creatinine clearance being 89.3 ml/min). No sign of KS recurrence was observed so far. To our knowledge, only another observation of a successful retransplantation in a recipient with a previous history of KS is reported [4]. In that case a traditional triple therapy (CsA, Azathioprine and prednisone) was used. So far, this is the first report under SRL regimen. SRL is a relatively new immunosuppressant with a wellknown antitumoral activity both in vitro [5] and in vivo [6]. Recent experiences have demonstrated that SRL in

Basiliximab in association with tacrolimus and steroids in caucasian cadaveric renal transplanted patients: significant decrease in early acute rejection rate and hospitalization time

Abstract:  Safety and tolerability of basiliximab in renal transplantation have been proven in different immunosuppressive regimens. Few informations are available about the association of basiliximab with tacrolimus and steroids. We present a retrospective analysis performed in Caucasian cadaveric renal transplant recipients, comparing a basiliximab, tacrolimus and steroids induction protocol (GrA: 51 patients) with a tacrolimus and steroids protocol (GrB: 46 patients). A significant decrease in acute rejection rate in the first 3 months (2.0% vs. 17.4%; p < 0.01) was noted. Interestingly, the recipients in GrA were at major immunologic risk for the younger age of recipients, the greater number of mismatches and the higher rate of second transplants. The hospitalization times resulted reduced of 5.3 d in GrA vs. GrB (20.8 d vs. 26.1 d; p < 0.05). The adverse events patterns and profiles were similar in the two treatments groups. One patient in each group had a post‐transplant lymphoprolipherative disorder. No significant difference was found in patient and graft survival. According to the results of this study, in a Caucasian adult population, basiliximab in association with tacrolimus and steroids is a safe and efficacious tool for acute rejection prevention and it is cost saving by reducing the hospitalization times.

B cell positive cross-match not due to anti-HLA Class I antibodies and first kidney graft outcome☆

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.

Secondary Hyperparathyrodism in Adult Predialysis and Dialysis Patients

Following the recommendations in the Kidney Disease Improved Global Outcome (KDIGO) clinical guidelines [1], the mineral and clinical disorders related to the impact of declining renal function on calcium-phosphorus homeostasis, previously known as “renal osteodystrophy”, are today, more appropriately, renamed as chronic kidney disease-mineral and bone disorders (CKD-MBD).