Giulia Ghirardo

Plasmapheresis-resistant acute humoral rejection successfully treated with anti-C5 antibody

Even if kidney graft survival has improved during the last decades, sensitized pediatric patients are an emerging problem. We describe a 17‐yr‐old male who lost his first graft due to chronic rejection becoming hyperimmunized (CDC PRA 99.61%). A desensitization protocol based on high‐dose IVIG, PP, and two Mabthera® infusions was performed with minor response (CDC PRA post‐desensitization 80%). One month after his second non‐living transplant, he developed a biopsy‐proven AMR; post‐transplant immunological monitoring showed the presence of donor‐specific anti‐DQ5 antibodies (DSA, MFI 20.000). He received methylprednisolone pulses and 45 PP sessions without clinical response; eculizumab was then used to salvage a kidney undergoing severe PP‐resistant rejection. A biopsy performed after the fourth eculizumab infusion showed complete resolution of AMR. Eculizumab infusions were then continued for the first year post‐transplantation. Two yr after transplantation, graft function is stable. Anti‐C5 therapy may represent an effective therapeutic option in pediatric patients with PP‐resistant AMR.

PAX2 gene mutations in pediatric and young adult transplant recipients: kidney and urinary tract malformations without ocular anomalies

Negrisolo S, Benetti E, Centi S, Della Vella M, Ghirardo G, Zanon GF, Murer L, Artifoni L. PAX2 gene mutations in pediatric and young adult transplant recipients: kidney and urinary tract malformations without ocular anomalies.

Three-yr safety and efficacy of everolimus and low-dose cyclosporine in de novo pediatric kidney transplant patients

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty‐seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5–3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5–10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three‐yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post‐transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post‐transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m2, respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch‐up growth. No malignancy or post‐transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low‐dose cyclosporine, and low‐dose prednisone leads to good long‐term efficacy in de novo pediatric KT recipients.

Detection of viral DNA in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients.

BACKGROUND In pediatric kidney transplant recipients, viral infections occur soon after transplant and may be transmitted from the graft. METHODS This study of 75 pediatric kidney transplants investigated whether genome sequences of parvovirus B19, Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and BK polyomavirus (BKV) could be detected in kidney graft samples (graft biopsy samples and preservation and washing solutions) collected before implantation and whether their presence was a risk factor for infections in the recipient. RESULTS B19 DNA was detected in approximately 30% of graft biopsy samples, preservation solutions, and washing solutions; EBV DNA was detected in approximately 20% of preservation and washing solutions but rarely in biopsy samples; and HCMV DNA and BKV DNA were rarely detected in graft biopsy samples. Seronegative recipients of B19 DNA-positive and EBV DNA-positive grafts had a significantly higher risk of infection during the early posttransplant period than did recipients of negative grafts. In particular, none of the B19-seronegative recipients of B19 DNA-negative grafts experienced infection soon after transplant, whereas most recipients of B19 DNA-positive grafts experienced infection within the first month after transplant. CONCLUSIONS Molecular testing of donor grafts for viruses that infect circulating and resident cells in the graft-such as B19 in the kidney-could be useful (in association with donor/recipient serostatus) for identifying recipients at high risk for posttransplant infections.

Lymphocele after pediatric kidney transplantation: Incidence and risk factors

Lymphocele is a well‐known postoperative complication after kidney transplantation. The aim of this study was to analyze time trend incidence, risk factors, and outcome of post‐transplant lymphocele in a large pediatric cohort. This is a retrospective single institution review of 241 pediatric kidney transplants performed from 2000 to 2013. Etiology of end‐stage renal disease, recipient age and gender, transplant year, BMI percentile for age, type of dialysis, living/non‐living related donor, acute rejection, and multiple transplantations were analyzed in association with lymphocele formation. Fourteen of 241 (5.81%) children developed a postoperative lymphocele. There has been a reduction in the incidence of lymphocele after 2006 (3.22% vs. 8.55%, p < 0.05). Significant risk factors for lymphocele were older age (≥11 yr), transplant before 2006, male gender, BMI percentile for age ≥95%, and multiple transplantations (p < 0.05). The one‐yr graft survival was significantly reduced in the group with lymphocele compared with control (81.2% vs. 92.51%, p < 0.04). This is the first pediatric report showing the following risk factors associated with post‐transplant lymphocele: age ≥11 yr, male gender, BMI for age ≥95%, and multiple transplantations. A lymphocele can contribute to graft loss in the first‐year post‐transplant.

Ureteral complications after renal transplant in children: timing of presentation, and their open and endoscopic management.

We retrospectively reviewed the records of 24 consecutive patients undergoing treatment for ureteral complications after RTx in the period 2001–2012 to determine the timing of presentation of the complications, and their open or endoscopic management. Three patients (12%) had a necrosis of the transplanted ureter soon after RTx. All required open urinary diversion in a native ureter. Ten cases (42%) developed ureteral obstruction. Time of presentation was variable mainly in relation to the underlying cause. Endoscopic treatment was successful in two cases with urinary stones and open surgery in two with mid‐ureteral obstruction. Six patients had VUJ stenosis, three underwent open reimplantation, whereas temporary double‐J stent placement was successfully performed in the remainder. Eleven patients (46%) had VUR. It seldom presented in the first year after RTx. Endoscopic treatment was attempted in all and was successful in all the six cases without vs. only one of the five with lower urinary tract pathology (p = 0.01). Endoscopic treatment is an option in patients with VUR in the absence of lower urinary tract pathology. It is an option also for the treatment of stones and can be attempted in case of VUJ stenosis. Ureteral necrosis always requires open treatment.

Lower urinary tract symptoms (LUTS) after renal transplant in non-urologic anuric patients

Castagnetti M, Zhapa E, Berrettini A, Ghirardo G, Murer L, Zanon GF, Rigamonti W. Lower urinary tract symptoms (LUTS) after renal transplant in non‐urologic anuric patients.
Pediatr Transplantation 2010: 14:859–862.

Delayed graft function in pediatric deceased donor kidney transplantation: Donor-related risk factors and impact on two-yr graft function and survival: A single-center analysis

There is mounting evidence that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death. Aim of this present study was to analyze the correlation of DGF with brain‐dead donor variables in a single‐center pediatric population and to evaluate DGF influence on patients‐ and grafts outcome. End‐points of the study were DGF prevalence, DGF donor‐related risk factors, graft function, patient‐ and graft survival rate, respectively, at six, 12, and 24 months FU. The univariate analysis showed that donor age above 15 yr and vascular cause of donor brain death represented risk factors for DGF. The multivariate analysis confirmed as independent risk factors for DGF donor age >15 yr. At six months FU, DGF showed a negative impact on graft function. In conclusion, among all considered brain‐dead donor resuscitation parameters, just non‐traumatic cause of death turned out to be of impact for DGF. Donor age >15 yr represented the only independent risk factor for prolonged DGF in our series of children. At two‐yr FU, DGF showed a transient negative impact on six‐month graft function.

Primary Intrarenal Posttransplant Lymphoproliferative Disorder Detected by Surveillance Protocol Biopsy

Moir et al. recently reported a case of Epstein–Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (PTLD), presenting as multiple cystic lesions, in a 67year-old renal transplant recipient. The renal lesions were initially detected by ultrasound and computed tomography, and then investigated by renal biopsy. The authors concluded that this rare PTLD case underlines the need for a high index of clinical suspicion; they recommended that a biopsy be performed for abnormal pararenal allograft masses (1).