Renal donor implication in the origin of BK infection: analysis of genomic viral subtypes.

UNLABELLED: BK virus (BKV) reactivation in immunocompromised kidney transplant patients can produce a tubulointerstitial nephropathy (BKVN). Molecular tools that test for DNA-BKV provide early detection and assist in management, but some aspects of the pathogenesis of this infection, such as donor causality, remain unclear. MATERIALS AND METHODS: Between November 2004 and January 2006, 55 Spanish kidney donors were studied for BK infection. A quantitative PCR assay was performed on urine and serum to detect BKV. To determine the origin of the viral infection, a transcription control region of the BK polymorphism sequence was designed to identify the viral subtype. RESULTS: Fifteen of 55 (27%) donors were BK-PCR positive: 13 in urine and 2 in serum and urine. Moreover, monitoring of recipient pairs detected BK-PCR positivity in 14 of 73 recipients. We studied eight BK-PCR positive recipients (corresponding to four pairs) and their respective donors. The same viral genome was observed in the four pairs, namely, the A250-1-a, WW-like, AS, and JL genotypes. Interestingly, one of the four pairs showed the donor and the two recipients to display exactly the same JL genotype. CONCLUSION: On the basis of our preliminary results analyzing the molecular fingerprints of donor and recipient pairs, we have presented new data implicating the donor, in at least some cases, as the source of BK infection.

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome.

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2-12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5-17) with an initial dose of 600 mg/m(2)/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5-5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m(2)/12 h (range 415-970), which maintained mean C(0)-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2-5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.

[Anti-CD25 monoclonal antibody against polyclonal antibodies in pediatric renal transplantation]. / Anticuerpo monoclonal anti-CD25 frente a anticuerpos policlonales en el trasplante renal pediátrico.

UNLABELLED: Although usually reversible, acute rejection of kidney graft is a negative factor in long-term graft survival. Commonly used in pediatric renal transplantation, immunosuppresive induction therapy is established to prevent it. New immunosuppressive agents have been developed in recent years and among them anti-CD25 monoclonal antibody appears to be specially interesting. AIM: To evaluate efficacy and safety of anti-CD325 monoclonal antibody (basiliximab) versus polyclonal antibodies as induction therapy in renal transplantation. MATERIAL AND METHODS: Thirty consecutive kidney transplants performed in children 4-16 years age in Hospital Infantil La Fe through 1997-2000. The first 15 patients received polyclonal antibodies as induction therapy, and 15 consecutive ones received monoclonal anti-CD25 antibodies. Receptor, donor and graft characteristics were similar in both groups. Also, maintenance immunosuppression was the same. RESULTS: The follow-up was over one year in all patients. Four patients in the polyclonal antibody group suffered one acute rejection episode and four other patients had some drug reaction. In the anti-CD25 treatment group there was one episode of acute graft rejection and no collateral effects were observed. Glomerular filtration rate, proteinuria, hypertension, infection episodes, graft and patient survival were similar in both groups. CONCLUSIONS: Induction therapy for pediatric renal transplantation with anti-CD25 antibody has been effective and safe. Compared with polyclonal antibodies as standard treatment, basiliximab reduced acute rejection episodes and had no collateral side effects. Graft and patient one year survival were identical in the two groups.

Anticuerpo monoclonal anti-CD25 frente a anticuerpos policlonales en el trasplante renal pediátrico / Efficacy of basiliximab versus policlonal antibodies as induction therapy in pediatric kidney transplantation

Introducción: Los episodios de rechazo agudo del injerto renal, aunque generalmente reversibles, constituyen un factor pronóstico negativo en la supervivencia del injerto a largo plazo. Su prevención es el objetivo a conseguir con la terapia inmunosupresora de inducción, generalizada en el trasplante renal pediátrico. Recientemente se han incorporado a ella nuevos agentes inmunosupresores, entre los que destaca el anticuerpo monoclonal anti-CD25 (basiliximab).Objetivo: Evaluar la eficacia y seguridad del anticuerpo monoclonal anti-CD25 (basiliximab) frente a los anticuerpos policlonales en la terapia de inducción del trasplante renal pediátrico.Material y métodos: Se analizan 30 trasplantes consecutivos, en niños de 4-19 años, realizados en el Hospital Infantil La Fe durante el período de 1997-2000.Las características del receptor, donante y trasplante en ambos grupos así como la inmunosupresión de mantenimiento fue similar, sólo se diferenciaban en la utilización de anticuerpos policlonales o monoclonales (anti-CD25) en la inmunosupresión de inducción, los 15 primeros recibieron anticuerpos policlonales y a los 15 siguientes anticuerpo monoclonal anti-CD25. Se realizó un seguimiento durante 12 meses.Resultados: En el grupo de los anticuerpos policlonales, 4 pacientes presentaron rechazo agudo, y se objetivaron 4 reacciones adversas al fármaco frente a un rechazo y ninguna reacción adversa en el grupo de los anticuerpos monoclonales anti-CD25, ambas diferencias fueron estadísticamente significativas (p < 0,01).El funcionalismo renal (filtrado glomerular, proteinuria, hipertensión), número de infecciones y supervivencia del paciente y del injerto no presentaron diferencias estadísticamente significativas entre ambos grupos.Conclusiones: El uso de anticuerpos monoclonales anti-CD25 (basiliximab) en la terapia de inducción del trasplante renal pediátrico ha resultado seguro, sin presentar reacciones adversas al fármaco ni incremento del número de infecciones, y eficaz con menor número de rechazos agudos y buen funcionalismo renal durante el primer año postrasplante. (AU)