Causes of late transplant failure in cyclosporine-treated kidney allograft recipients

Moroni, Gabriella; Binda, Valentina; Quaglini, Silvana; Sacchi, Lucia; Raffiotta, Francesca; Cosa, Francesco; Montagnino, Giuseppe; Favi, Evaldo; Ponticelli, Claudio

doi:10.1007/s10157-019-01740-7

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…KTx is the best therapeutic option for ESRD. Nevertheless, the need for chronic immunosuppression exposes transplant recipients to serious complications such as drug-related toxicity, cardiovascular disease, infections, and malignancy [ 23 – 26 ]. Among the others, HPyV infections represent as a major cause of post-transplant morbidity and premature allograft loss [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal study of human polyomaviruses viruria in kidney transplant recipients

Dolci,

Colico,

Ambrogi

et al. 2024

Clin Exp Med

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Introduction Immunosuppression after kidney transplantation (KTx) exposes recipients to Human Polyomaviruses (HPyVs) infections, whose natural history is still misunderstood. Methods Allograft biopsies, and urine from 58 donor-recipient pairs were collected before KTx (T0) and 1 (T1), 15 (T2), 30 (T3), 60 (T4), 90 (T5), 180 (T6), 270 (T7), 360 (T8), and 540 (T9) days after transplant. Specimens were tested for JC (JCPyV) and BK (BKPyV), by quantitative Real-Time PCR. The course of post-KTx HPyVs viruria, and the association between JCPyV viruria in recipients and donors, were evaluated. Results HPyVs were detected in 3/58 (5.2%) allograft biopsies. HPyVs viruria was present in 29/58 (50%) donors and 41/58 (70.7%) recipients. JCPyV DNA was detected in 26/58 (44.8%) donors and 25/58 recipients (43.1%), 19 of whom received kidney from JCPyV positive donor, whereas BKPyV genome was detected in 3 (5.2%) donors and 22 (37.9%) recipients. The median time of JCPyV, and BKPyV first episode of replication was 1, and 171 days post KTx, respectively. At T0, JCPyV viruria of donors was associated with increased risk of JCPyV replication post-KTx; recipients with JCPyV positive donors showed lower risk of BKPyV replication post-KTx. Conclusions The results suggested that JCPyV may be transmitted by allograft, and that its replication post KTx might prevent BKPyV reactivation. Future investigation regarding correlation between chronic exposure to immunosuppressive agents and HPyVs urinary replication are warranted.

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Section: Discussionmentioning

confidence: 99%

Longitudinal study of human polyomaviruses viruria in kidney transplant recipients

Dolci,

Colico,

Ambrogi

et al. 2024

Clin Exp Med

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“…Due to a widespread application of aggressive immunosuppressive protocols, we have witnessed a remarkable reduction of acute rejection-related allograft losses over the years [ 40 , 41 ]. The drawback of such a great achievement is that we are now facing a significant rise in post-transplant infectious diseases and drug-related adverse effects [ 42 , 43 , 44 ]. Among infectious complications, those caused by HPyVs represent a strenuous challenge for the transplant community.…”

Section: Discussionmentioning

confidence: 99%

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

Signorini

Dolci

Favi

et al. 2020

Viruses

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Human Polyomavirus (HPyV) infections are common, ranging from 60% to 100%. In kidney transplant (KTx) recipients, HPyVs have been associated with allograft nephropathy, progressive multifocal leukoencephalopathy, and skin cancer. Whether such complications are caused by viral reactivation or primary infection transmitted by the donor remains debated. This study aimed to investigate the replication pattern and genomic characterization of BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) infections in KTx. Urine samples from 57 KTx donor/recipient pairs were collected immediately before organ retrieval/transplant and periodically up to post-operative day 540. Specimens were tested for the presence of BKPyV, JCPyV, and MCPyV genome by virus-specific Real-Time PCR and molecularly characterized. HPyVs genome was detected in 49.1% of donors and 77.2% of recipients. Sequences analysis revealed the archetypal strain for JCPyV, TU and Dunlop strains for BKPyV, and IIa-2 strain for MCPyV. VP1 genotyping showed a high frequency for JCPyV genotype 1 and BKPyV genotype I. Our experience demonstrates that after KTx, HPyVs genome remains stable over time with no emergence of quasi-species. HPyVs strains isolated in donor/recipient pairs are mostly identical, suggesting that viruses detected in the recipient may be transmitted by the allograft.

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“…A single center reported that the use of cyclosporine for 20 years does not cause progressive increase in serum creatinine if kidney transplant recipients are carefully monitored during the follow-up. 7 A retrospective analysis of the clinical courses of more than 4000 cyclosporine-treated kidney allograft recipients followed from 1 to 10 years did not demonstrate any differences in the long-term rate of attrition of graft function between cyclosporine- and non–cyclosporine-treated patients. 8 Theoretically, patients can remain on CNI as long as the drug is providing some benefit and there are no adverse side effects.…”

mentioning

confidence: 91%

“…The risk of CNI-related nephrotoxicity is usually dose-dependent, and can be prevented by using low doses and monitoring kidney function. A single center reported that the use of cyclosporine for 20 years does not cause progressive increase in serum J o u r n a l P r e -p r o o f creatinine if kidney transplant recipients are carefully monitored during the follow-up [7]. A retrospective analysis of the clinical courses of over 4,000 cyclosporine-treated kidney allograft recipients followed from one to ten years did not demonstrate any differences in the long-term rate of attrition of graft function between cyclosporine-and non-cyclosporine -treated patients [8].…”

mentioning

confidence: 99%

Calcineurin Inhibitors in Membranous Nephropathy

Ponticelli

Praga

Moroni

2021

Kidney International Reports

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Causes of late transplant failure in cyclosporine-treated kidney allograft recipients

Cited by 8 publications

References 33 publications

Longitudinal study of human polyomaviruses viruria in kidney transplant recipients

Longitudinal study of human polyomaviruses viruria in kidney transplant recipients

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

Calcineurin Inhibitors in Membranous Nephropathy

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