Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

OBJECTIVES: Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. MATERIALS AND METHODS: Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. RESULTS: BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. CONCLUSIONS: BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

Advances in pharmacotherapies for cytomegalovirus infection: what is the current state of play?

INTRODUCTION: Cytomegalovirus (CMV) remains a serious opportunistic infection in hematopoietic cell transplant (HCT) and solid-organ transplant (SOT) recipients. Traditional anti-CMV drugs are limited by toxicities and the development of resistance. Letermovir and maribavir are newly approved antivirals for the prevention and treatment of CMV. AREAS COVERED: Prior reviews have discussed use of letermovir for prevention of CMV after HCT and maribavir for resistant or refractory (R/R) CMV post HCT or SOT. Subsequent data have expanded their use including letermovir for primary CMV prophylaxis in high-risk renal transplant recipients and new recommendations for extending prophylaxis through day + 200 in certain HCT patients. Data on the use of maribavir for first asymptomatic CMV infection post-HCT has also been published. This review compares the pharmacology of anti-CMV agents and discusses the updated literature of these new drugs in the prevention and treatment of CMV. EXPERT OPINION: Letermovir and maribavir are much needed tools that spare toxicities of ganciclovir, foscarnet, and cidofovir. High cost is a challenge preventing their integration into clinical practice in resource-limited countries. Transplant centers need to exercise restraint in overuse to avoid resistance, particularly in the setting of high viral loads.

The association of Torque Teno viral load with CMV and BKV infection in pediatric and adolescent kidney transplant patients.

BACKGROUND: Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. OBJECTIVES: To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. STUDY DESIGN: This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014-2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4-8 weeks at routine follow-up visits. RESULTS: 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15-4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. CONCLUSIONS: This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care.

Polyoma BK virus: an emerging opportunistic infectious agent of the human central nervous system

BK virus, a double-stranded DNA virus, is a member of the Polyomaviridae family which is known to infect humans. Clinical evidence of disease is mostly encountered in immunosuppressed individuals such as AIDS patients or those who undergo renal or bone marrow transplantation where complications associated with BKV infection manifest commonly as a polyomavirus nephropathy or hemorrhagic cystitis, respectively. Recent evidence suggests that in addition to the JC virus (the other member of the same family known to be strongly neurotropic and responsible for the progressive multifocal leukoencephalopathy), BK virus can infect and cause clinically relevant disease in the human central nervous system. In this mini-review, an analysis of the literature is made. A special focus is given to alert clinicians to the possibility of this association during the differential diagnosis of infections of the central nervous system in the immunocompromised host.

Papel de las infecciones víricas en pacientes inmunodeprimidos / Role of viral infections in immunosuppressed patients

ResumenSer receptor de un trasplante de órgano sólido, así como recibir tratamiento quimioterápico para una enfermedad hematólógica maligna, predispone claramente a padecer infecciones virales tanto comunes como oportunistas, de origen tanto comunitario como procedentes del donante de órganos y/o de una reactivación de un virus latente endógeno. Herpes virus y más especialmente citomegalovirus y virus de Epstein-Barr son los que con más frecuencia afectan a estos enfermos, así como los virus respiratorios. El tratamiento consiste en la combinación de reducir la inmunodepresión inducida junto con tratamiento antiviral. Se ha realizado una revisión de la literatura pormenorizada y actualizada de la epidemiología, la patogenia, las manifestaciones clínicas y la aproximación terapéutica de las infecciones virales en estos enfermos (AU)

Abstract Being a solid organ and hematopoietic stem cell transplant recipient as well as receivingchemotherapy for a malignant hematological disease clearly predispose the subject to avariety of viral infections, both common and opportunistic diseases. The patient may haveacquired these infections from the community as well as from the donor organ (donor-derivedinfections) and/or from reactivation of an endogenous latent virus. Herpes viruses and especiallythe cytomegalovirus and Epstein-Barr virus are among the most common of the opportunisticviral pathogens affecting these patients, in addition to respiratory viruses. Treatment consistsin antiviral drug therapies combined with the reduction in the degree of the induced immunosuppression.A review of the literature has been performed in order to update the epidemiology,pathogenesis, clinical manifestations and therapeutic approach of the viral infections in theseimmunocompromised patients (AU)

Recomendaciones GESITRA-SEIMC y RESITRA sobre prevención y tratamiento de la infección por citomegalovirus en pacientes trasplantados / Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus in transplanted patients

La infección por citomegalovirus (CMV) es una complicación importante del trasplante. La última década se ha caracterizado por los avances en su tratamiento, reduciendo su morbilidad y la mortalidad. Estos avances han sido decisivos en el diagnóstico y prevención. Se han desarrollado técnicas de diagnóstico rápidas y sensibles. Entre las estrategias de prevención destaca el uso correcto de los productos sanguíneos, las inmunoglobulinas y los fármacos antivirales, empleados en profilaxis o en terapia anticipada. El reciente desarrollo de fármacos eficaces por vía oral como el valganciclovir permitirá el tratamiento ambulatorio de los pacientes infectados. Es necesario trasladar este conocimiento a la práctica clínica diaria. Con este objetivo el Grupo de Estudio de la Infección en el Trasplante (GESITRA) de la Sociedad Española de Microbiología Clínica y Enfermedades Infecciosas (SEIMC) ha desarrollado este documento de consenso que incluye las últimas recomendaciones en el tratamiento de la infección por CMV postrasplante (AU)

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation (AU)