Infectious Complications in Chronic Kidney Disease and Renal Transplant Patients: Prevention, Diagnosis, Management, and Emerging Trends

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 17970

Special Issue Editors


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Guest Editor
1. Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy
2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Interests: renal transplantation; chronic kidney disease; mineral bone disorders in CKD and renal transplanted patients; markers of CKD progression; diet in the management of CKD
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Guest Editor
1. Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
2. Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
Interests: kidney transplantation; organ donation; immunosuppression; vascular access; polyomavirus
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Guest Editor
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Interests: human polyomaviruses epidemiology and replication in the immunocompromised hosts; viral infections in renal transplantation recipients
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Guest Editor
Department of Surgical Sciences, Università di Tor Vergata, 00133 Rome, Italy
Interests: kidney transplantation; living donor transplantation; governance and outcome analysis; health economics; infectious disease in transplantation

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) and renal transplantation (RTx) are associated with a higher risk of all-cause mortality and morbidity than the general population. Apart from cardiovascular disease, infectious complications actually represent the most relevant and perhaps preventable cause of death among these specific groups of patients. The increased susceptibility to infections observed in CKD and RTx recognizes several predisposing factors such as uremia, impaired primary host immunity, sustained exposure to microbiological agents during dialysis, and, especially in RTx patients, chronic immunosuppression.

In this Special Issue of Pathogens, we will provide an updated representation of the current prevention, diagnosis, and management strategies of common and rare infections in CKD and RTx patients. In addition, we will offer further insight into future directions and emerging trends in basic, clinical, and translational science relevant to the topic.

With those aims, we invite researchers to submit high-quality works for consideration. Original articles, as well as narrative reviews of particular interest and case reports of exceptional didactical value, will be considered.

“Infectious Complications in Chronic Kidney Disease and Renal Transplant Patients: Prevention, Diagnosis, Management, and Emerging Trends” will give specialists and scientists involved in the care of renal patients the opportunity to share their experience or point of view on several critical issues, with the primary objective of improving global knowledge and patients outcome.

Dr. Carlo Alfieri
Dr. Evaldo Favi
Prof. Dr. Serena Delbue
Dr. Roberto Antonio Simone CACCIOLA
Guest Editors

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Keywords

  • infectious diseases
  • renal transplantation
  • chronic kidney disease
  • end stage renal disease

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Published Papers (7 papers)

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Editorial

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3 pages, 193 KiB  
Editorial
Managing the “Sword of Damocles” of Immunosuppression: Prevention, Early Diagnosis, and Treatment of Infectious Diseases in Kidney Transplantation
by Roberto Cacciola and Serena Delbue
Pathogens 2023, 12(5), 649; https://doi.org/10.3390/pathogens12050649 - 27 Apr 2023
Viewed by 920
Abstract
The careful tailoring of the most appropriate immunosuppressive strategy for recipients of a kidney transplant (KT) regularly faces a risk of complications that may harm the actual graft and affect patient survival [...] Full article

Research

Jump to: Editorial

16 pages, 1626 KiB  
Article
The Enhanced Recovery after Surgery (ERAS) Pathway Is a Safe Journey for Kidney Transplant Recipients during the “Extended Criteria Donor” Era
by Roberta Angelico, Francesca Romano, Camilla Riccetti, Marco Pellicciaro, Luca Toti, Evaldo Favi, Roberto Cacciola, Tommaso Maria Manzia and Giuseppe Tisone
Pathogens 2022, 11(10), 1193; https://doi.org/10.3390/pathogens11101193 - 16 Oct 2022
Cited by 7 | Viewed by 2651
Abstract
Enhanced recovery after surgery (ERAS) protocols are still underused in kidney transplantation (KT) due to recipients’ “frailty” and risk of postoperative complications. We aimed to evaluate the feasibility and safety of ERAS in KT during the “extended-criteria donor” era, and to identify the [...] Read more.
Enhanced recovery after surgery (ERAS) protocols are still underused in kidney transplantation (KT) due to recipients’ “frailty” and risk of postoperative complications. We aimed to evaluate the feasibility and safety of ERAS in KT during the “extended-criteria donor” era, and to identify the predictive factors of prolonged hospitalization. In 2010–2019, all patients receiving KT were included in ERAS program targeting a discharge home within 5 days of surgery. Recipient, transplant, and outcomes data were analyzed. Of 454 KT [male: 280, 63.9%; age: 57 (19–77) years], 212 (46.7%) recipients were discharged within the ERAS target (≤5 days), while 242 (53.3%) were discharged later. Patients within the ERAS target (≤5 days) had comparable recipient and transplant characteristics to those with longer hospital stays, and they had similar post-operative complications, readmission rates, and 5 year graft/patient survival. In the multivariate analysis, DGF (HR: 2.16, 95% CI: 1.08–4.34, p < 0.030) and in-hospital dialysis (HR: 3.68, 95% CI: 1.73–7.85, p < 0.001) were the only predictive factors for late discharge. The ERAS approach is feasible and safe in all KT candidates, and its failure is primarily related to the postoperative graft function, rather than the recipient’s clinical status. ERAS pathways, integrated with strict collaboration with local nephrologists, allow early discharge after KT, with clinical benefits. Full article
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21 pages, 2120 KiB  
Article
Outcomes of Patients Receiving a Kidney Transplant or Remaining on the Transplant Waiting List at the Epicentre of the COVID-19 Pandemic in Europe: An Observational Comparative Study
by Marta Perego, Samuele Iesari, Maria Teresa Gandolfo, Carlo Alfieri, Serena Delbue, Roberto Cacciola, Mariano Ferraresso and Evaldo Favi
Pathogens 2022, 11(10), 1144; https://doi.org/10.3390/pathogens11101144 - 3 Oct 2022
Cited by 2 | Viewed by 2183
Abstract
Since the declaration of the COVID-19 pandemic, the number of kidney transplants (KT) performed worldwide has plummeted. Besides the generalised healthcare crisis, this unprecedented drop has multiple explanations such as the risk of viral transmission through the allograft, the perceived increase in SARS-CoV-2-related [...] Read more.
Since the declaration of the COVID-19 pandemic, the number of kidney transplants (KT) performed worldwide has plummeted. Besides the generalised healthcare crisis, this unprecedented drop has multiple explanations such as the risk of viral transmission through the allograft, the perceived increase in SARS-CoV-2-related morbidity and mortality in immunocompromised hosts, and the virtual “safety” of dialysis while awaiting effective antiviral prophylaxis or treatment. Our institution, operating at the epicentre of the COVID-19 pandemic in Italy, has continued the KT programme without pre-set limitations. In this single-centre retrospective observational study with one-year follow-up, we assessed the outcomes of patients who had undergone KT (KTR) or remained on the transplant waiting list (TWL), before (Pre-COV) or during (COV) the pandemic. The main demographic and clinical characteristics of the patients on the TWL or receiving a KT were very similar in the two periods. The pandemic did not affect post-transplant recipient and allograft loss rates. On the contrary, there was a trend toward higher mortality among COV-TWL patients compared to Pre-COV-TWL subjects. Such a discrepancy was primarily due to SARS-CoV-2 infections. Chronic exposure to immunosuppression, incidence of delayed allograft function, and rejection rates were comparable. However, after one year, COV-KTR showed significantly higher median serum creatinine than Pre-COV-KTR. Our data confirm that KT practice could be safely maintained during the COVID-19 pandemic, with excellent patient- and allograft-related outcomes. Strict infection control strategies, aggressive follow-up monitoring, and preservation of dedicated personnel and resources are key factors for the optimisation of the results in case of future pandemics. Full article
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18 pages, 2559 KiB  
Article
Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France
by Laurène Tardieu, Gillian Divard, Olivier Lortholary, Anne Scemla, Éric Rondeau, Isabelle Accoceberry, Rémi Agbonon, Alexandre Alanio, Adela Angoulvant, Laetitia Albano, Philippe Attias, Anne Pauline Bellanger, Dominique Bertrand, Julie Bonhomme, Françoise Botterel, Nicolas Bouvier, Matthias Buchler, Taieb Chouaki, Thomas Crépin, Marie-Fleur Durieux, Guillaume Desoubeaux, Gary Doppelt, Loïc Favennec, Arnaud Fekkar, Ophélie Fourdinier, Marie Frimat, Jean-Pierre Gangneux, Claire Garandeau, Lilia Hasseine, Christophe Hennequin, Xavier Iriart, Nassim Kamar, Hannah Kaminski, Raphael Kormann, Laurence Lachaud, Christophe Legendre, Moglie Le Quintrec Donnette, Jordan Leroy, Charlène Levi, Marie Machouart, David Marx, Jean Menotti, Valérie Moal, Florent Morio, Natacha Mrozek, Muriel Nicolas, Philippe Poirier, Marie-Noelle Peraldi, Benjamin Poussot, Stéphane Ranque, Jean-Philippe Rerolle, Boualem Sendid, Renaud Snanoudj, Jérôme Tourret, Marc Vasse, Cécile Vigneau, Odile Villard, Laurent Mesnard, Fanny Lanternier and Cédric Rafatadd Show full author list remove Hide full author list
Pathogens 2022, 11(6), 699; https://doi.org/10.3390/pathogens11060699 - 17 Jun 2022
Cited by 8 | Viewed by 2786
Abstract
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large [...] Read more.
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis. Full article
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9 pages, 610 KiB  
Article
High Mortality and Graft Loss after Infective Endocarditis in Kidney Transplant Recipients: A Case-Controlled Study from Two Centers
by Yanis Tamzali, Clément Danthu, Alexandra Aubry, Romain Brousse, Jean-François Faucher, Zhour El Ouafi, Pierre Rufat, Marie Essig, Benoit Barrou, Fatouma Toure and Jérôme Tourret
Pathogens 2021, 10(8), 1023; https://doi.org/10.3390/pathogens10081023 - 13 Aug 2021
Cited by 5 | Viewed by 2340
Abstract
Kidney transplant recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation, and outcome. While infective endocarditis (IE) is among such complications in KTRs, the literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. We performed a [...] Read more.
Kidney transplant recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation, and outcome. While infective endocarditis (IE) is among such complications in KTRs, the literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria) in adult KTRs from January 2010 to December 2018 were included, as well as two controls per case, and followed until 31 December 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan–Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus, and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated, age, vascular nephropathy, and elevated calcineurin inhibitor through levels were significantly associated with the occurrence of IE in our study. Patient and death-censored graft survival were greatly diminished five years after IE, compared to controls being 50.3% vs. 80.6% (p < 0.003) and 29.7% vs. 87.5% (p < 0.002), respectively. IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant. Full article
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10 pages, 419 KiB  
Article
COVID-19 Infection in Kidney Transplant Patients: An Italian One Year Single Centre Experience
by Mariarosaria Campise, Carlo Maria Alfieri, Marta Perego, Francesco Tamborini, Donata Cresseri, Maria Teresa Gandolfo, Valentina Binda, Anna Regalia and Piergiorgio Messa
Pathogens 2021, 10(8), 964; https://doi.org/10.3390/pathogens10080964 - 30 Jul 2021
Cited by 4 | Viewed by 2530
Abstract
COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two [...] Read more.
COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak). Thirty-seven patients were hospitalized (HP) and sixty-five were home managed (HM). Infection presented with fever (80%), cough (51%), and dyspnea (33%). HP were older (60 ± 11 vs. 50 ± 14 years, p = 0.001), had more severe respiratory symptoms (dyspnea 62.1%, p < 0.0001–cough 67% p = 0.008), and a longer length of disease (30 ± 28 vs. 21 ± 10, p = 0.04). The incidence of acute kidney injury (AKI) was 29.7% (p < 0.0001). Steroid dosage was increased in 66% of patients (p = 0.0003), while calcineurin inhibitors were reduced by up to one third in 45% of cases, p < 0.0001. Eleven patients died (13%). HM patients recovered completely without sequelae. In the overall cohort, AKI development (p = 0.006 OR 50.4 CI 95% 3.0–836) and age (p = 0.04 OR 1.1 CI 95% 1.0–1.2) were the most important factors influencing the probability of death during the infection. Although we report a relatively low incidence of infection (5.1%) the incidence of death is almost four times higher than it is in the general population. Full article
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15 pages, 930 KiB  
Article
Cytomegalovirus Disease in Renal Transplanted Patients: Prevalence, Determining Factors, and Influence on Graft and Patients Outcomes
by Carlo Maria Alfieri, Paolo Molinari, Mariateresa Gandolfo, Mariarosaria Campise, Donata Cresseri, Anna Regalia, Evaldo Favi, Min Li, Masami Ikehata, Serena Delbue and Piergiorgio Messa
Pathogens 2021, 10(4), 473; https://doi.org/10.3390/pathogens10040473 - 14 Apr 2021
Cited by 8 | Viewed by 2941
Abstract
The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, [...] Read more.
The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, data were recorded after 1-(T1) and 12-(T12) months of RTx. CMVd was defined either by CMV replication without clinical signs of disease (CMVr, 43%), or CMV replication with signs of disease (CMVs, 57%). During the 1st year of RTx, 45% of RTx-p had CMVd (CMVd+). CMVd+ patients were older than CMVd− patients. Female gender and Donor CMV-IgG+ (CMV IgG−D+)/recipient IgG- (CMV IgG−R-) status were more prevalent in CMVd+. At T1, CMVd+ had lower albumin, haemoglobin, and higher uric-acid and reactive C-protein than CMVd− and, at T1 and T12, received more steroids. Albumin-T1 was the unique factor in determining CMVd+, maintaining its significance also after the inclusion of IgG−D+/IgG−R− status to the model. CMVs had higher prevalence of CMV IgG-D+/IgG-R- than CMVr. CMVd, CMVr, and CMVs had no impact on graft loss (11% of RTx-p) and RTx-p death (8% of RTx-p). CMVd is highly prevalent during the 1st year of RTx. Albumin-T1 influences CMVd insurgence. CMVd did not impact on RTx and RTx-p loss. Full article
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