Infectious Complications Following Kidney Transplantation—A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota
Abstract
:1. Introduction
2. Changes in the Management to Donor-Derived Infections
3. New Approaches to the Management of Infections in the Era of Antimicrobial Resistance
4. Emergence of Gastrointestinal Microbiota and Transplant Associated Infections
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CDI | Clostridium difficile infection |
CMV | Cytomegalovirus |
DAA | Direct-acting antivirals |
EXPANDER | Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV Negative Recipients |
HCV | Hepatitis C virus |
HR | Hazards Ratio |
NAT | Nucleic Acid Testing |
QALY | Quality Adjusted Life Years |
PCR | Polymerase Chain Reaction |
THINKER | Transplanting HCV-infected Kidneys into Negative Kidney Recipients |
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Agent Class | Example | Genotype | Adverse Events | Drug-Drug Interactions | Contraindications | Probability of Drug Resistance |
---|---|---|---|---|---|---|
NS3/4A protease inhibitors | Boceprevir Telaprevir Simeprevir Asunaprevir Paritaprevir Grazoprevir | Narrow | Fatigue Anemia Nausea Dysgeusia Headache | Multiple via CYP3A and p-glycoprotein (e.g., ritonavir, erythromycin, rifampicin, efavirenz) | Low creatinine clearance; use of alpha-1 adrenoreceptor antagonists, anticonvulsants, oral contraceptive pills | High |
NS5A inhibitors | Daclatasvir Ledipasvir Ombitasvir Elbasvir Velpatasvir | Medium | Headache Fatigue Nausea Diarrhea Insomnia | Minimal; case reports of thyroid hormone, dihydropyridines, alpha and beta blockers, proton pump inhibitors, statins | Low creatinine clearance; previous Hepatitis B, use of systemic steroids and anticonvulsant therapy | Low |
NS5B polymerase inhibitors | Sofosbuvir (nucleoside) Dasabuvir (non-nucleoside) | Broad (nucleoside) Narrow (non-nucleoside) | Fatigue Symptomatic bradyarrhythmias | Minimal | Low creatinine clearance; use of anticonvulsant and antimicrobial therapy, HIV protease inhibitor therapy and herbal supplements (e.g., St John’s Wort) | Low |
Genotype | Suitable Regimens |
---|---|
Genotype 1 | Ledipasvir-sofosbuvir Sofosbuvir-velpatasvir Elbasvir-grazoprevir Glecaprevir-pibrentasvir Dasabuvir-omitasvir-paritaprevir-ritonavir Ombitasvir-paritaprevir-ritonavir-daclatasvir |
Genotype 2 | Sofosbuvir-velpatasvir Glecaprevir-pibrentsvir Dalatasvir-sofosbuvir Sofosbuvir-ribavirin |
Genotype 3 | Glecaprevir-pibrentasvir Sofosbuvir-velpatasvir Dalatasvir-sofosbuvir Sofosbuvir-ribavrin |
Genotype 4 | Ledipasvir-sofosbuvir Sofosbuvir-velpatasvir Elbsvir-grazoprevir Glecaprevir-pibretasvir |
Genotype 5 and 6 | Ledipasvir-sofosbuvir Sofosbuvir-velpatasvir Glecaprevir-pibrentasvir |
Study | Year | Study Design | N | Mean Age of Recipients (Years) | Organ Transplant | Intervention | Results |
---|---|---|---|---|---|---|---|
Durand [31] | 2018 | Open-label, non-randomised trial | 10 | 71 (median) | Kidney | Grazoprevir/elbasvir (Genotype 1); sofosbuvir added for Genotype 3 | HCV RNA not detectable Graft function stable No treatment adverse effects (sponsor: Merck Pharmaceuticals) |
Reese [30] | 2018 | Open-label, non-randomised trial | 20 | 56 | Kidney | Grazoprevir/elbasvir (Genotype 1) | HCV RNA not detectable Graft function stable No treatment adverse effects (sponsor: Merck Pharmaceuticals) |
Woolley [32] | 2019 | Open-label, non-randomised trial | 44 | 61 (median) | Heart and lung | 4 week-regimen of sofosbuvir/velpatasvir | 35/44 enrolled and completed 6 months follow-up (non-detectable HCV RNA, stable graft function no treatment adverse effects) |
Wadei [33] | 2019 | Case report | 1 | - | Liver | Glecaprevir/pibentasvir (delayed) | Delay in direct-acting anti-HCV drugs (DAA) resulted in severe membranoproliferative glomerulonephritis requiring haemodialysis |
Abdelbasit [34] | 2018 | Case series | 5 | 47 | Lung | Sofosbuvir/ledipasvir (Genotype 1); sofosbuvir/alpatasvir (Genotype 2) | HCV RNA not detectable Graft function stable No treatment adverse effects |
Schlendorf [35] | 2018 | Open-label, non-randomised trial | 13 | 53 | Heart | Ledipasvir/sofosbuvir (Genotype 1) and Sofosbuvir/Velpatasivr (Genotype 3) | 12/13 undetectable HCV RNA 1 death (pulmonary emboli) Graft function stable No treatment adverse events |
Cotter [40] | 2019 | Registry | 2635 | 57 | Liver | Various DAAs (registry study) | 3-year graft survival following use of DAAs increased to 88% from 79% |
Axelrod [41,42] | 2018 | Registry | 157,873 kidney and 58,509 liver transplants | - | Kidney and liver | Various DAAs (registry study) | Improvements in graft function and death post DAA |
Cholankeril [41,42] | 2018 | Registry | 3855 | 58 | Liver | Various DAAs (registry study) | 1-year post transplant survival pre-DAA 89.9% vs 91.9% post DAA |
Medication | Mechanism of Action | Adverse Events | Resistance Patterns | Drug-Drug Interactions |
---|---|---|---|---|
Letermovir | Inhibits viral terminase complex (UL51/JL56/UL89) | Nausea, diarrhea, vomiting, peripheral edema, cough, headache, fatigue and abdominal pain | None noted | None known, possibly with ciclosporin |
Maribavir | Inhibits CM UL97 serine/threonine kinase by competitively inhibiting the binding of ATP to the kinase ATP-binding site | Gastrointestinal disorders (diarrhea, dysgeusia, nausea, vomiting) | Emerging (T409M and H411Y) | CYP3A4 P-glycoprotein |
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Share and Cite
Chan, S.; Isbel, N.M.; Hawley, C.M.; Campbell, S.B.; Campbell, K.L.; Morrison, M.; Francis, R.S.; Playford, E.G.; Johnson, D.W. Infectious Complications Following Kidney Transplantation—A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota. Medicina 2019, 55, 672. https://doi.org/10.3390/medicina55100672
Chan S, Isbel NM, Hawley CM, Campbell SB, Campbell KL, Morrison M, Francis RS, Playford EG, Johnson DW. Infectious Complications Following Kidney Transplantation—A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota. Medicina. 2019; 55(10):672. https://doi.org/10.3390/medicina55100672
Chicago/Turabian StyleChan, Samuel, Nicole M Isbel, Carmel M Hawley, Scott B Campbell, Katrina L Campbell, Mark Morrison, Ross S Francis, E Geoffrey Playford, and David W Johnson. 2019. "Infectious Complications Following Kidney Transplantation—A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota" Medicina 55, no. 10: 672. https://doi.org/10.3390/medicina55100672