Personalized Medicine in Kidney Transplantation and Immunology

A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (25 July 2022) | Viewed by 26423

Special Issue Editor


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Guest Editor
Associate Professor, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Foggia, Italy
Interests: renal transplantation; immunology; immunosuppression

Special Issue Information

Dear Colleagues,

Transplantation in the last century has been the most potent and successful driver to study the immune system and the genetic individuality of HLA. These discoveries have led to clinical application of transplantation, saving life of patients affected by terminal organ failure. Organ transplantation has also driven the development of immunosuppressive agents to control activation of the immune system, so preventing acute rejection of transplanted organs, also allowing treatment of many autoimmune diseases.     Today, renal transplantation is the best treatment available for patients with end stage renal disease. Transplantation saves life, but we still have the task to optimize results by personalizing our treatment approach.  Personalized medicine is today one of the most important task of modern medicine, and it is absolutely clear that transplantation, by its nature, is the best examples of applied personalized medicine, as we personalize organ allocation and the immunosuppressive strategy in our patients.   

We are inviting you to participate in this discussion on personalized medicine, submitting your personal experience or personal view to be published in the special number of Journal of Personalized Medicine dedicated to “Renal transplantation and immunology”.

Dr. Franco Citterio
Guest Editor

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Keywords

  • Renal transplantation
  • Immunosuppression
  • Organ allocation
  • Infections
  • Organ preservation
  • Quality of life
  • Costs of transplantation
  • Hyperimmunized patient

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Published Papers (6 papers)

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Research

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15 pages, 1610 KiB  
Article
Number of Teeth and Nutritional Status Parameters Are Related to Intima-Media Thickness in Dalmatian Kidney Transplant Recipients
by Maja Dodig Novaković, Sanja Lovrić Kojundžić, Mislav Radić, Marijana Vučković, Andrea Gelemanović, Marija Roguljić, Katja Kovačević, Josip Orešković and Josipa Radić
J. Pers. Med. 2022, 12(6), 984; https://doi.org/10.3390/jpm12060984 - 16 Jun 2022
Cited by 2 | Viewed by 2223
Abstract
Although kidney transplantation significantly improves the quality of life of patients with end-stage renal disease (ESRD), the prevalence of cardiovascular disease (CVD) in kidney transplant recipients (KTRs) remains high. Atherosclerosis, post-transplantation metabolic changes, immunosuppressive therapy, and periodontitis contribute to elevated cardiovascular risk in [...] Read more.
Although kidney transplantation significantly improves the quality of life of patients with end-stage renal disease (ESRD), the prevalence of cardiovascular disease (CVD) in kidney transplant recipients (KTRs) remains high. Atherosclerosis, post-transplantation metabolic changes, immunosuppressive therapy, and periodontitis contribute to elevated cardiovascular risk in this population. The aim of the study was to evaluate carotid intima-media thickness (IMT) as a surrogate marker of atherosclerosis and to analyze the possible risk factors for IMT in Dalmatian KTRs. Ninety-three KTRs were included in this study. Data on clinical and laboratory parameters, body composition, anthropometry, advanced glycation end-product (AGE) measurements, blood pressure, and arterial stiffness were collected. All participants underwent ultrasound examination of IMT and evaluation of periodontal status. KTRs with carotid IMT ≥ 0.9 were significantly older, had a lower level of total cholesterol, fat mass, end-diastolic velocity (EDV), and had fewer teeth. They also had significantly higher values of pulse wave velocity (PWV) and resistive index (RI). We found positive correlations between carotid IMT and duration of dialysis, age, PWV, AGE, RI, and average total clinical attachment level (CAL). The regression model showed that IMT in KTRs is associated with higher PWV, lower fat mass, and fewer teeth. The results of our study suggest that nutritional and periodontal status are associated with carotid IMT in KTRs. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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Review

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13 pages, 926 KiB  
Review
Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies
by Claudio Ponticelli, Francesco Reggiani and Gabriella Moroni
J. Pers. Med. 2022, 12(10), 1557; https://doi.org/10.3390/jpm12101557 - 21 Sep 2022
Cited by 35 | Viewed by 4777
Abstract
Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, [...] Read more.
Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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16 pages, 963 KiB  
Review
Non-Immunologic Causes of Late Death-Censored Kidney Graft Failure: A Personalized Approach
by Claudio Ponticelli and Franco Citterio
J. Pers. Med. 2022, 12(8), 1271; https://doi.org/10.3390/jpm12081271 - 1 Aug 2022
Cited by 2 | Viewed by 2703
Abstract
Despite continuous advances in surgical and immunosuppressive protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Antibody-mediated rejection, recurrent autoimmune diseases, and death with functioning graft are the most frequent causes of late-kidney allograft failure. However, in addition to [...] Read more.
Despite continuous advances in surgical and immunosuppressive protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Antibody-mediated rejection, recurrent autoimmune diseases, and death with functioning graft are the most frequent causes of late-kidney allograft failure. However, in addition to these complications, a number of other non-immunologic events may impair the function of transplanted kidneys and directly or indirectly lead to their failure. In this narrative review, we will list and discuss the most important nonimmune causes of late death-censored kidney graft failure, including quality of the donated kidney, adherence to prescriptions, drug toxicities, arterial hypertension, dyslipidemia, new onset diabetes mellitus, hyperuricemia, and lifestyle of the renal transplant recipient. For each of these risk factors, we will report the etiopathogenesis and the potential consequences on graft function, keeping in mind that in many cases, two or more risk factors may negatively interact together. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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19 pages, 1974 KiB  
Review
Cardiovascular Risk after Kidney Transplantation: Causes and Current Approaches to a Relevant Burden
by Francesco Reggiani, Gabriella Moroni and Claudio Ponticelli
J. Pers. Med. 2022, 12(8), 1200; https://doi.org/10.3390/jpm12081200 - 23 Jul 2022
Cited by 10 | Viewed by 3840
Abstract
Background. Cardiovascular disease is a frequent complication after kidney transplantation and represents the leading cause of mortality in this population. Material and Methods. We searched for the relevant articles in the National Institutes of Health library of medicine, transplant, cardiologic and nephrological journals. [...] Read more.
Background. Cardiovascular disease is a frequent complication after kidney transplantation and represents the leading cause of mortality in this population. Material and Methods. We searched for the relevant articles in the National Institutes of Health library of medicine, transplant, cardiologic and nephrological journals. Results. The pathogenesis of cardiovascular disease in kidney transplant is multifactorial. Apart from non-modifiable risk factors, such as age, gender, genetic predisposition and ethnicity, several traditional and non-traditional modifiable risk factors contribute to its development. Traditional factors, such as diabetes, hypertension and dyslipidemia, may be present before and may worsen after transplantation. Immunosuppressants and impaired graft function may strongly influence the exacerbation of these comorbidities. However, in the last years, several studies showed that many other cardiovascular risk factors may be involved in kidney transplantation, including hyperuricemia, inflammation, low klotho and elevated Fibroblast Growth Factor 23 levels, deficient levels of vitamin D, vascular calcifications, anemia and poor physical activity and quality of life. Conclusions. The timely and effective treatment of time-honored and recently discovered modifiable risk factors represent the basis of the prevention of cardiovascular complications in kidney transplantation. Reduction of cardiovascular risk can improve the life expectancy, the quality of life and the allograft function and survival. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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15 pages, 326 KiB  
Review
Planned Pregnancy in Kidney Transplantation. A Calculated Risk
by Claudio Ponticelli, Barbara Zaina and Gabriella Moroni
J. Pers. Med. 2021, 11(10), 956; https://doi.org/10.3390/jpm11100956 - 26 Sep 2021
Cited by 7 | Viewed by 7066
Abstract
Pregnancy is not contraindicated in kidney transplant women but entails risks of maternal and fetal complications. Three main conditions can influence the outcome of pregnancy in transplant women: preconception counseling, maternal medical management, and correct use of drugs to prevent fetal toxicity. Preconception [...] Read more.
Pregnancy is not contraindicated in kidney transplant women but entails risks of maternal and fetal complications. Three main conditions can influence the outcome of pregnancy in transplant women: preconception counseling, maternal medical management, and correct use of drugs to prevent fetal toxicity. Preconception counseling is needed to prevent the risks of an unplanned untimely pregnancy. Pregnancy should be planned ≥2 years after transplantation. The candidate for pregnancy should have normal blood pressure, stable serum creatinine <1.5 mg/dL, and proteinuria <500 mg/24 h. Maternal medical management is critical for early detection and treatment of complications such as hypertension, preeclampsia, thrombotic microangiopathy, graft dysfunction, gestational diabetes, and infection. These adverse outcomes are strongly related to the degree of kidney dysfunction. A major issue is represented by the potential fetotoxicity of drugs. Moderate doses of glucocorticoids, azathioprine, and mTOR inhibitors are relatively safe. Calcineurin inhibitors (CNIs) are not associated with teratogenicity but may increase the risk of low birth weight. Rituximab and eculizumab should be used in pregnancy only if the benefits outweigh the risk for the fetus. Renin–angiotensin system inhibitors, mycophenolate, bortezomib, and cyclophosphamide can lead to fetal toxicity and should not be prescribed to pregnant women. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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11 pages, 565 KiB  
Review
Physical Inactivity: A Modifiable Risk Factor for Morbidity and Mortality in Kidney Transplantation
by Claudio Ponticelli and Evaldo Favi
J. Pers. Med. 2021, 11(9), 927; https://doi.org/10.3390/jpm11090927 - 18 Sep 2021
Cited by 16 | Viewed by 4726
Abstract
In patients with chronic kidney disease, sedentary behavior is widely recognized as a significant risk factor for cardiovascular disease, diabetes, obesity, osteoporosis, cancer, and depression. Nevertheless, the real impact of physical inactivity on the health of kidney transplant (KT) recipients remains uncertain. Over [...] Read more.
In patients with chronic kidney disease, sedentary behavior is widely recognized as a significant risk factor for cardiovascular disease, diabetes, obesity, osteoporosis, cancer, and depression. Nevertheless, the real impact of physical inactivity on the health of kidney transplant (KT) recipients remains uncertain. Over the last decade, there has been a renewed interest in exploring the effects of regular physical exercise on transplant-related outcomes. There is now mounting evidence that physical activity may reduce the burden of cardiovascular risk factors, preserve allograft function, minimize immunosuppression requirement, and ameliorate the quality of life of KT recipients. Many positive feedbacks can be detected in the early stages of the interventions and with a minimal exercise load. Despite these encouraging results, the perceived role of physical activity in the management of KT candidates and recipients is often underrated. The majority of trials on exercise training are small, relatively short, and focused on surrogate outcomes. While waiting for larger studies with longer follow-up, these statistical limitations should not discourage patients and doctors from initiating exercise and progressively increasing intensity and duration. This narrative review summarizes current knowledge about the deleterious effects of physical inactivity after KT. The benefits of regular physical exercise are also outlined. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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