Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review on incidence, risk factors, pathophysiology and management of immunosuppressive therapy

Abstract Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display “spontaneous” DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Information and consent in dentistry

Consent is the essential expression of the patient’s will, and thus, must be preceded by a procedure. The need for consent is based on ethical principles, legal regulations, codes of conduct and judicial doctrine. In order to be able to give valid consent, one must have the ability to make decisions. In any event if the patient is not able to do so, as in the case for minors or those with mental impairments, specific legal and medico-legal provisions must be made

Donation of the body for scientific purposes in Italy: ethical and medico-legal considerations

In recent years in Italy (and in the other European Countries) a new debated topic involves anatomists and the scientific world: donation of the body after death for scientific purposes. The aim of our analysis is to analyze the issue of voluntary body donation in Italy focusing first of all, on key principles of the disciplines of donation. Considering the rise of exhibitions and events in which death is spectacularized, the debate is focus on will, on respect and overall on the purpose for which the body is donated. Anatomical dissection is considered necessary in the direct learning of the human body, of surgical practices and new scientific techniques but the scarcity of programmes and regulations regarding the donation of bodies for study and research make it an uncommon practice. After discussing what are the constitutional principles underlying the issue we want to emphasize the need of a more effective and updated regulation to set limits and methods of a practice still essential for scientific progress

Donation of the body for scientific purposes in Italy: ethical and medico-legal considerations

In recent years in Italy (and in the other European Countries) a new debated topic involves anatomists and the scientific world: donation of the body after death for scientific purposes. The aim of our analysis is to analyze the issue of voluntary body donation in Italy focusing first of all, on key principles of the disciplines of donation. Considering the rise of exhibitions and events in which death is spectacularized, the debate is focus on will, on respect and overall on the purpose for which the body is donated. Anatomical dissection is considered necessary in the direct learning of the human body, of surgical practices and new scientific techniques but the scarcity of programmes and regulations regarding the donation of bodies for study and research make it an uncommon practice. After discussing what are the constitutional principles underlying the issue we want to emphasize the need of a more effective and updated regulation to set limits and methods of a practice still essential for scientific progress

[Cardiovascular risk in polycystic kidney disease]

Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications

The central importance of information in cosmetic surgery and treatments

The increase in the number of people who choose to have medical procedures done to improve their appearance may be due to changed social and cultural factors in modern society, as well to the ease of access and affordable costs of these cosmetic treatments

Medicolegal implications of surgical errors and complications in neck surgery: a review based on the Italian current legislation

Aim of the present paper is the review of the principal complications associated to endocrine neck surgery considering how expertise, full adoption of guidelines, appropriate technology and proper informed consent may limit the medicolegal claims at the light of the incoming new regulation of the medical professional legal responsibility. A literature search, using the Medline/PubMed database for full-length papers, was used. Postoperative recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism remain the principal causes of surgical malpractice claims . In the procedure of neck lymphadenctomy intra-operative haemorrhage, thoracic duct injury, injuries to loco-regional nerves can be observed and can be source of claims. After many years of increased medicolegal litigations, the Italian government is proposing a drastic change in the regulations of supposed medical malpractice in order to guarantee the patient’s right to a safe treatment and in the meantime to defend clinicians from often unmotivated and prejudicial legal cases. Surgical errors and complications in neck surgery are a relevant clinical issue. Only the combination of surgicaland clinical expertise, application of guidelines, appropriate technology and a routinely use of specific informed consent can contain potential medicolegal implications

Medicolegal implications of surgical errors and complications in neck surgery: A review based on the Italian current legislation

Aim of the present paper is the review of the principal complications associated to endocrine neck surgery considering how expertise, full adoption of guidelines, appropriate technology and proper informed consent may limit the medicolegal claims at the light of the incoming new regulation of the medical professional legal responsibility. A literature search, using the Medline/PubMed database for full-length papers, was used. Postoperative recurrent laryngeal nerve (RLN) palsy and hypoparathy-roidism remain the principal causes of surgical malpractice claims . In the procedure of neck lymphadenctomy intra-operative haemorrhage, thoracic duct injury, injuries to loco-regional nerves can be observed and can be source of claims. After many years of increased medicolegal litigations, the Italian government is proposing a drastic change in the regulations of supposed medical malpractice in order to guarantee the patient’s right to a safe treatment and in the meantime to defend clinicians from often unmotivated and prejudicial legal cases. Surgical errors and complications in neck surgery are a relevant clinical issue. Only the combination of surgical and clinical expertise, application of guidelines, appropriate technology and a routinely use of specific informed consent can contain potential medicolegal implications