The Novel Coronavirus 2019 Epidemic and the Kidneys

The Severe Acute Respiratory Syndrome Coronavirus 2 is a recent disease that originated in China by the end of 2019. The origins of the dis-ease can be traced to bats, but it has been transmitted to humans, and the inter-human transmission is particularly rampant which has led to a pandemic of unseen proportions. The organ principally involved is the lungs, and severe pneumonia with lack of oxygen leads to fatalities. The aim of this review was to study the involvement of the kidneys with regard to COVID-19 infection and how the disease may affect people on hemodialysis or those who have undergone a kidney transplant. Indeed, the virus, in addition to the lungs, may affect other vascularized organs to a common receptor on lung epithelium and the endothelium of any organ. The kidney, which has a large endothelium surface, is affected, and COVID-19 may lead to acute renal failure. On the other hand, the virus may easily spread among people who are on hemodialysis three times a week. People on hemodialysis may have low immunity, and the virus may have dangerous effects on such people. Finally, renal transplant patients may be easily affected, and the virus may have severe consequences, even death. We will summarize the principal prophylactic measures to be adopted and the therapeutic measures available. Clearly due to the recent occurrence of the pandemic the majority these measures lack a basis in evidence-based medicine and only highlight the efforts to limit COVID-19 induced damage

HBV Hepatitis and Related Renal Nephropathies: Pathogenesis and Treatment

The extrahepatic manifestations of hepatitis B virus (HBV) infection include reactive arthritis, vasculitis (panarteritisnodosa), and primary glomerulonephritis (membranous nephropathy, membranoproliferative glomerulonephritis, and, less frequently, IgA nephropathy, focal and segmental glomerulosclerosis, and minimal change disease). No specific histomorphological patterns have been reported in association with HBV infection. The treatment of HBV-related glomerulopathies is essentially antiviral. Peginterferon and nucleos(t)ide drugs are the treatment of choice. Corticosteroids have been proved to be ineffective (except in panarteritisnodosa), while immunosuppressants can lead to exacerbation of HBV infection

Therapeutic Apheresis in Glomerular Diseases after Kidney Transplantation

Therapeutic apheresis is an extracorporeal treatment that selectively separates abnormal cells or substances from the blood that are linked with or cause certain disease states. It is widely used in transplantation medicine as an adjunctive therapeutic option. In kidney transplantation (KT), recurrent and de novo glomerular diseases represent the third most common cause of graft failure beyond the first year after transplantation, as current therapeutic options are limited. Evidence to support the use of therapeutic apheresis in these conditions is scarce, as it is only supported by observational studies. The purpose of this review was to examine and clarify the potential role of therapeutic apheresis and describe current evidence in the treatment of recurrent and de novo glomerular diseases after KT

Direct-Acting-Antivirals Anti-hepatitis C Virus in Renal Transplant Patients: Relevance of Pharmacologic Interaction

Renal transplantation in patients affected by hepatitis C virus (HCV) infection has been a serious problem because of the use of immunosuppressants. HCV virus may be more aggressive in both the liver and the kidney. Several posttransplantation pathologies are known to be ascribed to the HCV virus. Virus eradication has been historically attempted with interferon (IFN) and ribavirin with poor results. In addition, IFN given posttransplantation may cause severe acute rejection. The introduction of direct antiviral agents (DAA) has revolutionized the treatment, and now it is possible to treat renal transplant patients with these agents leading to a HCV-free status in 3 months without the use of IFN. The major problem caused by these agents is their interference with the immunosuppressive agents. The pharmacokinetics of DAA and immunosuppressants often meet the same metabolic pathways and use the same cytochromes or proteic complexes. In some cases, this may lead to high or low immunosuppressant levels with the risk of rejection. In other cases, the DAAs are interested and they may be increase or decrease in a dangerous way. Therefore, a strict monitoring is always recommended

Chiroptical Properties and Absolute Configuration of Chiral, Open Chain Di- and Tri-substituted Allenes: a Polarizability Approach

A second order treatment of the optical activity of chiral diand tri-substituted open chain allenes, by means of the polarizability model of DeVoe, makes it possible to establish a simple relationship between optical rotatory power and absolute configuration of these compounds

Liver Transplantation for Monogenic Metabolic Diseases Involving the Kidney

Several metabolic monogenic diseases may be cured by liver transplantation alone (LTA) or by combined liver–kidney transplantation (CLKT) when the metabolic disease has caused end-stage renal disease. Liver transplantation may be regarded as a substitute for an injured liver or as supplying a tissue that may replace a mutant protein. Two groups of diseases should be distinguished. In the first group, the kidney tissue may be severely damaged while the liver tissue is almost normal. In this group, renal transplantation is recommended according to the degree of renal damage and liver transplantation is essential as a genetic therapy for correcting the metabolic disorder. In the second group, the liver parenchymal damage is severe. In this group, liver transplantation is essential to avoid liver failure. LTA may also avoid the progression of the renal disease; otherwise a CLKT is needed. In this review, we describe monogenic metabolic diseases involving the kidney that may have beneficial effects from LTA or CLKT. We also highlight the limitations of such procedures and the choice of alternative medical conservative treatments

New Therapies Targeting Cystogenesis in Autosomal Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease is the most common inherited kidney disease and results from mutations in the polycystin 1 gene (PKD1) or the polycystin 2 gene (PKD2). The disease is characterised by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells that destroy the architecture of the renal parenchyma and lead to kidney failure. Until recently, the causes and the molecular pathways that lead to cystogenesis remained obscure. In the last decade, enormous progress has been made in understanding the pathogenesis of autosomal dominant polycystic kidney disease and developing new therapies. The purpose of this review is to provide an update on the promising therapies that are being developed and tested, based on knowledge of recent advances in molecular and cellular targets involved in cystogenesis

Induction Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Renal Involvement: The Nephrologist's Point of View

Renal involvement with rapidly progressive glomerulonephritis is a common manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides characterised by end-stage renal disease and high mortality rates in untreated and late referral patients. Long-term renal survival has improved dramatically since the addition of cyclophosphamide and, more recently, rituximab in association with corticosteroids to remission induction therapeutic regimens. However, renal prognosis remains unfavourable for many patients and mortality is still significantly higher than in the general population. In this review, the open challenges to be addressed to optimise remission induction therapy, especially in patients with advanced kidney failure, are analysed. This concerns the first-line therapy (cyclophosphamide or rituximab) based on different parameters (estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, and safety) and the role of plasma exchange. Furthermore, the paper discusses future perspectives on induction remission therapy by reporting recent advances in new targeted therapies, with particular reference to avacopan, an orally administered selective C5a receptor inhibitor

Hepatitis C Virus Infection and Renal Disorders

Hepatitis C virus (HCV) infection is frequently associated with extrahepatic disorders, among which renal diseases are frequent. This article highlights the most frequent HCV-associated renal disorders, the impact of HCV infection on chronic renal disease and renal transplantation, and the role of current direct-acting antiviral therapies. HCV is associated with membranoproliferative glomerulonephritis, acceleration of end-stage renal diseases in patients with glomerulopathies, and a higher risk of death in patients affected by chronic kidney disease. Before the introduction of direct-acting antiviral drugs as treatment modality, renal transplantation was a challenging clinical problem because the drugs available until 2011 obtained a poor sustained virologic response, had several side effects, and caused acute rejection when used after transplantation. The knowledge of the viral structure and its replication allowed the discovery of new classes of direct-acting antiviral drugs that revolutionized this scenario. These new drugs are comparatively more effective and safer. Accumulating evidence suggests that it is possible to cure HCV-related glomerulonephritis, and obtain a sustained virologic response in patients with renal failure, or on dialysis, before commencing transplantation. Finally, it became possible to transplant HCV-positive kidneys into HCV-positive or HCV-negative recipients

Novel Therapeutic Strategies Targeting Molecular Pathways of Cystogenesis in Autosomal Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease that results from mutations in PKD1 or PKD2. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells that destroy the architecture of the renal parenchyma and lead to kidney failure. Until recently, the causes and the molecular pathways that lead to cystogenesis remained obscure. In the last decade, enormous progress has been made in understanding the pathogenesis of ADPKD and the development of new therapies. The purpose of this review is to update on the promising therapies that are being developed and tested based on knowledge of recent advances in molecular and cellular targets involved in cystogenesis