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Sodium glucose cotransporter type 2 inhibitors are a new class of drugs that act on the cardiovascular system, kidneys and metabolism in a multiple ways. Indeed, even though their principal action involves the transport of sodium and glucose in the convoluted distal tubule, they have multiple actions, such as antifibrotic and endothelial protective effects. Their principal mechanism consists of the loss of sodium and glucose. Therefore, they affect blood pressure and glucose metabolism. Their first use was in the diabetic general population; later, some studies documented their activity in the nondiabetic general population and in heart failure in chronic kidney disease patients. Only in recent years have several small studies documented the efficacy of these drugs in diabetic and nondiabetic kidney transplant patients; relatively large studies are rare, very recent, and open new routes for the development of these drugs.

Precision medicine is mainly based on reliable and noninvasive biomarkers. The aim of this review was to describe the newest biomarkers in the field of kidney transplantation and kidney rejection, one of the most common and severe complications. The standard tools used to identify acute rejection largely result in errors and have many drawbacks. In recent years, new and reliable biomarkers have been identified. These methods avoid risks, are noninvasive, and are able to detect rejection even in cases in which acute rejection is clinically asymptomatic and not otherwise identifiable, which is a frequent occurrence. In recent years, several biomarkers have been identified. Very recently, new relevant biomarkers with high positive predictive value and low negative predictive value have been identified. These are the donor-derived cell-free DNA found in the recipient, the gene expression profile of the donor found in the recipient, and the urinary cytokines that are modified in the graft tissue. The aim of this study was to identify the most recent findings in the literature on this topic and to describe the utility and possible limitations of such new biomarkers for kidney rejection.

The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation.

Infections remain a common complication of solid-organ transplantation and are a major factor of morbidity and mortality in renal transplant recipients. The incidence of infection in renal transplant patients is directly related to the net immunosuppressive effect achieved and the duration of the administration of immunosuppressive therapy. The major types of infections can be categorized according to the time post-transplant during which they occur: in the first month after transplantation post-surgical bacterial infections and in the period from one to four months post-transplant opportunistic infections, overall cytomegalovirus; late infections, beyond 6-12 months, are community-acquired infections. Opportunistic infections (like Pneumocystis carini, Listeria monocytogenes, and Aspergillus fumigatus) most frequently occur in the first 12 months post-transplant and can be modulated by prior exposures and the use of prophylaxis.

One of the major challenges in developing programs for kidney transplantation is represented by the presence of antibodies targeting the HLA of the donor in the recipients and, in particular cases, the incompatibility of the ABO blood groups among donor and recipient for living donors [...]

Medicine has evolved from the so-called experience-based medicine to evidence-based medicine, which is now evolving into precision-based medicine [...]

A checklist of 916 lichenised taxa is reported from the Paneveggio-Pale di San Martino Natural Park and its surroundings (Trentino-Alto Adige, N Italy), based on 7351 records from: (a) 72 literature sources, (b) eight public and private herbaria and (c) field observations by some of the authors. The study area appears as a hotspot of lichen diversity, hosting 30.1% of the lichen biota of the Alps in a territory that has 0.064% of their total surface area. This is mainly due to its high climatical, geological and orographic heterogeneity, but also to the long history of lichenological exploration, that started in the 19th century with Ferdinand Arnold and is still ongoing. The present work highlights the importance of detailed species inventories to support knowledge of biodiversity patterns, taxonomy and ecology and to properly address conservation issues. Fuscidea mollis var. caesioalbescens, Hydropunctaria scabra, Protoparmelia badia var. cinereobadia and Variospora paulii are new to Italy, 18 other taxa are new to Trentino-Alto Adige.

I should highlight that this manuscript is not a formal review on the topic, but a report from an ESOT meeting held on 22 June 2022. The assumption of immunosuppressants exposes kidney transplant recipients to the risk of infections, including COVID-19 infection. A transplant patient having COVID-19 infection raises several questions, including whether the immunosuppressive therapy should be reduced with the consequent risk of favoring acute rejections. Patient vaccination before transplantation is probably the gold standard to avoid the risk of COVID-19 infection after transplantation. In the case of transplant patients, three measures may be undertaken: vaccination, use of monoclonal antibodies and use of therapeutic antiviral small molecules. Concerning vaccination, it is still debated which one is the best and how many doses should be administered, particularly considering the new variants of the virus. The onset of virus variants has stimulated researchers to find new active vaccines. In addition, not all transplant patients develop antibodies. An alternative prophylactic measure to be principally used for patients that do not develop antibodies after vaccination is the use of monoclonal antibodies. These drugs may be administered as prophylaxis or in the early stage of the disease. Finally, the small antiviral molecules may be used again as prophylaxis or treatment. Their major drawbacks are their interference with immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers, however, have adopted an early antimetabolite withdrawal in addition to other interventions. The epidemiological problem concerns also dialysis patients and waitlisted patients who have a higher COVID-19 infection diffusion with respect to kidney transplant recipients. Several factors influence mortality among kidney transplant recipients. Among these factors are the age, race, and comorbidity factors, such as hypertension, diabetes mellitus, obesity, and previous respiratory problems. Treatment is still limited. The only effective antiviral drug is remdesivir that should be administered before the development of the cytokine storm. Vaccination seems to be useful, but due to the concomitant immunosuppression limiting its efficacy, at least three or four doses should be administered.

Previously, membranous nephropathies were divided into primary and secondary categories when the exact mechanism or pathogenetic factor were unknown. Approximately 70% accounted for primary membranous nephropathies. The remaining 30% were called secondary because they developed due to well-known diseases such as autoimmune diseases, tumours, infections, or drug assumptions. The discoveries of the M-type phospholipase A2 receptor and of thrombospondin type 1 domain containing 7A as causative antigens in a part of the so-called primary membranous nephropathies opened new knowledge on the effective causes of a large part of these diseases. The availability of novel techniques such as laser micro-dissection and tandem mass spectrometry, as well as immunochemistry with antibodies directed against novel proteins, allowed the confirmation of new antigens involved. The use of confocal microscopy and Western blot allowed detection of the new antigen on glomerular membrane, and the same antigen and relative antibodies have been detected in serum samples. Through these techniques, four new antigens were first detected, including neural epidermal growth factor 1 and semaphorin 3B in the so-called primary membranous nephropathy, and exostosin 1 and 2 and neural cell adhesion molecule 1 in lupus membranous nephropathy. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases. In addition, new antigens are on the horizon, and the story of primary membranous nephropathy is still to be completely written and understood.

The gut microbial community may be associated with complications after kidney transplantation. The indigenous microbiota has a significant and protective function that influences the transplant recipient response. Genetic or environmental factors may modify the indigenous microbiota and pathobionts appear. In this condition, several disturbances of the kidney graft may be observed. These include acute rejection, infection, diarrhoea, disturbance in the induction of tolerance, and modification of immunosuppressive drug metabolism. Recently, the use of prebiotics, probiotics, and synbiotics has been demonstrated to be effective in normalising these conditions and in restoring the generation of the normal indigenous microbiota. An improved understanding of the function and composition of the indigenous microbiota may help in finding further solutions to stabilise the microbiota after kidney transplantation.

Sexual life and fertility are compromised in end stage kidney disease both in men and in women. Successful renal transplantation may rapidly recover fertility in the vast majority of patients. Pregnancy modifies anatomical and functional aspects in the kidney and represents a risk of sensitization that may cause acute rejection. Independently from the risks for the graft, pregnancy in kidney transplant may cause preeclampsia, gestational diabetes, preterm delivery, and low birth weight. The nephrologist has a fundamental role in correct counseling, in a correct evaluation of the mother conditions, and in establishing a correct time lapse between transplantation and conception. Additionally, careful attention must be given to the antirejection therapy, avoiding drugs that could be dangerous to the newborn. Due to the possibility of medical complications during pregnancy, a correct follow-up should be exerted. Even if pregnancy in transplant is considered a high risk one, several data and studies document that in the majority of patients, the long-term follow-up and outcomes for the graft may be similar to that of non-pregnant women.

The morbidity and mortality from COVID-19 are particularly high among patients with underlying health disease conditions and chronic disease, among which are kidney transplant recipients (KTRs) [...]

Membranous nephropathy (MN) is the major cause of nephrotic syndrome in adults, accounting for 20% of cases with an annual incidence of 1 per 100,000 population. In the past 10 years, the role of podocytes has been identified. Environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes, including PLA2R, THBS1, and NELL1, which become targets of specific autoantibodies with subsequent complement activation. The discovery of these mechanisms has opened a new horizon in the treatment of MN, and novel drugs are available with more specific mechanisms of action. Rituximab, a monoclonal antibody directed against CD20 expressed on B lymphocytes, has been used in several trials and appears to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial). The recently published results of the MENTOR trial documented the superior efficacy of rituximab in patients observed for up to 24 months. In MN, the concept of targeting disease control has introduced novel therapies with specific blocking mechanisms, such as belimumab; nonspecific blocking mechanisms, such as those against adrenocorticotropic hormone; and new therapeutic options, such as ofatumumab, bortezomib, and eculizumab, which have recognised the pathological processes involved in the glomerular diseases.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a heterogeneous group of rare diseases characterised by necrotising inflammation of the small blood vessels and the presence of ANCA with specificity for proteinase-3 or myeloperoxidase. Genetic susceptibility along with malignancy, drug exposure, and environmental exposures to infectious agents and silica are involved in disease progression. To date, growing evidence has revealed that ANCA specificity defines homogeneous groups of patients more effectively than clinical diagnosis, since proteinase-3 ANCA and myeloperoxidase-ANCA are linked with different genetic backgrounds and epidemiologies. This review presents current and updated knowledge on the central aetiopathogenic role of genetic associations and environmental exposures in AAV; discusses the main mechanisms of ANCA immunogenesis; and highlights the value of ANCA specificity for future classification criteria.

Kidney transplant is the best therapy to manage end-stage kidney failure. The main barriers limiting this therapy are scarcity of cadaveric donors and the comorbidities of the patients with end-stage kidney failure, which prevent the transplant. Living kidney donor transplant makes it possible to obviate the problem of scarcity of cadaveric donor organs and also presents better results than those of cadaveric transplant. The principal indication of living kidney donor transplant is preemptive transplant. This allows the patient to avoid the complications of dialysis and it has also been demonstrated that it has better results than the transplant done after dialysis has been initiated. Priority indications of living donor transplant are also twins and HLA identical siblings. We also have very favorable conditions when the donor is young and male. On the contrary, the living donor transplant will have worse results if the donors are over 60-65 years and the recipients are young, and this can be a relative contraindication. There is an absolute contraindication for the living donation when the recipient has diseases with high risk of aggressive relapse in the grafts: focal and segmental hyalinosis that had early relapse in the first transplant; atypical hemolytic uremic syndrome due to deficit or malfunction of the complement regulatory proteins; early development of glomerulonephritis due to anti-glomerular basement membrane antibody in patients with Alport syndrome; primary hyperoxaluria. Extreme caution should also be taken in the evaluation of the kidney donors. The risks of developing renal failure or other complications are low if an adequate pre-donation evaluation has been made according to the international guidelines.

The extrahepatic manifestations of hepatitis B virus (HBV) infection include reactive arthritis, vasculitis (panarteritisnodosa), and primary glomer-ulonephritis (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. Cortico-steroids have been proved to be ineffective (except in panarteritisnodosa), while immunosuppressants can lead to exacerbation of HBV infection.

Introduction. Over the past two decades, our thinking has changed from considering rejection as primarily a T-cell mediated process to the realization that insufficient control of the humoral arm of a recipient’s immune system is the factor primarily responsible for the allograft dysfunction and loss. Acute Antibody Mediated Rejection (ABMR) in kidney transplantation is a severe complication that frequently occurs after transplantation and is due either to pre-transplant Donor Specific Antibodies (DSAs) or to de novo DSAs. New techniques to detect DSAs in the recipient serum and advances in the assessment of graft pathology have allowed us to recognize this entity in recent years. Methods. The treatment of ABMR is a multistep process consisting in the desensitization of the patients with preformed antibodies to prevent acute ABMR: in case of acute ABMR, the antibodies are removed from the serum and anti-B cells immunosuppressants are used. Results and Discussion. Along with our knowledge on acute ABMR, a distinct entity has been recognized: the chronic AMBR. Chronic ABMR is a frequent cause of late graft dysfunction and is characterized by a typical histopathologic feature. The treatment is often difficult and new drugs are now tested to control the disease.

Renal transplantation in patients affected by hepatitis C virus (HCV) infection has been a serious problem becauseof the use of immunosuppres-sants. 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 posttransplan-tation 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 inter-ested and they may be increase or decrease in a dangerous way. Therefore a strict monitoring is always recommended.

Acute kidney injury (AKI) is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributable to i) hypotension and decreased kidney perfusion secondary to hemodynamic or hemostatic factors, ii) drug-induced nephrotoxicity, iii) cytokine storm syndrome related to sepsis. However: i) early new-onset proteinuria and hematuria in many patients, ii) the identification of SARS-CoV-2 viral load in precisely defined kidney compartments, iii) ultrastructural evidence of direct viral infection of the kidneys, and most importantly, iv) morphological alterations associated to cytopathic action induced by the virus support the existence of SARS-CoV-2 associated nephropathy. In addition, collapsing glomerulopathy reported in African American patients with underlying APOL1 kidney risk alleles and SARS-CoV-2 infection is the evidence of a distinct form of SARS-CoV-2 associated nephropathy, the APOL1-SARS-CoV2-associated nephropathy.

The Severe Acute Respiratory Syndrome Coronavirus 2 is a recent disease that originated in China by the end of 2019. The origins of the disease 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 pan-demic 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 endothe- lium 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 occur- rence 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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major pandemic challenging health care. Infection has been reported in all ages, but older patients and immunosuppressant patients as the transplanted are at major risk. Prevention and treatment, whenever possible are the commonly used strategies. Three steps may be distinguished. In the first step prophylaxis is essential and based in avoiding any possible contact to infected people. Staying at home, masking the patient, carefully washing the hands are the most commonly used strategies. If the disease develops in a transplanted patient two steps must be added. In the first step the reduction of the immunosuppressive therapy must be considered together with the administration of antiviral drugs. In a second phase of the disease a severe lung involvement may develop mostly due to a inflammation citokine induced. In this phase in addition to a intensive ventilation requiring the intensive care unit, anticytokine drugs as tocilizumab should be considered.

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.

The incidence of acute rejection of the kidney allograft in the world has been around 15% during the period between 2001 and 2003. It is clinically defined as an elevation in the level of serum creatinine by more than 0.3 mg/dL and is diagnosed by kidney biopsy. On pathologic examination, the interstitium of the allograft is diffusely edematous and infiltrated by CD4 and CD8 lymphocytes. Tubulitis occurs when the lymphocytes and monocytes extend into the walls and lumina of the tubules. Presence of leukocytes determines infection or antibody-mediated rejection. Typically C4d staining is negative. Other causes of acute allograft dysfunction included prerenal factors, interstitial nephritis, infection, acute tubular necrosis, toxicity by drugs, and obstruction in the urinary tract. The primary diagnostic assessments include history, especially adherence to immunosuppressive therapy, physical examination, blood and urine laboratory tests, measurement of the serum levels of the drugs, and ultrasonography. Diagnosis of acute cellular rejection depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte, and proteomic study. Treatment of acute cellular rejection in kidney transplant recipients include pulse steroid for the first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 are used as the second line of treatment if graft function is deteriorating. Changing the protocol from cyclosporine to tacrolimus or adding mycophenolate mofetil or sirolimus might be effective. Prognosis depends on number of rejection episodes, the use of potent drugs, time of rejection from transplantation, and response to treatment.

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.

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.

Immunosuppressive therapy in renal transplantation can be distinguished in induction therapy and maintenance therapy. Induction therapy is an intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, the induction immunosuppressive strategies used at kidney transplant centers fall into one of these two categories. One strategy relies upon high doses of conventional immunosuppressive agents, while the other utilizes antibodies directed against T-cell antigens in combination with lower doses of conventional agents. Maintenance immunosuppressive therapy is administered to almost all kidney transplant recipients to help prevent acute rejection and loss of the renal allograft. Although an adequate level of immunosuppression is required to dampen the immune response to the allograft, the level of chronic immunosuppression is decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy; these risks directly correlate with the degree of overall immunosuppression. The optimal maintenance immunosuppressive therapy in kidney transplantation is not established. The major immunosuppressive agents that are available in various combination regimens are glucocorticoids (primarily oral prednisone), azathioprine, mycophenolate mofetil (MMF), enteric-coated mycophenolate sodium (EC-MPS), cyclosporine (in non-modified or modified [microemulsion] form), Tacrolimus, everolimus, rapamycin (sirolimus), and Belatacept.

Renal diseases involving glomerular deposits of fibrillary material are an important diagnostic challenge for an ultrastructural pathologist. Several renal diseases are characterised by the presence of fibrillary material in the glomeruli. Two disorders of this type, termed ‘fibrillary glomerulonephritis’ (characterised by fibrils measuring approximately 20 nm in diameter) and ‘immunotactoid glomerulonephritis’ (characterised by larger, microtubular deposits), have been described. The possible relatedness of these two disorders and their potential association with other systemic illnesses are the subjects of current debate. Other multisystemic diseases, including amyloidosis and various forms of cryoglobulinaemia, can also present with fibrillary or microtubular deposits in the kidney. The distinction between fibrillary glomerulonephritis, immunotactoid glomerulonephritis, and other processes that have similar ultrastructural features are discussed in this review. Recently, both in fibrillary glomerulonephritis and in immunotactoid glomerulonephritis, the presence of a DnaJ homolog subfamily member 9 has been detected. This antigen is not present in amyloidosis and could be involved in the pathogenesis of these diseases. This review will discuss the role and the relevance of this antigen.

Allograft rejection is defined as tissue injury produced by the effector mechanisms of the alloimmune response, leading to deterioration of graft function. There are two types of rejection: T-cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). Both types of rejection can be early or late, fulminant or indolent, as well as isolated or concomitant and can share pathologic features on biopsy. The immune response to an allograft is an ongoing dialogue between the innate and adaptive immune system, which if unresolved will lead to rejection of the transplanted cells, tissues, or organs. Activation of elements of the innate immune system, triggered by tissue injury sustained during cell isolation or organ retrieval and ischemia reperfusion, will initiate and amplify the adaptive response. T cells require a minimum of two signals for activation: antigen recognition and co-stimulation. Antibody-mediated rejection triggered by alloantibody binding and complement activation is increasingly recognized as a significant contribution to graft loss. Even though one component of the immune system may dominate and lead to rejection, this is usually multifactorial, resulting from the integration of multiple mechanisms. Identifying the molecular pathways that trigger rejection facilitates the identification of targets for the development of immunosuppressive drugs.

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To achieve an effective immune response it is important that T cells can recognize a wide variety of non-self antigens; this allows for restrained immune activation and subsequent antigen-specific killing. This task is accomplished through the generation of a repertoire of T cells in a single individual with specificity for an enormous number of potential foreign antigens presented as peptides on the surface of major histocompatibility complex (MHC) molecules. Variations in MHC structure among individuals increase the variety of peptides that can be presented to T cells; this mechanism protects the species as a whole by ensuring adequate T-cell responses to a given foreign organism. Although slightly different, these MHC polymorphisms expressed in the donor kidney are recognized after kidney transplantation between non genetically-identical humans, and induce alloresponses that in the absence of immunosuppression result in rejection of the allograft. In this chapter, we review basic immunological principles important to the field of kidney transplantation.

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.

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The complement system is involved in several renal diseases and in renal transplantation (RTx). The authors review the complement cascade and its involvement in innate and adaptive immunity in the field of RTx. The complement cascade is involved in several steps of RTx: ischaemia—reperfusion injury (IRI), T cell-mediated acute rejection (TMR), antibody-mediated rejection (ABMR), and progressive kidney injury and fibrosis. The high frequency of complement involvement in RTx is the subject of several studies because complement could be a relevant target in treating the aforementioned conditions. There is an increasing number of ongoing clinical trials aimed at verifying the efficacy and safety of many drug candidates. The anti-C5 monoclonal antibody is already approved to prevent and treat ABMR and is the subject of trials investigating the treatment of other conditions such as IRI, TMR, and progressive fibrosis. Other molecular targets, such as C1, C3, C5a, and C5a receptor, are the subject of international trials and could prove to be effective in the near future.

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.

Findings of abnormally pigmented amphibian individuals provide interesting insights on intraspecific phenotypic variability as well as on variation among populations inhabiting different habitats. Amphibian coloration is determined by chromatophores (specific epidermal cells), and a variety of abnormalities related to them have been reported. In this study we reported cases of albinism and leucism in six species of Italian amphibians, including some endemic species. For some taxa, like Hydromantes sarrabusensis, H. flavus, H. supramontis and Bufo viridis, we describe the first observations of albinism and leucism.

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.

This paper reviews the most important studies on chronic antibody-mediated rejection (cABMR), which is an important cause of late graft dysfunction after renal transplantation. Several antibodies seem to be responsible for chronic rejection; new techniques have allowed us to identify these antibodies in circulation. The pathogenetic role of the antibodies generally includes the complement pathway, but may also be complement-independent. This paper also examines the pathogenesis of chronic endothelial lesions, as well as the histopathological aspects. Antibodies responsible for chronic rejection may preexist before transplantation or may develop after transplantation. The possible therapeutic approaches are poor and principally based on early identification and desensitisation techniques. New B cell targeting drugs are aimed at an improved control of the relevant condition.