Treatment of the nephrotic syndrome associated with primary glomerulonephritis

The term nephrotic syndrome (NS) refers to a condition characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. The NS is often seen when the urinary protein excretion exceeds 3.5 g/day and is almost invariably present when proteinuria is greater than 5 g/day. In the NS there may be a constellation of biochemical and clinical abnormalities that can predispose to disabling and even fatal complications, such as infections, bone disease, arterial or venous thrombosis, cardiovascular disease, etc. In addition, the onset of NS is a marker for bad outcome for most glomerular diseases.The NS may be caused by a large variety of renal diseases. In this paper, however, we will limit ourselves to reviewing the treatment for those cases of NS associated with primary glomerulonephritis

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C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure

Monoclonal Antibodies for Systemic Lupus Erythematosus (SLE)

A number of monoclonal antibodies (mAb) are now under investigation in clinical trials to assess their potential role in Systemic Lupus Erythematosus (SLE). The most frequently used mAb is rituximab, which is directed against CD20, a membrane protein expressed on B lymphocytes. Uncontrolled trials reported an improvement of SLE activity in non-renal patients and other studies even reported an improvement of severe lupus nephritis unresponsive to conventional treatments. However two randomized trials failed to show the superiority of rituximab over conventional treatment in non renal SLE and in lupus nephritis. Preliminary trials reported promising results with epratuzumab, a humanized mAb directed against CD22, and with belimumab, a human mAb that specifically recognizes and inhibits the biological activity of BLyS a cytokine of the tumornecrosis-factor (TNF) ligand superfamily. Other clinical trials with mAb directed against TNF-alpha, interleukin-10 (Il-10), Il-6, CD154, CD40 ligand, IL-18 or complement component C5 are under way. At present, however, in spite of good results reported by some studies, no firm conclusion on the risk-benefit profile of these mAbs in patients with SLE can be drawn from the available studies

Non-Immunologic Causes of Late Death-Censored Kidney Graft Failure: A Personalized Approach

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

Fetal Toxicity of Immunosuppressive Drugs in Pregnancy

Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks. Some immunosuppressive drugs are teratogenic and should be replaced even before the pregnancy, while other drugs need to be managed with caution to prevent fetal risks, including miscarriage, intrauterine growth restriction, prematurity, and low birth weight. In particular, the increasing use of biologic agents raises the question of their compatibility with reproduction. In this review we present data on the indication and safety in pregnancy of the most frequently used immunosuppressive drugs

<i>De novo</i>membranous nephropathy

De novo membranous nephropathy (MN) is an uncommon complication of kidney transplantation, which shows histological findings similar to those seen in recurrent MN, but with some distinct differences. The clinical presentation may be variable, from asymptomatic to nephrotic proteinuria. The disease may run an indolent course or may have an accelerated course leading to allograft loss. De novo membranous nephropathy (MN) can develop in transplant recipients with viral hepatitis, Alport syndrome, ureteral obstruction, renal infarction, or in conjunction with recurrent IgA nephritis. Histologic signs of allograft rejection are often associated with or can antedate de novo MN. These findings suggest that donor-specific antibodies and antibody-mediated rejection might play a pathogenetic role in some patients with de novo MN. However, signs of rejection were absent in a number of cases, and in some instances the disease developed in recipients of "full house" HLA- matched kidneys. Thus, it seems possible that de novo MN is not because of allograft rejection per se, but is triggered by different injuries that can create an inflammatory environment, activate innate immunity, and expose hidden (cryptic) antigens, probably different from those observed to be involved in idiopathic MN. These events can lead to the production of circulating antibodies and in situ formation of immune complexes (IC) and the morphological lesion of MN