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This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroid-free immunosuppression in renal transplant recipients receiving everolimus. [ABSTRACT FROM AUTHOR]

Whether the long-term patient and renal survival of those diagnosed with lupus nephritis (LN) has improved over the decades is still debated. Eighty-nine patients diagnosed between 1968 and 1990 entered this study and their outcome was evaluated after 20 years. At presentation 54% of patients had class IV LN, 39.3% had renal insufficiency and 59.5% had nephrotic syndrome. Patients were divided into two groups: Group 1 consisted of 30 patients diagnosed between 1968 and 1980; Group 2 consisted of 59 patients diagnosed between 1981 and 1990. In Group 1 patient survival at 20 years was 84% versus 95% in Group 2 (p = 0.05). Survivals without end-stage renal failure were respectively 75% and 84% at 20 years (p = 0.05). Survivals without severe infection at 20 years were 44% in Group 1 and 66.5% in Group 2 (p = 0.02). Survivals without cardiovascular events at 20 years were: 53% in Group 1 and 90% in Group 2 (p = 0.005). At presentation, patients in Group 1 had higher serum creatinine (1.96 vs 1.15 mg/dl, p = 0.01), higher activity index (8 vs 5.5, p = 0.01), lower hematocrit (31% v s6%, p = 0.008) and lower serum C4 levels (p = 0.04) than Group 2 patients. Patients in Group 1 also received less frequent methylprednisolone pulses (43% v s81%, p = 0.0006). In Italian patients with LN, long-term life expectancy and renal survival progressively improved over the decades, while morbidity progressively declined. An earlier referral and refinement of therapy achieved this goal. [ABSTRACT FROM PUBLISHER]

Abstract: Despite their contribution in the success of organ transplantation, calcineurin inhibitors (CNIs) may be responsible for frequent and severe side effects that can affect graft survival and life expectancy. In this article, we have reviewed registry studies and randomized controlled trials (RCTs) that seek to avoid, withdraw, or minimize CNIs in renal transplant recipients. Attempts to completely avoid CNIs by administering mycophenolate mofetil (MMF) and/or sirolimus (SRL) have resulted in increased risks of rejection and side effects, with small advantage to improve renal graft function. Early withdrawal of CNIs after transplantation using administration of MMF can improve graft function but may be associated with a greater risk of acute or chronic rejection and graft failure. RCTs in which CNIs were replaced a few months after transplantation by SRL reported improved graft function among SRL-treated patients, but such a treatment was complicated by iatrogenic toxicity. Late replacement of CNIs with SRL did not produce a particular advantage and again was complicated by more frequent side effects. On the basis of these trials, it seems that CNI elimination can trigger rejection or side effects. Recent RCTs showed that minimization of CNI doses in association with everolimus does not increase the risk of rejection, allows one to obtain good graft function, and is well tolerated. Such an approach seems therefore preferable to complete elimination of CNIs with substitution of the current immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Abstract: The Evidence study (EVerolImus once-a-Day rEgimen with Neoral® versus Corticosteroid Elimination) sought to compare once-a-day administration with steroid withdrawal versus twice-daily administration among de novo kidney transplant recipients treated with everolimus, cyclosporine, and steroids. This article describes the study design and rationale of once-daily administration and steroid withdrawal among recipients of de novo kidney transplants treated with everolimus and cyclosporine. [Copyright &y& Elsevier]

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects primarily women, commonly in their reproductive years but does not influence fertility. For these reasons, the clinician has often to face the many problems of pregnancy in patients with SLE including the influence of SLE on fetal outcome and that of pregnancy on SLE. As there is increasing evidence of an important role of sex hormones in immunity, the influence of pregnancy on SLE is probably due to the changes in sex hormone levels during pregnancy that are more important than in any other period of life. Early reports emphasized a high fetal and maternal risk in particular in patients with lupus nephritis. However in the same period the prognosis of lupus nephritis was poor, so it was difficult to know whether pregnancy actually influenced the prognosis of the disease. More recent prospective studies indicate that pregnancy is safe for the majority of mothers if it is planned when SLE is quiescent. Instead, although fetal risk has been progressively reduced in the last 40 years, it continues to be higher than that occurring in pregnancies of healthy women. In particular the presence of antiphospholipid antibodies considerably worsen the fetal outcome. [ABSTRACT FROM AUTHOR]

Most patients with systemic lupus erythematosus (SLE) are suitable candidates for renal transplantation. However, a number of them may present some disease-related problems. As cardiovascular disease is a leading cause of morbidity and mortality in SLE patients, a careful pretransplant cardiovascular screening is recommended. A search for antiphospholipid antibodies is also useful as the presence of these antibodies can cause an early graft thrombosis. The risk of recurrence of SLE nephritis after transplantation may range between 2 and 30%. In most cases recurrence is characterized by mild histologic lesions. Only rarely does it lead to graft failure. Postransplant immunosuppression does not differ from that used routinely. Whenever possible, a steroid-free immunosuppression should be scheduled to prevent iatrogenic toxicity in patients who have already received long-term steroid treatment. The results of kidney transplantation largely depend on the clinical conditions at transplantation. In patients with poor clinical status or receiving an aggressive immunosuppression it is advisable to postpone the transplant. When some selection criteria are respected, the results of renal trasplantation in SLE patients are at least as good as in other transplant recipients. [ABSTRACT FROM AUTHOR]

The 3 main causes of primary nephrotic syndrome are minimal change nephropathy, focal segmental glomerulosclerosis and membranous nephropathy. Corticosteroids result in remission of proteinuria in most patients with minimal change nephropathy. Many patients, however, develop corticosteroid dependency. A course of cytotoxic drugs can also achieve remission but these agents cannot be administered for prolonged periods or in repeated cycles because their toxicity is cumulative. Review of the available literature indicates that cyclosporin may maintain remission of nephrotic syndrome in about 80% of patients with corticosteroid-sensitive disease, indicating an important role for this drug in patients with frequent relapses or corticosteroid dependency. Although cyclosporin is less effective in patients with focal segmental glomerulosclerosis, which is often corticosteroid-resistant, a number of studies indicate that it may be successful both in the few steroid-sensitive patients with frequent relapses and in some corticosteroid-resistant patients. In patients with membranous nephropathy, a 6-month course of corticosteroids and cytotoxic agents may favour remission of nephrotic syndrome and protect renal function. Several studies have shown that cyclosporin can improve proteinuria, and there is a tentative suggestion that it might also protect against renal function deterioration. The risk of nephrotoxicity can be minimised if cyclosporin is used at the correct doses and if renal function is carefully monitored during treatment. In summary, cyclosporin can be considered a useful tool for treating patients with nephrotic syndrome associated with primary glomerulonephritis. [ABSTRACT FROM AUTHOR]

Affinity purified immunoglobulin G (IgG) fractions from systemic lupus erythematosus (SLE) patients positive for anti-endothelial cell antibodies (AECA) bind human umbilical vein endothelial cell (HUVEC) monolayers. In vitro incubation of serial protein concentrations of SLE AECA IgG induces a dose-dependent endothelial activation: i) increase of functional adhesion of the monocytic cell line U937; ii) upregulation of E-Selectin, ICAM-I, VCAM-I expression evaluated by a cell solid-phase enzyme linked immunoassay; and iii) increased secretion of interleukin (IL)-6 in the culture supernatants. Control experiments carried out with HUVEC monolayers incubated with IgG fractions from normal healthy controls or from AECA negative SLE sera do not affect at all endothelial adhesion molecule expression or pro-inflammatory cytokine secretion. The AECA IgG effects are not related to both anti-phospholipid or anti-DNA activities. Taken together the findings suggest that these autoantibodies might be important in recruiting and in activating mononuclear leukocytes responsible for vessel wall infiltration and raise the possibility that AECA might display a pathogenic role in SLE vessel damage. [ABSTRACT FROM AUTHOR]

In 1976 a randomized trial of methyplprednisolone and chlorambucil in idiopathic membranous nephropathy was stated. This article updates that and describes the long-term outcomes in these patients. Details of study; Results; Discussion.

One of the characteristics of systemic lupus erythematosus (SLE) is the large inter- and intra-individual variability of the clinical course. Lupus nephritis is no exception. Some patients with kidney involvement may show rapid progression to renal failure, others may enter complete and stable remission after adequate therapy while a number of other patients, with similar clinical and histological pattern at presentation, may alternate periods of clinical quiescence with renal exacerbations of different severity. In this paper we focus on the incidence, the prognostic significance and the treatment of renal flares in patients with SLE nephritis. [ABSTRACT FROM AUTHOR]