Modern Immunosuppressive Therapy in Kidney Transplantation

Abstract

Immunosuppressive therapy is a key component for successful kidney transplantation. It is commonly believed that more intensive immunosuppression is needed initially to prevent rejection episodes and less immunosuppression is subsequently maintained to minimize the overall risk of infection and malignancy. The selection of drugs should be guided by a comprehensive assessment of the immunologic risk, patient comorbidities, financial cost, drug efficacy and adverse effects. Lymphocyte-depleting antibody induction is recommended for patients with high immunologic risk, while IL-2R antibody can be used for low or moderate risk patients. Patients with very low risk may be induced with intravenous steroids without using an antibody. A maintenance regimen typically consists of a low-dose of steroid combined with two of the four class drugs: calcineurin inhibitor (tacrolimus or cyclosporine), antimetabolite (mycophenolate mofetil or enteric coated mycophenolate sodium), mTOR inhibitor (sirolimus or everolimus) and costimulation blocker (belatacept). Currently in the USA, the most popular maintenance is the combination of corticosteroid, mycophenolic acid and tacrolimus. Steroid minimization, or calcineurin inhibitor free or withdrawal should be limited to the highly selected patients with low immunological risk. Recently, the novel biological agent belatacept-based maintenance has demonstrated a significantly better renal function and improved cardiovascular and metabolic profile, which may provide hope for an ultimate survival benefit.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients

“…Due to the numerous adverse effects, narrow safety margin and large intra-and inter-individual variability in pharmacokinetics, therapeutic monitoring is mandatory [1][2][3] . The normal pharmacokinetic curve of tacrolimus has a peak-andtrough pattern.…”

“…It binds to FK506-binding protein to form a complex that inhibits calcineurin phosphatase in Tlymphocytes [commonly referred as calcineurin inhibitor (CNI)]. Tacrolimus has been widely used as the primary immunosuppressive agent in kidney transplant patients [1] . Due to its narrow therapeutic index, optimal dosing with therapeutic monitoring is necessary.…”

Clinical Management of Kidney Allograft Dysfunction

“…Possible actions of IVIG include anti-idiotypic antibodies neutralizing DSA, inhibiting complement binding or activation and suppressing DSA synthesis [3] [21] [25]. Rituximab depletes B cells and it has been used to treat AMR [3] [20] [21]. Corticosteroids and ATG remain beneficial as they can control the B cell response by depleting or inhibiting the helper T cells.…”

“…Patient noncompliance with medications may be caused by their inability to tolerate the side effects or by the financial difficulty to afford drugs. Inadequate immunosuppression may also be caused by adding new drug or herbal supplement that induces cytochrome P-450 enzyme and increases the metabolism of calcineurin inhibitors and/or mTOR inhibitors, which leads to decline in the drug trough level [21]. Rescue therapy for refractory rejection is commonly based upon the administration of tacrolimus and/or mycophenolate to those not receiving them as maintenance prior to rejection episode [29] [30].…”

Transplante renal com doador vivo após dessensibilização com imunoglobulinas polivalentes: impacto nos anticorpos específicos contra o doador

“…Poucos são os efeitos colaterais relacionados à infusão dessa droga. Nos casos mais extremos, existem relatos de trombose vascular, meningite asséptica e anafilaxia grave (17) . Um paciente evoluiu com nefrotoxicidade pelos inibidores de calcineurina e uma perda de enxerto ocorreu por trombose no pós-transplante imediato.…”