Current and Emerging Therapies for Lupus Nephritis

Abstract

The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.

Renal histology in Indigenous Australians with lupus nephritis

“…Treatment consisted of OH-chloroquine, prednisolone and methotrexate use for extra-renal manifestations in patients with Class I and II lesions and hydrochloroquine, prednisolone (up to 1 mg/kg) and mycophenolate or cyclophosphamide for patients with proliferative LN (Class III/IV) in accordance with current recommendations. 11 Angiotensinconverting enzyme (ACE)-inhibitor treatment was preferred for arterial hypertension. Outcome measures were death as ascertained by electronic health records and ESRD as the documented need for chronic (> 3 months) renal replacement therapy or transplantation, while renal insufficiency was defined as recorded sustained doubling of serum creatinine for at least 6 months.…”

Update on Lupus Nephritis

“…All current widely-accepted treatment regimens for LN (summarized in Figure 2) incorporate high-dose corticosteroids for rapid control of inflammation and either MMF or cyclophosphamide to control inflammation and autoimmunity (60,79). All patients (unless contraindicated) should be treated with an antimalarial given the evidence that lack of antimalarial use may be associated with an increase in LN treatment failures (80).…”

Прецизионная Диагностика Люпус-Нефрита: Возможности И Роль Биомаркеров

“…В последние годы было протестировано несколько более специфических биологических агентов, многие из которых нацелены на специфические воспалительные пути. Тем не менее после более чем десяти лет клинических испытаний ни один из них не продемонстрировал дополнительной эффективности при ЛН по сравнению со стандартами лечения [6]. Вероятно, это отчасти связано с плохим отбором пациентов, с трудностями оценки адекватности проводимой терапии, отсутствием современных биомаркеров заболевания, позволяющих оценить не только эффективность лечения, но и прогноз.…”