Lupus Nephritis in Asia: Clinical Features and Management

Abstract

Background: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. Summary: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed. Corticosteroids combined with either cyclophosphamide (CYC) or mycophenolic acid (MPA) is the current standard-of-care induction regimen for severe LN irrespective of race or ethnicity. However, the preference for MPA or CYC, and possibly the optimum dose for MPA, is influenced by the patient's origin. Also, there is an insufficient evidence base for reduced-dose intravenous CYC in Asian patients. Health economics and access to prompt diagnosis and treatment are still challenging issues in some Asian regions. The former represents a significant obstacle limiting the access of patients to MPA despite the proven efficacy of the drug as an induction agent and its superiority over azathioprine (AZA) in preventing disease flares when used for long-term maintenance immunosuppression. Calcineurin inhibitors such as tacrolimus deserve further investigation in view of their additional effect on podocytes by reducing proteinuria and the promising data from Asian patients. Despite considerable advances in the clinical management of LN over the past few decades with resultant improvements in patients' outcomes, there are still knowledge gaps and unmet clinical needs. Asia has made substantial contributions to the evidence base that guides clinical management and continues to offer invaluable opportunities for research pursuits. Key Messages: Treatment responses and clinical outcomes in Asian patients with LN compare favorably with patients from other parts of the world. The prevention and treatment of infective complications remain significant challenges in managing LN in Asia. Facts from East and West: (1) The prevalence of SLE is lower among Caucasians than other ethnicities. A higher prevalence is observed among Asians and African Americans, while the highest prevalence is found in Caribbean people. The prevalence of LN in Asian SLE patients is much higher than in Caucasians as well. However, the 10-year renal outcome and renal survival rate appear to be better in Asians. (2) Polymorphisms of genes involved in the immune response, such as Fcγ receptor, integrin alpha M, TNF superfamily 4, myotubularin-related protein 3 and many others, might be partly responsible for the differences in prevalence between the different ethnic groups. European ancestry was shown to be associated with a decrease in the risk of LN even after adjustment for genes most associated with renal disease. (3) Access...

Long‐term renal outcomes in multi‐ethnic Southeast Asians with lupus nephritis: a retrospective cohort study

“…In contrast, 5‐year renal survival ranged between 48% and 84% in Africans . These results and our own confirm the general consensus that Asians with LN have favourable outcomes . Ethnicity also appeared to influence outcomes within our multi‐ethnic cohort as Chinese were more likely to have complete remission and less likely to develop progressive CKD, although the difference did not reach statistical significance ( P = 0.07).…”

“…27 These results and our own confirm the general consensus that Asians with LN have favourable outcomes. 6,16 Ethnicity also appeared to influence outcomes within our multi-ethnic cohort as Chinese were more likely to have complete remission and less likely to develop progressive CKD, although the difference did not reach statistical significance (P = 0.07). It has been postulated that blacks may be genetically predisposed to more severe lupus phenotypes.…”

“…It is thus important to identify risk factors for disease progression in LN. Evidence suggests that SLE and LN activity and progression may vary depending on race and ethnicity . Early studies more than a decade ago reported poor renal outcomes among Southeast Asian patients with LN but management of this condition has since evolved tremendously.…”

“…Evidence suggests that SLE and LN activity and progression may vary depending on race and ethnicity. 2,5,6 Early studies more than a decade ago reported poor renal outcomes among Southeast Asian patients with LN 7,8 but management of this condition has since evolved tremendously. Current understanding of long-term clinical outcomes in LN is generally derived from studies of homogeneous Caucasian, Chinese, Korean or Japanese populations, 4,[9][10][11][12][13][14] with less known about prognosis in other ethnic groups and regions in Asia.…”

Lupus in the far east: a modern epidemic

“…The most recent American College of Rheumatology guidelines also specifically suggest lower doses of mycophenolate mofetil as induction therapy for class III/IV lupus nephritis in Asian patients based on evidence from the Far East. 13 Asia has also taken the lead in the study of emerging approaches in novel treatment approaches to SLE and lupus nephritis, 14 such as the combination of cyclophosphamide with mycophenolate mofetil for induction, 15 as well as the use of tacrolimus and its use in 'multitarget therapy' for induction and maintenance of lupus nephritis, all with promising results. [16][17][18][19] The concept of interleukin 2 (IL-2) therapy for various immune-mediated diseases has also kindled much interest over the past few years, and He et al recently demonstrated the clinical efficacy of low-dose recombinant human IL-2 in CD4 + T cell modulation and improving disease activity in 38 SLE patients in China.…”