|Year : 2016 | Volume
| Issue : 3 | Page : 124-125
Racial differences in presentation and treatment outcome of lupus nephritis
Manish Rathi1, Aman Sharma2
1 Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||11-Aug-2016|
Department of Nephrology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rathi M, Sharma A. Racial differences in presentation and treatment outcome of lupus nephritis. Indian J Rheumatol 2016;11:124-5
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that can involve a variety of organs. Renal involvement in the form of lupus nephritis has been reported to occur in 30-80% cases.  The prevalence of SLE as well as the incidence and severity of renal involvement has been reported to be highly variable in different races. SLE is 2-5-fold more common among African-Americans compared with Caucasians. , Not only it is more common in African-Americans, but also it is associated with a higher level of disease activity and poorer outcomes. ,, Similarly, lupus nephritis is almost twice as frequent in African-Americans patients (62%) as compared to Caucasian patients (32%), and the prognosis in African-Americans patients with lupus nephritis is also significantly worse. , Similar to the manifestations and severity of disease, the treatment outcomes are also poor in African-Americans.  There are also some data that different induction regimens work differently according to the race of the patient. A subgroup analysis of the Aspreva Lupus Management Study has shown that the mycophenolate mofetil (MMF) is more effective in African-Americans as compared to intravenous (IV) cyclophosphamide (CYC).  However, as compared to African-Americans and Caucasians, not much is known about the disease prevalence, presentation, severity, and treatment response among Asians. Moreover, majority of the data for Asians come from the Chinese study and well-conducted trials studying the prevalence of disease or comparing various treatment options from other parts of Asia are lacking. In a randomized control trial from India, we have shown that both MMF and low-dose intravenous CYC have similar efficacy in proliferative lupus nephritis.  On the other hand, a study from Korea has demonstrated better results with CYC  while Chinese study has shown MMF to be better.  Furthermore, most of the studies in Asians are of short duration and long-term outcomes in Asians receiving different treatments are not clear.
In the present issue of Journal, Pakozdi et al. have published "Treatment outcomes from a multiethnic lupus cohort with proliferative nephritis."  In this study, 86 patients of biopsy-proven lupus nephritis between 1995 and 2013 with a minimum follow-up of 6 months and belonging to three different races were studied. Of these 86 patients, 38 (44.2%) were Afro-Caribbeans, 30 (34.9%) were South Asians, and 18 (20.9%) were Caucasians. The induction treatment consisted of oral CYC, low-dose IV CYC, high-dose IV CYC, or oral MMF along with oral steroids. This was followed by maintenance therapy consisting of either MMF or azathioprine with steroids.
Several interesting observations are noted in this study. Asians were younger at presentation and had delayed lupus nephritis after diagnosis of SLE as compared to Caucasians while extractable nuclear antigens were less frequent in Caucasians. Although there was no difference in mean proteinuria or biopsy classes according to the race, African-Americans presented with more severe renal dysfunction, higher serum creatinine, and more dialysis-requiring renal failure at presentation. At the end of 6 months of induction treatment, they noted that MMF achieved a higher remission rate of 70% as compared to 16.7% with CYC in African-Americans. However, since the patients with more severe renal presentation were more likely to receive CYC, a repeat analysis of treatment response in African-Americans with relatively preserved renal function was performed, which still showed significantly higher remission rates with MMF. Asians also showed better treatment response with MMF as compared to CYC both at 6 months and 24 months although it did not reach statistical significance while there was no difference between MMF and CYC in Caucasians. The infection rates and gonadal toxicity were more with CYC-treated patients as compared to MMF while there was no difference in the malignancy rate. In the long-term follow-up of these patients (median follow-up of 73 months), it was noted that in Asians and Caucasians response was quicker as compared to African-Americans; on the other hand, flares were more common in African-Americans as compared to other races. Similarly, the rate of developing end-stage renal disease (ESRD) was also highest among African-Americans; however, on multivariate analysis, lower baseline glomerular filtration rate was the only predictor of ESRD irrespective of race.
Although the strengths of this study are fair representation of Asian race and long duration of follow-up, the study has some limitations. The most important limitation of this study is small sample size with 86 patients in total, of which only 18 Caucasian patients. This may be one of the factors that the African-Americans race was not a major predicting factor affecting the rate of ESRD on multivariate analysis despite having worse renal presentation, more dialysis-requiring renal failures, and more flare rates. Another important limitation is that there was lot of variation in type of induction regimen used. Different regimens of CYC were also clubbed into one group, which is not without limitations as each regimen has its own efficacy. Similarly, maintenance regimen was also not uniform. Some of this heterogeneity is due to the retrospective nature of the study. Overall, this study suggests that Asians and Caucasians respond equally to both MMF and CYC unlike African-Americans where MMF is better; however, these results need to be confirmed in larger multicenter studies.
| References|| |
Mittal T, Rathi M. Rheumatological diseases and kidneys: A nephrologist′s perspective. Int J Rheum Dis 2014;17:834-44.
McCarty DJ, Manzi S, Medsger TA Jr., Ramsey-Goldman R, LaPorte RE, Kwoh CK. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum 1995;38:1260-70.
Siegel M, Lee SL. The epidemiology of systemic lupus erythematosus. Semin Arthritis Rheum 1973;3:1-54.
Alarcón GS, Roseman J, Bartolucci AA, Friedman AW, Moulds JM, Goel N, et al.
Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. Lumina Study Group. Lupus in minority populations, nature versus nurture. Arthritis Rheum 1998;41:1173-80.
Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: A study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus 1997;6:248-53.
Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73.
Seligman VA, Lum RF, Olson JL, Li H, Criswell LA. Demographic differences in the development of lupus nephritis: A retrospective analysis. Am J Med 2002;112:726-9.
Korbet SM, Schwartz MM, Evans J, Lewis EJ; Collaborative Study Group. Severe lupus nephritis: Racial differences in presentation and outcome. J Am Soc Nephrol 2007;18:244-54.
Contreras G, Lenz O, Pardo V, Borja E, Cely C, Iqbal K, et al.
Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int 2006;69:1846-51.
Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, et al.
Influence of race/ethnicity on response to lupus nephritis treatment: The ALMS study. Rheumatology (Oxford) 2010;49:128-40.
Rathi M, Goyal A, Jaryal A, Sharma A, Gupta PK, Ramachandran R, et al.
Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int 2016;89:235-42.
Koo HS, Kim YC, Lee SW, Kim DK, Oh KH, Joo KW, et al.
The effects of cyclophosphamide and mycophenolate on end-stage renal disease and death of lupus nephritis. Lupus 2011;20:1442-9.
Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, et al.
Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000;343:1156-62.
Pakozdi A, Rajakariar R, Sheaff M, Pyne D. Treatment outcomes from a multiethnic lupus cohort with proliferative lupus nephritis. Indian J Rheumatol 2016;11:14-21.