The clinical manifestations and response to treatment in South Africans with Lupus nephritis.

Abstract

Systemic lupus erythematosus (SLE) is an uncommon disease which is being recognised with increasing frequency in Africa, including South Africa. It is most common in young women and is associated with a significant morbidity and mortality due to involvement of many organ systems. Lupus nephritis (LN) occurs in about 40 - 60% of patients with SLE and is one of the most common causes of morbidity and mortality in SLE. Reviews of LN in Africa have reported on the spectrum of histological involvement in SLE but there is limited information on the degree of renal impairment at presentation and the response to treatment and outcome. Over the past decade mycophenolate mofetil (MMF) has been widely used as an effective and safer treatment option compared to cyclophosphamide in the management of LN. However, MMF has only been used in 0.4 -15.6% of patients with LN in Africa. This study was undertaken as an audit of our clinical practice to determine the histological classification and renal function at presentation in patients with LN seen at Inkosi Albert Luthuli Central Hospital (IALCH). We also undertook an assessment of the response to induction and maintenance therapy for LN and outcome of treatment during routine care in a tertiary referral centre. We wished to assess whether the presentation and response to treatment in Durban, South Africa is similar to the experience in other parts of the world. The multi-ethnic cohort of predominantly African blacks and Indians seen at our hospital, provided an opportunity to undertake an inter-ethnic comparison of the spectrum of histological classification, stage of chronic kidney disease at presentation, response to treatment and outcome. We conducted a retrospective descriptive study by reviewing the hospital records of patients with SLE who were seen in the Departments of Nephrology and Rheumatology at Inkosi Albert Luthuli Central Hospital from 2003 to 2012. All the patients who had renal involvement and in whom the results of a baseline renal biopsy and baseline laboratory tests were available, were included in the study. The demographic data, results of the renal biopsy and baseline haematological, biochemical and immunological tests were recorded. The records of patients who had Class III and Class IV LN, with or without Class V changes, and patients with Class V LN alone, were analysed further to assess the response to 6 months’ induction therapy and 12 months’ maintenance therapy. The treatment for LN and results of the follow up laboratory results were recorded. The age at diagnosis of LN, gender, results of biochemical and immunological tests, histological classification, treatment and outcome were analysed for all the patients in the study, and separately for African Blacks and Indians as they comprised the majority of the patients in the study. A separate analysis was performed for only those patients who required induction and maintenance therapy for LN (excluding patients with Class I, Class II and Class VI LN). We conducted an analysis of the demographic data, spectrum of histological classification, laboratory findings, stage of chronic kidney disease, treatment and outcome for all the treated patients and also compared the findings between African Blacks and Indians. A comparison of the patients with proliferative LN with membranous LN was undertaken to identify any differences in the demographic data, biochemical or immunological parameters, response to treatment and outcome. The response to treatment was determined for 6 months of induction therapy and after maintenance therapy for 12 months. Patients who achieved a partial or complete remission were classified as responders and patients who did not respond to treatment, were lost to follow up or died, were classified as non-responders. A further analysis of the responders and non-responders was undertaken to identify predictors of a poor response. We identified 105 patients with LN who comprised 52 (49.5%) Indians, 47 (44.8%) African Blacks, 4 (3.8%) Whites and 2 (1.9%) Mixed ethnicity. We found that Class V LN was more common (34.3%) than generally reported in most other studies. There was a higher prevalence of the milder Class II histology in our Indians while severe impairment of renal function (chronic kidney disease stage 5) was more common in African Blacks. There were 87 patients who required treatment for their LN. We found that 81.6% of our patients showed a response to induction therapy and 73.6% showed a response to maintenance therapy. Eight of our patients were lost to follow up prior to their final analysis and they were classified as non-responders, thus contributing to lowering our response rate. International literature has shown a better response to MMF in African Americans compared to Caucasians. We have been able to confirm the efficacy of MMF as induction and maintenance therapy for the first time in our Indians and African Blacks. Our study emphasizes the need to raise awareness of SLE among health professionals so that earlier diagnosis of LN can be made and patients can be treated before there is impaired renal function. We found that nearly 15% of our patients had stage 4 or stage 5 chronic kidney disease (eGFR <30 ml/min) at presentation, indicating significant impairment of renal function. We also found that there was a significant reduction in the response to treatment in patients who had a creatinine ≥132 μmol/l at presentation. This study contributes to the literature on lupus nephritis in Africa and we have shown that MMF is effective in our patients with LN. Thus it provides an alternative safer treatment option than the use of IV CYC.