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      Causes and predictors of mortality in biopsy-proven lupus nephritis: the Sarawak experience

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          Abstract

          Background

          Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can be fatal if left untreated. The causes and prognostic predictors of mortality in LN have been well studied in developed countries but evidence is lacking for developing countries. The objective of this study was to investigate the causes and predictors of mortality in a cohort of Malaysian patients with biopsy-proven LN.

          Methods

          We retrospectively studied all patients with biopsy-proven LN treated in Sarawak General Hospital during the period of 2000–15. Demographic data, clinical features and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of mortality.

          Results

          There was a total of 250 patients with 259 renal biopsies available for our analysis. Our patients were of multi-ethnic origins with a female predominance (90%). Their mean ± standard deviation age was 37.7 ± 12.8 years. The patients had a mean disease duration of 135.6 ± 81.9 months. Nephrotic syndrome was the most common presentation (29.6%) and acute renal failure was evident at initial presentation in 16% of patients. Class IV LN was the predominant biopsy class within the cohort (66.8%). The majority of patients achieved remission (81.2%) and had normal renal function (83.9%) at the last follow-up. The 5-, 10-, 15- and 20-year survival rates for our cohort were 93%, 88%, 82% and 77%, respectively. There were 37 deaths (14.8%), of which the main causes were: infection and flare (52.7%), infection alone (25.0%) and other causes (22.3%). Independent predictors of mortality in our cohort of LN patients were: the presence of acute kidney injury at presentation [hazard ratio (HR) 3.41; confidence interval (CI) 1.50–7.76], failure to achieve remission at 1-year post-induction therapy (HR 2.99; CI 1.35–6.65) and non-compliance with treatment (HR 1.89; CI 1.22–2.96). Age, ethnicity, class of LN and type of immunosuppressant used were not predictive of mortality.

          Conclusions

          Survival and renal outcomes in our LN cohort were comparable to most LN studies reported worldwide. Both flare and infection remained the main causes of death. The presence of acute renal failure at presentation, failure to achieve remission at 1 year post-treatment and non-compliance with treatment were independent prognostic predictors of mortality in LN.

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          Most cited references16

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          Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review.

          Antimalarial drugs (AMs), chloroquine (CQ) and hydroxychloroquine (HCQ), are frequently withdrawn in patients with lupus with either severe or remitting disease. However, additional effects beyond immunomodulation have been recently described. The aim of the present work was to analyse all the published evidence of the beneficial and adverse effects of AM therapy in systemic lupus erythematosus (SLE). A systematic review of the English literature between 1982 and 2007 was conducted using the MEDLINE and EMBASE databases. Randomised controlled trials (RCTs) and observational studies were selected. Case reports were excluded except for toxicity reports. The GRADE system was used to analyse the quality of the evidence. A total of 95 articles were included in the systematic review. High levels of evidence were found that AMs prevent lupus flares and increase long-term survival of patients with SLE; moderate evidence of protection against irreversible organ damage, thrombosis and bone mass loss. Toxicity related to AMs is infrequent, mild and usually reversible, with HCQ having a safer profile. In pregnant women, high levels of evidence were found that AMs, particularly HCQ, decrease lupus activity without harming the baby. By contrast, evidence supporting an effect on severe lupus activity, lipid levels and subclinical atherosclerosis was weak. Individual papers suggest effects in preventing the evolution from SLE-like to full-blown SLE, influencing vitamin D levels and protecting patients with lupus against cancer. Given the broad spectrum of beneficial effects and the safety profile, HCQ should be given to most patients with SLE during the whole course of the disease, irrespective of its severity, and be continued during pregnancy.
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            The frequency and outcome of lupus nephritis: results from an international inception cohort study.

            To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort.
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              A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. The Canadian Hydroxychloroquine Study Group.

              The antimalarial drug hydroxychloroquine is thought to be effective in controlling some of the manifestations of systemic lupus erythematosus, but its effectiveness has not been demonstrated conclusively. We conducted a six-month, randomized, double-blind, placebo-controlled study of the effect of discontinuing hydroxychloroquine sulfate treatment in 47 patients with clinically stable systemic lupus erythematosus. The patients were randomly assigned to continue their same dose of hydroxychloroquine (n = 25) or to receive placebo (n = 22) for 24 weeks. Ten patients in each group were also taking prednisone. The relative risk of a clinical flare-up, defined as the development of specific clinical manifestations of systemic lupus erythematosus or an increase in their severity, was 2.5 times higher (95 percent confidence interval, 1.08 to 5.58) in the patients taking placebo than in those continuing to take hydroxychloroquine (16 of 22 patients vs. 9 of 25 had flare-ups), and the time to a flare-up was shorter (P = 0.02). The relative risk of a severe exacerbation of disease that required withdrawal from the study was 6.1 times higher (95 percent confidence interval, 0.72 to 52.44) for the patients taking placebo (5 of 22 patients vs. 1 of 25 had severe exacerbations of disease). Changes in the dose of prednisone were not different in the two groups. Patients with quiescent systemic lupus erythematosus who are taking hydroxychloroquine are less likely to have a clinical flare-up if they are maintained on the drug.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                February 2018
                17 July 2017
                17 July 2017
                : 11
                : 1
                : 56-61
                Affiliations
                [1 ]Rheumatology Unit, Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia
                [2 ]Nephrology Unit, Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia
                [3 ]Rheumatology Unit, Department of Medicine, Sibu Hospital, Sarawak, Malaysia
                Author notes
                Correspondence and offprint requests to: Cheng Lay Teh; E-mail: tehchenglay@ 123456yahoo.com
                Article
                sfx063
                10.1093/ckj/sfx063
                5798016
                29423203
                d71a0ae5-997d-4e37-b0f8-de6d1fb36956
                © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 12 March 2017
                : 22 May 2017
                Page count
                Pages: 6
                Categories
                Lupus Nephritis

                Nephrology
                dialysis,lupus nephritis,mortality,outcome,systemic lupus erythematosus
                Nephrology
                dialysis, lupus nephritis, mortality, outcome, systemic lupus erythematosus

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