Understanding lupus nephritis: Diagnosis, management, and treatment options

Department of Medicine, Tuen Mun Hospital and Center for Assessment and Treatment of Rheumatic Diseases, Pok Oi Hospital, Hong Kong, China.
International Journal of Women's Health 05/2012; 4(1):213-22. DOI: 10.2147/IJWH.S28034
Source: PubMed

ABSTRACT Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.

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    ABSTRACT: PURPOSE: The options for long-term maintenance therapy in lupus nephritis (LN) remain controversial. This meta-analysis of randomized controlled trials (RCTs) assessed the prognosis and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) used as maintenance therapy for lupus nephritis. METHODS: The data of Cochrane Library, PubMed, EMBASE were retrieved to search the studies about the RCTs that compared MMF with AZA used as maintenance therapy for lupus nephritis. We extracted the data reflecting prognosis which including mortality, end-stage renal failure (ESRF), renal relapse, doubling serum creatinine, and adverse effects, then further analyzed the combined results of data and calculated the relative risk (RR). RESULTS: Four RCTs studies including 328 patients were enrolled into our meta-analysis. There was no difference between the patients receiving either MMF or AZA for maintenance therapy in preventing relapse, progression to end-stage renal failure, death and doubling of serum creatinine. MMF is not superior to AZA in terms of the risks of infection and gastrointestinal upset, but fewer patients receiving MMF developed leukopenia (RR 0.12; 95% CI, 0.04-0.39; P=0.0004) and amenorrhoea (RR 0.17; 95% CI, 0.04-0.72; P=0.02) than those receiving AZA. CONCLUSION: The current limited evidences suggest that MMF offers similar prognosis as AZA for maintenance therapy, while MMF appears safer than AZA in the treatment of lupus nephritis.
    Nephrology 10/2012; 18(2). DOI:10.1111/nep.12006 · 1.86 Impact Factor
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    ABSTRACT: Objectives: To study the effect of renal disease on standardized mortality ratio (SMR) and life expectancy of patients with systemic lupus erythematosus (SLE). Method: Patients with ≥4 ACR criteria for SLE who were longitudinally followed from 1995 to 2011 were studied. The cumulative survival rate, SMR and life expectancy was calculated, and the effect of renal involvement, histological classes, renal damage and end stage renal disease (ESRD) on these parameters was evaluated. Results: 694 SLE patients were studied (92% women; age of onset 32.9±13.4 years). Renal disease occurred in 368(53%) patients and the histological classes in 285 patients were: I(1%), II(6%), III(19%), IV(47%), III/IV+V(10%) and V(16%). Renal damage was present in 79(11%) patients and 24(3%) developed ESRD after 9.6±7.3 years. The age and sex adjusted hazard ratio(HR) of mortality in patients with renal disease, renal damage and ESRD compared with those without was 2.23[1.29-3.85] (p=0.004), 3.59[2.20-5.87] (p<0.001) and 9.20[4.92-17.2] (p<0.001), respectively. The proliferative types (adjusted HR 2.28[1.22-4.24]; p=0.01) but not pure membranous (adjusted HR 1.09[0.38-3.14]; p=0.88) type of lupus nephritis were associated with a significant increase in mortality. The age and sex adjusted SMRs of non-renal SLE patients, patients with lupus nephritis, proliferative nephritis, pure membranous nephritis, renal damage and ESRD were 4.8[2.8-7.5], 9.0[6.7-11.9], 9.8[6.5-14.1], 6.1[2.0-14.1], 14.0[9.1-20.5] and 63.1[33.6-108.0], respectively. Compared to the population, life expectancy was reduced by 15.1 and 23.7 years, respectively, in SLE patients with renal disease and renal damage. Conclusion: The presence of renal disease, in particular proliferative nephritis causing renal insufficiency, significantly reduces survival and life expectancy of SLE patients. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 08/2013; 65(8). DOI:10.1002/art.38006 · 7.87 Impact Factor
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    ABSTRACT: Objective The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy.Methods Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥2 immunosuppressive regimens. While prednisolone (≤10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months.ResultsTwenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V + III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal.Conclusions Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.
    Lupus 08/2013; 22(11). DOI:10.1177/0961203313502864 · 2.48 Impact Factor
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