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


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: 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. The data of Cochrane Library, PubMed, EMBASE were retrieved to search the studies about the RCT studies that compared MMF with AZA used as maintenance therapy for lupus nephritis. We extracted the data reflecting prognosis, which included 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). Four RCT 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% confidence interval (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. The current limited evidence suggests that MMF offers similar prognosis as AZA for maintenance therapy, while MMF appears safer than AZA in the treatment of lupus nephritis.
    No preview · Article · Oct 2012 · Nephrology
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    ABSTRACT: Objectives To study the effect of renal disease on standardized mortality ratio (SMR) and life expectancy (LE) of patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled ³4 ACR criteria for SLE who were prospectively followed in our unit from 1995 to 2011 were studied. The cumulative survival rate (by Kaplan Meier’s method), and age and sex adjusted standardized mortality ratio (SMR) was calculated. Life expectancy (LE) was studied by single decrement life table analysis. The effect of renal involvement, histological classes, renal damage and end stage renal disease (ESRD) on these parameters was evaluated. Results 694 patients were studied (92%). The mean age of onset of SLE was 32.9±13.4 years (range 6-78). 368 (53%) had evidence of renal disease according to the ACR definition of renal involvement (persistent proteinuria of >0.5g/day; cellular casts or histological evidence). 285 (77%) patients had undergone renal biopsy for at least once. The distribution of histological classes (ISN/RPS) was as follows: class I (1%), class II (6%), class III (19%), class III+V (10%), class IV (47%), class V (16%) and others (1%). At the time of analysis, the mean observation of our patients since SLEonset was 9.6±7.3 years. Thirty-four (4.9%) patients were lost to follow-up. Among patients with lupus renal disease, 79 (11%) patients had renal damage as assessed by the SLE damage index (SDI) and 24 (3%) patients developed ESRD. The cumulative 5, 10 and 15 year survival of patients with renal involvement was 92.3%, 88.8% and 84.3%, respectively, which was significantly lower than that of patients without renal involvement (97.0%, 93.7% and 91.6%, respectively; p=0.004). Cox regression demonstrated that the age and sex adjusted hazard ratio (HR) of mortality in patients with renal disease and renal damage compared with those without renal involvement was 2.23 [1.29-3.85] (p=0.004) and 3.59 [2.20-5.87] (p<0.001), respectively (Table 1). The corresponding hazard ratio for mortality in patients who developed ESRD was 9.20 [4.92-17.2] (p<0.001). Patients with proliferative types of lupus nephritis (class III, IV and III/IV+V) had significantly increased mortality compared to those without renal disease (adjusted HR 2.28 [1.22-4.24]; p=0.01). In contrast, pure membranous lupus nephropathy was not associated with increased mortality (adjusted HR 1.09 [0.38-3.14]; p=0.88). Adjustment for the use of immunosuppressive regimens in the Cox regression models did not materially affect the overall hazard ratios for mortality. The age and sex adjusted SMRs of all SLE patients, SLE patients without renal disease, SLE patients with renal disease, proliferative nephritis, pure membranous nephropathy, renal damage and renal failure compared to the general population were 7.3 (95% confidence interval [CI] 5.7-9.3), 4.8 (CI 2.8-7.5), 9.0 (CI 6.7-11.9), 9.8 (CI 6.5-14.1), 6.1 (CI 2.0-14.1), 14.0 (CI 9.1-20.5) and 63.1 (CI 33.6-108), respectively. LE was reduced by 12.4, 15.1 and 23.7 years, respectively, in SLE patients, SLE patients with renal disease and SLE patients with renal damage as compared to the general population. Conclusions The presence of renal disease, in particular proliferative types of nephritis causing renal function impairment, significantly reduces survival and life expectancy of SLE patients. Disclosure of Interest None Declared
    Preview · Article · Aug 2013 · Arthritis & Rheumatology
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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.
    No preview · Article · Aug 2013 · Lupus
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