Relation between serological data at the time of biopsy and renal histology in lupus nephritis

Summary As autoantibodies are thought to participate in the pathogenesis of renal inflammation in systemic lupus erythematosis (SLE) we investigated associations between serological markers of disease activity in SLE and the activity of renal histopathological lesions in thirty-five patients with lupus nephritis (LN). We found the following prevalence of serum auto-antibodies in LN: IgG antinuclear antibodies (ANA) 100%, IgM ANA 69%, IgA ANA 60%, IgG anti-dsDNA 60%, IgM antidsDNA 71%, IgA anti-dsDNA 60%, anti-RNP 20%, anti-Sm 14%, anti-SSA 31%, anti-SSB 14%, anti-histone 37%, anti-cardiolipin 80% and antibody to ribosomal protein (anti-P) 6%. No correlation was found between serological parameters and the WHO-classification of biopsies. The activity-index of histological lesion, assessed according to the NIH-renal histology scoring system, correlated with IgM ANA and IgM anti-dsDNA titers. Of all the specific features of histological renal inflammation, glomerular proliferation showed the best overall correlation with serological parameters of disease activity. Anticardiolipin antibodies were correlated with overall disease activity, but not with renal histological activity. Thus, serological markers of disease activity did not adequately reflect the amount of renal inflammation in LN and cannot replace renal biopsy as a diagnostic tool.     

Lupus nephritis: association between serology and renal biopsy measures

The relationship between serologic tests and renal histologic change over time was examined in 55 patients with lupus nephritis. After a median interval of 40 months on various immunosuppressive drug regimens, C3 complement levels were improved in 78% of patients and anti-DNA levels were improved in 85%. Comparison of initial and followup renal pathology showed that the activity index of the biopsy improved in 82%, while the chronicity index worsened in 71% of patients. Normalization of C3, but not anti-DNA levels, was associated with a lowering of the activity index on repeat biopsy. Prolonged depression of serum C3 levels was associated with a trend (p = 0.066) towards worsening of the chronicity index, but the change in chronicity index showed no relationship to the duration of elevated anti-DNA. Our studies indicate that abnormal levels of C3 complement are predictive of the degree of persistently active glomerular disease, but that duration of abnormal C3 or anti-DNA are less consistent predictors of the acquisition of chronic, irreversible renal lesions.     

Lupus nephritis: 211 cases

PURPOSE: Renal involvement is one of the most severe and frequent manifestations of systemic lupus erythematosus. Prognosis factors are variable in the different studies. We analyze in 211 patients clinical, biological and histologic characteristics of lupus nephritis and the different prognosis factors. METHODS: It's a retrospective study in 211 with lupus nephritis followed-up between 1975 and 2003. RESULTS: There were 195 women and 16 men aged meanly of 28,8 years. At first presentation, we noted hypertension in 32,3% of cases, nephrotic syndrome in 47,7% of cases and renal failure in 51,6% of cases. histologic examination of kidney revealed class III in 59 cases, class IV in 97 cases and class V in 33 cases. Two hundred and five patients were treated by corticosteriods associated with immunosupressive agents in 95 cases. After a mean follow-up of 103 months (2-289 months), we obtained remission in 55,3% deterioration of renal function in 34,8% with end stage renal failure in 14,7% and relapses occurred in 51% of cases. Thirty-three patients died. Age <24 years, hypertension, nephrotic syndrome and initial renal failure were statistically associated with deterioration of renal function. CONCLUSION: Lupus nephritis is severe in our patients with predominance of proliferative forms. Age <24 years, hypertension, nephrotic syndrome and initial renal failure were statistically associated with deterioration of renal function.     

Lupus nephritis: current issues

Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. For recalcitrant disease, new immunosuppressive and immunomodulating agents, immunoablative high dose CYC, nucleoside analogues, apheresis, and the biological response modifiers can be considered.     

Lupus nephritis: induction therapy

Effective induction therapy is of pivotal importance in minimizing renal parenchymal damage by the active immune-mediated inflammatory processes in severe proliferative lupus nephritis. Preservation of nephron mass is prerequisite to long-term renal survival. Data from US-based studies have shown improved efficacy with induction treatment comprising corticosteroid and cyclophosphamide, compared with corticosteroid treatment alone. Data from European studies have shown similar efficacy with a modified treatment regimen, in which smaller doses of cyclophosphamide were given at weekly or fortnightly intervals over a shortened treatment duration, and the treatment related adverse effects appeared less frequent with the reduced-dose regimen. We have also reported that sequential immunosuppression with prednisolone and oral cyclophosphamide as induction followed by azathioprine maintenance was associated with a high incidence of remission and relatively favourable long-term renal outcome in Chinese patients. However, cyclophosphamide treatment is associated with considerable adverse effects, which could be potentially fatal. Mycophenolate mofetil selectively inhibits lymphocyte proliferation, and thus targets an instrumental step in the pathogenesis of systemic lupus erythematosus. There is accumulating evidence that the combined use of mycophenolate mofetil and corticosteroid presents an effective treatment for severe proliferative lupus nephritis in different ethnic groups, and is associated with much fewer adverse effects compared with cyclophosphamide-based regimens. Recent data from our group also demonstrate the long-term efficacy of mycophenolate mofetil in preserving renal survival, when used continuously as both induction and maintenance therapy.     

Lupus nephritis: treatment with mycophenolate mofetil

OBJECTIVE: To evaluate the safety and efficacy of mycophenolate mofetil (MMF) treatment in patients with lupus nephritis. METHODS: Eighteen patients with biopsy-proven lupus nephritis (17 females, one male; mean age 31.6 yr; mean lupus duration 92 months; mean duration of nephritis 57 months; nine with focal proliferative glomerulonephritis, three with diffuse proliferative glomerulonephritis, six with membranous nephropathy) were included. With five exceptions, all patients had been treated previously with cyclophosphamide and were selected because of either toxicity or inadequate clinical response to treatment. MMF was given at 2 g daily in combination with steroids for up to 31 months (mean 15.3 months). The side-effects of MMF were recorded and efficacy was assessed as the renal function profile. RESULTS: Complete remission was observed in 10/18 patients and another 4/18 went into partial remission. Both creatinine clearance and proteinuria were significantly improved during MMF treatment in patients with the proliferative forms of nephritis. MMF demonstrated a steroid-sparing effect in the whole population. Treatment failure was recorded in 4/18 patients, all with membranous nephropathy. Two patients developed gastrointestinal complaints and infectious meningitis occurred in one patient. CONCLUSION: MMF appears to be an efficacious and safe treatment in patients with proliferative forms of lupus nephritis who do not respond to or cannot tolerate conventional treatment. The efficacy of MMF in lupus membranous nephropathy remains unclear.     

狼疮性肾炎治疗的新认识

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种由多种因素引起机体免疫失调产生一系列自身抗体所导致的多系统、多器官受累的自身免疫性综合征.在疾病初期,有尿检或者肾功能异常者占25%～50%,而肾活检显示几乎所有SLE患者均有不同程度的肾损害.严重的肾脏损害增加了SLE的病残率及病死率.狼疮性肾炎(lupus nephritis,LN)是目前导致我国继发性肾损害的首要原因.     

狼疮性肾炎治疗中的感染问题

感染是狼疮性肾炎(lupus nephritis,LN)常见并发症之一,也是导致患者死亡的重要原因之一.呼吸道、皮肤组织、泌尿道等是感染好发部位.LN患者发生感染主要与疾病本身活动、糖皮质激素和免疫抑制应用、肾功能损害、低蛋白血症等有关.致病病原体种类较多,以细茵最常见,病毒、真茵次之,结核茵感染也并不少见.临床可表现为发热、咳嗽、咳痰、头痛、抽搐、精神行为异常和白细胞尿等,与系统性红斑狼疮病情活动常不易鉴别,应从感染本身的特点和狼疮活动的特点来寻找鉴别诊断的线索,病原学检查是确诊依据.治疗的药物选择首先应根据病情严重程度、可能的致病痛原体等决定,细菌感染以广谱抗茵素治疗为主,病情严重时常需联合抗病毒、抗真菌治疗.对于重症患者,药物选择应强调早期、联合、高效.视病情轻重调整免疫抑制剂剂量,必要时减量至停用.一般糖皮质激素仍可适量使用.积极治疗原发病、合理使用糖皮质激素和免疫抑制剂对预防和治疗感染至关重要.     

Lupus nephritis: a challenging cause of rapidly progressive crescentic glomerulonephritis

The outcomes of 32 lupus patients with rapidly progressive crescentic glomerulonephritis were studied. Lupus nephritis accounted for 51.6% (32/62) of all patients with biopsy proven rapidly progressive crescentic glomerulonephritis during a six year observation period that includes 961 consecutive native kidney biopsies. Median entry serum creatinine was 221 micromol/l. All patients received induction therapy with pulse methylprednisolone (n =27) or intravenous cyclophosphamide (n = 5). Maintenance therapies included prednisolone alone (group 1), prednisolone plus intermittent pulse intravenous cyclophosphamide (IVCY) (group 2) and prednisolone plus daily oral cytotoxic drugs (group 3). Twelve patients eventually had uremia. Seven further patients died of infection during therapy. One patient still had renal insufficiency and twelve patients had favorable clinical outcome (serum creatinine < 200 micromol/l). Patients in group 3 were more likely to have favorable clinical outcome than group 2 (P = 0.01; Fisher's exact test). Survival analysis found that the three year survival of 'group 2' was 27.6% while that of 'group 3' was 83.3%. Our results suggest that lupus nephritis is not an infrequent cause of crescentic glomerulonephritis. Therapy with IVCY is not necessary associated with good outcome. Selected patients can be effectively treated with daily oral cytotoxic drugs as a reasonable alternative therapy.     

Lupus vasculopathy combined with renal infarction: unusual manifestation of lupus nephritis

A 30-year-old woman with a 10-year history of systemic lupus erythematosus was admitted to our hospital because of the onset of hypertension and renal dysfunction. Renal arteriogram revealed multiple renal infarctions, and cut-off or tapering-stenosis in the interlobular arteries. Renal biopsy showed concentric intimal thickening with narrowed lumen in some arterioles and deposition of IgG/IgM/complement 3 in the wall of arteriole without any active lesions or immune complex deposition in glomeruli. The present case indicates that this type of renal vascular lesion in lupus nephritis, lupus vasculopathy, may cause renal infarction and the loss of renal function without active glomerular lesions.     

Lupus nephritis outcomes: health maintenance organizations compared to non-health maintenance organizations

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) in USA increasingly have their care centered in health maintenance organizations (HMO). We examined whether HMO and non-HMO SLE patients with renal involvement, who had the same university rheumatologist, differed in their utilization of health care or renal outcomes. METHODS: Consecutive patients with SLE with renal involvement (n = 24), 10 enrolled in an HMO, 14 not, were studied. Laboratory values were prospectively determined. RESULTS: At the first visit to the rheumatologist, there was no significant difference between HMO and non-HMO patients in laboratory values. There was no difference in the 2 groups in the final prednisone dose (HMO 12 mg vs non-HMO 15.9 mg) or use of azathioprine (20% vs. 57%; p = 0.07) or cyclophosphamide (60% vs. 57%). The serum creatinine was higher in the HMO patients (HMO 1.1 mg/dl vs. non-HMO 0.78 mg/dl; p = 0.05). No difference was found in the number of rheumatology visits. There was a significant difference in the number of communications from the rheumatologist to the HMO versus the HMO to the rheumatologist (p = 0.026). CONCLUSION: Other than the serum creatinine, there are no differences in the treatment or renal outcomes for HMO compared to non-HMO patients with SLE seeing the same rheumatologist. There is a potential barrier in physician communication, however, with the majority of communications going from the rheumatologist to the HMO provider.