Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.     

一种狼疮性肾炎的临床活动性指数

筛选与狼疮性肾炎疾病活动程度相关性最好的临床与实验室指标，并建立一种疾病活动性的计分方法。方法以临床医师的判断作为疾病活动程度的外部标准，对１１７例狼疮性肾炎患者的资料进行单因素相关分析和多元回归分析。结果筛选出１４个最能提示疾病活动性的参数，并以各参数在多元回归分析中的回归系数作为其各自的加权分（略加简化），建立了一种狼疮性肾炎疾病活动程度的计分方法，即活动性指数。结论这一活动性指数能较简便、合理、有效地测定狼疮性肾炎的活动程度。     

Ⅴ型狼疮肾炎的诊断与治疗

系统性红斑狼疮(SLE)是最常见的自身免疫性疾病,狼疮肾炎(LN)是SLE患者临床较常见且严重的并发症,至少50%以上的SLE患者临床上有肾脏受累的证据。Ⅴ型狼疮肾炎,又称膜性狼疮肾炎,在肾活检确诊LN中的比例为8%～20%。目前Ⅴ型LN的治疗尚无统一方案。所有Ⅴ型LN患者都应尽早开展以减少蛋白尿、控制血压、降低血脂、抗凝治疗为主的非免疫抑制治疗,其中肾素-血管紧张素系统阻断剂起重要作用。伴有严重蛋白尿、肾功能损害或非免疫抑制治疗无效的患者,需接受免疫抑制治疗,具体方案为糖皮质激素联合硫唑嘌呤或烷化剂或钙调磷酸酶抑制剂或吗替麦考酚酯。免疫抑制治疗的方案选择及疗效仍需大样本临床研究进一步证实。     

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.     

Outcomes in renal transplant recipients with lupus nephritis: experience at a single center

Background: The long-term prognosis of renal transplant recipients with systemic lupus erythematosus is still controversial. The outcome of these patients depends on the population studied, race/ethnicity, socioeconomic conditions, donor-related factors and recurrent lupus nephritis (LN), among other factors. Objective: This study was conducted to evaluate kidney transplantation outcomes for adult Brazilian patients with LN at a single center. Subjects and method: The archival records of all patients with LN who had received a kidney transplant at Santa Casa of Sao Paulo Hospítal were reviewed. Kaplan–Meier method was used to determine the survival rate. Results: We identified 18 patients with LN subjected to 22 kidney transplants during the 20-year interval. Two patients received three renal grafts. The majority of the patients were female, with 33.7 ± 10 years at the time of the transplantation, and half of them were African descendants or mixed. Sixteen transplants were performed from deceased donors and six from living-related donors. The patient survival rate was 90%, and graft survival was 68% at 10 years. Chronic allograft nephropathy was the major cause of graft loss. Two patients developed extra-renal manifestations of lupus. There was no clinical or histological evidence of recurrent LN. Conclusion: Renal transplantation is a method which can provide a long-term survival for patients with SLE and end-stage renal disease.     

DNA免疫吸附治疗狼疮性肾炎的近期疗效观察

目的 观察DNA免疫吸附对系统红斑狼疮性肾炎患者的临床疗效.方法 选择26例活动性系统性狼疮性肾炎患者,采用DNA免疫吸附柱法进行52例次免疫吸附治疗并观察其临床变化、抗核抗体、抗双链DNA抗体及免疫球蛋白水平等影响程度.结果 经吸附治疗后患者临床症状明显改善,尿蛋白减轻,抗核抗体滴度治疗前[(3.9±0.6) CO/L]、后[(1.0±0.3)CO/L]比较差异有统计学意义(P＜0.01)、抗双链DNA抗体治疗前[(797±103) IU/L]、后[(94±29)IU/L]比较差异也有统计学意义(P＜0.01),而对C3、C4及肝肾功能、电解质等则无明显影响.结论 DNA免疫吸附疗法是治疗狼疮性肾炎一种疗效好、无明显不良反应的新方法,尤其适用于重症系统性红斑狼疮.     

Recurrent lupus nephritis in a rejected renal allograft

SUMMARY: The case of a 48-year-old female patient who underwent renal transplantation because of an end-stage renal disease after membranous glomerulonephritis (WHO class V) in systemic lupus erythematosus (SLE) is presented. the patient lost one cadaveric allograft immediately after transplantation because of renal vein thrombosis, presumably caused by anti-Cardiolipin antibodies. A second cadaveric allograft showed a stable function for several years before slowly deteriorating. an abrupt increase of serum creatinine led to the suspicion of a final episode of acute rejection. A biopsy was performed, which showed an overlap of rejection and recurrent iupus nephritis in an advanced chronically damaged allograft. the lupus nephritis recurred as the same WHO class V as in the native kidney, but without significant predictive clinical or serological signs of SLE activity. the case presented and a review of the literature indicate that the frequency of recurrent lupus nephritis might be underestimated, and earlier surveillance biopsies in transplanted SLE patients should be considered.     

Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up.

BACKGROUND: Whether corticosteroid and immunosuppressive therapy may be safely withdrawn in patients with proliferative lupus nephritis is still unclear. METHODS: In 32 patients with biopsy-proven proliferative lupus nephritis previously put into remission, therapy was gradually tapered off. RESULTS: When immunosuppressive therapy was stopped (median: 38 months; 25th-75th percentile: 24-81 months, after biopsy), 24 patients were in complete remission and eight had a median proteinuria of 1.05 g/24 h (25th-75th percentile: 0.91-1.1 g/24 h) with normal renal function. After stopping therapy, patients were followed for a median of 203 months (25th-75th percentile: 116-230 months). Fifteen patients (Group 1) never developed lupus activity. The other 17 patients (Group 2) developed lupus exacerbations in a median of 34 months (25th-75th percentile: 29-52 months) after stopping therapy and were re-treated. The only significant differences between the two groups were the longer median durations of treatment, 57 months (25th-75th percentile: 41.5-113.5 months) vs 30 months (25th-75th percentile: 18-41 months; P<0.009), and remission, 24 months (25th-75th percentile: 18-41) vs 12 months (25th-75th percentile: 7-20 months; P<0.02), before stopping therapy in Group 1 than in Group 2. At last follow-up, 12 patients of Group 1 were in complete remission, two had mild proteinuria and one had died. In Group 2, one patient died, 14 were in complete remission, one had mild proteinuria and in another patient serum creatinine doubled. CONCLUSIONS: Some patients with severe lupus nephritis who enter stable remission can be maintained without any specific treatment for many years. Those patients who have new flares can again go into remission with an appropriate treatment. The longer the treatment and remission before withdrawal, the lower the risk of relapse.     

Prolonged membranous lupus nephritis with change of anti-ssDNA antibody titer and repeated renal relapse

We report a case of a 44-year-old woman with nephrotic syndrome who underwent renal biopsy three times. On each occasion, light microscopy showed membranous nephropathy with mild to moderate thickening of the glomerular capillary walls. Immunofluorescence microscopy showed predominant deposition of immunoglobulin (Ig) G, IgG1, IgG2, IgG3, and IgG4; C3; and C1q along the glomerular capillary walls and deposition of IgM and IgA in some parts of the walls. Electron microscopy revealed the accumulation of electron-dense deposits in the mesangium and the subepithelial area of the glomerular basement membrane. Virus-like particles were detected in the subendothelial cells in all three biopsy specimens. A definitive diagnosis of systemic lupus erythematosus (SLE) was made at the time of the second admission, when she was 31 years old. A diagnosis of membranous lupus nephritis was then made on the basis of the pathological and clinical findings. A change in anti-single-stranded (ss)DNA antibody titers was of particular interest in this patient. Occasional small increases in anti-double-stranded (ds)DNA antibody were found, but increased anti-ssDNA antibody titers occurred before there was any elevation of urinary protein during renal relapse, and a sustained increase in the titers was shown subsequently. Hypocomplementemia occurred in parallel with the increase of anti-ssDNA antibody. Immunosuppressive therapy with steroid promptly eliminated anti-dsDNA antibody, but anti-ssDNA antibody remained positive. The patient had normocomplementemia and proteinuria was absent. Later, anti-ssDNA antibody decreased. Renal function has remained in the normal range for 20 years.     

环磷酰胺代谢酶基因多态性与中国汉族难治性狼疮肾炎的相关性

目的探讨中国汉族难治性狼疮肾炎(LN)和环磷酰胺(CTX)代谢酶基因多态性的相关性。 方法对2012年1月至2015年12月在海口市人民医院初发系统性红斑狼疮(SLE)的132例患者进行分析,其中LN组88例,非LN组44例;LN组中难治性LN 46例,非难治性LN 42例。比较各组临床指标差异。采用PCR-RELP检测CTX代谢酶基因,采用单因素方差分析CYP2C19*2、CYP2C19*3、CYP2B6*4、CYP2C9*3和CYP3A5与LN及难治性LN、非难治性LN的相关性。 结果(1)CYP2C19*2、CYP2C19*3、CYP2B6*4和CYP3A5频率分布符合Hardy-Weinberg平衡分布;(2)LN组较非LN组,血肌酐(Scr)(t＝2.68,P＝0.008)和SLEDAI明显升高(t＝4.07,P≤0.001),血红蛋白(Hb)(t＝－2.368,P＝0.019)和血白蛋白(ALB)(t＝－4.514,P＝0.000)明显降低,差异具有统计学意义;(3)单因素方差分析显示LN组CYP2C19*3 GC携带者与CC、GG携带者比较血尿素氮(BUN)显著升高[(13.3±13.02)mmol/L与(6.57±5.22)mmol/L与(7.08±6.11) mmol/L,F＝5.770,P＝0.004];难治性LN组中,GC携带者较CC、GG携带者Scr显著升高：[(436.22±286.38)μmol/L与(161.7±144.33)μmol/L与(66±19.02)μmol/L, F＝8.411, P＝0.001]差异均有统计学意义;(4) CYP3A5*3 GG携带者肾脏受累明显增多(χ²＝6.991,P＝0.03);在难治性LN组中CYP3A5*3 GG基因型Scr较高(F＝0.213,P＝0.81)但差异无统计学意义。 结论CTX代谢酶CYP2C19*3基因多态性对中国汉族难治性LN的疗效可能有影响,GC携带者疗效更差;CYP3A5*3 GG基因型携带者的肾脏受累更多见。     

Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy

Infection is the major complication of cyclophosphamide therapy in patients with lupus nephritis. The objectives of this study were to report and compare the rate of infection between children with lupus nephritis who had received intravenous pulse cyclophosphamide (IVCY) and those who had received oral cyclophosphamide (OCY) and to determine the risk factors for infection during treatment with cyclophosphamide in these groups. Records of nine patients who had received IVCY from the beginning [pure intravenous cyclophosphamide (PIVCY) group], 11 patients who had received prior oral cyclophosphamide and later switched to IVCY [combined intravenous cyclophosphamide (CIVCY) group] and 41 patients who had received OCY were reviewed. Infection occurred in 21 of 61 patients (34%). In the PIVCY group, four episodes of infection occurred in three of nine patients (33%). In the CIVCY group, six episodes of infection occurred in four of 11 patients (36%). In the OCY group, 18 episodes of infection occurred in 14 of 41 patients (34%). The rate of infection between these groups was not different (P=0.99). None of the following parameters were risk factors for infection: cumulative dose of cyclophosphamide, leukopenia and neutropenia. On the contrary, white blood cell (WBC) count and polymorphonuclear cell (PMN) count were significantly less in the no-infection group (P=<0.001, P<0.001, respectively), with odds ratios for leukopenia (WBCs <4,000 mm³) and neutropenia (PMNs <1,500 mm³) between the infection and the no-infection group equal to 0.18 (95%CI 0.05–0.63) and 0 (95%CI 0–0.19), respectively. Most of the patients who had infection received prednisolone at a dosage of more than 0.5 mg/kg per day (67% of the PIVCY group, 50% of the CIVCY group and 83% of the OCY group). Fatal infections occurred in two patients who had concomitant active systemic lupus erythematosus (SLE). Although lymphopenia (lymphocyte count <1,500/mm³) was not the risk factor for infection, it was observed that six of seven patients with herpes zoster had lymphopenia. Herpes zoster seemed to occur more frequently in the OCY group (15%) than in the whole IVCY group (5%), but there was no statistical difference (P=0.41). We conclude that the rate of infection in the IVCY and OCY group was not different. Infection is likely to occur in patients receiving a concomitant high dose of prednisolone. The occurrence of fatal infection in patients with active disease should be noted. No single risk factor was detected in this study.     

Outcome in African-American children of neuropsychiatric lupus and lupus nephritis

The present study reviews the course of lupus nephritis (LN) with the added complication of neuropsychiatric systemic lupus erythematosus (NPSLE) in a predominantly African-American population in order to identify the risk factors accounting for the increased morbidity and mortality in African-American children. Previous studies, including those at our center, have demonstrated the poor prognosis for African-American children with LN. A possible factor is the involvement of the central nervous system (CNS), resulting in a heightened risk of morbidity, although to date there are no reports suggesting an association between NPSLE and patient and renal survival in children with lupus nephritis. To this end, we retrospectively analyzed charts of 72 children with lupus nephritis seen at our center from 1965 to 1999. These 72 patients formed two groups, with group 1 consisting of patients with lupus nephritis and NP manifestations and group 2 only lupus nephritis. We then examined various demographic factors such as age, sex and race along with the histopathologic class of lupus nephritis, occurrence of hypertension, incidence of end stage renal disease (ESRD), time to ESRD and mortality in both groups with the aid of Fisher’s exact t-test and the chi-square test. Briefly, the results revealed significantly higher class III or IV histopathologic lesions on biopsy, incidence of hypertension, progression to ESRD and mortality in children with NPSLE and LN (group 1) compared to LN alone (group 2) in spite of aggressive immunosuppressive therapy. In conclusion, we report that NPSLE with LN is associated with an increased rate of ESRD and mortality in our predominantly African-American children. Received: 26 March 2001 / Revised: 13 August 2001 / Accepted: 13 August 2001     

Lupus vasculopathy combined with acute renal failure in lupus nephritis

Several risk factors have been associated with the prognosis of lupus nephritis. However, few studies have focused on renal vascular lesions (such as thrombi due to immune complexes) as a prognostic factor in this disease. Here we present a case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited acute renal failure and severe hypertension on admission. Renal pathology findings included diffuse proliferative glomerulonephritis (class IVb) and lupus vasculopathy (LV) with immune complex deposition within glomerular capillaries and the preglomerular arteriolar lumen. Her clinical condition deteriorated rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It improved after 5 days of plasmapheresis and remained stable for up to 6 months under regular treatment. We suggest that renal biopsy performed early in SLE patients with renal involvement should be studied carefully for the presence of vascular lesions. Additionally, plasmapheresis can be considered in patients with LV refractory to other modalities of therapy.     

Long-term mizoribine intermittent pulse therapy for young patients with flare of lupus nephritis

Mizoribine (MZR) is a novel purine synthesis inhibitor that was developed in Japan. We previously reported the efficacy and safety of oral MZR intermittent pulse therapy, which is associated with elevated peak serum MZR levels, in selected patients with lupus nephritis. However, the efficacy and safety of long-term MZR intermittent pulse therapy (administered for over 24 months) in lupus nephritis patients at high risk for relapse has not yet been reported. Our study included five patients with a long history of systemic lupus erythematosus (SLE), including four patients with proliferative lupus nephritis (WHO class IV) and one patient with WHO class II lupus nephritis, in whom remission had been achieved through treatment with high-dose corticosteroids combined with cytotoxic agents. For the most recent flares, all the patients were treated with MZR intermittent pulse therapy without increase in the dose of corticosteroids. MZR was administered at 5–10 mg/kg per day (up to 500 mg) as a single daily dose on two days of the week (Monday and Thursday) for over 24 months. Concomitantly administered corticosteroid dose was gradually reduced or continued unchanged. At presentation, the urinary protein excretion, serum complement hemolytic activity (CH50) and serum anti-dsDNA antibody titer were 1.7±1.0 g/day, 16.6±3.8 U/mL (normal, 23–46 U/mL) and 143.7±151.1 IU/mL (normal,<12.0 IU/mL), respectively. At the latest observation point, after a mean interval of 31 months (24–34 months) after the initiation of MZR pulse therapy, the urinary protein excretion and serum anti-dsDNA antibody titer were significantly decreased (0.3±0.2 g/day and 18.5±19.1 IU/mL, respectively; P<0.05), and the serum CH50 value had returned to within normal range (33.6±7.8 U/mL, P<0.05). Despite the reduced minimum dose of prednisolone required to maintain clinical remission at the time of the post-treatment evaluation after MZR pulse therapy as compared with that at the time of the pretreatment evaluation (9.0±4.5 vs. 17.5±7.9 mg/day; P=0.0656), the calculated flare rate was significantly decreased (0.15±0.2 vs. 0.6±0.11 times per year; P<0.05). The serum creatinine level remained within normal range in all the study participants. Furthermore, the platelet count increased following the MZR pulse therapy in two patients who had suffered from chronic thrombocytopenia. No serious adverse effects were observed. From the view point of the balance between suppression of disease activity and the adverse effects of treatment, we believe that long-term MZR pulse therapy may be the treatment of choice in selected patients with lupus nephritis at high risk for relapse. However, this was only a pilot study conducted on a small number of subjects, without a control group. Further studies to confirm the long-term efficacy and safety of oral MZR intermittent pulse therapy in larger numbers of patients are needed.     

Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis

Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.