血浆抗内皮细胞抗体检测在弥漫增生性狼疮性肾炎中的临床价值

目的:探讨抗内皮细胞抗体与弥漫增生性狼疮性肾炎的相关性。方法:将39例狼疮患者分为弥漫增生性狼疮性肾炎组和非弥漫增生性狼疮性肾炎组。用间接免疫荧光法检测上述两组血浆抗内皮细胞抗体的阳性率及浓度。结果:在39例狼疮患者中,抗内皮细胞抗体的阳性率为38.5%。弥漫增生性狼疮性肾炎组AECA的阳性率和浓度均高于非弥漫增生性狼疮性肾炎组,但差异无统计学意义。AECA预测弥漫增生性狼疮性肾炎的ROC曲线下面积为0.63,95%可信区间为0.45～0.81,P=0.20。结论:血浆抗内皮细胞抗体在弥漫增生性狼疮性肾炎中有较高的阳性率,但不能作为预测指标。     

Renal haemodynamic characteristics and their correlation with renal pathology in patients with systemic lupus erythematosus

SUMMARY: To clarify the characteristics of renal haemodynamics and their correlation with renal pathology in patients with systemic lupus erythematosus (SLE), renal function and renal biopsy findings from 101 SLE patients were analysed retrospectively. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were examined simultaneously. Filtration fraction (FF) was calculated from the values obtained for GFR and RPF (GFR/RPF). The GFR was low in one-third and within normal limits in two-thirds of class IV patients with lupus nephritis (LN). In contrast, high RPF was observed in half of class IV patients. As a result, over 70% of class IV patients possessed a very low FF (less than 15%). The sensitivity of very low FF for class IV LN was significantly higher than that of low GFR. In conclusion, low FF was frequently recognized, especially in patients with diffuse proliferative LN. Decreased FF was a highly sensitive indicator of diffuse proliferative LN. Thus, determination of renal haemodynamics, including FF, may be a useful clinical parameter for evaluating renal involvement in patients with SLE.     

Lupus-like nephritis in an HIV-positive patient: report of a case and review of the literature

The most common manifestation of HIV/AIDS in the kidney is the collapsing variant of focal segmental glomerular sclerosis, HIV-associated nephropathy (HIVAN). Other forms of renal disease in HIV-infected patients include mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, IgA nephropathy, minimal change disease and proliferative immune-complex GN. We present the case of a 42-year-old Caucasian male with HIV infection, treatment associated peripheral neuropathy, nephrotic syndrome and progressive renal failure. The initial and subsequent kidney biopsies showed diffuse proliferative glomerulonephritis resembling diffuse proliferative (WHO class IV) lupus nephritis. There was no clinical or serological evidence of systemic lupus erythematosus (SLE). Proteinuria improved with ACE-inhibitors, and renal function remained relatively stable while receiving highly active antiretroviral therapy (HAART). A precipitous decline in renal function to end-stage renal disease followed a brief period of withdrawal from potent antiretroviral therapy during which the viral load rebounded. Considering previously reported cases, it appears that lupus-like nephritis is a rare but well-defined pattern of immune-complex-induced renal injury seen in HIV-infected patients. It appears to be markedly responsive to HAART.     

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis.

BACKGROUND: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy. METHODS: In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition. RESULTS: A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment. CONCLUSIONS: Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephritis.     

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.     

Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis

CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the possible role of this interaction in the pathogenesis of systemic lupus erythematosus (SLE), expression of CD134 and CD134L on peripheral blood leukocytes was studied, and no significant differences between SLE patients and control individuals were found. Immunohistology on renal biopsies from patients with lupus nephritis or other renal disorders, using a recombinant human CD134-containing chimeric molecule to detect CD134L, demonstrated the abundant presence of CD134L in all cases of proliferative lupus nephritis in a granular distribution predominantly along the epithelial side of the glomerular capillary wall. Confocal laser scanning microscopy indicated colocalization with subepithelial immune deposits. In none of the other renal disorders examined, including nonproliferative forms of lupus nephritis, was glomerular staining for CD134L detected in a similar pattern. Endothelial CD134L expression was frequently observed in different types of vasculitis. CD134 was detected on perivascular infiltrating leukocytes and on part of the tubular epithelium, but not on glomerular resident cells. Immunohistology for several other TNF(R) family members revealed in proliferative lupus nephritis a similar distribution for TNFR1 as was observed for CD134L. In contrast, glomerular expression of TNFR2 was similar in all cases examined. The glomerular presence of CD134L and TNFR1 in proliferative lupus nephritis in association with subepithelial immune deposits may be of pathogenetic significance and have diagnostic value.     

Lupus nephritis: a clinical review for practicing nephrologists

The renal manifestations in systemic lupus erythematosus (SLE) are protean and difficult to categorize into clinical syndromes and histologic classes. Lupus nephritis is frequently unrecognized until full-blown nephritic and/or nephrotic syndrome with renal failure emerge. Epidemiologically, approximately one third of SLE patients from unselected populations have renal involvement early during the disease. Most renal abnormalities emerge within the first few years of SLE diagnosis. Currently, most nephrologists agree that an early renal biopsy is worthwhile in those SLE patients with abnormal urinalysis and/or reduced renal function. First, it provides a histologic categorization of the glomerulonephritis as well as an assessment of the degree of activity and chronicity. Second, it provides vital prognostic information. Third, it is beneficial in planning a more rational therapy with or without potentially toxic immunosuppressive agents. Over the last 3 decades, many controlled clinical trials for treatment of lupus nephritis have been completed with a few therapeutic immunosuppressive regimens. Among those agents used. cyclophosphamide and azathioprine provide a reduction of morbidity in those patients afflicted with proliferative forms of lupus glomerulonephritis. A new immunosuppressive agent, mycophenolate mofetil, is being studied for treatment of proliferative forms of lupus glomerulonephritis in a controlled clinical trial at our institution. Immunosuppressive agents and the availability of dialysis and transplantation have improved the survival of patients with lupus nephritis, in particular those with proliferative forms.     

T and B lymphocyte function in patients with lupus nephritis: correlation with renal pathology

The relationship between in vitro measures of T and B cell responses of peripheral blood lymphocytes and histological findings on renal biopsy was examined in 32 patients with lupus nephritis. T cell mediated responses, assessed by mixed leucocyte reaction (MLR) and cell mediated lympholysis (CML), were decreased, while spontaneous immunoglobulin secretion by B cells, measured by plaque forming cell (PFC) assay, was increased above normal in the whole patient population. There were no significant differences in these T or B cell responses between patients with the diffuse proliferative and the membranous forms of lupus nephritis. Using a semi-quantitative index of the histologic activity of diffuse proliferative lupus nephritis, a good correlation was noted between the degree of abnormality of B cell responses and the level of activity seen on renal biopsy. The nature of the relationship between B cell abnormalities and the expression of lupus nephritis warrants further study.     

Recent advances in the treatment of lupus nephritis

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) which is associated with significant morbidity and mortality. The concept of two phases of therapy for lupus nephritis, such as an induction phase and a maintenance phase, is widely accepted. Since the renal involvement in SLE is heterogeneous, the treatment of lupus nephritis is governed by its pathological type and ranges from nonspecific measures, such as maintenance of adequate blood pressure control and blockade of the renin–angiotensin–aldosterone system, to the use of immunosuppressive agents. Cyclophosphamide (CYC) in combination with prednisone has been the standard method of treatment of the proliferative forms of lupus nephritis. However, the high rates of progression to end-stage renal disease coupled with the adverse effects of CYC and prednisone have led to an intensive search for more effective and less toxic therapies for lupus nephritis. We review the options available for the treatment of proliferative and membranous lupus nephritis and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.     

Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis

This study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-alpha, IL-1beta, and IL-6 secretion (P < 0.05). Early induction of TNF-alpha was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-alpha, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis.     

Recurrent lupus nephritis in the second allograft of a patient with systemic lupus erythematosus

Lupus glomerulonephritis is a common and serious complication of systemic lupus erythematosus (SLE) affecting up to 50% of lupus patients. Recurrent lupus nephritis is rare, complicating as low as 1% of the lupus transplant population according to some authors. However, it may be underreported with more realistic recurrent rates oscillating from 2.8 to 8.7%. We report the case of a patient with SLE who lost her first allograft 4 years after transplantation with a diagnosis of de novo fibrillary glomerulopathy. She underwent a second renal transplantation and her renal function was stable for the past 5 years. She now presented with skin rash, arthralgias and positive lupus serologies. Her creatinine was slightly elevated and proteinuria was also noted. A renal biopsy performed revealed a recurrent focal proliferative lupus nephritis (WHO III). Retrospectively, we believe that her first allograft was also lost to recurrent lupus nephritis. This is a unique case of recurrent lupus nephritis in the second allograft of a patient with SLE.     

Minimal change disease in systemic lupus erythematosus

We report the clinical and pathologic findings in 7 patients with systemic lupus erythematosus and minimal change disease. All 7 patients presented with full nephrotic syndrome including peripheral edema, nephrotic range proteinuria (mean 9.6 g/day), and hypoalbuminemia (mean 1.8 g/dl). In all cases, renal biopsy revealed diffuse foot process effacement in the absence of significant peripheral capillary wall immune deposits, findings consistent with minimal-change disease. In addition, 5 cases displayed mesangial electron-dense deposits, with or without associated mesangial proliferation, consistent with underlying lupus nephritis class II. In all cases, steroid therapy induced a rapid remission of nephrotic syndrome. Minimal change disease is an underrecognized and readily reversible form of nephrotic syndrome in systemic lupus erythematosus. Because it may occur superimposed on mild mesangial proliferative lupus nephritis, this entity may be misinterpreted as an atypical presentation of lupus nephritis class II. Proper recognition of this entity requires careful integration of the renal biopsy immunofluorescence and electron microscopic findings.     

Clinicopathology of childhood-onset renal systemic lupus erythematosus

AIMS: To determine the clinicolaboratory renal manifestations; glomerular, extra-glomerular histopathologic lesions; renal tubular dysfunction (RTD) frequency and outcome of a short-term renal follow up in Nigerian children with systemic lupus erythematosus (SLE). METHODS: A non-randomized prospective study of consecutive cases of childhood-onset SLE with nephropathy was conducted. Baseline/follow-up clinicolaboratory data were collected. Each patient was followed up for 12 months. RESULTS: Seven of the 11 children studied were girls. The median age at diagnosis was 11.0 years. Median diagnosis time interval (1.9 years) and median time of renal disease onset (1.0 year) were similar. Hypertension, nephrotic syndrome and acute renal failure (ARF) occurred in 45.5%, 54.5% and 63.7% of the patients, respectively. The glomerular lesions were non-proliferative lupus nephritis (LN) in 9.0% (class II LN); focal (class III LN) and diffuse (class IV LN) proliferative LN (PLN) in 27.0% and 64.0%, respectively. Tubulointerstitial nephritis (TIN, 91.0%) and RTD (64.0%) were common. ARF (P = 0.033) and RTD (P = 0.015) were significantly associated with severe TIN. Complete renal remission rate at end-point was 71.4%. Relapse and renal survival rates were 14.3% and 86.0%, respectively. RTD was persistent in 43.0%. CONCLUSION: Renal function disorders, diffuse PLN and extra-glomerular lesions were frequent. Significant association of ARF and RTD with severe TIN in this series suggests the need for early renal tubular function (RTF) assessment in our SLE patients. Deranged RTF may be marker of severe TIN in SLE warranting early confirmatory renal biopsy and aggressive interventional treatment.     

Systemic lupus erythematosus: A follow-up study of Japanese patients with end-stage renal failure treated with haemodialysis

Summary: In order to explore the clinical course of Japanese patients with systemic lupus erythematosus (SLE) in end-stage renal failure, the clinical findings from 26 patients who had received haemodialysis were analysed. Each patient was followed for 72 months from the onset of clinical lupus nephritis to the initiation of haemodialysis. In most patients, renal disease progressed to end-stage renal failure despite clinical quiescence of SLE, which remained inactive throughout haemodialysis treatment. Seven patients (27%) had clinically active SLE with high dose prednisolone (mean; 49.3 mg per day) at initiation of haemodialysis. These patients had relatively rapid progression of their renal failure and 2 patients died within 1 month of their first haemodialysis. During the follow-up period from starting haemodialysis for an average of 44 months, most patients received ongoing haemodialysis while their SLE remained clinically inactive. Six patients (23%) died, 5 of those within 1 month from starting hemodialysis. the results of this long-term follow up of a large number of haemodialysis patients with lupus nephritis indicate that: (i) most patients with lupus nephritis undergoing haemodialysis have an excellent survival rate; and (ii) patients with active SLE at initiation of haemodialysis have a high mortality rate (within 1 month). We therefore conclude that more effective treatment for SLE in the presence of renal failure is required for these patients.     

Fibrillary glomerulonephritis and renal failure in a child with systemic lupus erythematosus

Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerulopathy characterized by randomly arranged immunoglobulin (Ig) deposits on electron microscopy. Only seven pediatric cases have been reported, and the incidence in adults is about 1.5%. A 12-year-old boy presented with systemic lupus erythematosus (SLE) with World Health Organization Class IV lupus nephritis. A repeat biopsy carried out due to a poor response to standard immunosuppressive therapy and worsening renal functions revealed diffuse proliferative glomerulonephritis with fibrillary deposits. Despite aggressive immunosuppression with plasmapheresis and rituximab, the patient developed end stage renal disease. This is an atypical pediatric case characterized by SLE-associated FGN and a poor prognosis.     

The Fc gamma RIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-analysis

BACKGROUND: The Fc gamma RIIIA-V/F158 polymorphism affects immunoglobulins (Ig)G1- and IgG3-binding capacity and may modulate the expression of renal disease in patients with systemic lupus erythematosus (SLE). We aimed to determine whether this polymorphism confers risk for the development of lupus nephritis and SLE in general. METHODS: A meta-analysis was performed based on the Medline and Embase databases (last update, August 2002), perusal of abstracts from major meetings (1999 to 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators. RESULTS: A total of 16 comparisons from 11 studies involving V/F158 genotyping of 1154 patients with lupus nephritis, 1261 SLE patients without nephritis, and 1455 disease-free controls were included. Comparison of lupus nephritis patients with non-nephritis SLE subjects revealed a significant overrepresentation of the low-binding F158 allele among patients who developed renal disease [odds ratio (OR) 1.20, 95% confidence interval (95% CI) 1.06 to 1.36, P = 0.003)], without significant between-study heterogeneity. FF homozygotes had the highest risk of renal disease as compared to VV homozygotes (OR 1.47, 95% CI 1.11 to 1.93, P = 0.006). It was uncertain whether the F158 allele influenced susceptibility to SLE per se (OR 1.19, 95% CI 0.99 to 1.43, P = 0.063 for SLE patients without nephritis versus disease-free controls; 0.01 < P < 0.10 for heterogeneity) and the observed trend for an association was driven mostly by the smaller studies (P = 0.058 for publication bias). No such bias was detected for analyses on susceptibility to lupus nephritis. CONCLUSION: The Fc gamma RIIIA-V/F158 polymorphism has a significant impact on the development of lupus nephritis.     

Lupus nephritis: an update

Lupus nephritis (LN) is an inflammatory condition of the kidneys that encompasses various patterns of renal disease including glomerular and tubulointerstitial pathology. It is a major predictor of poor prognosis in patients with systemic lupus erythematosus (SLE). Genetic factors, including several predisposing loci, and environmental factors, such as EBV and ultraviolet light, have been implicated in the pathogenesis. It carries a high morbidity and mortality if left untreated. Renal biopsy findings are utilized to guide treatment. Optimizing risk factors such as proteinuria and hypertension with renin-angiotensin receptor blockade is crucial. Immunosuppressive therapy is recommended for patients with focal or diffuse proliferative lupus nephritis (Class III or IV) disease, and certain patients with membranous LN (Class V) disease. Over the past decade, immunosuppressive therapies have significantly improved long-term outcomes, but the optimal therapy for LN remains to be elucidated. Cyclophosphamide-based regimens, given concomitantly with corticosteroids, have improved survival significantly. Even though many patients achieve remission, the risk of relapse remains considerably high. Other treatments include hydroxychloroquine, mycofenolate mofetil, and biologic therapies such as Belimumab, Rituximab, and Abatacept. In this paper, we provide a review of LN, including pathogenesis, classification, and clinical manifestations. We will focus, though, on discussion of the established as well as emerging therapies for patients with proliferative and membranous lupus nephritis.     

Clinicopathological study of the WHO classification in childhood lupus nephritis

Over the past 10 years, at our center, 25 children diagnosed with systemic lupus erythematosus (SLE) have undergone an early renal biopsy; 15 underwent a second biopsy. The objective of this study was to determine whether clinical and laboratory parameters used to evaluate lupus disease activity and nephritis correlated with the WHO class on biopsy. At diagnosis, the presence of proteinuria, hematuria, a lower serum albumin, and the need for blood pressure medication were all associated with a worse class of lupus nephritis (P<0.05). On follow-up biopsy, however, none of these parameters correlated with the WHO class. Thus, it appears that while the WHO classification is useful for categorizing disease at presentation, it may be less useful for the evaluation of disease progression. Other biopsy indices need to be evaluated in serial renal biopsies to better understand the progression of lupus nephritis once treatment has been initiated.     

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.     

Ultrastructural 'fingerprint' in cryoprecipitates and glomerular deposits: a clinicopathologic analysis of fingerprint deposits.

Organized glomerular electron-dense deposits with a fingerprint pattern are well known in some patients of lupus nephritis or cryoglobulinemia. In general, these two diseases are always discussed separately as the causes of such deposits. However, 3 of our 5 lupus patients with glomerular fingerprint deposits also had cryoglobulinemia. One of the remaining 2 patients died and the other was lost to follow-up. The purpose of our study was to seek an appropriate clinicopathologic assessment of fingerprint deposits. All these patients showed overt proteinuria, active urinary sediment, a high degree of activity of lupus nephritis, and diffuse proliferative glomerulonephritis (WHO class IV). Their cryoprecipitates and renal biopsy specimens were investigated by means of immunochemistry, immunofluorescence and electron microscopy. The ultrastructural 'fingerprint' structures were exactly the same in the cryoprecipitates and in the glomerular deposits in 2 of 3 lupus patients with cryoglobulinemia, as were IgG, IgM and IgA. Therefore, these observations furnish emerging morphologic evidence for the glomerular deposition of immune complexes of circulating cryoglobulins in lupus nephritis. In addition, electron microscopic fingerprint deposits on renal biopsy or cryoprecipitate can be regarded as a very sensible marker of concomitant or subsequent development of diffuse lupus nephritis. If the patient is accompanied by nephritic syndrome, an early trial of immunosuppressive therapy may be warranted.