Renal immunofluorescence and the prediction of renal outcome in patients with proliferative lupus nephritis

The risk for endstage renal failure in patients with proliferative lupus nephritis (PLN) depends largely on the severity and reversibility of the inflammatory process as determined by light microscopy (LM). As the intrarenal formation of immune complexes is thought to initiate this inflammation, we studied whether renal immunofluorescence microscopy (IFM) provides clinical or prognostic information in addition to LM findings. Clinical data at the time of renal biopsy and during a mean follow-up of 46 months were extracted from the records of 69 SLE patients with proliferative LN (WHO class III/IV). Biopsy specimens were analyzed by LM for AI and CI, while IFM was performed on cryostat sections with the use of antisera against IgG, IgM, IgA, C3, C1q and fibrin. IFM findings were recorded in terms of the localization (glomerular, tubular or vascular) and intensity of fluorescence (score from zero to three). IFM findings were then related to clinical and LM findings and its prognostic value studied by survival analysis. Glomerular immune deposits were present in 99% of patients, tubular deposits in 38% and vascular deposits in 17%. A 'full-house' pattern (all three Ig classes) was found in 67% of biopsies and C3 and C1q deposits in 93% and 74% respectively. Median scores for AI and CI were 6 (1-18) and 3 (0-10); aside from a negative correlation between IgA deposits and CI, we found no other correlation between the amount or type of immune deposits and AI or CI. IgM deposits were associated with high serum levels of anti-dsDNA, while IgG deposits correlated with high ESR and serum creatinin levels. IFM scores were not related to steroid dose at the time of biopsy and neither type of glomerular, tubular or overall renal immune deposits had prognostic value for renal survival. Renal immunofluorescence does not reflect light microscopy findings in patients with PLN and does not contribute prognostic information in patients with PLN. Lupus (2000) 9, 504-510.     

Correlation of membranous glomerular ultrastructural changes with disease severity and outcome in lupus patients initiating cyclophosphamide therapy

The aim of this study was to assess the utility applying an electron microscopy (EM) scoring system used in idiopathic membranous nephritis based on the location of subepithelial and/or intramembranous electron dense deposits in interpretation of renal biopsies from patients with lupus nephritis. We selected patients with electron dense deposits traditionally associated with membranous changes on EM from 84 patients treated with bolus cyclophosphamide, with five years follow-up. An EM scoring system designed for idiopathic membranous nephritis was applied (stages I or II, mild changes; stages III or IV, advanced changes). Twenty-seven out of 84 had membranous changes by light microscopy, of whom 22 had satisfactory tissue for EM membranous analysis. Eleven out of 22 had mild EM changes (EM stage I or II); 11 had advanced disease (EM stage III). Advanced EM stage was associated with a higher serum creatinine at entry when tests were adjusted for WHO class (2.62 +/- 0.6 versus 1.31 +/- 0.28 mg/dL, P < 0.022 by ANOVA), and EM stage was independent of NIH activity or chronicity indexes or disease duration. After five years, adverse outcomes (death or dialysis) were seen in one of the 11 patients with EM stages I-II versus five of the 11 EM stage III patients (P < 0.07). Advanced membranous type electron dense deposition in lupus as assessed by EM was associated with worse renal function in patients with comparable WHO classification and NIH activity and chronicity indexes. In this group of lupus patients initiating cyclophosphamide for severe nephritis, EM stage provided important additional information regarding the extent of renal injury.     

Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis

OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients. METHODS: Skin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes. RESULTS: IgG deposits were found in 87% of the patients with lupus nephritis, in 33% of the patients with inactive disease, and in 71% of the parapemphigus patients. Using polyclonal antihistone antibodies, histones were detected in 87% of lupus nephritis patients, but in none of the other SLE patients or the diabetes controls (P < 0.0001). Among the parapemphigus controls, 14% of samples stained positive in one of the polyclonal antihistone stainings (P < 0.0001). Using monoclonal antibodies, histones and DNA were identified in 21% of the lupus nephritis patients. Although none of the other groups showed positive staining for nucleosomes, 7% of the lupus nephritis biopsy samples were positive using antinucleosome monoclonal antibodies. Colocalization of nucleosomal antigens and IgG was confirmed using confocal laser microscopy. CONCLUSION: These findings suggest that nucleosome-mediated binding of autoantibodies to basement membranes may also occur at sites in the body other than in the glomerulus.     

Lupus nephritis: Clinical course as related to morphologic forms and their transitions

An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms.     

Acute renal failure secondary to interstitial lupus nephritis.

A patient with systemic lupus erythematosus (SLE), followed up over a six-month period, exhibited numerous immunologic abnormalities and varied renal pathologic features. Initial findings included minimal glomerular lesions, serum antibodies directed solely against nuclear RNA protein, and lupus band test showing pure IgM deposition. These findings suggested a good prognosis. Subsequently, the patient developed acute renal failure secondary to an interstitial lupus nephritis, without progression of the glomerular abnormality. Serum antibodies to the nuclear non-nucleic acid macromolecule and single stranded and native DNA were demonstrated concurrently. New skin deposits of IgG and IgA in addition to IgM also were observed. This patient demonstrates the potential progression of lupus renal disease despite the initial favorable prognostic indicators.     

Adrenomedullin--a potential disease activity marker and suppressor of nephritis activity in systemic lupus erythematosus

OBJECTIVES: To investigate whether plasma adrenomedullin (AM) level is elevated in lupus nephritis and to examine if plasma AM level is correlated with systemic lupus erythematosus (SLE) disease activity and severity of lupus nephritis after multivariate adjustment. METHODS: Consecutive SLE patients and healthy volunteers of age >/=16 were recruited from the rheumatology clinics of two hospitals in Hong Kong. SLE patients with nephritis fulfilled the American College of Rheumatology criteria for renal involvement and had percutaneous renal biopsy performed. Subjects were divided into three groups: (i) SLE patients with nephritis, (ii) SLE patients without nephritis and (iii) normal controls. The demographic and clinical variables were compared between these groups of patients and plasma AM level was determined by radioimmunoassay. Factors associated with plasma AM level were explored by regression analysis with adjustment of confounding factors. RESULTS: Sixty SLE patients (39 with nephritis and 21 without) and 23 normal subjects were studied. The plasma AM level of SLE patients was significantly higher than that of normal controls. SLE patients with nephritis had significantly higher plasma AM level than those without nephritis and normal controls (P<0.001). In regression analysis, proteinuria was negatively associated with plasma AM level (P=0.006) whereas SLE disease activity index was positively associated with plasma AM level after multivariate adjustment (P=0.002). CONCLUSIONS: Plasma AM is elevated in lupus nephritis, which correlates with lupus disease activity. It is negatively associated with urine protein excretion although it is unrelated to the type of renal pathology per se. Plasma AM may play a role to suppress the activity of lupus nephritis.     

Binding of synthetic double-stranded DNA by serum from patients with systemic lupus erythematosus: correlation with renal histology.

Detection of antibody to double-stranded DNA by direct binding assays has proved useful in clinical management of patients with systemic lupus erythematosus (SLE). Recent confusion regarding specificity of these antibodies for SLE appears to be due, at least in part, to contamination of natural DNA preparations with nondouble-stranded DNA antigens. Measurement of binding of a synthetic, self-complementary DNA copolymer (dAT) rather than of natural DNA (KB) has been shown to obviate some of these difficulties, apparently because of freedom of dAT from nondouble-stranded DNA antigens. Among the advantages found in this way was a higher degree of specificity of antibodies to double-stranded DNA for clinically-judged active lupus nephritis than had been suspected. Since activity of nephritis is difficult to assess clinically, histologic data were sought to confirm these observations. Thirty-two kidney specimens were examined by light and/or electron microscopy. The degree of histologic activity and the amount and location of glomerular electron-dense deposits were semiquantitated blindly. The binding of both dAT and KB DNA was measured by the ammonium sulfate method. Correlation with the amount of electron-defense deposits was highly significant for dAT binding and somewhat less so for KB DNA binding as determined by both parametric and nonparametric statistical methods. Significant correlation with histologic activity was found for dAT but not KB DNA binding. These results are consistent with previous data and suggest that dAT binding may provide a useful, noninvasive means of clinically assessing both nephritis activity and the intensity of glomerular immune-complex deposition as reflected by the amount of electron-dense deposits. If it can be confirmed that the latter provides long-term prognostic information, then dAT binding (and perhaps its reponse to therapy) may also prove of value in this regard.     

Serum lactate dehydrogenase and its isozymes in lupus nephritis

The relationship between the renal pathologic activity of systemic lupus erythematosus (SLE) and serum lactate dehydrogenase (LDH) was examined in 28 patients with active SLE involving only the kidney. Serum levels of total LDH, LDH1, and LDH2 were significantly higher in the patients with diffuse proliferative lupus nephritis (World Health Organization class IV) than in those with milder renal disease (classes I through III and V). Total LDH levels showed good correlations with the activity index and the total pathologic score of the renal pathologic scoring system, and with the glomerular hypercellularity and overall deposits. The elevated level of LDH was mainly due to elevated levels of its isozymes LDH1 and LDH2. These results suggest that the elevation of serum LDH levels in patients with SLE reflects the renal pathologic changes due to lupus nephritis.     

Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure

OBJECTIVE: To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis. METHODS: Ninety-one patients with lupus nephritis were included in the study. Renal biopsies were classified according to the WHO criteria and examined for the presence of active and chronic histological changes. Predictors of endstage renal disease (ESRD) were identified by univariate and multivariate analyses. RESULTS: The median followup time was 6.1 years (0.1-30.0 yrs). In all cases, immunosuppressive treatment was initiated or intensified within one month following renal biopsy. The cumulative incidence of ESRD after 1, 5, and 10 years was 3.5%, 15%, and 17%, respectively. A variety of clinical and biopsy findings including several histological markers of chronic renal damage were identified as univariate predictors of ESRD. In multivariate regression analyses, duration of nephritis symptoms > 6 months prior to biopsy, s-creatinine > 140 micromol/l, diffuse proliferative glomerulonephritis, and tubular atrophy emerged as the strongest combination of independent risk factors (relative hazard ratios: 9.3, 5.6, 8.9, and 3.1, respectively). CONCLUSION: Our results confirm the negative prognostic impact of hypercreatininemia, class IV histopathology, and tubular atrophy in lupus nephritis. Our data show that delay between onset of nephritis and renal biopsy constitutes an important risk factor of ESRD. Patients with SLE should have kidney biopsy as soon as clinical signs of nephritis are evident in order to accelerate treatment decisions and minimize risk of inflammation-induced irreversible kidney damage.     

Late development of systemic lupus erythematosus in patients with glomerular "fingerprint" deposits

Two patients presenting with nephrotic syndrome but without evidence of collagen vascular disease had organized glomerular immune deposits with a "fingerprint" pattern. This finding has been previously associated with lupus nephritis and, in our institution, has been seen in 6% of the biopsy specimens from patients with lupus nephritis. Clinical signs and symptoms of systemic lupus erythematosus in these two patients did not develop until 2 and 5 years later, respectively. The cases of these patients suggest that glomerular deposits with a fingerprint pattern may be a specific marker for lupus erythematosus even when overt clinical features of this disease are lacking. Patients with this finding on renal biopsy should have an extended follow-up for possible development of lupus erythematosus.     

Clinicopathological features and outcomes of SLE patients with renal injury characterised by thrombotic microangiopathy

Objectives

Non-immune complex (IC)-mediated renal thrombotic microangiopathy (TMA) has been reported in patients with systemic lupus erythematosus (SLE), but most studies included patients with both renal TMA and IC-mediated lupus nephritis (LN). In this study, the clinicopathological features and outcomes of renal injury characterised by only renal TMA were retrospectively analyzed.

Methods

Patients with glomerular and/or vascular TMA in the absence of subendothelial or epithelial immune deposits were screened from 2,332 biopsied of SLE patients. The TMA lesions were divided into glomerular, vascular or both. Acute tubular-interstitial injury was semi-quantitatively analyzed. The podocyte foot process effacement (FPE) was measured by electronic microscopy.

Results

Two hundred fifty-seven (11.0%) renal biopsies revealed TMA, among which 237 biopsies showed TMA coexisting with LN, and 20 (0.9%) biopsies had only renal TMA without or with only mesangial immune deposits. All patients manifested with acute kidney injury and haematological disorders. Among them, 11 (55%) required renal replacement therapy, 12 (60%) had nephrotic syndrome and 13 (65.0%) showed microvascular haemolytic anaemia with thrombocytopenia. Seventeen (85%) biopsies revealed both glomerular TMA and vascular TMA, two had only glomerular TMA and one had vascular TMA. Eight (40%) had no glomerular immune deposits and 12 (60%) showed only mesangial immune deposits. The acute tubulointerstitial injury in patients requiring dialysis was more severe than those not needing dialysis ((43.6 ± 24.9) % vs. (21.7 ± 20.1) %, p = 0.047). FPE of podocytes was positively correlated with proteinuria (r² = 0.347, p = 0.006). All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange. The renal function of 11 patients requiring dialysis initially recovered after 16.0 (interquartile range [IQR] 9.0, 30.0) days of treatment. During the follow-up of 58.0 (IQR 36.0, 92.3) months, remission was achieved in 19 (95%) patients; only one patient had no response. No patient died or progressed to end-stage renal disease; six patients (30%) relapsed.

Conclusion

Renal TMA, usually accompanying severe renal injury, was not uncommon in SLE patients with renal disease and should be distinguished from immune complex–mediated severe classes of LN. Early intensive immunosuppressive treatment may be associated with a good long-term renal outcome.

Persistent increase in plasma thrombomodulin in patients with a history of lupus nephritis: endothelial cell activation markers

OBJECTIVE: To investigate the presence of continuing endothelial cell activation in patients with systemic lupus erythematosus (SLE) and its relationship with lupus nephritis. METHODS: We measured plasma concentrations of soluble thrombomodulin (sTM), vascular cellular adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWf), sP-selectin, and ED1-fibronectin in 75 SLE patients with a median SLE disease activity index (SLEDAI) of 4. Forty patients with a history of lupus nephritis, confirmed by renal biopsy in 33, were compared with 35 patients without lupus nephritis and 25 controls. For subgroup analysis in patients with clinically stable remission we excluded patients with a SLEDAI > 6 or with evidence of renal disease activity. RESULTS: In the total SLE patient group sTM, sVCAM-1, vWf, and sP-selectin were significantly elevated compared with controls. In patients with a history of lupus nephritis plasma levels of sTM and vWf were significantly increased compared with SLE patients without nephritis. After adjustment for significantly associated variables, especially creatinine clearance and age, in a multivariate linear regression analysis, sTM remained significantly elevated in patients with a history of lupus nephritis (difference 28.9 ng/ml, 95% CI 11.5-46.4). In the subgroup analysis of 57 patients, the results remained unchanged. CONCLUSION: The increase of sVCAM-1, sP-selectin, sTM, and vWf reflects a state of persistent endothelial cell activation. Multivariate regression analysis shows that the elevated sTM levels are strongly associated with a history of lupus nephritis, independent of creatinine clearance or disease activity, suggesting endothelial cell activation specifically localized in the kidneys.     

系统性红斑狼疮五年生存率及预后因素分析

目的 回顾性分析系统性红斑狼疮(SLE)患者5年生存率、死亡原因及影响预后的因素. 方法 收集我院1998-2005年住院初发的243例SLE患者的临床及血清学资料,并进行随访.用非参数乘积法分析生存率,比例风险模型(Cox参数回归)分析预后因素. 结果 从诊断时计算SLE患者1、3、5年生存率分别为96%、94%和91%.肾功能衰竭和感染是最常见的死亡原因,其次是神经精神狼疮和肺动脉高压.多因素分析显示诊断时狼疮肾损害和神经精神狼疮是死亡的独立危险因素,而诊断时年龄、性别、血液系统异常、低补体、抗dsDNA抗体阳性、肺损害、心脏损害以及联合免疫抑制剂治疗对存活影响无统计学意义. 结论 早期诊断及控制SLE脏器损害,同时预防感染,是提高患者生存率的关键.     

Renaler Lupus erythematodes

This article describes important histopathologic findings in lupus nephritis including differential diagnosis. Lupus nephritis is mainly a disease of the glomerulus; although preglomerular and postglomerular vasculature as well as the tubulointerstitium may be involved. Using light microscopy, immunohistology, and electron microscopy techniques in combination with intensive clinical examination including serology will lead to the diagnosis of lupus nephritis. An internationally accepted classification of lupus nephritis, the glomerular activity index, and the tubulointerstitial chronicity index are helpful in determining treatment strategies and prognosis. A semiquantitative score of interstitial fibrosis and tubular atrophy are reliable prognostic parameters. Differential diagnosis of lupus glomerulonephritis includes patients with thrombotic microangiopathy, HIV infection, membranoproliferative glomerulonephritis, and IgA nephritis.     

Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis

OBJECTIVE: Reactive intermediate production is an essential component of the innate immune response that is induced during disease activity in murine lupus. This study was undertaken to determine whether a marker of systemic nitric oxide (NO) production correlates with prospectively studied disease activity in human systemic lupus erythematosus (SLE) and lupus nephritis patients. METHODS: Eighty-three SLE patients and 40 control subjects were studied longitudinally. The SLE group included 23 patients with lupus nephritis documented by renal biopsy and 26 with a history of lupus nephritis. During each visit, following a 24-hour low-nitrate diet, traditional markers of disease activity and damage were determined. Serum nitrate plus nitrite (NOx) levels were determined by chemiluminescence detection. RESULTS: NOx levels were higher in SLE patients than in controls during the first visit. In univariate longitudinal analyses, NOx levels were associated with SLE Disease Activity Index scores. In multivariate analyses, NOx levels were associated with serum levels of C3 and creatinine and the urinary protein:creatinine ratio. Among patients with lupus nephritis, those with proliferative lesions had higher NOx levels, and higher NOx levels were associated with accumulation of renal damage and lack of response to therapy. CONCLUSION: This is the first study to prospectively demonstrate longitudinal associations between serum NOx levels and markers of SLE and lupus nephritis disease activity. The more pronounced association with proliferative lupus nephritis and with longitudinal response to lupus nephritis therapy provides a rationale for the study of reactive intermediates as biomarkers of disease activity and therapeutic targets in proliferative lupus nephritis.     

Kidney biopsy in systemic lupus erythematosus. II. Survival analyses according to biopsy results

Renal biopsy specimens from 123 patients with systemic lupus erythematosus (SLE) seen between 1970 and 1984 were assessed according to the World Health Organization classification and according to the presence of proliferative, active, or chronic renal lesions. Survival analysis was used to study the determinants of mortality. Survival rates were higher for patients with minimal lesions, intermediate for patients with focal or diffuse proliferative nephritis, and low for patients with glomerular sclerosis. The presence of proliferative and chronic lesions was associated with a higher risk of dying. Renal biopsy results are helpful in predicting prognosis for all-cause mortality in patients with SLE.     

Systemic lupus erythematosus in Tunisia: demographic and clinical analysis of 100 patients

There is a wide variation in the natural history of systemic lupus erythematosus (SLE) among different ethnic and geographical groups. Studies in Arabs are few and those in North Africans and especially in the Tunisian population do not exist. This study aims to demonstrate the demographic, clinical and laboratory characteristics of SLE Tunisian patients and to identify those at high risk for renal and neuropsychiatric involvements. One hundred patients with SLE (American College of Rheumatology criteria), seen at the Department of Internal Medicine of the University Hospital La Rabta in Tunisia over a 15-year period (1987 to 2001) were retrospectively enrolled. There were 92 women and eight men with an average age at the onset of disease of 32 years. Nineteen patients were aged over 50 years at the moment of SLE diagnosis (late-onset SLE). Of the patients, 78% had articular involvement, 53% photosensitivity and 63% malar rash. Serositis occurred in 45 patients of whom 16 had pericarditis and 29 had pleuritis. Nephritis was diagnosed in 43% of the cases and consisted always of glomerular nephritis, in three cases of which tubulointerstitial lesions were also observed. Comparison of patients with and without renal involvement showed that lupus nephritis was significantly associated with pericarditis (P = 0.03), arterial blood hypertension (P < 0.0001), cryoglobulinemia (P = 0.07) and antiphospholipid syndrome (P = 0.03). The SLEDAI at SLE diagnosis was significantly higher for lupus nephritis patients. Twelve patients with lupus nephritis died compared with three patients in the remaining group (P < 0.0001). Neuropsychiatric manifestations were observed in 25% of the cases. The mean age at SLE onset was significantly lower, the mean SLEDAI at SLE diagnosis and the mortality were significantly higher in the neuropsychiatric group than in the remaining group. Immunological features included antinuclear antibodies (100%), anti-DNA antibodies (56%), anti-Sm antibodies (61%), anticardiolipin antibodies (62%), anti-beta2GP1 (13%) anti-Rnp (23%) and hypocomplementemia (48%). The frequencies of pulmonary hypertension (25 versus 2%, P < 0.00001) and vascular thrombosis (25 versus 2%, P < 0.00001) were significantly higher in patients with positive anti beta2GP1 antibodies. The five-year survival rate in our series was 86%. The most frequent causes of death were active SLE and infections.     

Renal outcome and vascular morbidity in systemic lupus erythematosus (SLE): lack of association with the angiotensin-converting enzyme gene polymorphism

OBJECTIVES: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. METHODS: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction-based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. RESULTS: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. CONCLUSIONS: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism.     

Systemic lupus erythematosus. III. Observations on clinical renal involvement and follow up of renal function: Dutch experience with 110 patients studied prospectively.

A prospective study of 110 patients with systemic lupus erythematosus (SLE) was undertaken to evaluate the reliability of clinical signs of lupus nephritis, which developed in 39 (35%) patients. Those patients with SLE who showed no clinical signs of lupus nephritis had an excellent survival rate (10 year survival 93%) and retained normal renal function (serum creatinine less than 130 mumols/l); clinical lupus nephritis developed mainly in the first three years after diagnosis of SLE and was associated with a decreased survival rate (10 year survival 62%). Increased mortality was found in male patients with lupus nephritis over 25 years of age and in female patients with lupus nephritis under 25 years of age, while renal failure rates did not differ between these groups. Treatment of lupus nephritis with high dose prednisone alone or in combination with immunosuppressants did not result in differences in patient survival or renal function preservation. It was concluded that clinical variables are a reliable guide in the management of patients with SLE, and routine use of renal biopsy in these patients is rejected.     

The Time-Dependence of Long-Term Prediction in Lupus Nephritis

Objective. To assess the clinical, laboratory, and renal biopsy predictors of long-term outcome in lupus nephritis and to investigate the time-dependence of these predictors. Methods. Eighty-seven lupus nephritis patients were studied retrospectively for the outcomes renal failure and fatality due to renal involvement. In addition to a conventional Cox model analysis, a new generalized time-dependent analytic approach was developed and used to assess the time-dependence of a predictor variable's importance. Results. The mean followup time was 11.9 years. Renal failure (n = 19) was significantly predicted by measures of renal function (abnormal serum creatinine levels, proteinuria, duration of prior renal disease) and immunologic activity (elevated DNA binding, hypocomplementemia, and thrombocytopenia), by overall lupus disease activity measures (le Riche index, Lupus Activity Criteria Count), and by the activity index, the tubulointerstitial index, and the amount of subepithelial deposits on renal biopsy. In general, the laboratory predictors were significantly better prognostic markers in the early years after biopsy, the disease activity measures were best in the later years, and the biopsy variables were significant predictors over the entire observation period. In contrast to the renal failure outcome, the best predictors for death not directly related to lupus nephritis (n = 17) were the extent of comorbid diseases (principally vascular diseases), older age, and the chronicity index. All three predicted well over the extended observation period. Conclusion. The major predictor variables for renal outcomes and nonrenal outcomes are distinct. The time-dependence of the predictive ability of some variables may be important in managing individual patients. The new generalized time-dependent analytic technique may have widespread application in studies to identify prognostic factors for established disease or risk factors for the development of disease.