Q J Med 2001; 94: 19-26
© 2001 Association of Physicians
Cardiovascular risk factors and the long-term outcome of lupus nephritis
From the Systemic Autoimmune Diseases Unit and 1 Department of Nephrology, Department of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain, and 2 Rheumatology Department, Benemérita University School of Medicine, Puebla, México
Received 14 June 2000 and in revised form 20 October 2000
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11–67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Systemic lupus erythematosus (SLE) is the most clinically and serologically diverse of the autoimmune connective tissue diseases; it may affect any organ of the body and displays a broad spectrum of clinical and immunological manifestations. The diversity of its clinical manifestations, with very distinct forms of presentation, include articular and mucocutaneous involvement, renal disease, haematological abnormalities and central nervous system disease.1
Renal disease is a frequent complication of SLE that can greatly influence the prognosis. Many factors affect the prognosis of this highly pleomorphic disorder, and the diversity of predictors identified in various clinical studies has led to some controversy. Clearly, the mortality rate is higher for SLE patients with nephritis than in those without renal involvement,2,3 and some 10%–60% of SLE patients with nephritis eventually develop end-stage renal failure that requires dialysis or transplantation.4–8 Some series have reported a 10-year kidney survival rate of around 80%, even in patients with diffuse lupus nephritis (LN).9,10 Several factors may have contributed to these encouraging results, but more appropriate use of corticosteroids and immunosuppressive agents has certainly played a major role. Unfortunately, the continuous use of these drugs, as well as the persistent disease activity, may expose patients with SLE to several late complications,11–16 and in addition significant morbidity and mortality persist. In this study, we prospectively analysed the outcome and clinical features of 70 patients with LN followed in a single reference centre for over 10 years, focusing especially on the role of cardiovascular risk factors in the renal outcome and mortality of this subset of SLE patients.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
Our total cohort included 431 consecutive patients with SLE (381 female and 50 male, mean age 32 years, SE 0.7, range 11–80) who had been registered in our Unit from 1970 to 1988. All patients fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE.17 The study began in 1988 with a consecutive and prospective design, and included 70 patients with LN and 70 age-sex-matched SLE patients without evidence of nephropathy. The groups had a similar prevalence of the major non-renal SLE features. At inclusion, information was obtained on age, race, smoking habit, menopausal status, diabetes and hypertension. Hypertension was defined as blood pressure >140/90 mmHg, respectively, in two consecutive determinations. We treated the hypertension of our LN patients with calcium-channel blockers, angiotensin-converting-enzyme inhibitors or angiotensin receptor antagonists (with careful supervision for development of hyperkalaemia and azotaemia) adding, if necessary, diuretics or ß-blockers. Fasting total cholesterol and triglyceride levels were measured in blood samples using standardized laboratory tests. Normal renal function was defined as a plasma creatinine <124 µmol/l. Proteinuria was considered to be nephrotic when urinary protein excretion exceeded 3 g/day and non-nephrotic when 0.2–3 g/day. Altered urine sediment was considered when >3 red blood cells or 5 white blood cells or any casts (either red cell, hemoglobin, granular, tubular or mixed) were observed per high power field. Renal biopsies were reviewed by two pathologists and categorized according to the modified classification proposed by the WHO:18 I, normal or minimal disease; II, mesangial nephritis; III, focal proliferative nephritis; IV, diffuse proliferative nephritis; and V, membranous nephritis. Patients with normal renal function, proteinuria <0.2 g/day and inactive urine sediment were considered to be patients without nephropathy. The outcomes studied were renal failure (creatinine >125 µmol/l), end-stage renal failure and death.
Laboratory studies
The immunological tests included determination of antinuclear antibodies (ANA) by indirect immunofluorescence using mouse liver as substrate, antibodies to double-stranded DNA by Farr's technique, precipitating antibodies to the extractable nuclear antigens (U1-RNP, Sm, Ro/SS-A and La/SS-B) by counterimmunoelectrophoresis and rheumatoid factor (RF) by latex fixation and Waaler-Rose tests. Complement factors (C3 and C4) were estimated by the nephelometry (Behring BNA nephelometer) and CH50 by Lachmann's haemolytic technique.
IgG and IgM anticardiolipin antibodies (aCL) were estimated by an ELISA technique as described by Gharavi et al.19 with minor modifications.20 The lupus anticoagulant (LA) was measured by coagulation assays (prothrombin time, activated partial TP time, kaolin clotting time, diluted Russell's viper venom time and tissue TP inhibition time) following the recommendations of the subcommittee on LA of the Scientific and Standardization Committe of the International Society of Thrombosis and Hemostasis.21
Statistical analysis
We used conventional 
2 and Fisher's exact test to analyse qualitative differences, Student's test for the comparison of means in large samples of similar variance, and the non-parametric Mann-Whitney U test for small samples. A value of p<0.05 was taken to indicate statistical significance. When several independent variables appeared to have statistical significance in the univariate analysis, a logistic regression test was performed for multivariate analysis in order to rule out possible related variables. The odds ratio (OR) was calculated for assessing the risk of appearance of each variable, with 95%CI. Results of the analysis of continuous variables are indicated as mean and standard error (SE) of the mean. This statistical analysis used the SPSS program.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Characteristics of LN patients
Seventy patients (64 female, 6 male) with LN entered this prospective study. Their mean age at entry was 35 years (SE 1.7, range 11–67). The first manifestation of renal involvement was altered urine sediment in 28 (40%) patients, nephrotic syndrome in 24 (34%), renal failure in eight (12%), nephrotic syndrome in three (4%) and other features in the remaining 7 (10%) patients. Tissue for optic microscopy study was obtained from 63 (90%) patients. Renal biopsies showed diffuse proliferative nephritis (class IV) in 20 (32%) patients, focal proliferative nephritis (class III) in 16 (25%), mesangial nephritis (class II) in 15 (24%), membranous nephritis (class V) in eight (13%) and minimal disease (class I) in four (5%) patients.
After presentation with LN, 27 patients with the most severe disease received immunosuppressive agents plus corticosteroids: cyclophosphamide (1.5 mg/kg/day) was administered in 17 patients (intravenously in 14 patients and orally in 3) and azathioprine (2 mg/kg/day) in 12 (two patients received both agents). Intravenous cyclophosphamide was administered monthly during 6 months and every 3 months during the following 1.5 years, and azathioprine was prescribed for 2 years. Immunosuppressive drugs were recommended particularly for patients with marked subendothelial deposits. Furthermore, 32 patients received oral prednisone (>0.5 mg/kg/day) alone.
Comparison between patients with and without LN
Fifteen (21%) patients from the LN group and 18 (25%) from the control group were lost to follow-up. Additionally, seven patients from the control group developed nephropathy in the course of follow-up, and were also eliminated from the analysis. Thus, we compared 55 LN patients and 45 patients without LN. We analysed their clinical and immunological features, therapy, and cardiovascular risk factors at the onset of follow-up (Table 1
). LN patients showed a higher prevalence of positive anti-dsDNA antibodies (84% vs. 49%, p<0.001, RR 2.41, CI 1.35–4.29) and a lower prevalence of RF (4% vs. 15%, p=0.04, RR 0.38, CI 0.11–1.31) in the univariate analysis at the onset of follow-up, although only positive anti-dsDNA antibodies (p=0.03) was an independent variable in the multivariate analysis.
|
LN patients showed a higher prevalence of previous treatment with corticosteroids higher than 0.5 mg/kg/day (58% vs. 4%, p<0.001, RR 2.70, CI 1.92–3.80), azathioprine (22% vs. 4%, p=0.01, RR 1.71, CI 1.27–2.32) and cyclophosphamide (31% vs. 0%, p<0.001, RR 2.18, CI 1.73–2.76) in the univariate analysis, although only treatment with corticosteroids (p=0.001) was an independent variable in the multivariate analysis.
LN patients had a higher prevalence of hypertension (44% vs. 9%, p<0.001, RR 2.00, CI 1.47–2.70), hyperlipidaemia (44% vs. 2%, p<0.001, RR 2.32, CI 1.75–3.08) and antiphospholipid antibodies (45% vs. 22%, p=0.01, RR 1.55, CI 1.11–2.17) in the univariate analysis, although only hyperlipidaemia (p=0.04) was an independent variable in the multivariate analysis.
Finally, patients with LN had more infections (47% vs. 18%, p=0.001, RR 1.74, CI 1.25–2.42) and higher mortality (16% vs. 2%, p=0.02, RR 1.76, CI 1.32–2.35) during follow-up than those without LN.
Renal outcome
At the last visit, 37 LN patients (67%) had normal plasma creatinine, 13 (24%) had renal failure and five (9%) had entered end-stage renal failure (of these patients, four received a renal transplant, but one had acute rejection of the graft and currently requires dialysis).
We analysed the presence of several features at the onset of follow-up to see if they might predict progression to renal failure (Table 2). Patients with normal renal function showed a higher prevalence of altered urine sediment as a first manifestation of their LN (51% vs. 17%, p=0.01, RR 1.58, CI 1.11–2.25) and WHO class II at renal biopsy (35% vs. 6%, p=0.02, RR 1.59, CI 1.18–2.13), while those who developed renal failure showed a higher prevalence of WHO class IV at renal biopsy (50% vs. 19%, p=0.02, RR 2.44, 1.19–5.00). Only altered urine sediment (p=0.03) was an independent variable in the multivariate analysis. Patients treated with azathioprine were more likely to develop renal failure (50% vs. 8%, p<0.001, RR 3.58, CI 1.84–6.98).
|
We analysed the presence of some cardiovascular risk factors at the onset of follow-up to see if they might predict progression to renal failure, and found that hyperlipidaemia (78% vs. 27%, p<0.001, RR 4.52, CI 1.71–11.99) and hypertension (67% vs. 32%, p<0.01, RR 2.58, CI 1.14–5.88) were associated with development of renal failure in the univariate analysis, although only hyperlipidaemia (p=0.04) was an independent variable in the multivariate analysis.
Finally, patients who developed renal failure presented more infections (72% vs. 35%, p=0.009, RR 2.90, CI 1.20–7.03) and mortality (33% vs. 8%, p=0.02, RR 2.56, CI 1.31–5.00) during the follow-up in the univariate analysis, although only infection (p=0.02) remained as an independent variable on multivariate analysis.
Mortality
Nine (16%) of the 55 LN patients died during the follow-up, compared with only one (2%) patient without LN (p=0.02, RR 1.76, CI 1.32–2.35). Actuarial analysis of survival in both groups is shown in Figure 1. The causes of mortality in the nine patients with LN were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies), sepsis in three patients and lung cancer in the remaining patient. The patient from the control group died of a cardiovascular event. In LN patients, mortality correlated with renal function measured at the last visit: three (8%) of the 37 patients with normal renal function died, compared with six (33%) of the 18 who developed chronic renal failure (p=0.03, RR 4.11, CI 1.16–14.59). We analysed several features at the onset of the study to see if they might predict mortality in these patients (Table 3). We found that patients treated with azathioprine showed a higher mortality (56% vs. 15%, p=0.02, RR 4.48, CI 1.42–14.13).
|
|
We also analysed the presence of our cardiovascular risk factors at the onset of follow-up to see if they might predict mortality; hyperlipidaemia (78% vs. 37%, p=0.03, RR 4.52, CI 1.03–19.83) and antiphospholipid syndrome (56% vs. 17%, p=0.03, RR 4.04, CI 1.27–12.86) were associated with mortality. Finally, patients who died had progressed to renal failure more frequently than survival patients (67% vs. 26%, p=0.03, RR 4.11, CI 1.16–14.59).
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
The course of LN is difficult to predict for a number of reasons, including the extreme heterogeneity of clinical characteristics, different criteria for selection, the incidence of histological changes, and the different therapeutic schedules used. No single factor seems to be more important in estimating prognosis, and this indicates the use of a range of demographic, clinical, laboratory and histopathological parameters in estimating the course and prognosis of the disease and in deciding upon therapy.22
We analysed the outcome of 70 patients with LN followed prospectively for a period of ten years in a single centre. Eighteen (33%) of our 55 surviving patients progressed to renal failure, and only five (9%) of these progressed to end-stage renal failure. Similar results were obtained by Moroni et al.23 and, more recently, by Bono et al.24 These data show that in patients who retain kidney function after more than 10 years of LN, renal status may remain satisfactory. In fact, most of our patients (67%) had normal renal function at the last visit. Whether this reduced clinical activity reflects a spontaneous remission of the disease over time, or was induced by the therapy, is difficult to assess.
We also evaluated the prognostic role of some clinical, immunological and histological characteristics of the LN patients. Demographic factors such as age, sex or race have emerged as important prognostic indicators in some25–27 but not all28–34 previous studies. We did not find that these factors were predictors of renal function outcome in our study. On the other hand, almost a third of our patients with proliferative or membranous nephritis (class III, IV and V) finally developed renal failure, compared with only two (by posterior transformation into class IV) patients with class I or II. The present study confirms and extends previous observations regarding the prognostic importance of renal histological evaluation in patients with LN.35 Some studies have suggested a protective effect of RF and anti-La/SS-B antibodies in the development of LN.1,2,36–38 We confirmed that LN patients showed a lower prevalence of RF, but failed to demonstrate a protective effect of anti-La/SS-B.
We have shown that potentially modifiable risk factors (hypertension and hyperlipidaemia) and SLE-specific factors (antiphospholipid antibodies, corticosteroid therapy) are associated with renal outcome and mortality in patients with a long-term outcome of LN. Firstly, patients with LN showed a higher prevalence of hypertension, hyperlipidaemia, antiphospholipid antibodies and corticosteroid therapy (>0.5 mg/kg/day) at the onset of follow-up, compared with an age- and sex-matched group of SLE patients who did not develop LN. Secondly, LN patients who developed renal failure had a higher presence of hypertension and hyperlipidaemia at the onset of follow-up. Lastly, LN patients who died had a higher prevalence of hyperlipidaemia and antiphospholipid syndrome at the onset of follow-up. However, hypertension and hyperlipidaemia may be the consequence of those types of LN that are most likely to progress to chronic renal failure, particularly type IV with nephrotic syndrome.
The true prevalence of vascular disease in women with SLE is unknown, but could certainly be higher than that defined by cardiovascular events alone.39 With improved corticosteroid and immunosuppressive SLE therapy, there is a growing pool of women at increased risk of developing cardiovascular disease, which is now one of the leading causes of death. Hypertension and hyperlipidaemia have been identified as risk factors associated with atherosclerosis and coronary artery events in previous SLE studies.11,40 While corticosteroids have been identified as a risk factor for cardiovascular disease by some investigators,40–42 several other studies11,43 have failed to detect an association. On the other hand, cardiovascular complications seem to be more likely in patients with a long duration of SLE. In a large series, Gladman and Urowitz11 reported a 9% incidence of angina pectoris and/or myocardial infarction that occurred on average 89 months after the onset of SLE. Jonsson et al.16 reported that patients with SLE who developed myocardial infarction had significantly longer duration of the disease (19.5 years) than those who had no such complication (6.5 years). Recently, Bono et al.24 found that 25% of LN patients with long-term disease died of cardiovascular events. We have confirmed that cardiovascular disease is one of the main causes of morbidity and mortality in young adults with long-term LN. Nevertheless, it is difficult to attribute the cause of death to a single factor or group of factors, as demonstrated by the lack of significance in the multivariate analysis.
In view of the high incidence of late cardiovascular complications, appropriate dietetic measures, the prohibition of smoking, and intensive antihypertensive and antihyperlipidaemic treatment should be strongly recommended in patients with SLE.23 We recommend that SLE patients should be started on antihypertensive agents earlier in order to keep arterial pressure levels at a recommended level of 
125/75 mm Hg. The marked increased mortality in LN from accelerated atherosclerosis mandates a higher state of vigilance in our SLE patients, and they must be monitored closely for symptoms and signs of cardiovascular disease. Primary prevention, by checking and treating hyperlipidaemia, hyperglycaemia and hypertension, counselling patients to stop smoking and exercise, and helping them lose weight, is of paramount importance. Additionally, we should use the lowest dose of corticosteroids, adding other drugs such as antimalarial agents. The maintenance of corticosteroid therapy at low doses in the quiescent phases might also help in reducing the risk of atherosclerotic lesions in the long term. Finally, our study shows that a new comorbid factor, the antiphospholipid syndrome, has been identified as an important prognostic marker of mortality in this subset of SLE patients with long-term evolution of LN. Frampton et al.44 have reported that 44% of LN patients had antiphospholipid antibodies. The presence of an associated antiphospholipid syndrome in SLE patients may contribute to the development of nephropathy, and represent a new factor related to mortality in LN patients.
In conclusion, our study shows that although patients with long-term LN can maintain stable renal status, and there may be good kidney survival rates after more than 10 years of nephropathy, hypertension, hyperlipidaemia and antiphospholipid syndrome constitute risk factors associated with a higher mortality and the development of renal failure in this subset of SLE patients. Therefore, a more aggressive control of the cardiovascular risk factors (especially, hypertension and hyperlipidaemia) may be beneficial in the late prognosis of patients with long-term LN.
|
Acknowledgments |
|---|
This study was supported by Grants FIS 97/0669 and FIS 99/0280 from the Fondo de Investigaciones Sanitarias. M. Ramos-Casals is a Research Fellow supported by Grants from Hospital Clinic (‘Premis Fi de Residència 1999’) and from Generalitat of Catalonia (2000FI 00332).
|
Notes |
|---|
Address correspondence to Dr J. Font, Unitat de Malalties Autoimmunes Sistèmiques, Hospital Clínic, C/Villarroel 170, 08036-Barcelona, Spain. e-mail: font{at}medicina.ub.es
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1000 patients. Medicine (Baltimore)1993; 72:113–24.[Medline]
2. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1000 patients. Medicine (Baltimore)1999; 78:167–75.[Medline]
3. Rosner S, Ginzler EM, Diamond HS, Weiner M, Schlesinger M, Fries JF, et al. A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death. Arthritis Rheum1982; 25:612–17.[Web of Science][Medline]
4. Cameron JS. Lupus nephritis in childhood and adolescence. Pediatr Nephrol1994; 8:230–49.[Web of Science][Medline]
5. Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum1991; 34:945–50.[Web of Science][Medline]
6. Gruppo Italiano Per Lo Studio Della Nefrite Lupica (GISNEL). Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 10 years after the diagnosis. Am J Kidney Dis1992; 19:473–9.[Web of Science][Medline]
7. Magil AB, Puterman ML, Ballon HS, Chan V, Lirenman DS, Rae A, et al. Prognostic factors in diffuse proliferative lupus glomerulonephritis. Kidney Int1988; 34:511–17.[Web of Science][Medline]
8.
Derksen RHWM, Hené RJ, Kater L. The long-term clinical outcome of 56 patients with biopsy-proven lupus nephritis followed at a single center. Lupus1992; 1:97–103.
9. Austin HA, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med1986; 314:614–19.[Abstract]
10. McLaughlin JR, Bombardier C, Farewell VT, Gladman DD, Urowitz MB. Kidney biopsy in systemic lupus erythematosus. III Survival analysis controlling for clinical and laboratory variables. Arthritis Rheum1994; 37:559–67.[Web of Science][Medline]
11. Gladmann DD, Urowitz MB. Morbidity in systemic lupus erythemaosus. J Rheumatol1987; 14(Suppl):223–6.
12. Ginzler EM, Schorn K. Outcome and prognosis in systemic lupus erythematosus. Rheum Dis Clin North Am1988; 14:67–78.[Web of Science][Medline]
13. Galve E, Candell-Riera J, Pigrau C, Permanyer-Miralda G, García del Castillo H, Soler-Soler J. Prevalence, morphologic type and evolution of cardiac valvular disease in systemic lupus erythematosus. N Engl J Med1988; 319:817–23.[Abstract]
14. Bernardine HB, Roberts WC. The heart in systemic lupus erythematosus and the change induced in it by corticosteroid therapy. Am J Med1975; 58:243–284.[Web of Science][Medline]
15. Ginzler E, Berg A. Mortality in systemic lupus erythematosus. J Rheumatol1987; 14:218–22.
16. Jonsson H, Nived O, Sturfelt G. Outcome in systemic lupus erythematosus: a prospective study of patients from a defined population. Medicine (Baltimore)1989; 68:141–50.[Medline]
17. Tan EM, Cohen AS, Fries J, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for classification of SLE. Arthritis Rheum1982; 25:1271–2.[Web of Science][Medline]
18. Churg J, Sobin LH. Renal Disease: Classification and Atlas of Glomerular Disease. New York, Igaku-Shoin, 1982; 127–49.
19.
Gharavi AE, Harris E, Asherson RA, Hughes GRV. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis1987; 46:1–6
20.
Cervera R, Font J, López-Soto A, Casals F, Pallarés L, Bové A, et al. Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective study of a series of 100 patients. Ann Rheum Dis1990; 49:109–13.
21. Brandt JT, Triplett AA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemostas1995; 74:1185–90.[Web of Science][Medline]
22. Golbus J, McCune WJ. Lupus nephritis: Classification, prognosis, immunopathogenesis and treatment. Rheum Dis Clin North Am1994; 20:213–41.[Web of Science][Medline]
23.
Moroni G, Banfi G, Ponticelli C. Clinical status of patients after 10 years of lupus nephritis. Q J Med1992; 84:681–9.
24.
Bono L, Cameron JS, Hicks JA. The very long-term prognosis and complications of lupus nephritis and its treatment. Q J Med1999; 92:211–18.
25.
Wallace DJ, Podell T, Weiner J, Klinenberg JR, Forouzesh S, Dubois EL. Systemic lupus erythematosus-survival patterns. Experience with 609 patients. JAMA1981; 245:934–8.
26. Nossent HC, Henzen-Logmans SC, Vroom TM, Berden JHM, Swaak TJG. Contribution of renal biopsy data in predicting outcome in lupus nephritis. Analysis of 116 patients. Arthritis Rheum1990; 33:970–7.[Web of Science][Medline]
27. Austin HA, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, et al. Prognostic factors in lupus nephritis. Contribution of renal histologic data. Am J Med1983; 75:382–91.[Web of Science][Medline]
28. McLaughlin J, Gladman DD, Urowitz MB, Bombardier C, Farewell VT, Cole E. Kidney biopsy in systemic lupus erythematosus. II. Survival analyses according to biopsy results. Arthritis Rheum1991; 34:1268–73.[Web of Science][Medline]
29. Ballou SP, Khan MA, Kushner I. Clinical features of systemic lupus erythematosus. Differences related to race and age of onset. Arthritis Rheum1982; 25:55–60.[Web of Science][Medline]
30. Edworthy SM, Bloch DA, McShane DJ, Segal MR, Fries JF. A ‘state model’ of renal function in systemic lupus erythematosus: its value in the prediction of outcome in 292 patients. J Rheumatol1989; 16:29–33[Web of Science][Medline]
31.
Esdaile JM, Levinton C, Federgreen W, Hayslett JP, Kashgarian M. The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature. Q J Med1989; 72:779–86.
32. Esdaile JM, Abrahamowicz M, MacKenzie T, Hayslett JP, Kashgarian M. The time-dependence of long-term prediction in lupus nephritis. Arthritis Rheum1994; 37:359.[Web of Science][Medline]
33. Levey AS, Lan SP, Corwin BL, Kasinath BS, Lachin J, Neilson EG, et al. Progression and remission of renal disease in the lupus nephritis collaborative study: results of treatment with prednisone and short-term oral cyclophosphamide. Ann Intern Med1992; 116:114–24.
34. Austin HA III, Boumpas DT, Vaughan EM, Balow JE. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int1994; 45:544–50.[Web of Science][Medline]
35. Sloan RP, Schwartz MM, Korbet SM, Borok RZ. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. J Am Soc Nephrol1996; 7:299–305.[Abstract]
36. Howard TW, Iannini MJ, Burge JJ, Davis JS. Rheumatoid factor, cryoglobulinemia, anti-DNA, and renal disease in patients with systemic lupus erythematosus. J Rheumatol1991; 18:826–30.[Web of Science][Medline]
37. Hill GS, Hinglais N, Tron F, Bach JF. Systemic lupus erythematosus. Morphologic correlations with immunologic and clinical data at the time of biopsy. Am J Med1978; 64:61–79.[Web of Science][Medline]
38. Wasicek CA, Reichlin M. Clinical and serological differences between systemic lupus erythematosus patients with antibodies in Ro versus patients without antibodies to Ro and La. J Clin Invest1982; 69:835–43.
39. Manzi S, Selzer F, Sutton-Tyrrell K, Fitzgerald SG, Rairie JE, Tracy RP, et al. Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum1999; 42:51–60.[Web of Science][Medline]
40. Petri M, Perez-Gutthann S, Spence D, Hochberg MC. Risk factors for coronary artery disease in systemic lupus erythematosus. Am J Med1992; 93:513–19.[Web of Science][Medline]
41. Badui E, García-Rubi D, Robles E, Jiménez J, Juan L, Deleze M, et al. Cardiovascular manifestations in systemic lupus erythematosus: prospective study of 100 patients. Angiology1985; 36:431–41.
42. Bulkley BH, Roberts WC. The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy: a study of 36 necropsy patients. Am J Med1975; 58:243–64.
43. Hosenpud JD, Montanaro A, Hart MV, Haines JE, Specht HD, Bennett RM, et al. Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus. Am J Med1984; 77:286–92.[Web of Science][Medline]
44. Frampton G, Hicks J, Cameron J. Significance of anti-phospholipid antibodies in patients with lupus nephritis. Kidney Int1991; 39:1225–31.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. B. Appel, G. Contreras, M. A. Dooley, E. M. Ginzler, D. Isenberg, D. Jayne, L.-S. Li, E. Mysler, J. Sanchez-Guerrero, N. Solomons, et al. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis J. Am. Soc. Nephrol., May 1, 2009; 20(5): 1103 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Austin III, G. G. Illei, M. J. Braun, and J. E. Balow Randomized, Controlled Trial of Prednisone, Cyclophosphamide, and Cyclosporine in Lupus Membranous Nephropathy J. Am. Soc. Nephrol., April 1, 2009; 20(4): 901 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Gordon, D Jayne, C Pusey, D Adu, Z Amoura, M Aringer, J Ballerin, R Cervera, J Calvo-Alen, C Chizzolini, et al. European consensus statement on the terminology used in the management of lupus glomerulonephritis Lupus, March 1, 2009; 18(3): 257 - 263. [Abstract] [PDF]
|
|
|
|
 |
|
 D-C Varela, G Quintana, E C Somers, A Rojas-Villarraga, G Espinosa, M-E Hincapie, W J McCune, R Cervera, and J-M Anaya Delayed lupus nephritis Ann Rheum Dis, July 1, 2008; 67(7): 1044 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Siso, M Ramos-Casals, A Bove, P Brito-Zeron, N Soria, S Munoz, A Testi, J Plaza, J Sentis, and A Coca Previous antimalarial therapy in patients diagnosed with lupus nephritis: Influence on outcomes and survival Lupus, April 1, 2008; 17(4): 281 - 288. [Abstract] [PDF]
|
|
|
|
 |
|
 S. R. Orth and S. I. Hallan Smoking: A Risk Factor for Progression of Chronic Kidney Disease and for Cardiovascular Morbidity and Mortality in Renal Patients Absence of Evidence or Evidence of Absence? Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 226 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ejerblad, C. M. Fored, P. Lindblad, J. Fryzek, P. W. Dickman, C.-G. Elinder, J. K. McLaughlin, and O. Nyren Association between Smoking and Chronic Renal Failure in a Nationwide Population-Based Case-Control Study J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2178 - 2185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Orth Smoking and the Kidney J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1663 - 1672. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||