Wednesday, November 2, 2011

Lupus Nephritis...

Lupus Nephritis is essentially when lupus goes into your kidneys and starts to attack them.  Very strong toxic drugs are needed to lower your immune system to try to stop it from attacking your kidneys, dialysis, and kidney transplants maybe needed depending on what stage your kidney disease is in.  I know quite a few people with lupus nephritis and it is very sad knowing the hell that they go through.  I know a lot of young people on dialysis and wonder how they get through all their chemo therapies, kidney transplants etc.  I learned a really sad fact while corresponding with a fellow lupie that was in end stage kidney failure, she said she had to be considered in remission before she was able to be put on a donor kidney list.  I was shocked, because achieving remission in lupus is very hard.  I know a lot of web sites even reputable ones that say lupus is a disease of flares and remissions.  New studies prove that although we are a disease of flares, remissions are hard to come by.  We are a disease of flares, and more quiet times. I tried to find the study that a rheumy did on his patients but I cannot find it anymore, bummer, because I like to have hard evidence to back up my statements.  If I find it later I will post it, I think it was in the lupus news last year.  That doctor found that only 6% of his patients ever went into a true remission, a true remission is when you have no symptoms and you are on no lupus medications.  Usually the symptoms of lupus come back when you taper off your lupus medications.  Sending out all my love to those who suffer with lupus.

Alternative Names

Nephritis - lupus; Lupus glomerular disease


Systemic lupus erythematosus (SLE, or lupus) is an autoimmune disease. This means there is a problem with the body's immune system.
Normally, the immune system helps protect the body from infection or harmful substances. But in patients with an autoimmune disease, the immune system cannot tell the difference between harmful substances and healthy ones. As a result, the immune system attacks otherwise healthy cells and tissue.
SLE may damage different parts of the kidney, leading to interstitial nephritis, nephrotic syndrome, and membranous GN. It may rapidly worsen to kidney failure.
Lupus nephritis affects approximately 3 out of every 10,000 people. In children with SLE, about half will have some form or degree of kidney involvement.
More than half of patients have not had other symptoms of SLE when they are diagnosed with lupus nephritis.
SLE is most common in women ages 20 - 40. For more information, see: systemic lupus erythematosus.


Symptoms of lupus nephritis include:
For general lupus symptoms, see the article on SLE.

Exams and Tests

A physical exam shows signs of decreased kidney functioning with body swelling (edema). Blood pressure may be high. Abnormal sounds may be heard when the doctor listens to your heart and lungs.
Tests that may be done include:
This list may not be all-inclusive.
A kidney biopsy is not used to diagnose lupus nephritis, but to determine what treatment is appropriate.


The goal of treatment is to improve kidney function and to delay kidney failure.
Medicines may include corticosteroids or other medications that suppress the immune system, such as cyclophosphamide, mycophenolate mofetil, or azathioprine.
You may need dialysis to control symptoms of kidney failure, sometimes for only a while. A kidney transplant may be recommended. People with active lupus should not have a transplant because the condition can occur in the transplanted kidney.

Outlook (Prognosis)

How well you do depends on the specific form of lupus nephritis. You may have flare-ups, and then times when you do not have any symptoms.
Some people with this condition develop chronic kidney failure.
Although lupus nephritis may return in a transplanted kidney, it rarely leads to end-stage kidney disease.

When to Contact a Medical Professional

Call your health care provider if you have blood in the urine or swelling of your body.
If you have lupus nephritis, call your health care provider if you notice decreased urine output.


There is no known prevention for lupus nephritis.


Appel GB. Glomerular disorders and nephrotic syndromes. In: Goldman L, Ausiello D, eds. Cecil Medicine . 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 122.
Appel GB, Radhakrishnan J, D’Agti V. Secondary glomerular disease. In: Brenner BM, ed. Brenner and Rector's the Kidney . 8th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 31.
More Information on This Topic

Systemic lupus erythematosus (more commonly known as "lupus") is an autoimmune disease in which your immune system produces proteins, known as autoantibodies, which attack your own body. Lupus nephritis occurs when lupus autoantibodies affect the filtering structures (glomeruli) of your kidneys. This abnormal process results in kidney inflammation and may lead to blood in the urine, (hematuria), protein in the urine (proteinuria), impaired kidney function or even kidney failure.


Your doctor may suspect lupus nephritis if your urine is bloody or has a foamy appearance, if you have high blood pressure, or if you show signs of swelling in your hands or feet. Diagnostic tests for lupus nephritis at Mayo Clinic include:
  • Renal function testing. Mayo nephrologists use a variety of tests, including blood tests and 24-hour urine collection, to accurately measure your kidney function. Iothalamate clearance testing, which uses a special contrast agent to track how well your kidneys are filtering, may be done if traditional tests don't provide clear measurement of your kidney function. Mayo Clinic is one of the few centers to specialize in iothalamate clearance testing using a dedicated renal pathology laboratory.
  • Kidney biopsy. Biopsy is the gold-standard test to confirm the diagnosis of many kidney diseases, including lupus nephritis. It can also help determine the severity of the disease. Because of the large number of people treated for kidney diseases, Mayo Clinic specialists are very experienced with the kidney biopsy procedure. Having a biopsy performed at Mayo Clinic ensures that it will be done by those with a great deal of experience and an outstanding track record for safety.


Although there is no cure for lupus nephritis, the ultimate treatment goal is to stop progression of the disease, induce remission and help patients avoid the need for dialysis or kidney transplantation. Treatment plans help people manage symptoms such as high blood pressure, protein in the urine (proteinuria), and swelling (edema) in the hands and feet.
Traditional treatments used to slow the progress of the disease include:
  • Dietary protein and salt restriction — A specialized diet can improve kidney function.
  • Blood pressure medications — Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) can control blood pressure and keep protein from leaking from the kidneys into the urine.
Specialized treatments used when traditional therapies don't work include:
  • Steroids, cyclophosphamide and immunosuppressants — Some people do not respond well to traditional drug therapies, but may respond to individualized immunosuppressive therapies that could include drugs like prednisone, cyclophosphamide, azathioprine (Imuran) and mycofenolate (Cellcept). Mayo Clinic has expertise in creating treatment plans that maximize medication benefits and minimize side effects.
  • Novel therapies — Mayo Clinic tests new drugs and therapeutic strategies in clinical trials offered through the Mayo Nephrology Collaborative Group.
For people who progress to kidney failure, treatment options include:
  • Dialysis — Mayo Clinic offers state-of-the-art dialysis treatment, including the option for in-home dialysis.
  • Kidney transplantation — All three Mayo locations offer kidney transplant. Mayo has performed thousands of kidney transplants with better than average results. 
  • What Is the Current Recommended Treatment for Lupus Nephritis?

    Medical Author: William C. Shiel Jr., MD, FACP, FACR
    Medical Editor: Leslie J. Schoenfield, MD, PhD

    Lupus nephritis is kidney disease that is caused by lupus. To start, it must be understood that there are many forms of kidney disease that are referred to as lupus nephritis. Each form is distinguished by characteristic patterns of abnormalities as defined by a kidney biopsy. (A biopsy is the removal of a sample of tissue for microscopic examination.) Typically, the findings on a kidney biopsy of a lupus patient are classified according to the appearance of the tissue and immune abnormalities seen under the microscope.
    In addition to the numerous unique forms of lupus kidney disease, other types of kidney diseases that are not from lupus can sometimes occur in a patient with lupus. While treatment for lupus nephritis can sometimes be initiated without a kidney biopsy, more often, a biopsy is done before starting treatment. Thus, when the blood tests and the overall state of the lupus disease so require, the biopsy can define the cause of the kidney disease when it is in question. The biopsy can also guide treatment when it demonstrates the presence of such severe kidney damage that a favorable response to potentially toxic medications is unlikely.
    Any particular form of lupus nephritis has a variety of treatments available that are effective. Moreover, the treatment for individual patients with lupus nephritis depends not only on their own particular form of kidney disease, but also on the manner in which lupus is affecting other areas of their body, their overall health, and their personal wishes. Also, medical control of conditions that could further injure the kidneys, such as elevated blood pressure and medication-induced kidney toxicity, is essential.
    In general, lupus nephritis is a result of inflammation in the kidneys that is associated with an overactive immune (defense) system. As a consequence, antibodies against the patient's own tissues (auto-antibodies) form antibody-tissue (antibody-antigen) unions (complexes) that in turn deposit in the kidney and initiate a destructive inflammatory reaction. In fact, very often, the severity of the kidney disease parallels the severity of the immune abnormalities that can be measured in the blood of patients with lupus (such as DNA antibody, complement levels, etc.). Accordingly, treatment usually involves medications that reduce inflammation and suppress the immune system. When lupus nephritis leads to kidney failure, however, kidney dialysis or transplantation is necessary to sustain life.
    Corticosteroids, such as prednisone and prednisolone, are accepted as the initial treatment for lupus nephritis. The steroids may be given by mouth or intravenously. Also, high dose corticosteroids (methylprednisolone) that are given in single, large doses (pulses) intravenously for three consecutive days are also a useful initial treatment for lupus nephritis, which is then followed by corticosteroids by mouth. The immune suppression medications that are used to treat lupus nephritis include azathioprine (Imuran) and cyclophosphamide (Cytoxan), both of which can be given by mouth. Cyclophosphamide is also given as an intravenous, single large dose (pulse) in certain situations. These pulses are continued monthly for six months and every three months thereafter. Recently, the immunosuppressant drug mycophenolate mofetil (Cellcept) has been used successfully to treat lupus kidney disease and seems to represent another option.
  • Lupus Nephritis Treatment (cont.)

    Other treatments that are used for lupus nephritis, but are still unproven or controversial, include plasmapheresis, intravenous immunoglobulin infusions, and fish oils containing omega-3 fatty acids. Plasmapheresis is a procedure in which the blood is filtered through a special machine to separate the plasma, which is the liquid portion of the blood, from the cells of the blood. The plasma is removed and replaced, typically with another solution such as saline or albumin. Intravenous immunoglobulin is a sterile solution of concentrated antibodies extracted from healthy people that is given straight into a vein. The immunoglobulin is used to treat disorders of the immune system or to boost the immune response to serious illness. Omega-3 fatty acids have been shown to reduce inflammation in the kidneys of mice with a lupus-like illness.
    In treating lupus nephritis, special considerations must be given to each individual's particular situation and lifestyle. For example, because cyclophosphamide can damage the ovaries, a woman who desires a future pregnancy might not be a candidate for this treatment. Furthermore, a woman who develops lupus nephritis during pregnancy faces risks of injury to the unborn baby as well as possible permanent kidney impairment from untreated lupus nephritis. Likewise, pregnancies in women with lupus nephritis require intense fetal and maternal monitoring. It should also be noted that birth control pills containing synthetic estrogens are essentially contraindicated (forbidden or not recommended) in women with active lupus nephritis.
    Novel approaches to the treatment of lupus nephritis, such as using adenosine analogues, and combinations of existing medications, are being studied. Indeed, many of these approaches are on their way to being put to use in the near future. Some of these treatments, involving the blocking of various molecules that stimulate the cells of inflammation, are being studied at the National Institutes of Health in Bethesda, Maryland.
    Finally, attempts are being made to completely reconstitute the immune system in patients with lupus by using bone marrow transplantation and stem cell transplantation. All of these approaches are in the very preliminary stages of development and are not yet accepted as useful. What is clear is that the treatment of lupus nephritis in decades to come will not be the same as it is today.
  • The very long-term prognosis and complications of lupus nephritis and its treatment


    Although the short- and medium-term (5–10 years) outcome of patients with lupus nephritis has been studied extensively, there are very few data on the second and subsequent decades. We studied outcome in 110 local patients investigated at a single centre before 1986, who all had potential follow-up of more than 10 years (actual 2–31 years, median 15.5 years). At last follow-up, 40 patients were dead and 70 alive, nine of whom were on maintenance dialysis or transplanted, actuarial survivals being 84%, 72%, 62%, 61% and 54% at 5, 10, 15, 20 and 25 years for the group as a whole. Survival was better in the cohort 1976–86 (n=60) than in that from 1963–75 (n=50) (90, 81 and 76% vs. 78, 56 and 43% at 5, 10 and 15 years, p<0.001). Sepsis (12) and myocardial infarction (8) were the principal causes of death. Of living patients with renal function, 38% had normal urine and renal function, 11 were off all treatment (19%), 62% had persistent proteinuria and 18% had reduced but generally stable renal function. Renal failure, in those patients who developed it, occurred during the first decade and none of 67 patients actually followed more than 10 years subsequently went into renal failure. Induction treatment was with prednisolone, combined with azathioprine in more severe forms of nephritis, and from the middle 1970s to 1986, 30 with methylprednisolone and in 12 cases plasma exchange. Seventeen other patients were treated using oral cyclophosphamide during the 1960s. No patient received i.v. cyclophosphamide as induction therapy, although nine patients had this form of treatment later, largely because of non-compliance. Serious complications of lupus and/or its treatment occurred in 49%: sepsis in 32, ischaemic heart disease in 20, thrombosis in one and avascular necrosis of bone in eight. In contrast, fracturing osteoporosis occurred in only three, and cataracts requiring surgery and diabetes mellitus in none. The very long-term outlook of lupus nephritis, especially its more severe forms, has improved, but that with current management strategies only a minority of patients are able to stop treatment altogether, and the incidence of serious complications is high.


    Lupus is a disease with a peak incidence in adolescence and young adulthood, affecting principally young women.1,,2 Until the past 30 years, the prognosis for those with lupus nephritis as part of their disease was very poor, but as prognosis has improved under empirical treatment and more patients survive long term, the later phases of the disease over decades rather than years have become increasingly important.2 This is especially so because the immunosuppressive treatment which has so dramatically altered the outlook carries with it major toxicity.
    Nevertheless, data are lacking on outcome of young women with lupus nephritis who survive their first decade. Only the papers of Moroni and colleagues,3 and Donadio et al.4 give information on outcome from 10–20 years from onset. Thus we set out to analyse retrospectively the outcome of our patients studied at Guy's Hospital from 1963 to 1986, who had a potential follow-up of 10 to >30 years.


    Records were available on 243 patients with lupus nephritis who had been studied and followed at Guy's Hospital renal unit between 1963 and 1996. All patients had had a renal biopsy and all had at least four manifestations of lupus as described by the American College of Rheumatology.5 Of these 243, 166 had their initial investigation in 1986 or earlier, and thus had 10 years' or more of potential follow-up. Forty-three of these 166 patients were excluded because they came from outside the UK, and the reasons for referral and selection processes might differ from local patients; in addition, follow-up was less complete in this group. Similarly, six patients whose initial investigation as carried out elsewhere within the UK and had tertiary or quaternary referral for various reasons to our unit, were excluded. This left 116 patients, in 110 of whom adequate records were available to allow description of their outcome and the complications they had suffered. All 64 local patients of the 79 included in the paper published in this journal in 19799 were included in the present study.


    Presentation and initial treatment

    Details of the 110 patients at the time of presentation and investigation are shown in Tables 1–3. Eighty-two were local Caucasians, 17 black African/Afro-Caribbean, seven Indo-Asian and four Oriental. Ninety-seven patients (88%) were female and 13 (12%) male. Median age at presentation was 30.2 years (range 7–67 years). Presentation (Table 1) was predominantly with proteinuria, the nephrotic syndrome being the commonest single renal presentation. Two-thirds of patients had had other manifestations of lupus diagnosed before their renal disease became evident.
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    Table 1 
    Clinical presentation of the renal disease
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    Table 2 
    Renal histology on initial biopsy
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    Table 3 
    Initial immunosuppression received as induction therapy
    Approximately half of the patients showed diminished renal function as judged by estimation of glomerular filtration rate using a single injection of 51Cr edetate. About one quarter were hypertensive, or had a requirement for hypertensive treatment.

    Renal histological findings at presentation

    All patients had a renal biopsy (Table 2): two-thirds of these showed aggressive patterns of lupus nephritis (WHO classes III and IV) whilst one-fifth (21 patients) showed a membranous pattern of glomerulopathy, although the majority of these had some mesangial deposits. Patients with `mixed' patterns of membranous and focal or diffuse proliferation were classified as class III or IV, respectively.6

    Induction treatment

    The specific immunosuppression received by the patients as induction therapy is shown in Table 3. The majority of patients with more severe histological appearances received prednisolone plus azathioprine, although 17 patients in the 1960s and early 1970s had courses of oral cyclophosphamide lasting from 3 months to 2 years in duration.7 No patient received intravenous bolus injections of cyclophosphamide for induction, although nine patients received this form of treatment later in their course as part of maintenance therapy, all within the past 5–10 years. In contrast, patients with milder forms of histological lupus nephritis were in general treated with prednisolone alone, or in a few cases no specific treatment to begin with.

    Follow-up: treatment, outcome and complications

    One hundred and six of the 110 patients were followed until 1996, or until death, for 2–31 years (median 15.5 years). Only four patients were lost to follow-up, 2–18 years from initial investigation. Maintenance treatment consisted of oral prednisolone together with azathioprine in 70 patients and oral cyclophosphamide in nine patients, all treated between 1965 and 1970. Nine patients subsequently received 6–18 months' treatment with intravenous cyclophosphamide, using the protocol of the National Institutes of Health,8 because of relapses failing to respond to azathioprine and prednisolone or intravenous methylprednisolone with suspicion of non-compliance. In general, treatment was continued for a minimum of 5 years from onset before withdrawal of treatment was considered, and in six patients, had to be re-started because of relapse following deliberate or patient-motivated cessation of immunosuppression, in two patients as late as 22 and 25 years following presentation of renal disease. A further patient taking 10 mg of prednisolone had a severe biopsy-proven renal relapse 28 years after presentation followed by irreversible loss of renal function. Because of this prolonged maintenance treatment, relapses were infrequent and no analysis was done of outcome in relation to number of relapses.


    Actuarial analyses of survival of patients form the onset of renal disease are shown in Figure 1. Data are shown also separated for the first decade and the second decade of this study. There is a marked improvement in survival in the 1976–86 cohort compared with the 1963–75 cohort (p<0.01, Kaplan-Meier). For comparison the survival of a more recent cohort, not included in this study, is shown who were investigated and treated between 1987 to 1996: survival was 83% at 10 years, similar to the 1976–86 cohort. Thus during the past decade there has been no further improvement in survival.
    Figure 1.
    Actuarial survival estimates for the whole group (n=110) 1963–86; and two sub-cohorts, 1963–75 (n=50) and 1976–86 (n=60). Survival is better in the more recent cohort than in those seen before 1976 (p<0.001, Kaplan-Meier estimate). Data from a more recent cohort (1987–96, n=70) are included for comparison (open circles) and do not differ from those seen during 1976–86.
    It was not the purpose of this study to analyse the predictive value of features at onset, in view of our approach of varying therapy according to clinical and histological severity of disease (Table 3). However, in a univariant analysis no clinical parameters emerged as significant in this respect. Figure 2 shows actuarial analyses of patient survival according to a glomerular appearances on renal biopsy, and b normal or reduced GFR at onset. In neither case does the difference exceed a likelihood of 0.05 (Kaplan-Meier).
    Figure 2.
    a Actuarial survival estimates of patients with lupus nephritis according to histological class in the WHO classification from renal biopsies obtained at onset. There is no significant difference between any of the curves (Kaplan-Meier). b Actuarial survival estimates of patients with lupus nephritis and a glomerular filtration rate estimated by a single injection of 51Cr-ethylene diamine tetracetate of greater or less than 80 ml/min/1.73 m2. There is no statistical difference between any of the curves at a 0.05 level (Kaplan-Meier).
    Figure 3 shows the timing of onset of renal failure in the study group. Despite the fact that in 67 patients actual follow-up exceeded 10 years, no further cases of renal failure were observed from 10–25 years (although since this study was completed in 1996 the patient with the very late relapse mentioned above required dialysis after 29 years follow-up).
    Figure 3.
    Actuarially-calculated appearance of end-stage renal disease in the whole cohort of 110 patients. At 10 years, 67 patients were still in follow-up, having neither died nor entered renal failure. Nevertheless, no further patient entered renal failure during the subsequent 15 years of the study up to 1996, by which time 16 patients were still being followed (see text).

    Most recent status

    The most recent status of the 110 patients is shown in Table 4. Two-thirds of the patients were still alive with renal function, their median age being by this time 46 years. Altogether, 18 patients developed end-stage renal disease and received dialysis or transplantation, except one, in whom renal replacement treatment was withheld. The renal status of those with surviving renal function in relation to treatment is shown also in Table 4. Eleven patients were well and off all treatment. The majority were still receiving immunosuppression, the majority in the form of prednisolone, but some received prednisolone plus azathioprine in an attempt to permit reduction in the dose of corticosteroids.
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    Table 4 
    Most recent status of patients with lupus after very long-term follow-up
    Forty patients had died, and the causes of death (as far as they could be determined) are shown in Table 5. The main causes of death were sepsis and cardiovascular disease; only three patients had developed malignancy, all lymphomas. Of 12 patients who died from causes other than vascular disease and who had post mortems, eight showed more or less severe coronary atheroma. In a number of cases the causes of death were either obscure or multiple, and only the major cause of death is listed for each patient in Table 5.
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    Table 5 
    Causes of death in patients who died

    Complications of disease and treatment

    The complications recorded are shown in Table 6. No patient developed diabetes mellitus, although one patient had suffered type I diabetes before developing lupus. Systematic ophthalmoscopic examination was not carried out, although a number of patients were recorded as showing small posterior cataracts. However no lens removal was needed in any patient in this cohort, although we are looking after one other patient biopsied abroad, who required bilateral operations after 25 years' corticosteroid treatment. Likewise, although a number of women had DEXA bone density estimations after up to 20 years or more follow-up from onset under continuous corticotherapy, with results ranging from high normal to major thinning, only three patients had severe osteoporosis, in two leading to actual fractures. Cardiac echocardiography was not systematically practised during this period, but only one patient required valve replacement for Libman-Sachs endocarditis, in association with a persistently high titre of IgG anti-phospholipid antibody. Altogether 54 (49%) of patients suffered 68 major complications, and 12 patients died as result of these.
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    Table 6 
    Complications suffered


    The data presented here concern the largest series of patients with lupus nephritis and follow-up of more than a decade hitherto reported in detail. Nevertheless, the deficiencies in this type of study are well known. It is a retrospective open case-note study, gathered over a period during which management changed, not only of the lupus but also of hypertension, infections and other associated problems. Data were not gathered in a systematic and prospective fashion on likely complications. Inevitably, the outcomes reported are to some extent a historical record, and do not represent the likely outcome of patients presenting today, as our own more recent data show the apparent improvement in survival noted in almost all series. However they do indicate qualitatively, and to some extent quantitatively, the type of problems faced in the long term by lupus patients.
    Certain features are surprising and some reassuring, for example the lack of induction of steroid-related diabetes, in sharp contrast to findings over a similar period of time following transplantation. It may be that the genotype associated with predisposition to lupus in some way protects against induction of diabetes. With better use of use of immunosuppression, infections are likely to play a lesser role, at least in patients seen today, but the actual incidence of infections (for example herpes zoster) does not seem to have diminished during the period of study, despite improved survival.
    Some of the common complications noted in our cohort of patients (thrombosis, infection, induction of lymphoproliferative disorders, avascular necrosis of bone) are shared by the disease of lupus itself and its immunosuppressive treatment,1,,2 and are unlikely to disappear. It is a sobering thought moreover that half the patients suffered one or more major complications, and this must be set against the improvement in outcome discussed below. Most of the deaths resulted from complications in whole or in part induced by treatment, particularly sepsis, and not by the lupus per se, although it might be argued that if the treatment is being applied appropriately then death because of a complication of treatment is a secondary effect of the disease. We have analysed causes of death in lupus, including some of the present patients, in more detail in a previous paper.10
    The genesis of some of the complications found in lupus such as thrombosis or vascular is multifactorial.2 Antiphospholipid antibodies are only one mechanism that operates to promote thrombosis in patients with lupus, and low plasma factor S concentrations probably are of equal importance. In addition, the many nephrotic patients will suffer from the pro-coagulant effects of hypoproteinaemia. We have reported previously that 44% of our patients with lupus nephritis had anti-phospholipid antibodies,11 and more than half were nephrotic, so a high incidence of thrombosis is not surprising. The pathogenesis of the grossly increased incidence in coronary artery disease compared with normal young or middle-aged women (eight deaths from ischaemic heart disease and eight other women with atheroma at post mortem) is not clear, but apart from possible involvement of enhanced coagulation, interactions between hypercholesterolaemia and circulating immune complexes may contribute;11 a role for corticosteroids remains controversial.
    As in the published literature on short-term outcome of lupus nephritis,2 long-term outcome in our study improved during the period of study, and short-term outcome in a subsequent cohort improved even further, both for survival and chronic renal failure. The latter event is now quite rare in lupus nephritis, affecting only about 15% of our patients even in the very long term. It is likely that current cohorts of patients may experience even less renal failure. In our study, almost all cases of end-stage renal disease emerged during the first decade, although we are following a number of patients who have a reduced GFR and increased plasma creatinine concentrations long after this point, and one patient required dialysis 29 years from onset after the present study had been completed. However, many patients in moderate renal insufficiency appear to have stable renal function.
    That these improvements are largely the result of immunosuppressive treatment, first with prednisolone alone in the 1950s and 1960s, and then together with cytotoxic agents in the 1970s and since, has never been formally tested against a control group receiving no specific treatment.12 Nevertheless it is generally accepted that this is almost certainly the case, and both a single-agent trial13 and meta-analyses of controlled trials14,,15 suggest that the addition of a cytotoxic agent improves outcome over prednisolone alone, although others dissent from this view.16,,17 Our data do not permit us to compare different immunosuppressive regimens usefully, and no study to date has demonstrated a superior effect of one immunosuppressive regimen over another (including intravenous bolus cyclophosphamide) when added to prednisolone.2,8,12,16,17,,19
    We did not attempt any detailed analysis of the predictive power of clinical and histological parameters in this group of patients, given its small size and the variable treatments received during the long period of the study, but a simple univariate analysis did not show any clinical parameter at presentation to be predictive of survival, including glomerular filtration. Nor did glomerular appearance (Figure 2b) predict outcome, although previously we have shown the value of interstitial changes in determining this.18 The loss of predictive value probably results from the very success of current empirical treatment regimens, graded according to clinical and histological severity, in improving survival.
    The ultimate goal of management in lupus is the complete suppression of disease and cessation of treatment. Only 11 (19%) of our patients were able to or were allowed to stop treatment altogether. The only other detailed study of patients with lupus beyond 10 years' follow-up is that of Moroni et al.3 They studied 25 Caucasian patients followed more than 10 years (mean 16.7 years), 10 of whom (42%) had discontinued all treatment. These data suggest that at least half of patients with lupus will experience disease requiring immunosuppression for two decades or more. It this connection, it is worth noting that neither our study nor that of Moroni et al. used intravenous bolus cyclophosphamide as induction treatment, and only nine of our patients received it during follow-up for resistant disease, or suspected non-compliance with oral treatment. The short-and medium-term survival of the patients in both these series using predominantly azathioprine as long-term maintenance treatment is equally as good as that reported using i.v. cyclophosphamide.2 It would be interesting to compare these data with similar figures for patients treated with intermittent i.v. cyclophosphamide for one or two years. However only nine patients in the i.v. cyclophosphamide group of the NIH trials had been followed for more than 10 years, and only one for 15 years;19 and so far no data have been reported on their very long-term outcome or final treatment status.


    We would like to thank the many colleagues who helped in the care of these patients in the Adult and Paediatric Nephrology units, and the Histopathology department at Guy's over the period of more than 30 years during which these data were collected. Fred Compton gave valuable assistance with the actuarial analyses.

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