Lupus is an archetypical, multisystem disease affecting almost every tissue or organ in the body. Kidney disease is rarely the first manifestation of Lupus; it may come later in the course of the disease and, by then, it is extremely serious and dominates the clinical picture and often leads to renal failure. The disease is due to the deposition, in the kidney, of anti-DNA antibodies or immune complexes which contain these antibodies. Subsequently, various mediators of immune reactions (complement, coagulation, and/or leukocytes) are activated resulting in inflammation. In this short review I plan to outline only a few aspects of this complex condition.
Kidney involvement is one of the most serious complications of Lupus. It has a major aspect on morbidity and mortality.the incidence of renal disease in Lupus varies with the criteria used to define renal involvement and the selection of patients. In early stages of Lupus renal abnormalities can be detected in 25-50% patients. It is reasonable to assume that the average 2/3 of patients with well documented Lupus will develop renal symptoms in the later stages of the disease. However, if kidney tissue from Lupus patients (obtained by biopsy) is analysed using refined histology techniques such as immunofluorescence or electron microscopy, abnormalities can be found in almost all cases, regardless of the presence of clinical symptoms.
Lupus nephritis is highly variable in its histological manifestation and in its clinical presentation. The only way to define the histology type of Lupus nephritis is by examining a small sample of kidney tissue obtained by biopsy. Kidney biopsy is necessary in all patients with Lupus who have abnormal urine and/or reduced renal function. It provides information about prognosis and may influence treatment. The World health organisation (WHO) have defined five histology types of Lupus nephritis.
The clinical spectrum of Lupus nephritis range from asymptomatic low grade proteinuria to a rapidly progressive course with hypertension, oedema and leading to renal insufficiency within days. Testing the urine is elementary in detecting renal involvement in Lupus. various degrees of proteinuria, blood in the urine and abnormalities of urine sediment are the most frequent abnormalities. All patients with Lupus nephritis have proteinuria. In up to 1/4 of all patients with Lupus, at some stage of their disease, proteinuria may be massive with nephrotic Syndrome as a disease manifestation. the most reliable estimate of the degree of renal dysfunction is creatinine clearance. Creatinine clearance is reduced in 40-80% of Lupus nephritis patients.
The hallmark and a diagnostic sign is the presence of autoantibodies against several nuclear (nucleosomal)antigens, mainly dsDNA. The exacerbation of Lupus nephritis is often preceded by a rise in the titre of anti-ds-DNA antibodies in blood, fall in the serum concentrations of complement components, C3 and C4, an increase in the serum concentration of immune complexes and the erythrocyte sedimentation rate is usually high.
Extensive literature has been accumulated on the treatment of Lupus nephritis and a variety of opinions are held regarding the best and safest approach to the therapy. A patient with Lupus Nephritis presents a complex therapeutic approach. Treatment of Lupus nephritis is prolonged, complex and potentially toxic. However, prognosis and outcome of the disease can usually be improved dramatically by treatment. the considerations regarding the treatment of renal disease rest on an accurate assessment of the type and severity of renal involvement. patients with mild glomerulonephritis (Type 1 and Type II WHO classification) will generally have a good prognosis, do not require therapy or will usually respond to short courses of treatment. more severe forms of lupus nephritis (Type III, IV and V) require aggressive therapy with cytotoxic (cyclophosphamide, mycophenolate mofetil, azathiaprine, tacrolimus), high (pulse) doses of steroids and in some resistant, difficult and severe cases, plasmapheresis. The question of when to stop treatment of Lupus nephritis is often asked. treatment is usually long, but it can be stopped at such time as immunological tests are back to normal, proteinuria disappears and renal function is stable.
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As far as the prognosis of Lupus nephritis; five year survival of treated patients with Lupus nephritis from 1990 to 1995 was 82%. Only 10-15% of patients with lupus nephritis progressed to end-stage renal failure. Renal failure supervenes usually within the first decade of follow-up. A proportion of Lupus nephritis patients in endstage renal failure still require immunosuppression. Finally, recurrence of Lupus nephritis is renal transplant cases is rare.
Lupus nephritis and pregnancy
It appears that maternal morbidity is substantially reduced if conception takes place when the disease is in remission. Lupus nephritis may present during pregnancy and, if this is the case, Lupus is usually severe. Even though disagreements exist as to whether pregnancy has an adverse effect on the course of Lupus and Lupus nephritis, there are convincing reports that the frequency of flare is higher during pregnancy. This exacerbation during pregnancy may be wide-ranging, causing increased proteinuria and leading to renal failure. Pre-eclampsia with hypertension and proteinuria may be mistaken for the flare of lupus. Very severe exacerbation of lupus in pregnancy may require termination of pregnancy. It is generally accepted that if exacerbation requires termination, the disease will not necessarily improve, but it is unlikely to become worse.
Pregnancies with women with Lupus and Lupus nephritis are also marked by an increase in foetal loss and increased foetal morbidity. Since IgG antibodies cross the placenta, there is a risk of lupus in the new-born. These manifestations of lupus disappear in 3-6 months. Some babies have congenital heart block associated with anti-SSA antibodies in the maternal serum and the baby’s heart lesions may be permanent.
Some of the guide lines for women with lupus and for pregnant lupus nephritis patients are as follows:
1. Pregnancy should be encouraged when the disease has been in remission for 6 months.
2. Drugs that may be frequently used in non-pregnant women such as cyclohosphamide, methotrexate, warfarin and andiotensin converting enzyme inhibitor type drugs should be switched to another drug with an analogous effect.
3. Blood pressure should be well controlled.
4. Regular, frequent (1-4 times/month) follow ups are advised. Foetal status should be closely monitored.
5. Urine analysis, urea and creatinine, lupus serology, serum urate, platelet count and C3 and C4 levels should be checked especially in pregnant women with proteinuria.
6. Flares of lupus nephritis during pregnancy should be treated with steroids and azathiaprine. Steroids, azathiaprine, methyldopa and diuretics are safe in pregnancy.
7. Continuation of immunosuppressive treatment for at least 2 months after delivery is advised. Activity of lupus is frequently related to prolactin level, and as high levels of prolactin are found in lactating mothers, this may play a role in postpartum flares of lupus.
In summary, if adequately diagnosed, treated and followed, pregnancy in lupus nephritis women can take place without major complications and can have a successful outcome.
by Dr Momir Macanovic
Consultant Nephrologist, Dorset County Hospital, Dorchester.