Lupus Nephritis - New Guidelines Issued

Lupus nephritis is a kidney disorder caused by a complication of systemic lupus erythematosus (SLE). Unlike previous guidelines, the new ACR guidelines are specific to lupus nephritis and include newer treatments, techniques for detecting renal disease, as well as treatment of pregnant SLE patients with kidney involvement.

The guidelines are published in Arthritis Care & Research.

SLE is a long-term autoimmune disorder that causes organ damage, joint pain, inflammation and fatigue. According to estimates up to 322,000 individuals in the United States are diagnosed with the disorder. One of the most serious complications of SLE is lupus nephritis. Lupus nephritis is an inflammation of the kidney which can lead to renal failure.

Evidence indicates that 35% of adult Americans have evidence of lupus nephritis at the time of SLE diagnosis, and that 60% of patients with SLE develop nephritis during the first decade after SLE diagnosis.

According to earlier studies, the survival rate for individuals with lupus nephritis after 10 years of SLE diagnosis is reduced to 88%, and that survival rate for African Americans is even lower.

Dr. Bevra Hahn, one of the lead guideline contributors and Professor of Medicine at the University of California, Los Angeles (UCLA), said:

“Lupus nephritis can be life-threatening, and proper management of the disease is vital to prevent permanent organ damage and preserve quality of life for patients.

Given the serious threat of kidney involvement in SLE and the availability of newer therapies, it was necessary to create specific guidelines for managing the care of patients with lupus nephritis.”

In order to establish the guidelines, three panels of researchers reviewed medical literature from 1966 through 2010 for all evidence relevant to “lupus kidney disease.”

Lupus Nephritis
Lupus nephritis is inflammation of the kidney that is caused by systemic lupus erythematous (SLE). Also called lupus, SLE is an autoimmune disease. With lupus, the body’s immune system targets its own body tissues. Lupus nephritis happens when lupus involves the kidneys.

An estimated one-third to one-half of lupus patients develop lupus nephritis within the first six months to three years of their lupus diagnosis. When the kidneys are inflamed, they can’t function normally and can leak protein. If not controlled, lupus nephritis can lead to kidney failure.

Recommendations in the guidelines include:

- Adjunctive treatment (background therapy with hydroxychloroquine, ACE inhibitors, control of blood pressure to goal of 130/80 or lower for almost all SLE patients with nephritis)
- Recommending renal biopsy for previously untreated patients with active nephritis
- Detecting vascular disease in SLE patients with renal abnormalities
- Treating nephritis in pregnant women
- Changing treatments in patients who do not respond well to initial therapy.
- Induction of improvement in patients
- with ISN Class III/IV lupus glomerulonephritis
- with Class IV or IV/V plus cellular crescents
- with Class V “pure membranous” lupus nephritis
-  Maintaining improvement in patients responsive to induction therapy (with azathioprine or mycophenolate mofetil)

Even though new treatments are available, research has shown that the incidence of end-stage renal disease from lupus has risen over the past two decades, specifically among African Americans, young patients, and those in the southern U.S.

Dr. Hahn explained:

“We look forward to seeing a reduction in these trends with implementation of these guidelines as part of high-quality, comprehensive care for SLE patients.”

The authors are aware of the guideline’s limitations in terms of not having agreed upon terms for remission, flare and response as well as limited data to recommend the dosage of steroids and tapering of immunosuppressive therapies.

Dr. Hahn Concludes:

“Ongoing evaluation and expansion of the guidelines is necessary to further improve outcomes for patients with SLE and nephritis.”

The etiology of the disease is not well-known. Genetic, infectious, hormonal, and other environmental factors seem influence on its pathogenesis. Some cases are related to hereditary deficiencies of the complement and others can be induced by drugs. The development of autoimmunity has been attributed to inadequate elimination of autoreactive lymphocytes. A dysregulation of the apoptosis and inadequate removal of apoptotic cells and nuclear rests seem important in the pathogenesis (Stuart L y Hughes J, Nephrol Dial Transplant 17:697, 2002 [PubMed link] [Free-Full-text]). The renal damage can be secondary to activation of the complement and local liberation of proinflammatory cytokines. Some intrarenal antigens, like components of the extracellular matrix and glycoproteins, can serve as target of the autoimmune attack. Deposition of circulating immune complexes with local activation of inflammation is another recognized mechanism of tissue damage. In addition, antiphospholipid antibodies can promote thrombosis or vascular injury. In lesions with membranous features (class V) there is cytotoxic injury of podocytes by antibodies and complement.

There is renal involvement in the great majority of patients with SLE at some time of the evolution: 66-90%. The presence of subendothelial deposits in glomerular capillaries is crucial in the induction of severe damage and they correlate with endocapillary proliferation, necrosis, karyorrhexis and crescents. Renal disease is one of the most frequent causes of death in SLE and it is one of the alterations that more attention must receive on the patients’ treatment.

Clinical features: The disease appears in an ample age range, but it is more frequent in young adults; the relation man: woman is of 1:9 and there is greater incidence in Afro-American than in Caucasians.

Extrarenal manifestations are ample and variable, and include alterations of the skin, joins, heart, lung, hematologic (cytopenias), neurological (convulsions, psychosis, peripheral nervous system involvement), mucous (ulcerations), serositis, and so on.

###

Written By Grace Rattue

Provided by ArmMed Media