Jun. 21, 2012

New American College of Rheumatology Guidelines for Lupus Nephritis

American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, and Grossman JM. (2012). Arthritis Care & Research (Hoboken) 64: 797-808.

What is the topic?

Lupus nephritis, or lupus-related inflammation of the kidney, is one of the most serious complications of systemic lupus erythematosus. While only about 35% of adults with lupus show evidence of nephritis at the time of a lupus diagnosis, about 50-60% will develop nephritis within 10 years of diagnosis.

The American College of Rheumatology (ACR) last published guidelines for the management of systemic lupus in 1999. At that time, recommendations to manage lupus nephritis included an initial pulse steroid treatment followed by a high-dose daily steroid treatment in combination with an immune-suppressing drug, like cyclophosphamide. There have been several advances in the care and treatment of lupus nephritis since that time and these new guidelines incorporate the latest knowledge about the management of lupus nephritis.

What did the researchers hope to learn?

The researchers set out to update the ACR guidelines for the management of lupus nephritis. These guidelines had not been updated since 1999.

Who was studied?

The researchers utilized extensive literature searches to help them craft these new recommendations for the management of lupus nephritis.

How was the study conducted?

The recommendations contained herein were developed by use of a modified RAND/University of California at Los Angeles (UCLA) Appropriateness Method, a combination of literature review and expert opinion. The following three groups each implemented specific functions to help develop the recommendations: a Core Executive Panel, a Working Group, and a Task Force Panel. The Core Executive Panel and Working Group, together, reviewed existing guidelines and developed clinical scenarios. The Task Force Panel voted on the appropriateness of interventions in the various scenarios.

A review of existing relevant literature was performed by searching Medline (through PubMed) for medical subject headings and relevant keywords (such as “lupus kidney diseases”) for references published in English between January 1, 1966 and January 22, 2010. Articles from this search strategy were excluded from consideration if they fell into one of the following categories: review article, opinion article, cohort studies not including patients 18 years of age or older, cohort or prospective trials containing fewer than 29 patients, studies not requiring patients to meet a pre-established definition of systemic lupus or lupus nephritis, or studies including less than six months of follow-up of patients.

The Working Group and Core Executive Panel wrote an Evidence Report, which detailed clinical scenarios relevant to lupus nephritis care and treatment. These scenarios were voted on by the Task Force Panel in order to elicit opinions about the appropriateness of decisions relevant to the care and treatment of lupus nephritis. The completed documents were then submitted to the ACR for review and approval by the ACR Guidelines Subcommittee, ACR Quality of Care Committee, and ACR Board of Directors.

What did the researchers find?

For purposes of the recommendations contained herein, lupus nephritis is defined as clinical and laboratory manifestations that meet ACR criteria for lupus nephritis. These include a spot urine protein/creatinine ratio greater than 0.5 or lupus nephritis as indicated by a kidney biopsy. The Core Executive Panel agreed that a diagnosis of lupus nephritis should be considered valid if based on the opinion of a rheumatologist or nephrologist.

The Task Force Panel recommended that all patients with clinical evidence of active, but previously untreated lupus nephritis, should undergo a kidney biopsy (unless strongly contraindicated) so that kidney disease could be classified by current criteria of the International Society of Nephrology (ISN)/Renal Pathology Society (RPS).

The Task Force Panel recommended that treatment should be based in large part on the classification of type of lupus nephritis by ISN/RPS criteria. Class I and class II lupus nephritis generally do not require immune-suppressing drugs. In general, class III and class IV lupus nephritis require aggressive therapy with steroids and immune-suppressing drugs. Class V lupus nephritis should be treated in the same manner as class III or IV when found simultaneously as class III or IV. Class V lupus nephritis alone should be treated with prednisone (0.5 mg/kg/day) plus mycophenolate mofetil (2-3 grams total daily dose). Class VI lupus nephritis generally requires preparation for kidney replacement therapy instead of immune-suppressing drug treatment.

The Task Force Panel recommended that all patients with lupus nephritis should be treated with hydroxychloroquine unless there is contraindication. Also, all lupus nephritis patients with protein in the urine at a certain threshold, (0.5 g/24 hours or equivalent by protein/creatinine ratios), except pregnant patients, should have drug therapy with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptors blockers.

The Task Force Panel recommended that careful attention should be paid to control of high blood pressure in lupus patients, with a target of < 130/80 mm Hg. In addition, drug therapy with statins (cholesterol-lowering drugs) should be introduced in patients with low-density lipoprotein cholesterol > 100 mg/dl. Lastly, women of child-bearing potential with active or prior lupus nephritis should receive counseling regarding pregnancy risks conferred by lupus nephritis and its treatments.

What were the limitations of the study?

Limitations include the absence of agreed-upon definitions for terms such as "remission", "flare", and "response". Also, at this time, specific recommendations cannot be made for dosing of steroids or tapering of immune-suppressing drug treatment.

What do the results mean for you?

Lupus nephritis remains one of the most devastating complications of lupus. The authors hope that the institution of these recommendations may lead to reduced incidence of end-stage renal disease among people with lupus.

It should be noted that guidelines and recommendations developed and/or endorsed by the ACR are intended to provide guidance, but not to dictate, the care of a particular patient, and while intended to promote desirable outcomes, cannot guarantee any specific outcome. The ACR considers the application of these guidelines and recommendations to be voluntary, and that their application be made by a physician in light of each patient’s particular circumstances.


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