DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.
Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).
Dr. Bevra Hahn
In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.
For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.
The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.
They also address special situations such as pregnancy.
The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.
The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.
The task force panel also addressed adjunctive treatments, specifically recommending that:
• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.
• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.
• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.
Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.
The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.
"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.