The management of adult and pediatric lupus nephritis should be guided by renal biopsy, with a goal of achieving complete renal response, according to updated recommendations from the European League Against Rheumatism and the European Renal Association–European Dialysis and Transplant Association.

The update, including 28 final statements on lupus nephritis (LN) management derived using an evidence-based approach and expert consensus, is the first since 2008, when EULAR recommendations on the management of systemic lupus erythematosus (SLE) were issued.

"Since then, several controlled trials have been published upon which updated recommendations can be based," Dr. George K. Bertsias of the University of Crete, Iraklion, Greece, and his colleagues reported. The study was published online July 31 in Annals of the Rheumatic Diseases.

The new recommendations call for renal biopsy in patients with any sign of kidney involvement, particularly those with reproducible proteinuria of 0.5 g/24 h or greater, and especially if glomerular hematuria and/or cellular casts are present (Ann. Rheum. Dis. 2012 July 31 [doi:10.1136/annrheumdis-2012-201940]).

"Because of the potentially aggressive nature of [lupus nephritis], the thresholds for performing a renal biopsy should be low," the investigators said, noting that biopsy can also be considered in cases of persisting isolated glomerular hematuria, isolated leucocyturia (after other causes such as infection or drugs are excluded), and the rare occurrence of unexplained renal insufficiency with normal urinary findings.

Biopsy should be performed within a month of disease onset – ideally before institution of immunosuppressive therapy. But treatment with high-dose glucocorticoids should not be delayed if biopsy cannot be readily performed, the investigators said.

The aim of immunosuppressive treatment should be complete response, defined as a urine protein:creatinine ratio of less than 50 mg/mmol, which is roughly equivalent to proteinuria of less than 0.5 g/24 h.

"Ultimate goals of treatment are long-term preservation of renal function, prevention of flares, avoidance of treatment-related harms, and improved quality of life and survival," the investigators said, adding that treatment choices must be based on a decision reached jointly by patient and physician.

Immunosuppressive therapy is generally not warranted in classes I and VI LN, unless there is extra-renal lupus activity.

In adults, the recommended initial treatment for most cases of class III-IV disease is mycophenolate mofetil (target dose of 3 g/day for 6 months) or an equivalent dose of enteric-coated mycophenolic acid sodium, or low-dose intravenous cyclophosphamide at a total dose of 3 g over 3 months in combination with oral glucocorticoids (0.5 mg/kg per day). To increase efficacy, treatment should be combined initially with three consecutive pulses of intravenous methylprednisolone at 500-750 mg, followed by oral prednisone at 0.5 mg/kg per day for 4 weeks, with this dosage reduced to 10 mg/day or less by 4-6 months.

In pure class V disease with nephrotic-range proteinuria, the recommended treatment is mycophenolate mofetil at a target dose of 3 g/day for 6 months in combination with oral prednisone at a dose of 0.5 mg/kg per day.

In children whose LN tends to be more severe with increased damage accrual, management and monitoring recommendations are similar to those for adults. Management should include "a coordinated transition program to adult specialists" to optimize long-term outcomes.

The joint European League Against Rheumatism and the European Renal Association–European Dialysis and Transplant Association recommendations also address:

• Adjunctive treatments. For example, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are recommended for patients with proteinuria or hypertension, and hydroxychloroquine is recommended to improve outcomes by reducing renal flares and limiting accrual of renal and cardiovascular damage.

• Monitoring and prognosis of lupus nephritis. Visits are recommended every 2-4 weeks for the first 2-4 months after diagnosis, and repeat biopsies in certain patients, such as those experiencing relapse, are also recommended.

• Management of end-stage renal disease in LN. The recommendations state that all types of renal replacement can be used in patients with lupus, and transplantation can be performed when lupus activity has been absent or at a low level for 3-6 months.

• Antiphospholipid syndrome–associated nephropathy. Hydroxychloroquine and/or antiplatelet/ anticoagulant treatment should be considered.

• LN in pregnancy. Hydroxychloroquine can be used, as can low-dose prednisone, azathioprine and/or calcineurin inhibitors when needed. Acetylsalicylic acid should be considered to reduce risk of preeclampsia.

The recommendations are important, given that about half of all patients with SLE will develop LN, thereby increasing their risk of renal failure, cardiovascular disease, and death.

"The realization that in the case of patients with LN internists/rheumatologists and nephrologists are involved, prompted us to develop recommendations for LN under the joint auspices of the EULAR and the [ERA-EDTA], with experts from both disciplines," they explained, noting that "the panel was enriched with renal pathologists and pediatricians with expertise on LN."

The American College of Rheumatology similarly released updated recommendations on LN in May.

Support for the development of the EULAR/ERA-EDTA recommendations was provided via grants from the EULAR Standing Committee on Clinical Affairs and the ERA-EDTA. The authors reported having no competing interests.

Biopsy Must Guide Lupus Nephritis Management