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Diagnosis and treatment of lupus nephritis flares—an update

Abstract

Relapses or flares of systemic lupus erythematosus (SLE) are frequent and observed in 27–66% of patients. SLE flares are defined as an increase in disease activity, in general, requiring alternative treatment or intensification of therapy. A renal flare is indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of active disease. The morbidity associated with renal flares is derived from both the kidney damage due to lupus nephritis and treatment-related toxic effects. Current induction treatment protocols achieve remission in the majority of patients with lupus nephritis; however, few studies focus on treatment interventions for renal flares in these patients. The available data, however, suggest that remission can be induced again in a substantial percentage of patients experiencing a lupus nephritis flare. Lupus nephritis flares are independently associated with an increased risk of deterioration in renal function; prevention of renal flares might, therefore, also decrease long-term morbidity and mortality. Appropriate immunosuppressive maintenance therapy might lead to a decrease in the occurrence of renal and extrarenal flares in patients with SLE, and monitoring for the early detection and treatment of renal flares could improve their outcomes.

Key Points

  • Renal flares are associated with impaired renal prognosis and increased cumulative exposure of patients to drug toxic effects

  • Proteinuric flare is defined as persistently increased proteinuria (>0.5–1.0 g daily) after a complete response, or doubling of proteinuria (to >1.0 g daily) after a partial response

  • A nephritic flare is defined as an increase or recurrence of urinary sediment with or without increased proteinuria, and is usually associated with a decline in renal function

  • Reappearance of urinary casts and increased titres of antibodies to double-stranded DNA can predict renal flares

  • Whether monitoring of novel urinary or serum biomarkers can be used to predict lupus nephritis flares remains to be proven in prospective clinical trials

  • Prolonging the duration of maintenance therapy and careful clinical monitoring seem to decrease the incidence and severity of renal flares

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B. Sprangers and G. Appel researched the data for the article. B. Sprangers wrote the article. B. Sprangers, G. Appel and M. Monahan provided substantial contributions to discussion of the content and to review and/or editing of the manuscript before submission.

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Correspondence to Gerald B. Appel.

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G. B. Appel has consulted for and received research grants from Aspreva–Vifor, Genentech, La Jolla Pharmaceuticals and Roche. He has also served on the Bristol–Myers Squibb adjudication committee for lupus nephritis. The other authors declare no competing interests.

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Sprangers, B., Monahan, M. & Appel, G. Diagnosis and treatment of lupus nephritis flares—an update. Nat Rev Nephrol 8, 709–717 (2012). https://doi.org/10.1038/nrneph.2012.220

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