Monitoring Strategies in Lupus Nephritis

George K Bertsias, James E Balow
US Nephrology, 2011;6(2):116-121
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Abstract

Renal disease in patients with systemic lupus erythematosus follows a highly variable course, with periods of quiescence alternating with flares of activity. Although current immunosuppressive agents induce remission in most patients with lupus nephritis, a considerable proportion will flare, resulting in accrual of kidney damage and deterioration of renal function. Monitoring of urine sediment, proteinuria, renal function, and selected serologic tests—despite their individually weak predictive values for hard outcomes at particular points in time—is used for monitoring the activity of lupus nephritis and guiding treatment. Recently, substantive efforts have been directed toward a search for biomarkers (including novel genes and gene products) that are associated with pathogenic lupus activity, or that predict incipient renal flares and ultimately the risk of developing progressive renal failure. Although these biomarkers may be the Holy Grail of lupus nephritis monitoring, further validation of current candidates in large prospective cohorts of patients will be required.
Keywords
Lupus, kidney disease, biomarker, immunosuppressive therapy, flare
Disclosure The authors have no conflicts of interest to declare.
Received: September 25, 2011 Accepted October 31, 2011
Correspondence: James E Balow, MD, NIDDK, National Institutes of Health, Building 10—CRC, Room 5-2551, Bethesda, MD 20892. E: jimb@mail.nih.gov

One or more forms of glomerulonephritis develop in more than half of patients with systemic lupus erythematosus (SLE) (see Table 1).1 Despite substantive improvement in the outcomes of lupus nephritis over the past several decades, the prognosis of severe or relapsing forms of lupus nephritis remains unsatisfactory, evidenced by the fact that 20 % of patients or more develop end-stage kidney disease 10 years after onset of glomerulonephritis.2,3 Treatment with immunosuppressive agents, typically involving an initial induction phase of high-dose corticosteroids and adjunctive chemotherapy with cyclophosphamide or mycophenolate mofetil (MMF), produces complete remission within six months in only 40–60 % of patients.4 It is clear that ongoing maintenance therapy with mycophenolate or azathioprine is necessary to minimize the risk of relapse after six months, no matter how substantive the remission during the phase of more intensive induction therapy. Nonetheless, severe flares of lupus nephritis occur with substantial frequency during the maintenance phase, some of which provide strong indications for the recycling of intensive induction therapy. Proteinuria flares, while readily detected by standard laboratory monitoring, have lesser prognostic importance than nephritic flares, which, unfortunately, are often unrecognized in the early stages because of the notorious under-reporting of urine sediment abnormalities in most high-throughput clinical laboratories.3,5,6 Another shortcoming of the current therapeutic options is that high-dose and/or protracted use of standard immunosuppressive therapies for recalcitrant lupus renal disease are associated with some intrusive toxicities, such as infertility, metabolic disorders, opportunistic infections, neurodegenerative disorders, and malignancies.

Although the ultimate approach to improve the outcomes of patients with lupus nephritis is to develop new therapies that induce long-lasting remission, cause less harm, and are better tolerated,7 most recent randomized controlled trials with novel biologics, such as rituximab,8 have failed to confirm their superiority over traditional combinations of corticosteroids and cytotoxic agents. Consequently, at present, the most rational strategy is to attempt to optimize the use of conventional therapeutic agents. Toward achieving this goal, the effective monitoring of renal disease activity in patients with SLE is of utmost importance.

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