Narrative Review
Ten Common Mistakes in the Management of Lupus Nephritis

https://doi.org/10.1053/j.ajkd.2013.10.056Get rights and content

Management of patients with lupus nephritis can be complex and challenging. We suggest that there are some widely held misconceptions about lupus, and unfortunately, these underpin the treatment of many patients. There is little evidence to support the common assumption that intravenous pulse cyclophosphamide is the best treatment for lupus nephritis. Although there is much focus on which immunosuppressive agent to use, too little attention is paid to the proper dose and duration of corticosteroids and concomitant therapy with antimalarial agents. Many clinicians reflexively perform kidney biopsies when these biopsies may be high risk and not influence therapy. There is little emphasis on or awareness of nonadherence to therapy, which is an underappreciated cause of treatment resistance. Resolution of proteinuria and hematuria can take a long time, and immunotherapy should not be intensified based on urine sediment alone. Furthermore, the intensity of the immunosuppression must be considered in the context of lupus nephritis class and duration of kidney damage. Finally, clinicians are aware of the risks of pregnancy in the face of active lupus, but assume that their patients also are aware of this and forget to discuss this with them. With a combined experience of more than 50 years in managing children and adults with lupus, we offer our impression of recurrent mistakes in the management of lupus in general, with a focus on treatment of lupus nephritis.

Section snippets

Assuming that intravenous cyclophosphamide is the gold-standard induction agent for lupus nephritis

Following the initial publication by Austin et al9 in 1986, intravenous (IV) cyclophosphamide has been considered the gold standard for treatment of lupus nephritis. Based on this study, the National Institutes of Health (NIH) has promoted high-dose cyclophosphamide as a first-line induction agent for lupus nephritis, and this regimen is used by many rheumatologists and nephrologists. The cyclophosphamide dosage is 0.5-1.0 g/m2 monthly for 6 months, followed by repeat dosing every 3 months for 1

Improper dosing of corticosteroids

The National Kidney Foundation’s KDIGO (Kidney Disease: Improving Global Outcomes) and other guidelines (American College of Rheumatology and the European League Against Rheumatism/European Dialysis and Transplantation Association) recommend an initial prednisone dosage of 1 mg/kg, with a slow taper over 6-12 months.20 The guidelines also recommend using low-dose prednisone (≤10 mg/d) for maintenance therapy, and for relapse, the same dose of prednisone that was effective in inducing original

Not using antimalarial agents routinely

Antimalarial agents such as hydroxychloroquine have been used to treat mucocutaneous, musculoskeletal, serosal, and constitutional manifestations of SLE. In randomized controlled trials and post hoc analyses, hydroxychloroquine has been shown to reduce the risk of damage accrual,21 improve survival,22, 23 and decrease the frequency of lupus flare.24, 25 It also has been shown to improve kidney outcomes. There is an increased probability of remission in patients with membranous nephritis treated

Using urinary sediment for response criteria

The panel convened by the American College of Rheumatology to examine outcome markers in lupus nephritis recommends using urinary sediment for assessing response.31 According to the committee, improvement was defined as changing from active urinary sediment to inactive urinary sediment (eg, ≤5 red blood cells, ≤5 white blood cells, and no red blood cell or white blood cell casts). They defined worsening as active sediment in a patient who previously had inactive urinary sediment and for

Not scaling the intensity of immunosuppression to the different classes of lupus nephritis, especially class V membranous lupus

Membranous lupus nephritis (MLN) accounts for approximately 10%-20% of cases of lupus nephritis.33 Although the risk of decrease in kidney function is not as great as that with the endocapillary proliferative variants, up to 20% of patients with MLN require dialysis or kidney transplantation within 10 years of diagnosis.34, 35, 36 Kidney survival is only 50% in patients with MLN at 20 years,36 but a recent study demonstrated kidney survival > 80% at 15 years.37 Furthermore, there is a sizable

Missing nonadherence to therapy as a cause of treatment failure

A common concern in the medical field is whether patients adhere to the regimen of care recommended by the physician and the extent of their persistence over time. According to research, the highest estimate is that 50% of individuals with chronic disease comply with the recommendations of their physicians, irrespective of disease, treatment, or age.43 Adherence and persistence are low, even for patients who have diseases that carry a high or moderate risk of death.44, 45, 46

Similarly, in SLE,

Not reducing or minimizing immunosuppressive exposure in patients with advanced kidney disease

In a patient with stage 4 or 5 CKD secondary to lupus nephritis, a renal-limited flare might not warrant another course of aggressive immunosuppressive therapy. There will be significant scarring in the kidney and the patient will have very little or no benefit from another course of aggressive therapy. The intensity of immunotherapy should be guided by extrarenal manifestations.

For patients who are on dialysis therapy, the immunosuppressive dose should be minimized, if possible, because they

Forgetting to monitor side effects of immunosuppression and to use prophylaxis

All the immunosuppressants used in managing lupus nephritis have side effects that need close monitoring and use of appropriate prophylaxis. Unfortunately, some of this recommended monitoring gets overlooked and patients end up with significant preventable health care problems.

The following are the commonly missed side effects.

Performing a biopsy on the kidney, especially in a high-risk patient, when it will not affect therapy

Diagnosis of lupus nephritis based on only clinical features is not very reliable, emphasizing the need for kidney biopsy. Histopathologic findings in lupus nephritis can be very diverse and kidney biopsy not only determines the diagnosis and prognosis, but guides the management. Kidney biopsy also helps rule out other kidney disease that may affect patients of similar age and sex. These include renal thrombotic microangiopathy, acute tubular necrosis, drug-induced interstitial nephritis, focal

Neglecting to address pregnancy

Approximately 90% of patients with lupus are women. When given the diagnosis of lupus, many are concerned about becoming pregnant. Advising these patients about pregnancy and managing them during pregnancy can be challenging. It is important to involve a high-risk obstetrician and a rheumatologist who have experience in managing pregnant patients with lupus.

Many patients with active lupus have no idea that pregnancy at this time is fraught with risk for both mother and fetus. It is incumbent

Acknowledgements

Support: None.

Financial Disclosure: Dr Silverman is a consultant for Eli Lilly and Glaxo Smith Kline. The remaining authors declare that they have no relevant financial interests.

References (63)

  • E. Catherinot et al.

    Pneumocystis jirovecii pneumonia

    Infect Dis Clin North Am

    (2010)
  • H.M. Bastian et al.

    Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis

    Lupus

    (2002)
  • B.A. Pons-Estel et al.

    The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics.”

    Medicine (Baltimore)

    (2004)
  • M. Adler et al.

    An assessment of renal failure in an SLE cohort with special reference to ethnicity, over a 25-year period

    Rheumatology (Oxford)

    (2006)
  • M.M. Ward et al.

    Clinical prognostic factors in lupus nephritis. The importance of hypertension and smoking

    Arch Intern Med

    (1992)
  • R. Cervera et al.

    Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients

    Medicine (Baltimore)

    (2003)
  • A. Zonana-Nacach et al.

    Disease activity, damage and survival in Mexican patients with acute severe systemic lupus erythematosus

    Lupus

    (2007)
  • H.A. Austin et al.

    Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs

    N Engl J Med

    (1986)
  • F.A. Houssiau et al.

    Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide

    Arthritis Rheum

    (2002)
  • F.A. Houssiau et al.

    The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide

    Ann Rheum Dis

    (2010)
  • T.M. Chan et al.

    Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group

    N Engl J Med

    (2000)
  • T.M. Chan et al.

    Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis

    J Am Soc Nephrol

    (2005)
  • G.B. Appel et al.

    Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

    J Am Soc Nephrol

    (2009)
  • E.M. Ginzler et al.

    Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis

    N Engl J Med

    (2005)
  • L.M. Ong et al.

    Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis

    Nephrology (Carlton)

    (2005)
  • J.V. Donadio et al.

    Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide

    N Engl J Med

    (1978)
  • D.T. Felson et al.

    Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis

    N Engl J Med

    (1984)
  • A. McKinley et al.

    Oral cyclophosphamide for lupus glomerulonephritis: an underused therapeutic option

    Clin J Am Soc Nephrol

    (2009)
  • Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis

    Kidney Int Suppl

    (2012)
  • B.J. Fessler et al.

    Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual

    Arthritis Rheum

    (2005)
  • G.S. Alarcon et al.

    Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L)

    Ann Rheum Dis

    (2007)
  • Cited by (0)

    View full text