Systemic lupus erythematosus (SLE)
, an autoimmune disorder, has variable
symptoms depending on the organ system which is affected. SLE of the kidney is known as lupus
and, despite current therapeutic choices, 10% to 15%
patients reach end-stage renal disease (ESRD) and need dialysis or transplant
is more common in women than men (12:1),
African-Americans (10 fold more as compared to whites) and lower income
population. Nearly 35% adult newly-diagnosed SLE patients suffer from
nephritis, while 50%-60% SLE patients develop nephritis within 10 years of
diagnosis. The presence of renal complications results in poor prognosis
especially in African-American SLE patients.
American College of Rheumatology (ACR) describes lupus nephritis as continuous proteinuria
(protein in urine) of more than 0.5 g/day and/or urinary casts. Urinary
casts are cylindrical structures produced by the kidney in disease states. A
kidney biopsy is required to diagnose lupus nephritis.
International Society of Nephrology and the Renal Pathology Society (ISN/RPS)
modified World Health Organization (WHO) classification of lupus nephritis into 6
classes as per the seriousness and degree of disease.
goals include improvement in kidney function and delay in kidney failure. An angiotensin-converting enzyme (ACE)
inhibitor or angiotensin receptor blocker (ARB) is suggested for patient
with proteinuria âĨ0.5 g/day (ISN/RPS class I-II). On the other hand, ISN/RPS
classes III-IV lupus nephritis
patients need to be treated with immunosuppressive
drugs (drugs that suppress immunity).
Antimalarials, such as hydroxychloroquine, are recommended for all SLE patients with
nephritis since they effectively decrease disease progression and promote
Cyclophosphamide plus corticosteroids produces better results than
corticosteroids when used alone. However this combination in lupus nephritis patients significantly increases the risk of side
effects such as amenorrhea (stoppage of menstrual cycles), cervical
dysplasia (abnormalities in cells of the cervix), herpes zoster and infection.
A lower dose of cyclophosphamide used along with azathioprine maintenance
therapy could possibly reduce this complication.
clinical trial showed that Mycophenolate
mofetil (MMF) was as effective as intravenous cyclophosphamide when the
drugs were used to treat lupus nephritis in combination with prednisolone. The
former combination was linked with fewer infections, nausea, vomiting and hair
loss but higher incidence of diarrhea.
cyclophosphamide or mycophenolate mofetil combined with corticosteroids can be
used as initial therapy for lupus
clinical study has shown lower mortality
and reduction in kidney function with
MMF or azathioprine as compared with cyclophosphamide used during the
maintenance phase of treatment; all the drugs were combined with
corticosteroids in the study.. Thus,
MMF or azathioprine is recommended during the maintenance phase of treatment of
drugs for treating lupus nephritis
that are under investigation include rituximab, belimumab and tacrolimus.
conclusion, existing treatment options are successful in treating lupus nephritis. Cyclophosphamide or MMF plus corticosteroid combination is an option as
a first in line treatment for lupus
nephritis. After recovery from disease, azathioprine or MMF combined with a
corticosteroid is best suited as maintenance treatment.
Reference: Current Therapies
for Lupus Nephritis; Zachary et al; US Pharmacist 2012