Lupus Nephritis :From Basics To Practice

Lupus Nephritis :From
Basics To Practice
Dr
Yasser Matter
Nephrology and Kidney Transplantation
Specialist
Urology and Nephrology center
Mansoura University -Egypt
yassermatter86@gmail.com
yassermatter@mans.edu.eg

Outlines
• Epidemiology
• Pathogenesis & etiology
• Diagnosis (C/P& Lab &pathology)
• Treatment (induction & maintenance& some
updates)
• Prognosis
• Special situations
LN & APL
LN & transplantation
LN & contraception
LN & pregnancy
LN & vaccination

Epidemiology
• Up to 40% of SLE cases will have LN
• The peak incidence of lupus is age 15 to 45 years
• More prevalent in women than men(10:1)
• risk factors :
Younger age, lower socioeconomic status, more
ACR criteria for SLE, longer disease duration,
family history of SLE, black races & hypertension

Pathogenesis
• Autoantibodies are crucial to the pathogenesis of
both SLE and LN In SLE which lead to immune
complex formation (circulating or in situ).
• Immune complexes promote an inflammatory
response by activating complement and attracting
inflammatory cells, including lymphocytes,
macrophages, and neutrophils.
• Autoantibodies are directed against nuclear
elements (anti-dsDNA antibodies).

• The histologic type of lupus nephritis that
develops depends on numerous factors,
including the antigen specificity and other
properties of the autoantibodies and the type
of inflammatory response .
• The immune deposits in lupus nephritis occur
in the mesangium, subendothelial, and/or
subepithelial compartments of the
glomerulus

Lupus Nephritis :From Basics To Practice

Mesangium and subendothelial
deposits which are present in
communication with the vascular
space with influx of inflammatory cells
Subepithelial deposits
Which are are separated from the
circulation by the GBM with no influx of
inflammatory cells
These changes manifest
histologically by a mesangial or focal
or diffuse proliferative
glomerulonephritis
These changes manifest clinically by
an active urine sediment (red cells,
white cells, and cellular and granular
casts), proteinuria, and often an
acute decline in renal function
The injury is limited to the glomerular
epithelial cells. Histologically, these
patients most commonly have
membranous nephropathy.
the primary clinical manifestation is
proteinuria, which is often in the
nephrotic range.

• Large intact immune complexes or anionic antigens
(which cannot cross the anionic charge barrier in the
glomerular capillary wall) are deposited in the
mesangium and subendothelial space.
• Cationic antigen that can cross the GBM; and an
autoantibody directed against epithelial cell antigens
lead to subepithelial deposits .
• Another important determinant of the site of immune
complex formation may be related both to the charge
of the antibody and to its antigen-binding region,
since the antibody may bind to antigens at different
sites in the glomerular capillary wall, thereby leading to
different histologic and clinical manifestations

• It has also been suggested that the IgG subclass
may be a determinant of the inflammatory
response that is induced by immune complex
deposition. IgG1 and IgG3 fix complement and
soassociated with diffuse proliferative
glomerulonephritis , while IgG2& IgG4 don't fix
complement and mostly associated with
membranous nephropathy

Etiology
• There are multiple susceptibility factors, which
result in abnormal immune responses, which
vary among different patients , These factors
include:
• Genetic factors
• Immunologic factors
• Environmental factors

Genetic factors
• Multiple genes, many of which are not yet
identified, mediate this genetic predisposition
eg PDGF receptor A gene, the gene for the
sodium-dependent glucose cotransporter
SLC5A11.
• HLA-DR2 and HLA-DR3 are associated with SLE
• HLA-DR4 is associated with a lower prevalence
of SLE and appears to be protective

Immunologic factors
• The initial autoantibody response appears to be
directed against the nucleosome, which arises
from apoptotic cells.
• Patients with SLE have poor clearance of cellular
debris.
• Nuclear debris from apoptotic cells induces
dendritic cells to produce interferon-α, which is a
potent inducer of the immune system and
autoimmunity.

Autoreactive B lymphocytes, which are normally
inactive, become active in SLE because of a
malfunction of normal homeostatic mechanisms,
resulting in escape from tolerance. This leads to the
production of autoantibodies.

Environmental factors
• UV light
• EBV
• Smoking
• Alcohol
• Silica dust

Clinical manifestations
• All patients with SLE should be evaluated for
kidney involvement at initial diagnosis and at least
yearly thereafter even if they do not have
symptoms of kidney disease.
• It is also recommended that patients be re-
evaluated for LN if SLE flares.
• It is important to exclude nonlupus causes of renal
insufficiency, especially if the urinalysis does not
show abnormal proteinuria and hematuria

laboratory tests
Routine laboratory
tests
Urinalysis for blood
(suggests active
glomerular disease) and
protein,
microscopy for red cell
casts, uPCR or uACR.
• CBC, SCr, LFTs, serum
albumin ,Choleterol,
urinary 24h protein
• CRP (typically not raised
unless serositis; can be a
useful discriminator).
Immunological tests
ANA (>95%; sensitive but not specific)
Anti-dsDNA (increased specificity ,less sensitive)
C3 and C4 (reduced)
Anticardiolipin antibodies and lupus anticoagulant
Anti-C1q antibodies (associated with activity)
Sm antibodies ( strongly associated with the diagnosis
of lupus and the presence of nephritis but are present
in only about 25% to 30% of patients)

Renal biopsy
When ?
• If proteinuria more than 500 mg/d, with or without
other clinical abnormalities.
• Any level of proteinuria or hematuria with impaired
kidney function that cannot be attributed to another
cause.
• There is observational evidence that proteinuria of
500–1000 mg/d (or lower) may be associated with
significant kidney pathology and it has been well
established that early diagnosis and treatment of LN
improves prognosis

ISN 2004 classification of lupus
nephritis

Other lesions that may present in a
case of LN
• Thrombotic microangiopathy & APL .
• Vasculitis
• RPGN
• Pauci immune GN
• Tubulointerstial disease (rare)

Class I: Minimal mesangial lupus
nephritis
• Normal glomeruli by light microscopy, but
mesangial immune deposits by IF.

Class II: Mesangial proliferative lupus
nephritis
• Purely mesangial hypercellularity of any degree or
mesangial matrix expansion by light microscopy,
with mesangial immune deposits.
• A few isolated subepithelial or subendothelial
deposits may be visible by immunofluorescence or
electron microscopy, but not by light microscopy.

Class III: Focal lupus nephritis
• Active or inactive focal, segmental (less than half
of the glomerular tuft ) or global (ALL THE
GLOMERULUS ) endocapillary or extracapillary
glomerulonephritis involving <50% of all glomeruli,
typically with focal subendothelial immune
deposits, with or without mesangial alterations.

Class III or focal and segmental lupus glomerulonephritis is characterized by focal
involvement of glomeruli in which there are segmental lesions as demonstrated
here with one entirely normal appearing glomerulus (left) adjacent to glomerulus
with a segmental area of adhesion and necrosis (right) (hematoxylin and eosin,
×200).

Class IV: Diffuse lupus nephritis
• Active or inactive diffuse, segmental or global
endocapillary or extracapillary
glomerulonephritis involving ≥50% of all
glomeruli, typically with diffuse subendothelial
immune deposits, with or without mesangial
alterations.
• This class is divided into diffuse segmental (IV-S)
lupus nephritis when ≥50% of the involved
glomeruli have segmental lesions, and diffuse
global (IV-G) lupus nephritis when ≥50% of the
involved glomeruli have global lesions.

Class V: Membranous lupus nephritis
• Global or segmental subepithelial immune
deposits or their morphologic sequelae by
LM and by IF or EM, with or without mesangial
alterations.
• Class V lupus nephritis may occur in combination
with class III or IV in which case both will be
diagnosed.

Class VI: Advanced sclerotic lupus
nephritis
• ≥90% of glomeruli globally sclerosed without residual activity.

Point System in Calculating Lupus
Nephritis Biopsy Activity and Chronicity
 Activity: (24)
 Mesangial proliferation
 Hyaline lesions
 Cellular crescents
 Necrosis
 Neutrophils/
glomerulus
 Interstitial inflammation
 Chronicity: (12)
 Sclerotic glomeruli
 Fibrous crescents
 Atrophic tubules
 Interstitial fibrosisX2
< 25%: 1
25-50%: 2
>50%: 3

Vascular damage in lupus nephritis
Thrombus (arrow)
occludes a glomerular capillary loop in this class IV biopsy
specimen (Silver methenamine/hematoxylin stain.)

Interstitial lupus nephritis
Interstitial infiltrate invading and destroying tubules (tubulitis). Tubular basement
membranes, which stain black with silver, are digested in the areas of tubulitis
(arrow).

Extensive podocyte foot process
effacement and a small amount of dense
deposits in mesangial area in the
absence of capillary wall deposits

Role of protocol biopsy
• The role of protocol repeat kidney biopsies in LN is
controversial
• Repeat biopsies have demonstrated considerable
discordance between clinically- and histologically
defined disease activity.
• After completing 6–8 months of immunosuppressive
therapy, 20%–50% of complete clinical renal
responders still had histologic evidence of ongoing
active inflammation (Silent lupus nephritis), and
40%–60% of patients with no histologic evidence of
disease activity still had persistent, high-grade
proteinuria

Principles
• The overarching goal of LN treatment is to prevent CKD and
ESRD.
• The treatment is consisted of adjuvant therapy , induction
phase (3-6 months) and maintenance phase (the duration is
not exactly defined but may be continued for 3 or 4
yearsunless there is contraindication ).
• Complete remission : is defined as reduction in proteinuria
below 0.5 g/24 h or urine protein-creatinine ratio below 0.5
g/g, absence of glomerular hematuria or red blood cell (RBC)
casts, and normalization or stabilization of GFR.

• Partial remission :is defined as proteinuria >0.3 but
<3.5 g per 24 hours or a decrease in proteinuria by at
least 50% from the initial value and <3.5 g per 24
hours.
• Renal flare: is defined as proteinuric by an isolated
increase in proteinuria, typically at least a doubling
and to more than 1 g/24 h; or as nephritic, by a
reproducible increase in serum creatinine of at
least 30% (or a decrease in GFR by at least 10%)
and an active urine sediment with an increase in
glomerular hematuria of 10 or more RBCs per high-
power field regardless of changes in proteinuria

class I and class II
• class I and class II need no therapy directed at the
kidney.
• The majority will have a benign long-term kidney
outcome, and the potential toxicity of any
immunosuppressive regimen will negatively alter
the risk/ benefit ratio of treatment.

class I and class II
• Extrarenal manifestations should be treated with
immunosuppression if indicated.
• An exception is the group of lupus patients with
lupus podocyte injury, who often respond to a
short course of high-dose corticosteroids +/- CNI
similar to patients with MCD or FSGN.

Proliferative Lupus Nephritis
(class III / IV )

Membranous Lupus Nephropathy
(class V LN)

• Membranous nephropathy is often diagnosed in
association with proliferative forms of LN. In these
patients, treatment is directed at the proliferative
component.
• An alternative approach for the treatment of class
V + class III or class IV LN, called multitargeted
therapy, combines low doses of corticosteroids,
MMF, and a CNI and has shown success in an Asian
cohort

KDIGO Clinical Practice Guideline

Resistant LN
Definition
• failure to achieve either complete or
partial remission and is associated with a
worse long-term prognosis compared to
patients who attain remission.
• Assessment for the development of
remission requires a minimum of three
months and, in some patients, as long as
12 months after the initiation of
induction therapy.

Treatment
• For patients with proliferative LN who are resistant to
mycophenolate mofetil (MMF) plus glucocorticoids as first-
line therapy, we recommend intravenous cyclophosphamide
plus glucocorticoids ( Grade 1B ). The regimen is the same as
that used for induction therapy.
• For patients with proliferative LN who are resistant to
cyclophosphamide plus glucocorticoids as first-line therapy,
we recommend treatment with MMF plus glucocorticoids (
Grade 1B ). The regimen is the same as that used for
induction therapy.
• For patients who have failed treatment with or are unable to
tolerate both cyclophosphamide and MMF, we suggest
rituximab although randomized trials have not been
performed and long-term follow-up is not available ( Grade
2C ). The preferred regimen is 0.5 to 1 g given on days 1 and
15, or 375 mg weekly for four weeks.

Diffuse proliferative and membranous LN
• For patients with concurrent proliferative and
membranous LN who are resistant to
cyclophosphamide , we recommend combined
treatment with MMF and tacrolimus ( Grade 1B ).

Relapsing LN
Definition of mild Relapsing LN
• increased activity of urine sediment and possibly a modest (eg,
less than 50 percent) increase in protein excretion but with a
stable serum creatinine.
Treatment of mild Relapsing LN
• Among patients who are no longer on maintenance therapy, a
trial of oral prednisone (60 mg/day for one week, tapered to 30
mg every other day for three months) can be considered.
• For those initially treated with cyclophosphamide who are now
on azathioprine maintenance therapy, one can increase the dose
of prednisone as well as azathioprine, particularly if the
azathioprine dose has been tapered.
• For those who were initially treated with MMF for induction and
who are now off maintenance therapy, MMF may be restarted.
For patients who are still on maintenance therapy with lower
doses of MMF, the MMF dose can be increased to 2 to 3 g/day.

Definition of Moderate to severe Relapsing LN
defined as an active urine sediment plus a rise in serum creatinine
with or without increased proteinuria. These manifestations are
often accompanied by a flare in extrarenal manifestations of lupus.
Treatment of Moderate to severe Relapsing LN
• If cyclophosphamide was used for induction and the patient is
taking azathioprine for maintenance, we suggest a trial of MMF
and cessation of azathioprine ( Grade 2C ).
• If MMF was used for induction and maintenance and MMF has
been discontinued, we suggest reinstitution of MMF ( Grade 2B ).
• If MMF was used for induction and maintenance and relapse
occurs while the patient is still taking MMF, we recommend
cyclophosphamide ( Grade 1B ).
• Among patients who continue to relapse despite the above
interventions, we suggest a trial of rituximab

Proposed treatment algorithm for various
pathological subtypes of lupus nephritis

Notes regarding cyclophosamide

Side effect or certain condition How to minimize /Notes
Hemorrhagic cystitis • Increased hydration and frequent voiding
is recommended to help prevent cystitis
• utilize mesna to protect against
hemorrhagic cystitis
• Discontinue cyclophosphamide with
severe hemorrhagic cystitis
Fertility effects
(interferes with oogenesis and
spermatogenesis)
• Try to reduce dose and duration of
treatment
• women should be offered prophylaxis with
leuprolide and men testosterone
• Ovarian tissue cryopreservation/sperm
banking are other options
In case of Hepatic impairment • Serum bilirubin 3.1-5 mg/dL or
transaminases >3 times ULN: Administer
75% of dose.
• Serum bilirubin >5 mg/mL: Avoid use.

In case of Renal Impairment • Cl cr ≥10 mL/minute: No dosage
adjustment required.
• Cl cr <10 mL/minute: Administer 75%
of normal dose.
• Hemodialysis: Moderately dialyzable
(20% to 50%); administer 50% of
normal dose; administer after
hemodialysis
Hematologic toxicity
(Lifetime maximum of 36 g cyclophosphamide
in patients with SLE increase chance of
hematologic malignancies later
in life.)
• Dose reduction or treatment
interruption.
• Reducing initial dose by 30% to
50% if bone marrow function
compromised
Monitoring Parameters • CBC with differential and platelets,
BUN, UA, serum electrolytes, serum
creatinine; monitor for signs/symptoms
of hemorrhagic cystitis

Administration • Should be administered on an
empty stomach to avoid variability
in MPA absorption ;however, may
be taken with food if necessary in
stable renal transplant patients.
Gastrointestinal effects
Abdominal pain (25% to 63%),
nausea (20% to 55%), diarrhea
(31% to 51%), constipation (19% to
41%), vomiting (33% to 34%),
anorexia (25%), dyspepsia (22%)
• Decrease the dose to the
tolerable dose if no CI or shift
to other drug.
• Others may shift from
CELLCEPT to MYFORTIC in view
of coated tablets or fractionate
the dose to be every 6 or 8
hours instead of BID .
Toxicity Neutropenia
(ANC <1.3 x 10 3 /μL)
• Dosing should be interrupted or
the dose reduced

MMF +Contraceptives • decrease the serum concentration
of Contraceptives (Estrogens
&Progestins )
• Women of childbearing potential
who are receiving mycophenolate
mofetil should consider using an
alternative and/or additional form
of contraception
MMF+CYCLOSPORINE • decrease the serum
concentration of
Mycophenolate. Specifically,
cyclosporine may decrease
concentrations of the active
metabolite mycophenolic acid
MMF +Magnesium Salts • May decrease the serum
concentration of Mycophenolate
• Management: Separate doses of
mycophenolate and oral
magnesium salts

MMF +MetroNIDAZOLE • May decrease the serum
concentration of Mycophenolate.
Specifically, metronidazole may
decrease concentrations of the
active metabolite of
mycophenolate
MMF+quinolones • May decrease the serum
concentration of
Mycophenolate. Specifically,
quinolones may decrease
concentrations of the active
metabolite of mycophenolate
MMF +Acyclovir-Valacyclovir
MMF +Ganciclovir-Valganciclovir
• Mycophenolate may increase the
serum concentration of Acyclovir-
Valacyclovir / Ganciclovir-
Valganciclovir.
• Acyclovir-Valacyclovir /Ganciclovir-
Valganciclovir may increase the
serum concentration of
Mycophenolate

MMF + Antacids • May decrease the absorption of
Mycophenolate.
• Management: Separate doses of
mycophenolate and antacids by at
least 2 hours.
• Exceptions: Sodium Bicarbonate
Monitoring Parameters • Complete blood count (weekly for
first month, twice monthly during
months 2 and 3, then monthly
thereafter through the first year);
renal and liver function; signs and
symptoms of infection; pregnancy
test (immediately prior to initiation
and 8-10 days later in females of
childbearing potential, followed by
repeat tests during therapy);
monitor skin (for lesions suspicious
of skin cancer); monitor for signs
of lymphoma

Renal Impairment • Cl cr >50 mL/minute: No
adjustment recommended.
• Cl cr 10-50 mL/minute:
Administer 75% of normal dose.
• Cl cr <10 mL/minute: Administer
50% of normal dose.
• Hemodialysis (dialyzable; ~45%
removed in 8 hours): Administer
50% of normal dose; supplement:
0.25 mg/kg
Hematologic toxicity
(leukopenia, thrombocytopenia, and
anemias, including macrocytic
anemia or pancytopenia)
• Reduce dose or temporarily
withhold treatment.
AZA + xanthine oxidase inhibitors
(allopurinol)
risk for increased myelosuppression
• Dose adjustment of
azathioprine may be
recommended when used
concurrently with allopurinol

Administration • after meals or in divided doses
may decrease adverse GI events
Gastrointestinal toxicity
(Severe nausea, vomiting, diarrhea,
rash, fever, malaise, myalgia,
hypotension, and liver enzyme
abnormalities may occur within the
first several weeks of treatment)
• Generally reversible upon
discontinuation.
Hepatotoxicity
(transaminase, bilirubin, and alkaline
phosphatase elevations)
Hepatic sinusoidal obstruction
syndrome (SOS; veno-occlusive
disease (RARE)
• Generally reversible upon
discontinuation.
• Permanently discontinue

New therapies for LN
Rituximab Deplete autoreactive B cells and thereby
attenuate the production of autoantibodies
involved in disease
manifestations.
Belimumab • B-cell-activating factor (BAFF)-
neutralizing antibody
• Reduce renal flares and proteinuria in
patients with SLE
Abatacept • co-stimulatory inhibitor that targets
B7-1 (CD80) on the surface of
dendritic cells or B cells .
• blocks co-stimulation of CD28 on T
cells
Eculizumab (anti C5) and CCX-168 • Inhibitors of the complement system .
• have therapeutic value in patients with
concurrent thrombotic microangiopathy
or anti-neutrophil cytoplasmic
antibody-associated vasculitis.

New therapies for LN
Calcineurin inhibitors
(CNIs)
• have immune modulatory effects
but also direct effects on podocytes
& useful in patients with lupus-
associated podocyte injury
ABT-199 (Inhibition of the apoptosis
regulator BCL-2)
• prevent the development of
tubulointerstital inflammation in a
mouse model of lupus nephritis
anti-IL-23 antibodies • IL-23 activation might have a role in
the development of glomerular
crescents, suggesting that anti-IL-23
antibodies might be beneficial
infliximab • Inhibit inflammatory tumour necrosis
factor (TNF )
sirukumab • Inhibit inflammatory IL-6

Cessation of immunosuppression
• There is no strong evidence to guide the
decision to withdraw maintenance therapy.
• Case series suggest that the risk of relapse is
inversely proportional to length of prior
treatment.
• Therapy for at least 5 years is advisable.

Monitoring
• Patients with SLE who have had LN should
have clinical evaluation, GFR,serum
creatinine, CBC ,proteinuria, and urinary
sediment monitored every 1-3 months
according to the case.
• Serologies such as C3 and C4 levels and anti-
dsDNA should also be monitored quarterly or
biannually.

Prognosis
• 10% to 15% of lupus patients develop ESRD.
• lupus represents only 1% to 2% of patients with
ESRD.
• The relapse rate for LN ranges from 35% to 60%,
depending on the population studied, the criteria
for relapse, and the maintenance therapy used.
• Outcomes are variable and depend on disease
severity and response to treatment. Overall
mortality is about 10% at 10 years for lupus
nephritis (approximately double that of non-renal
disease).

LN
&
ANTIPHOSPHOLIPID
ANTIBODY SYNDROME

• Up to 30% of cases of LN is associated with APL .
• Diagnosis is done by presence of Lupus (LA)
anticoagulant , Anti-cardiolipin (ACL) antibodies &
Beta-2 glycoprotein I , but up to 15% of patients
are negative for LA & ACL .
• Clinically , patients have have a history of systemic
thromboses, fetal loss, neurologic disorders, and
thrombocytopenia.
• Histologically, picture of TMA.
• Mechanism is unknown , but may be due to
abnormal endothelial function, enhanced platelet
aggregation, reduced production of prostacyclin
and other endothelial anticoagulant factors, and
activation of plasminogen

• Treatment (KDIGO Guideline )
• We suggest that the antiphospholipid antibody
syndrome (APS) involving the kidney in systemic
lupus patients, with or without LN, be treated by
anticoagulation (target international normalized
ratio [INR] 2–3). (2D)
• We suggest that patients with systemic lupus and
thrombotic thrombocytopenic purpura (TTP)
receive plasma exchange as for patients with TTP
without systemic lupus. (2D)

• Clinical activity of SLE should be quiescent before
transplantation FOR at least 6 MONTHS.
• The patient should not require cytotoxic agents or
more than 10 mg of prednisone before
transplantation to maintain quiescence.
• Clinically active SLE typically improves with the
development of chronic renal failure, but may not
do so in some patients, particularly African
American women

• Some patients are clinically quiescent but maintain
persistently abnormal levels of serologic markers of
disease activity while on dialysis.
• It is the degree of clinical activity that should
determine transplant candidacy.
• Some suggest starting transplant
immunosuppressives several weeks to 1 month
before living donor transplantation to suppress the
serologic activity in case of clinical quiescence
• Recurrent LN occurs in 2% to 11% of transplanted
kidneys

• All patient treated by (MMF/CYCLOPHOSPHAMIDE)
should be counseled to use contraception Method
and not to conceive before medical consultation.
• No contraceptive method is ideal; all have benefits
and drawbacks.
• Barrier methods, such as the diaphragm , cervical
cap and condoms , are safe, inexpensive, but have
high failure rates (16% to 31%, depending on the
method chosen and parity of the user).
• The progesterone only minipill is unlikely to worsen
lupus activity or promote thrombosis, but has high
discontinuation rates.

• Depot medroxyprogesterone acetate (DMPA)(every
3months), offers the advantage of greater typical-
use efficacy than progesterone-only pills, However,
menstrual irregularities are frequent with
detrimental effects on bone density.
• The copper IUD offers a non-hormonal alternative
for long-term contraception. However, menorrhagia
is frequent among users of copper IUDs.
• The levonorgestrel-releasing intrauterine system
(LNG-IUS),(Mirena) may be a better alternative
than the copper IUD but associated with Amenorrhea

• If unprotected sex occurs, due to either
contraceptive nonuse or method failure,
emergency contraception (EC) eg oral
levonorgestrel can reduce the likelihood of
unintended pregnancy.
• women with lupus who choose to use an IUD
should be educated about the slightly increased
risk of upper genital tract infection in the first
month after insertion, and should also be
instructed on self-exams to check for
unrecognized IUD expulsions.

• oral contraceptives, containing lower concentrations of
estrogen, are probably safe in patients with mild, well-
controlled SLE.
• Avoid their use in women already at increased risk of
clotting, especially patients with antiphospholipid
antibodies, the nephrotic syndrome, and/or a history of
thrombophlebitis.
• Avoid use of oral contraceptives in patients with known
coronary or cerebrovascular disease, uncontrolled
hypertension, migraine headache with focal neurologic
symptoms, and/or women who continue to smoke
cigarettes who are ≥35 years of age
• Patients with active nephritis may be at increased risk
of renal exacerbation when exposed to oral
contraceptives

• Pregnancy in women with lupus nephritis is
associated with an increased risk of fetal loss (up
to 75 %) and with worsening of the renal and
extrarenal manifestations .
• women with lupus nephritis should be encouraged
to delay pregnancy until the disease can be
rendered inactive for at least six months .
• It has been suggested that a biopsy may be
performed if there is a sudden unexplained
deterioration in renal function or markedly
symptomatic nephrotic syndrome occurring before
28 weeks gestation. Biopsy after week 28 is not
recommended.

Strategies for renal biopsy in the pregnant patient
with SLE

Flow diagram of the
management of lupus
nephritis in pregnancy

• Patients with a significant flare of lupus nephritis
should be treated with high-dose prednisone.
• There is little if any experience with pulse
methylprednisolone in pregnancy, and its effects on
the fetus are unknown.
• azathioprine can be used cautiously.
• The fetus should be delivered as soon as possible.
• Thrombocytopenia during lupus pregnancies may
have multiple causes, including antiplatelet
antibodies, toxemia, and antiphospholipid
antibodies .Treatment includes high-dose
prednisone and intravenous immune globulin .

• In the absence of any historical features of the
antiphospholipid syndrome (APS) (eg, recurrent
pregnancy loss, venous or arterial
thromboembolism), we recommend that patients
with SLE and high levels of aCL or the presence of
an LA receive low-dose aspirin therapy, although
the data regarding the management of these
patients are equivocal.
• Prophylactic unfractionated heparin or low
molecular weight heparin is used in presence of
history of thrombosis eg, recurrent pregnancy
loss, venous or arterial thromboembolism.

NEONATAL LUPUS
• passively transferred autoimmune disease that occurs
in some babies born to mothers with anti-Ro/SSA
and/or anti-La/SSB antibodies.
• The most serious complication in the neonate is
complete heart block.
• Maternal use of hydroxychloroquine (HCQ) may be
associated with reduced rates of the cardiac
manifestations in the newborn, including congenital
heart block and isolated cardiomyopathy.
• Women with anti-Ro/SSA and anti-La/SSB may have
detectable amounts of these antibodies in breast milk,
but there is no evidence that neonatal lupus results
from breast feeding.

LN & vaccination
• All of the studies reported here agree that live vaccines
are not safe and should not be recommended to
patients with SLE.
• it is recommended that vaccines should not be given to
patients with very active SLE or those with active
nephritis.
• SLE patients with quiescent disease should be
encouraged to receive the influenza vaccine according
the recommendations given by the Immunization
Practices Advisory Committee.

LN & vaccination
• Although vaccines are safe clinically, a transient
increase of the titers of a wide range of autoantibodies
may occur after vaccination.
• This autoantibody activity is usually short term and has
no clinical consequences.
• In individual cases vaccines may be associated with
exacerbation of SLE; however, no specific clinical or
laboratory variables have been identified as associated
with flare of SLE following vaccination.

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