1. American College of
Rheumatology Guidelines for
Screening, Treatment, and
Management of Lupus Nephritis
Dr. Amit Agrawal
2. Disease Burden
• 35% of adults with SLE have clinical evidence of
nephritis at the time of diagnosis.
• 50–60% developing nephritis during the first 10
years of disease.
• Higher in men than in women.
• Survival with SLE - 95% at 5 years
• 92% at 10 years
• Lupus nephritis reduces survival 88% at 10 years
3. Case definition
• Persistent proteinuria 0.5 gm per day
• Or greater than 3+ by dipstick
And/or
• Cellular casts including red blood cells,
hemoglobin, granular, tubular, or mixed
4. • Spot urine protein/creatinine ratio of >0.5
Active Urinary Sediment:
• >5 RBCs/hpf
• >5WBCs/hpf in the absence of infection
• cellular casts limited to RBC or WBC casts
5. Renal Biopsy
• All patients with clinical evidence of active LN,
previously untreated, undergo renal biopsy
(unless strongly contraindicated) so that
glomerular disease can be classified by current
ISN/RPS classification
• Evaluated for activity and chronicity and for
tubular and vascular changes
8. Principles of treatment
• Class I and Class II- do not require
immunosuppressive treatment.
• Class III And Class IV aggressive therapy with
glucocorticoids and immunosuppressive agents
• Class V when combined with class III or IV should
be treated in the same manner as class III or IV
• Class VI requires preparation for renal
replacement therapy rather than
immunosuppression
9. • All SLE patients with nephritis be treated with
a background HCQ unless there is a
contraindication
Rationale:
• Lower rates of Flare
• Reduced renal damage
• Less clotting events
10. • LN patients with proteinuria >0.5 gm per 24
hours should have blockade of the renin–
angiotensin system, which drives
intraglomerular pressure
Rationale:
• Reduces proteinuria by 30%, and
• Significantly delays doubling of serum
creatinine
• Delays progression to end-stage renal disease
11. • Control of hypertension, with a target of
<130/80 mm Hg
• Statin therapy be introduced in patients with
low-density lipoprotein cholesterol >100
mg/dl
16. Class I LN (minimal-mesangial LN)
• Treatment as dictated by the extrarenal
clinical manifestations of lupus
RATIONALE:
• Class I LN has no clinical kidney
manifestations.
• Class I LN is not associated with long-term
impairment of kidney function
17. Class II LN (mesangial-proliferative LN)
• Treat patients with class II LN and proteinuria
<1 g/d as dictated by the extrarenal clinical
manifestations of lupus.
• Class II LN with proteinuria >3 g/d be treated with
corticosteroids or CNIs as described for MCD.
RATIONALE:
There are no evidence-based data on the
treatment of class II LN.
18. Class III LN (focal LN) and class IV LN
(diffuse LN)
• Initial therapy with corticosteroids , combined
with either cyclophosphamide or MMF
• if patients have worsening LN (rising SCr,
worsening proteinuria) during the first 3
months of treatment, a change be made to an
alternative recommended initial therapy, or a
repeat kidney biopsy be performed to guide
further treatment
21. Other Initial Regimens
• Azathioprine
• Cyclosporine
• Combination of tacrolimus and MMF
(sometimes called ‘‘multitarget’’ therapy).
22. Important considerations
• Lifetime maximum of 36 g cyclophosphamide
in patients with systemic lupus.
• The dose of cyclophosphamide should be
decreased by 20%(CrCl 25–50 ml/min) or 30%
(10–25 ml/min)
23. Choice of Initial Therapy
• In severe class III/IV LN, a cyclophosphamide-
containing protocol for initial therapy may be
preferred.
• In patients with less severe proliferative LN, an
initial regimen not containing
cyclophosphamide should be considered.
24. Class III LN and class IV LN
maintenance therapy
• Patients with class III and IV LN receive
maintenance therapy with
• Azathioprine (1.5–2.5 mg/kg/d) or
• MMF (1–2 g/d in divided doses), and
• low-dose oral corticosteroids
25. • CNIs with low-dose cortico-steroids be used
for maintenance therapy in patients who are
intolerant of MMF and azathioprine.
• After complete remission is achieved,
maintenance therapy be continued for at least
1 year before consideration is given to
tapering the immunosuppression.
26. • If complete remission has not been achieved
after 12 months of maintenance therapy,
consider performing a repeat kidney biopsy
before determining if a change in therapy is
indicated.
• While maintenance therapy is being tapered, if
kidney function deteriorates and/or proteinuria
worsens, treatment be increased to the previous
level of immunosuppression that controlled the
LN.
27. Duration of Therapy
• There is no evidence to help determine the
duration of maintenance therapy.
• The average duration of immunosuppression
was 3.5 years in seven RCTs.
• Immunosuppressive therapy should usually be
slowly tapered after patients have been in
complete remission for a year.
28. • Immunosuppression should be continued for
patients who achieve only a partial remission.
• The strategy of trying to convert a partial
remission to a complete remission by
increasing corticosteroids or using alternative
immunosuppressive agents is not supported
by evidence.
29. Predictors of Response to Treatment of
Class III/IV LN
Predictors for not achieving remission:
• SCr at the start of treatment
• Magnitude of increase in SCr during relapse
• Delay in starting therapy for more than 3
months after a clinical diagnosis of LN.
• Severity of proteinuria
• Failure to achieve complete remission a major
risk factor for kidney relapse.
30. Monitoring Therapy of Class III/IV LN
• Proteinuria
• SCr
• Urine sediment
• C3 and C4,
• Anti–double-stranded DNA antibodies
31. Class V LN (membranous LN)
• Patients with class V LN,normal kidney
function, and non–nephrotic-range
proteinuria be treated with antiproteinuric
and antihypertensive medications, and only
receive corticosteroids and immunosup-
pressives as dictated by the extrarenal man-
ifestations of systemic lupus.
32. • Pure class V LN and persistent nephrotic
proteinuria be treated with corticosteroids
plus an additional immunosuppressive agent:
• cyclophosphamide
• CNI
• MMF
• Azathioprine
33. General treatment of LN
• All patients with LN of any class are treated
with hydroxychloroquine(maximum daily dose
of 6–6.5 mg/kg ideal body weight), unless
they have a specific contraindication to this
drug.
34. Class VI LN (advanced sclerosis LN)
• Treated with corticosteroids and immuno-
suppressives only as dictated by the extrarenal
manifestations of systemic lupus.
35. Relapse of LN
• Relapse of LN after complete or partial
remission be treated with the initial therapy
followed by the maintenance therapy that was
effective in inducing the original remission
• If resuming the original therapy would put
the patient at risk for excessive lifetime
cyclophosphamide exposure, then we suggest
a non cyclophosphamide based initial regimen
be used.
36. • Consider a repeat kidney biopsy during
relapse if there is suspicion that the histologic
class of LN has changed, or there is
uncertainty whether a rising SCr and/or
worsening proteinuria represents disease
activity or chronicity.
38. Treatment of resistant disease
• In patients with worsening SCr and/or protei-
nuria after completing one of the initial
treatment regimens, consider performing a
repeat kidney biopsy to distinguish active LN
from scarring.
• Treat patients with worsening SCr and/or
proteinuria who continue to have active LN on
biopsy with one of the alternative initial treat-
ment regimens.
39. • Nonresponders who have failed more than
one of the recommended initial regimens may
be considered for treatment with rituximab,
i.v.immunoglobulin, or CNIs.
40. Systemic lupus and thrombotic
microangiopathy
• The antiphospholipid anti-body syndrome
(APS) involving the kidney in systemic lupus
patients, with or without LN,be treated by
anticoagulation target INR 2–3.
• Patients with systemic lupus and thrombotic
thrombocytopenic purpura (TTP) receive
plasma exchange as for patients with TTP
without systemic lupus.