Management of Lupus Nephritis

1. Dr Kiran Kumar M,
Senior Resident,
Dept of Nephrology, NIMS

2. Immunosuppressive
therapy
Diffuse proliferative LN
(Class IV LN) (Class III LN)
Membranous LN (class V LN)
•Severe nephrotic syndrome
•Elevated Sr Cr
•Asstd proliferative disease
Focal proliferative LN

3. RISK FACTORS FOR PROGRESSION
At the time of initial
presentation
• Elevated Sr Cr
• HTN
•Nephrotic proteinuria,
•Anemia (Hct < 26%)
• Black and Hispanic race
• Tubulointerstitial disease
•Cellular crescents
After initial
presentation and during
therapy
• Frequency and severity
of relapses (renal flares)
• Complete /partial
remission of proteinuria,
hematuria
•Severity of azotemia

4. • Delayed therapy — due to presumed mild
disease
– Increased glomerular injury
– Progressive tubulointerstitial fibrosis
– Glomerulosclerosis
– Lesser response to immunosuppressive drugs
• Better long-term prognosis a/w attaining
clinical remission
– Complete or partial remission is a/w improved
outcome compared to no remission

5. Complete
remission
•Inactive urine
sediment
•Sr Cr ≤ 1.4 mg/dL
•Protein excretion
≤330 mg/day
Partial
remission
• 50 %reduction in
proteinuria to less
than 1.5 g/day
•Stable Sr Cr

6. Predictive of
remission
•Lower chronicity index
on renal biopsy
•White race
•Lower baseline
proteinuria
•Lower Sr Cr
Lower likelihood of
remission
•Male gender
•Earlier development of
nephritis from the time
of diagnosis of lupus

7. Immunosuppressive
therapy for LN
Induction therapy
Administration of potent
immunosuppressive drugs to
achieve remission of
immunologic disease
Avg duration : 6 months
Maintenance
therapy
Given for a prolonged
period to prevent relapse

8. Indications of immunosuppressive
therapy in LN
• Proliferative LN at high risk for progressive
renal failure
– All pts with diffuse proliferative GN
– Most pts with focal proliferative GN
– Membranous LN - Rx against the proliferative
component

9. Focal proliferative GN
• Approximately 10 to 20 % of pts
• Accuracy of diagnosis – sampling error
– 10 to 20 glomeruli may be necessary
Severe involvement on renal
biopsy - 40 to 50 % of glomeruli
affected with
areas of necrosis
crescent formation
subendothelial deposits
Clinical findings
Nephrotic range
proteinuria and/or
Hypertension
Should be
treated as if
they have
diffuse
proliferative
disease

10. Focal proliferative LN with
•< 25 % of the glomeruli
involvement
•only segmental areas of
proliferation without necrosis
•no necrotizing or crescentic
lesions
Clinical findings
•Normotensive
•Subnephrotic proteinuria
•Normal serum creatinine
Glucocorticoids alone –
Prednisolone 60 mg/day
for 1 wk, tapered to
15 mg/day during the
first 3 mths of therapy,
and then continued for
another 3 mths
Glucocorticoids
plus Azathioprine
(2mg/kg/day) X 2 years
Therapeutic
goals
•Loss of
hematuria
•Reduced
proteinuria

11. • Some authors
– Sampling errors- crescents/necrosis missed
– Rx- Steroids + MMF
• Standard induction therapy indicated ( in
apparently mild disease)
– Do not respond within 3 mths
– Develop signs of more severe disease
• Extensive focal necrotizing lesion
• Increasing proteinuria
• HTN and/or
• Rise in Sr Cr

12. Induction therapy
KDIGO guideline
12.3: Class III LN (focal LN) and class IV LN (diffuse LN)—
initial therapy
12.3.1: We recommend initial therapy with corticosteroids
(1A), combined with either cyclophosphamide
(1B) or MMF (1B).
12.3.2: We suggest that, 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. (2D)

13. Cyclophosphamide vs MMF
• Ancestry –
– Black and Hispanic patients may be more likely to
achieve remission with MMF – limited data
• Disease severity –
– More severe disease - elevation in Sr Cr
&/or crescents - cyclophosphamide
• pts in the MMF trials did not generally have severe
disease
• Patient preference - gonadal toxicity

14. Glucocorticoids
IV Methypred (500 to
1000 mg given over 30
min daily for 3days)
•Induce a rapid
immunosuppressive
effect
Oral Prednisolone
•No severe disease- 0.5 to
1 mg/kg per day
• ALMS trial- start 60mg/day
• then tapered every 2 wks by
10 mg/day until 40 mg/day
•Then tapered by 5 mg/day until
10 mg/day was reached
• Further tapering allowed if the
pt was stable for 4 wks

15. Cyclophosphamide
NIH trial
IV Cyclo +
Prednisolone
Aza + Prednisolone Prednisolone alone
90% 60% 20%
Follow up for
10-12 years
Probability of avoiding
renal failure
Gourley MF, Austin HA 3rd, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in
patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996; 125:549.

16. NIH trial (n=82pts)
Class IV LN
Mthly IV Methpred X 1
yr
Mthly IV Cyclo X 6
mths f/b 3 mthly X 24
mths
Methpred + Cyclo
5 months follow up
Remission : 29%
Relapse : 36%
Remission : 62%
Relapse : 7%
Adverse events
more
Remission : 85%
Relapse : 0
Treatment
failure less likely
Treatment
failure less likelyAfter 11 years

17. • Treatment failure - significantly less likely with
combination therapy
– Doubling of the Sr Cr, requiring supplemental
immunosuppression
– Death
Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse
methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus
nephritis. Ann Intern Med 2001; 135:248
• 2004 meta-analysis – cyclo+steroid vs steroid
– Reduced the risk of doubling of the Sr Cr in 4 trials of 228
pts (24 vs 40%)
– No effect on mortality in 5 trials of 226 pts (21 vs 17 %)
– Increased the risk of ovarian failure in 3 trials of 147 pts
(47 vs 19 %)
Flanc RS, Roberts MA, Strippoli GF, et al. Treatment for lupus nephritis. Cochrane Database
Syst Rev 2004; :CD002922

18. • Dosing of cyclophosphamide — higher-dose regimen and
lower-dose regimen:
• Higher-dose regimen –
– pulse IV cyclophosphamide (0.5 to 1 g/m2) monthly for six to seven
mths
– Historically, this initial course was followed by additional IV doses
given quarterly for at least 2yrs
• Lower-dose regimen (Euro-Lupus)
– 500 mg IV every 2 weeks for a total of 6 doses
• Oral cyclophosphamide
– 1.0–1.5mg/kg/d (maximum dose 150mg/d) for 2–4 mths
– Equivalent efficacy to i.v. cyclo in prospective observational studies
– Equivalent to MMF in Chinese pts
– More adverse effects

19. EURO-LUPUS trial
• Comparative trial of primarily white pts
– Mild to moderate renal insufficiency (mean Sr Cr 1.15 mg/dL)
– Low dose Vs higher-dose IV cyclo regimens  each followed by
maintenance therapy with azathioprine
– Equivalent outcomes at a median of 41 mths
• Treatment failure (16 vs 20%)
• Renal remissions (71 vs 54%)
• Renal flares (27 vs 29%)
– Similarity in outcomes persisted at 10 yrs, regardless of the
baseline severity in renal function
• Houssiau FA, Vasconcelos C, D'Cruz D, 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; 46:2121

20. MMF as Induction agent
• An alternative to cyclophosphamide as initial
therapy for proliferative LN
• Several prospective trials – MMF equivalent (but
not superior) to cyclophosphamide
• Largest trial – ALMS trial
– MMF provides greater benefit than
cyclophophamide among black and Latino pts
– Was comparable to mthly IV cyclophosphamide
among white or Asian pts

21. Mthly IV cyclo
(0.75 g/m2 first dose, f/b 5
infusions of 0.5 to 1.0 g/m2)
Aspreva Lupus Management Study (ALMS)
N = 370
Class IV ± V – 68 %
Class III ± V - 16 %
Pure Class V- 16%
Mean urine PCR 4.1
Mean Sr Cr - 1.1 mg/dL
MMF (0.5 g BD in wk 1, 1.0 g BD in
wk 2, and a target of 1.5 g BD
thereafter or if not tolerated,
1.0 g three times to two times
daily)
•At 24 wks - no difference between groups
•Pt attaining normal Cr – MMF (70%) vs cyclo (68%)
•Proteinuria < 500mg/24hrs – MMF (24%) vs Cyclo (27%)
•Greater benefit among black and Latino pts
•No difference in response rate b/w focal or diffuse proliferative and membranous
LN
• Rate of adverse events was not different
Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus
nephritis. J Am Soc Nephrol 2009; 20:1103

22. • Meta-analysis - 45 trials -2846 pts 
– No significant diff b/w cyclo and MMF-based induction
therapy with respect to
• Mortality
• Incidence of ESRD
• Relapse during induction
– MMF - numerically higher rate of complete remissions
(19.5 vs 13.8%)- not statistically significant
– Major infections - similar with both drugs
– MMF - less ovarian failure and alopecia
• Henderson L, Masson P, Craig JC, et al. Treatment for lupus nephritis. Cochrane
Database Syst Rev 2012; 12:CD002922

23. MMF trials
•MMF induction regimen provides similar
efficacy
•MMF may be more effective than
cyclophosphamide and therefore preferred in
black and Hispanic patients ( weak data)
Limitations of the trials
•Duration of follow-up was short (6 to 12 months)
• pts did not have severe disease
•mean Sr Cr -1.1 mg/dL
•mean protein excretion - 3 to 4.7 g/day

24. • Less preferred therapies
• Tacrolimus
– Multicenter non-inferiority trial - 61 Chinese
– Steroids + tacrolimus (trough level of 5 to 10 ng/mL) vs
Steroids + cyclophosphamide (500 to 1000 mg/m2 mthly
for 6 pulses)
– At 6 mths - no diff among groups in the number who
achieved complete remission
Chen W, Tang X, Liu Q, et al. Short-term outcomes of induction therapy with tacrolimus versus
cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial. Am J Kidney Dis
2011; 57:235.
• Short term follow up – limited data- not recommended
for induction
• May be given for pts who cant tolerate cyclo or MMF

25. • Rituximab
Lupus Nephritis Assessment with Rituximab
(LUNAR) study (n=144)
Class III or IV
MMF 1 gm TID X 52 wks
IV methpred 1 gm BD X first 3 days
IV infusion of 1 g of rituximab at
baseline and at 2, 24, and 26
weeks
IV infusion of placebo on baseline
and at 2, 24, and 26 weeks
•Incidence of complete/ partial remission was numerically higher
with Rituximab (57 vs 46 %) - not statistically significant
•Rituximab - greater reductions in anti-DNA titers and larger
improvements in complement level
•2 pts died in the Rituximab group - not related to rituximab
Henderson LK, Masson P, Craig JC, et al. Induction and maintenance treatment of proliferative lupus nephritis:
a meta-analysis of randomized controlled trials. Am J Kidney Dis 2013; 61:74.

27. • Proliferative LN + TMA – Cytotoxic therapy
beneficial
– Plasmapheresis - no added benefit
• significant adverse events, including serious infection
and death
– Plasmapheresis only
• antiphospholipid antibody syndrome,
• auto-antibodies to ADAMTS1
• Flanc RS, Roberts MA, Strippoli GF, et al. Treatment for lupus nephritis. Cochrane
Database Syst Rev 2004; :CD002922

28. MAINTENANCE IMMUNOSUPPRESSION
• Up to 50 % of pts relapse following reduction
in or cessation of immunosuppressive therapy
• Relapse rates
– 5 to 15 per 100 pt-yrs
– Average - 8 per 100 pt-yrs for the first 5 years of
f/u
• Relapse-more common with partial remission

29. Choice of maintenance agent
• Optimal choice - not well defined
– Preferred agent – MMF
• Optimal duration - not well defined
– 12 to 24 mths of oral azathioprine or MMF best
studied
• Alternatives to MMF or azathioprine
– Cyclosporin –effective; more adverse
– Cyclophosphamide – less effective ;higher rate of
infection and amenorrhea

30. MMF or AZA or Cyclo
Randomised trial
(n=59)(whites=3)
Induction therapy
Steroids + 4-7 cycles of
IV Cyclo
Low dose steroid +
MMF (500-
3000mg/day)
Low dose steroid +
Azathioprine (1 -3
mg/kg/day)
Low dose steroid +
IV cyclo (0.5 – 1
gm/m2 every 3
mths
29 months 30 months 24months
Event free survival
rate – 90%
Event free survival
rate – 80%
Event free survival
rate – 45%
More infections,
amenorrhoea,
relapses
Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med
2004; 350:971

31. Azathioprine vs MMF
• Meta-analysis - six trials (n = 514 pts)
– 3 trial compared aza with MMF for maintenance
– No significant differences in the risk of mortality
or ESRD
– MMF - significantly lower rate of renal relapse
(16.4 vs 30.2 %)
– Rate of adverse effects was similar with both
drugs
• Henderson L, Masson P, Craig JC, et al. Treatment for lupus nephritis.
Cochrane Database Syst Rev 2012; 12:CD002922

32. MAINTAIN Nephritis Trial
• Randomized, open-label trial (n=105 ) - European patients (83
Caucasian)
• Class IV - 61, Class III - 33, and class V – 11
• All pts - 3 daily 750 mg doses of IV methpred f/b oral
glucocorticoids + six 500 mg IV cyclo over 10 wks
• On wk 12, maintenance therapy was initiated with
either azathioprine (2 mg/kg per day) or MMF (2 g/day)
• Renal relapse was defined as one or more of the following:
– recurrence or development of nephrotic syndrome
– ≥ 33% increase in Sr Cr within 1 mth
– threefold increase in proteinuria accompanied by hematuria
• Houssiau FA, D'Cruz D, Sangle S, et al. Azathioprine versus mycophenolate mofetil for long-term
immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010; 69:2083

33. • At 3 years
– No significant diff b/w MMF and aza groups in
• Rate of renal relapse (19 vs 25 %)
• Systemic flares
• Steroid withdrawal
– Protocol biopsies 2 yrs revealed no significant
histologic differences between the groups
– Adverse events were similar

34. ALMS Maintenance Trial
• Multinational study (N=227) - who had achieved
remission with either MMF or Cyclo randomly
assigned to MMF (1 g BD) or aza (2 mg/kg per
day) as maintenance therapy for 36 mths
– Treatment failure at 36 mnths - significantly lower
with MMF (16 vs 32 %)
– Superiority of MMF was independent of the type of
induction therapy, race, or region
• Dooley MA, Jayne D, Ginzler EM, et al. Mycophenolate versus azathioprine as
maintenance therapy for lupus nephritis. N Engl J Med 2011; 365:1886

35. KDIGO guidelines
12.4.1: We recommend that, after initial therapy is complete, 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 (r10 mg/d
prednisone equivalent). (1B)
12.4.2: We suggest that CNIs with low-dose corticosteroids be used for maintenance
therapy in patients who are intolerant of MMF and azathioprine. (2C)
12.4.3: We suggest that, after complete remission is achieved, maintenance therapy
be continued for at least 1 year before consideration is given to tapering the
immunosuppression. (2D)
12.4.4: 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. (Not Graded)
12.4.5: While maintenance therapy is being tapered, if kidney function deteriorates
and/or proteinuria worsens, we suggest that treatment be increased to the
previous level of immunosuppression that controlled the LN. (2D)

36. DISEASE RESISTANT TO INDUCTION THERAPY
• Defined as the failure to achieve either complete
or partial remission
– a/w worse long-term prognosis compared to pts who
attain remission
– Assessment for the development of remission requires a
minimum of 3 mths
– A repeat renal biopsy is indicated in selected patients with
resistant LN
• clear understanding of the extent of immunologic remission is
essential

37. Treatment of resistant disease
• Treat cyclophosphamide-resistant pts with
MMF, and MMF-resistant pts with cyclo
• Induction & maintenance regimens used in
resistant LN are the same as those used for
primary therapy
• Pts who fail treatment with both cyclo and
MMF may be treated with Rituximab

38. Rituximab for cyclophosphamide and MMF resistance
• Long-term efficacy and toxicity have not been fully defined
• Largest reported experience - 23 pts
– Class III or IV LN - persistent disease activity despite a variety of drugs -
cyclo (11 pts) or MMF (12 pts) as well as other drugs
(eg, cyclosporine, azathioprine)
– Rituximab (0.5 to 1 g on days 1 and 15) was added to the existing
immunosuppressive regime
– 3 mths f/u
• 5/23 - complete response (normal serum creatinine, inactive urine sediment,
and protein excretion <500 mg/day)
• 7/23 - partial response (>40 % improvement in renal parameters)
• Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, et al. Clinical and immunological effects of
Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res
Ther 2006; 8:R83

39. • Melander C et al
– 20 pts ( class IV - 15 pts or Class V - 5 pts)
– 18 pts – resisitant or relapsing
– Rituximab - 375 mg/m2 weekly X 4 weeks
– 10 pts received additional doses of rituximab as maintenance
therapy because of an increase in B cell count
– Mean follow-up of 22 mths
• 5/15 class IV achieved complete remission
• 5/15 - partial remission, defined as decrease in protein excretion by at
least 50 percent and stabilization of the eGFR
• Melander C, Sallée M, Trolliet P, et al. Rituximab in severe lupus nephritis: early B-
cell depletion affects long-term renal outcome. Clin J Am Soc Nephrol 2009; 4:579

40. MMF plus tacrolimus
• Cortés-Hernández J et al
• Cortés-Hernández J, Torres-Salido MT, Medrano AS, et al. Long-term outcomes--mycophenolate
mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases. Nephrol Dial
Transplant 2010; 25:3939
Observation study (n=17; class IV-15,
class V-2)
Tacrolimus (.075mg/kg/day) was
added to MMF
6 pts (35 %) - complete
response
•Protein excretion <0.3 g/day
•normal sediment
•normal or stable renal
function
6 pts (35%) - partial
response
•Protein excretion
<2.9 g/day
•stable or improved
renal function

41. Relapsing
diasease
Incidence –
5 to 15 per 100 patient
years
Risk factors
•More severe disease at baseline
•Delay in reaching remission
•Attainment of partial compared
to complete remission
Definition
•recurrent immunologic
activity
• active urine sediment
(a "nephritic" relapse)
• increases in protein
excretion
•Increase in Sr Cr
Monitoring - 3-4 mthly
•Urinalysis
•urine PCR
•Sr CR
•Serologic factors (C3,
C4 , anti-dsDNA titers )

42. • Slowly progressive inactive LN should NOT be treated
with immunosuppressive agents
– Aggressive antihypertensive and antiproteinuric therapy -
RAS blockade
– Target BP < 130/80 mmHg
– Target protein excretion < 500 to 1000 mg per day
• Pts - increase in anti-dsDNA titers or new
hypocomplementemia following a clinical remission
– Monitored more carefully (particularly over the ensuing 3
months)
– Generally not treated SOLELY for changes in serologic
activity

43. Treatment of relapse
• Mild relapse- increased activity of urine sediment and
possibly a modest (< 50%) increase in protein excretion but
with a stable Sr Cr
– Not on maintenance - oral prednisone (60 mg/day for one
wk, tapered to 30 mg A/D for 3 mths)
– Initially treated with cyclo who are now on aza maintenance
therapy - increase the dose of prednisone as well as
azathioprine
– initially treated with MMF for induction and who are now off
maintenance therapy - MMF may be restarted
– still on maintenance therapy with lower doses of MMF- the
MMF dose can be increased to 2 to 3 g/day

44. • Moderate – severe diasease
• Active urine sediment plus a rise in serum creatinine
with or without increased proteinuria
– Cyclo was used for induction and the pt is
taking aza for maintenance- MMF is preferred
– MMF was used for induction and the pt is no
longer taking maintenance - either MMF or cyclo
• Cyclo is preferred if relapse occurs while the pt is still
taking MMF for maintenance
– Pts who continue to relapse, like those with
resistant LN - trial of rituximab

45. Treatment of Class IV + V LN
• More likely to be resistant to standard
induction regimens with cyclophosphamide
• Have worse long-term renal outcome
• Respond better to combined induction
therapy with MMF + Tacrolimus

46. Prospective trial (n=40)
Class IV+V LN
3 doses of IV methpred f/b
prednisolone
MMF (0.75 to 1 g/day)
+
Tacrolimus (3 to
4 mg/day)
IV cyclophosphamide
Follow up of 9 mths
complete remission –
65%
Follow up of 9 mths
complete remission –
15%
Glassock RJ. Multitarget therapy of lupus nephritis: base hit or home
run? J Am Soc Nephrol 2008; 19:1842

47. Membranous Lupus Nephritis
• NON-IMMUNOSUPPRESSIVE THERAPY
Angiotensin inhibition – no RCTs
•ACE-I or ARB - recommended in
virtually all pts with proteinuric CKD
•Lowers intraglomerular pressure
 reduce the rate of disease
progression
•Target < 1000 mg/day
•At least 50 - 60%from the baseline
level+ protein excretion < 3.5 g/day
Control of BP
•Target < 130/80 mm Hg
•slow the progression of proteinuric
chronic kidney disease
• cardiovascular protection
Lipid-lowering
•control of serum LDL cholesterol is
the main indication
•slow the progression of the
underlying renal disease
Anticoagulation
•Risk of thrombotic events - DVT,
RVT, PE
• prophylactic anticoagulation
•massive proteinuria
•serum albumin < 2.0 g/dL

48. Indications for immunosuppressive therapy
• One or more of
1. Persistent severe and symptomatic nephrotic
syndrome
2. Increased or rising Sr Cr
3. Mixed membranous and proliferative lesions on
Bx which may be present at diagnosis or develop
late

49. Nephrotic syndrome
• morbidity - thromboembolism,
hyperlipidemia, accelerated
atherosclerosis
•higher rate of progressive disease
•lower likelihood of attained
remission
Concurrent proliferative LN
—
•worse prognosis
•more rapid loss of renal
function
•higher rate of end-stage
renal disease

50. NIH trial of cyclophosphamide vs cyclosporine
42 pts with pure membranous LN
median protein excretion - was 5.4 g/day
median eGFR - 83 mL/min per 1.73 m2.
A/D prednisone
40 mg/m2 X 8
wks & then
tapered to
10 mg/m2)
A/D prednisone
+ pulse IV
cyclo every
other month
A/D
prednisone +
cyclosporine
200 mg/m2 5
mg/kg] per day
in two divided
doses
•Follow up – 1 yr
•Complete remission - protein excretion < 0.3 g/day
•Partial remission - protein excretion < 2.0 g/day with > 50 %
reduction in proteinuria
Austin HA 3rd, Illei GG, Braun MJ, Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in
lupus membranous nephropathy. J Am Soc Nephrol 2009; 20:901

52. • Pts with remission of proteinuria were
followed for up to 10 yrs
– Relapse after cessation of therapy was
significantly later and less frequent with
cyclophosphamide (20 % within 50 mths vs 60 %
within 36 mths with cyclosporine)
– All of the cyclophosphamide relapses occurred
four years or more after cessation of therapy.

53. • Role of MMF
– Current role of MMF in the treatment of patients with
pure membranous LN is not clear
– 2 trials – ALMS & another RCT- long term follow up is
not reported
• Chlorambucil versus methylprednisolone
– Ponticelli group - Methpred alone (8 pts) and
Methpred + chlorambucil alternated every other
month for 6 mths
– Intermittent Methpred + chlorambucil –
• higher rate of complete or partial remission (90 vs 38 %)
• lower rate of renal flares (10 vs 88 %).

54. Timing of immunosuppressive therapy
Class V LN
Severe , symptomatic
nephrotic syndrome
(usually with a
serum albumin <2.5 g/dL
No or mild to moderate
nephrotic syndrome and
a serum albumin >
2.5 g/d
•Immunosuppressive
therapy
•Angiotensin inhibition
•rigorous BP control
maximum
angiotensin
inhibition X 3-6 mths
Proteinuria <
3.5 g/day
Continue
ACE-i/ARBs
Proteinuria >
3.5 g/day
Continue
ACE-i/ARBs +

55. KDIGO guidelines
• 12.5: Class V LN (membranous LN)
• 12.5.1: We recommend that 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 immunosuppressives as dictated by the extrarenal
manifestations of systemic lupus. (2D)
• 12.5.2: We suggest that patients with pure class V LN and persistent
nephrotic proteinuria be treated with corticosteroids plus an additional
immunosuppressive agent: cyclophosphamide (2C), or CNI (2C), or MMF
(2D), or azathioprine (2D).
• Joint European League Against Rheumatism and European Renal
Association-European Dialysis and Transplant Association (EULAR/ERA-
EDTA) - mycophenolate mofetil as first-line therapy