LN is a serious complication of SLE, we have to predict, early diagnose & rapidly treat & follow up meticulously to prevent ESRD

1. Updates in lupus nephritis

2.  When lupus nephritis patient come into your
clinic, He/she is already lost significant number
of nephrons…
 So we are already lagging behind the race!

3. Race against nephron loss

4. What is severe lupus nephritis ?
 Lupus nephritis is always severe….

5. What do we have for LN ?
 We have “the sequential therapy paradigm” :
1- Initial Induction of remission
2- Subsequent therapy to maintain remission

6. EULAR and European renal association (ERA),
current standard of care protocol
“Sequential therapy”

7. Maintenance:

8. What do we achieve with standard of care protocol
“sequential therapy” ?
-Results are unsatisfactory…! there is unmet need in LN
- CRR can be achieved in only in 20 -30 % of cases.!
CRR (UPCR ≤ 0.5 gm /24h , S. creatinine ≤ ULN and not
increased > 15 % from baseline value & < 10 RBCs per high
power field without casts )
- 20 - 25 % relapses 3-5 Y
- 5 - 20 % patients ---→CKD----→ ESRD at 10 Y

9. To win the race against LN
 1-Treat to target approach
 2- Switch from “sequential ” to “combination therapy”
 Correct comorbidities

10. Treat to target approach
 Clinical target
 Pathological target
 Immunopathological target

11. Proteinuria

12. Target “ ≤ 0.7g proteinuria / 24 h achieved at 12 months”

14. After one year of therapy of LN

15. ReBioLup at the end of the 1st year

17. “Window of opportunity”
 “The first 6 months of lupus nephritis” we have a true
opportunity to achieve complete renal response (CRR).
Every effort should be done to achieve 50% decrease in
proteinuria during the 1st 3 m and CRR by the end of 6
m. ( ≤ 0.5 p/c ratio)
 Recent recommendation is to start combination
therapy as early as during the1st 3 months specially in
proliferative LN (III/IV).

18. Combination therapy ?
 Four new FDA approved medicine in 2020 -
2021 to treat LN on top of the well known
“standard of care protocol ”

19. Vaclosporine (Lupkynis), new CNI inhibitor, FDA
approved in Jan 2021, it is the 1st approved oral
treatment in difficult to treat LN.
It should be used on top of standard of care regimenwithMMF
best during the 1st 6 months of therapy

24. Belimumab (Benlysta),1st FDA approved
biological therapy in active LN (Dec. 2020)
 It is full humanized monoclonal ab that binds to
soluble(BLyS/BAFF), a B lymphocyte stimulator protein
 Benlysta doesn’t bind B cells directly, it binds to BLys-→
inhibiting the survival and differentiation of B cells.

27. Obinutuzumab (Gazyva), anti –CD 20 monoclonal ab
much more potent B cell depletion than Rituximab
 Nobility study (n=125) in adults withdifficult to treat LN
class III / IV :
 Obinutuzumab + MMF 2g + CS ≤ 10mg
 Placebo + MMF 2g + CS ≤ 10 mg
→ higher rate of CCR at one year in the Obinutuzumab
arm vs Placebo
The drug acts on both glomerular and tubulointerstitial
disease

28. Anifrolumab (Saphnelo) : an anti –interferon 1 receptor
Monoclonal ab, FDA approved in Aug 2021
TULIP LN phase II study (n=145) adults e proliferative LN III,
IV,V:
 Anifrolumab (IR) (900 mg for 3 doses) + Standard of care
MMF 2g + low dose steroids ≤10 mg vs
 Placebo + 2 gm MMF+ ≤ 10 mg CS ---→ 52 weeks
Higher rate CRR (40- 45% )of patients with intensifiedregime
Anifrolumab(not the basic regime),compared to placebo

29. How to choose treatment----→ Look at the kidneys
 Extrarenal disease.. (NPSLE)
 Look at tubulo-interstitialtissue infiltration by immune cells lymphocytes
Scattered or aggregates of lymphoidfollicles.
 Search for Antibody Secreting Cells (ASC)in tubulointerstitial tissue
specially seen in class IV proliferativeLN

30.  Look at global kidney transcriptome by compare lupus vs control fresh
kidney biopsy you can find interferon gene signature (best ttt by interferon
blockade)
 Single cell ASC transcriptomeby PCR analysis for gene involvedin
proliferation:
Plasmablast ----→in fresh kid biopsy in untreated LN
Plasmacells ---→ are present in refractory LN cases during flares

31. Liquid biopsy!
 We look at the ASC in the kidney and in the urine using single cells
PCR analysis , the kidney and the urine are matched very well
 So we might use the urine as a liquid biopsy to evaluate the
molecularsignature to choose one treatment overthe other