DIAGNOSIS AND MANAGEMENT OF LUPUS NEPHRITIS WONDERFUL

1. LUPUS NEPHRITIS
PREPARED BY
DR MOHAMMED AL SHAER
NEPHROLOGY SPECIALIST-KFHM

2. DEFENETION AND EPIDEMIOLOGY
• DEF DETAIDEM XELPMOC EUMMI NA SI TI:
ELS NI SRUCCO TAHT SITIRHPENOLUREMOLG
STNEITAP.
• EPID SI ECNALAVERP DNA ECNAEDICNI:
SROTCAF YNAM YB DECENELFNI:
• AGE
• GENDER
• ETHNICITY:30% in White, 60% in Black and
Hispanic, and 40% to 80% in Asian patients with SLE
• GENETICS AND ENVIROMENTAL

3. PATHOGENESIS OF LUPUS NEPHRITIS
Autoantibodies are crucial to the pathogenesis of
LN.
Patients with LN have autoantibodies against
dsDNA, Sm antigen, C1q, nucleosomes, and other
antigens.
Glomerular immune complexes activate
proinflammatory mechanisms, including the
complement pathway result in complement
mediated kidney damage.
There is direct binding of dsDNA antibodies to the
glomerular basement membrane (GBM)

4. DIAGNOSIS
o CLINICAL AND LABORATORY
o HISTOPATHOLOGICAL

6. RENAL FEATURES
of SLE

8. IMMUNOLOGICAL
 ANA < 90% of untreated patients with lupus.
 Anti-dsDNA <75% of untreated lupus patients.
 Sm antibodies is very specific but not sensetive
)25% to 30% of patients(
 Anti-C1q have been more closely associated with
the activity of LN than anti-dsDNA.
 COMPLEMENTS HC:/ C3 and C4 are usually
depressed especially in LN. )low C4 with normal C3
in a patient with lupus may reflect genetic C4 deficiency or
the presence of cryoglobulins(.

9. CLASSIFICATIONS
HISTOPATHOLOGY AND

10. PROTEIN EXCRETION < 500 MG/DAY.
ACTIVE URINARY SEDIMENT
WITH PERSISTANT
HEMATURIA.
RISING SERUM CREATININE THAT IS
NOT CLEARLY ATTRIBUTABLE TO
INDICATIONS OF RENAL
BIOPSY
ELS NI

11. PATHOLOGY
 ISN/RPS GNIDROCCA SITIRHPEN SUPUL YFISSALC
EVIF OT YRUJNI RALUREMOLG OT
SESSALC.
 LESS COMMON GLOMERULAR PATHOLOGIES OMITTED FROM
ISN/RPS SYSTEM LIKE LUPUS PODOCYTOPATHY AND PAUCI
IMMUNE CRESCENTIC GN (anlogous to ANCA-associated
vasculitis(
 Although IgG is the dominant glomerular Immunglobulin in LN,
IgA and IgM along with the complement components C1q and C3
are often seen as well, giving the “full-house” pattern that is
highly suggestive of LN.
 Strong glomerular C1q staining is also suggestive of
LN.
 Fibrin staining, corresponding to active lesions especially
in crescents, if present.
 Tubuloreticular inclusions, are thought to reflect a high interferon

14. MININMAL
MESANGEAL
(CLASS I(
The glomeruli are normal
by light microscopy, but
immunofluorescence and
electron microscopy
reveal mesangial immune
deposits.
Affected patients
typically have a
normal urinalysis and
serum creatinine
concentration.

15. Mesangial proliferative
LN (class II)
Mesangial hypercellularity
and/or expansion with
mesangial immune
deposits.
Microscopic hematuria;
proteinuria, if present, is
usually low-grade.
Preserved renal
function; hypertension
infrequent; excellent
renal prognosis*

16. Focal LN III (A): Purely active lesions:
focal proliferative LN III (A/C): Active
and chronic lesions: focal proliferative
and sclerosing LN III (C): Chronic inactive
lesions with glomerular scars: focal
sclerosing LN
Segmental or global endocapillary
or extracapillary
glomerulonephritis affecting less
than 50% of glomeruli with
mesangial and subendothelial
immune deposits.
UE:Microscopic hematuria;
proteinuria.
Hypertension possible; renal
insufficiency and nephrotic
syndrome not unusual; variable
renal prognosis .

17. CLASS IV
DIFFUSE PROLIFERATIVE
IV: Diffuse LN IV-S (A) or IV-G (A):
Purely active lesions: diffuse
segmental (S) or global (G)
proliferative LN IV-S (A/C) or IV-G
(A/C): Active and chronic lesions:
diffuse segmental or global
proliferative and sclerosing LN IV-S
(C) or IV-G (C):
Inactive with glomerular scars:
diffuse segmental or global
sclerosing LN S: >50% of affected
glomeruli have segmental lesions G:
>50% of affected glomeruli have
global lesions.
Microscopic hematuria; proteinuria.
Hypertension; renal insufficiency
and nephrotic syndrome frequent;
variable renal prognosis

19. CLASS V(MEMBRANOUS(
Glomerular basement
membrane thickening with
subepithelial and mesangial
immune deposits
High-grade proteinuria;
microscopic hematuria
possible.
Preserved renal function;
nephrotic syndrome
common; renal prognosis
good* Anti-PLA2R
antibody negative.

22. RISK FACTORS FOR PROGRESSION
I. Elevated serum creatinine.
II. HTN.
III.Nephrotic range proteinuria.
IV.Anemia with a hematocrit below 26 %
V. Black and Hispanic race and ethnicity.
VI.Renal biopsy findings.
VII. Frequency and severity of relapses.
VIII.Complete or partial response.

24. HYDROXYCHLOROQUINE
• IT IS RECOMMENDED BY ACR THAT ALL PATIENTS
WITH SLE AND NEPHRITIS SHOULD USE
HYDROXYCHLOROQUINE UNLESS
CONTRAINDICATED g.e(Retinopathy due to 4-
aminoquinolone,hypersensetivity,long term in children(
• IT WAS FOUND TO DECREASE RENAL FLAIRES,IMPROVE
RENAL SURVIVAL AND SLOW PROGRESSION TO ESRD.
• PATIENTS RECEIVING HYDROXYCHLOROQUINE
SHOULD HAVE REGULAR FUNDOSCOPIC EXAM.

26. MANAGEMENT OF LUPUS
NEPHRITIS

27. CLASS I AND CLASS II TREATMENT
In general, the immunosuppressive
treatment of extrarenal lupus
manifestations is sufficient for class I
and II LN.
In class II if you have proteinuria > one
gram ,low dose steroids can be used(

28. TREATMENT OF CLASS III/IV OR
CLASS V/III OR IV

29. I-NON IMMUNOSUPPRESSIVE
THERAPY

30. NON IMMUNOSUPPRESSIVE THERAPY
HYDROXYCHLOROQUINE
Aggressive BP
control
ACEi OR ARBs if having
protienuria
 Lipid lowering with statin
therapy
OTHER CONSERVATIVE
MEASURES

31. TREATMENT OF CLASS III/IV OR CLASS V
PLUS III OR IV
IT CONSISTS OF TWO PHASES:
• INDUCTION: given in an attempt to induce a
renal response and disease quiescence.It consists
of STEROIDS plus either IV CYCLOPHOSPHAMID(or
oral)OR MYCOPHENOLATE(MMF(
• MAINTENANCE:It helps to maintain the response
and decrease the risk of developing end-stage
renal disease (ESRD). Mycophenolate mofetil
and azathioprine are the most commonly used
plus tapering doses of oral steroids.

32. HISTORY OF PROLIFERATIVE LUPUS NEPHRITIS
TREATMENT
• AT 2004 EVERY PATIENT WAS RECEIVING
CYCLOPHOSPHAMIDE:
• CHILD OR ADULT.
• WHITE OR BLACK.
• HAS SIDE EFFECTS OR NO.

33. EURO-LUPUS NEPHRITIS
TRIAL

41. THAT WAS WITHIN 3-4 YEARS..
WHAT ABOUT AFTER 10 YEARS...!

44. MYCOPHENOLATE INDUCTION

46. ALL PATIENTS RECEIVED NIH PROTOCOL
WITH CYCLOPHOSPHAMID FOR SIX
MONTHS.
AFTER THAT DIVIDED INTO THREE GROUPS
I. FIRST CONTINUED ON CYCLOPH .
II. SECOND ON MYCOPHENOLATE.
III. THIRD ON AZATHIOPRINE .

49. WHAT WAS THE SIDE EFFECTS
OF THESE DRUGS !

51. BECAUSE THEY FOUND THAT ORAL
AGENTS HAS LESS SIDE
EFFECTS,ANOTHER QUESTION WAS
RIASED!
WHY NOT TO USE THE MMF FROM
THE FIRST DAY !

54. THAT WAS WITHIN 6 MONTHS,
WHAT HAPPENS AFTER 3 YEARS

56. STUDY PROBLEMS
ALL PATIENTS ARE FROM THE US AND
CROSS OVER THAT OCCURED. SO WHAT
TO DO!

57. BIGGER NO 370 PATIENTS.
INTERNATIONAL:THIRD FROM US,THIRD
FROM CHINA AND A THIRD FROM
EUROPE AND SOUTH AMERICA.
ALMS STUDY

62. MAINTENANCE PHASE IN ALMS STUDY

70. CLASS V MEBRANOUS TREATMENT