SLE- LUPUS NEPHRITIS Case presentation grand round- Hypothyroidism

1. Case Presentation
By :Darayus P. Gazder

2. History:
• A 35 year old married female with no known comorbids admitted
on 24th November 2016 presented with Complains of:
• Generalized swelling all over body since 20 days
• Abdominal pain since 1 day

3. History of Presenting Complains
• According to my patient she was in her usual state of health 20 days
ago, when she developed swelling all over her body. It was sudden in
onset, progressively started from the feet and moved upwards,
symmetrically. Swelling was present around her abdomen, arms and
wrist. According to her she noticed her face also became puffy and her
weight had increased in these 20 days.
• Since 1 day, she developed abdominal pain which was gradual in onset,
heavy in character, in the epigastric region of the abdomen, non
radiating pain. She rated the pain as moderate in intensity which later
increased in intensity and was rushed to the hospital, where she
received pain killers and her pain subsided.. Pain was associated with
decreased appetite and about 3-4 episodes of vomiting. Vomiting was
projectile, colour was greenish and there was no blood in the vomitus.
• There is no H/O sore throat, skin rashes, chest pain, dyspnea, PND,
urinary complains, jaundice or headaches

4. System Review
Respiratory System
•Cough:+ve
•Sputum
•Haemoptysis
•Chest pain
•SOB/Dyspnoea
•Hoarseness
•Wheezing
Cardiovascular
•Chest pain
•Paroxysmal Nocturnal Dyspnoea
•Orthopnoea
•Short Of Breath(SOB)
•Palpitations
•Cyanosis
Gastrointestinal/Alimentary
•Oral ulcers: +ve
•Nausea/vomiting:+ve
•Difficulty in swallowing: +ve
•Abdominal pain/distension +ve
•Constipation
•Regurgitation/heart burn
•Haematemesis, melaena,
haematochagia
•Jaundice
Nervous System
•Visual/Smell/Taste/Hearing
Speech problem
•Head ache
•Fits/Faints/LOC
•Muscle weakness
•Abnormal sensation
•Change of behaviour
-ve
-ve
-ve
-ve

5. System Review
Urinary System
•Frequency
•Urgency
•Hesitancy
•Terminal dribbling
•Nocturia
•Back/loin pain
•Incontinence
•Character of urine
Musculoskeletal System
•Pain
•Swelling
•Back or neck pain
•Red eyes
•Deformities
•Skin rash
•Painful/ cold fingers
Endocrine System
•Swelling in neck:+ve
•Fatigue:+ve
•Skin: Dry
•Hair:
a)Thinning of hair, patchy
Alopecia
b) Loss of eyebrow hair
•Cold intolerance:+ve
•Thirst
•Sweating
•Tremors
-ve
-ve
-ve

6.  Past Medical History:
Joint pains and swelling since 2 years, symmetrical on and off in hands,
wrists. Associated with morning stiffness >30 minutes
 Past Surgical History:
4 C-sections. No H/o blood transfusions
 Drug history:
No Known Drug Allergies
 Family history:
There is a H/o Hypertension and diabetes in the family.
No history of Ischemic heart disease, tuberculosis, asthma, thyroid
disorders, autoimmune diseases or cancers in the family

7. Obstetric History
No. of
Pregnancies Date of delivery
Duration of
Pregnancy
Any abnormality in
Pregnancy Mode of Labour Place of Delivery Puerperium Child
1 2007 10 weeks Abortion Spontaneous Home
2 2009 FT C/Section HOSPITAL F
3 2012 FT C/Section HOSPITAL F
4 2013 FT C/Section HOSPITAL M
5 Apr-16 FT C/Section HOSPITAL M

8. Gynecological History
• Age of menarche: 12yrs
• Irregular menstruation
• No H/o Contraceptive use.

9. • Personal History:
Sleep: Normal / Bowel: Normal / Micturition: Normal / Appetite: Dec/
Addictions: None
Social History:
She is a housewife and has 4 children. Eats meals cooked at home.

10. Examination:
• General Impression:
A 35 year old female lying on bed, with generalized swelling all
over the body, periorbital edema with cannula in right hand, well
oriented in time, person and place.
Vitals:
• Blood Pressure:130/90 mm/Hg
• Pulse: 70/min,
• Temperature: A/F
• Respiratory Rate:16/min
• Oxygen saturation: 96% room air
Weight 70kg , Height: 5’ 6’’ BMI: 25.17 kg/m2

11. General Physical Examination:
 Thyroid: Diffuse, non-tender, smooth enlargement of her
thyroid. Not moving with protrusion of the tongue. No
mass or nodules felt. No eye signs were present.
 Throat: Hyperemic, presence of oral ulcer on palate and
buccal mucosa
 Anemia: +ve
 Pedal Edema: +ve [Grade 2 Pitting edema]
 Jaundice: -ve
 Clubbing: -ve
 Koilonychia: -ve
 Lymph Nodes: -ve
 Dehydration: -ve

12. Examinations:-
ABDOMEN:
• Inspection: Distended, Previous C-section scar and white coloured
striations were present, umbilicus was central inverted.
• Palpation: Tense, tender in the epigastric region. No visceromegaly.
• Percussion: Fluid thrill and shifting dullness were not appreciated.
• Auscultation: Gut sounds were audible
RESPIRATORY:
• Inspection: Normal shape of chest, Movements were equal on both
sides. No deformity or scar marks.
• Palpation: Trachea: Central, chest movements were equal.
• Percussion: Dullness at the bases
• Auscultation: Decreased air entry on the bases, Crepitation's present
CVS:
• Inspection: No chest deformities, bulging, prominent veins or scars
• Palpation: Apex beat 5ICS MCL. No thrill or heave
• Auscultation: S1+S2+0
CNS: GCS 15/15. Intact.

13. Differentials??
• Enlarged thyroid, Weight gain,
Constipation, hair loss, dry skin
edema, menorrhagia
Hypothyroidism
• Hypertension, Weight gain, Fatigue,
Periorbital , Pedal edema, Pitting
edema
Nephrotic
syndrome
• Arthralgia, fatigue, oral ulcers,
arthritis, photosensitivity, malar
rash, hair loss
SLE

14. PREVIOUS INVESTIGATIONS:

15. CBC UNIT RANGE
Hb 9.9 mg/dl 11.1-14.5
MCV 79.1 fL 80-100
MCH 24.7 Pg 27-34
MCHC 31.2 gm/dL 31-36
WBC 5.4 109 per liter 4 to 10
PLATELETS 223 109 per liter 150-450
UCE
Na 141 Meq/L 135-145
K 4.4 Meq/L 3.5-5.5
CL 112 Meq/L 98-107
HCO3 22.6 Meq/L 22-29
UREA 43 mg/dl 10 to 50
CREATININE 0.8 mg/dl 0.6-1.5
LFT
TB 0.1 mg/dl <1.3
DB 0 mg/dl <0.3
SGPT 11 IU/L Upto 31
SGOT 18 IU/L 7-56
ALK P 50 U/L 39-117
GGT 46 IU/L 11 to 50
S. ALBUMIN 1.6 g/dL 3.5-5.2
A. AMYLASE 57 U/L 28-100
TFT
S.TSH 41.4 uIU/mL 0.4-4.2
FREE T3 1.8 Pg/mL 2.1-4.4
FREE T4 0.56 ng/dL 0.89-1.76

16. URINE D/R

17. Neck Ultrasound
Thyroid gland is enlarged in size.
Coarse echotexture of thyroid parenchyma with increased vascularity is noted.
Needs clinical correlation
Ultrasound ABDOMEN and Pelvis:
Normal size subtle coarse liver.
Thick walled contracted gall bladder, wall thickness measures 0.48cm.
Bilateral pleural effusion seen.
Mild amount of ascites fluid is noted.
Anterior lower abdominal wall is thickened and edematous.
Normal scan of Pelvis

18. TREATMENT AND HOSPITAL
COURSE:
• She was started on:
• Inj N/S @60ml/hr
• Tab Thyroxine 50mcg 4+0+0
• Inj Omeprazole 40mg 1+0+0
• Tab Domperidone 1+1+1
• Inj No-Spa (Drotaverine) 0+0+1
• Further investigations were sent:
• 1) Urine Protein/Cr ratio
• 2) Lipase, TgAb, TPOAb, HbsAg, Anti-HCV
• 3) ANA, ESR, FLP, CXR
• Nephrology consult was given.

19. HospitalAdmission
Day1-2
S> Sore throat, Odynophagia
O> Awake, Alert, Adequate urine output Puffiness around eyes
>Vitals: Stable
>Abdomen: distended, non tender, No visceromegaly
>Throat: Hyperemic, Oral thrush, Ulcers
> Grade 2 Bi-pedal edema/ Pitting
URINARY PROTEINS 264
URINARY CREATINIE 177.72
RATIO 1.48
ESR 0 to 20 mm/hr 67
HEP PROFILE Negative
S.CHOLESTEROL <200 mg/dl 259
S.TRIGLYCERIDES <150 mg/dl 112
HDL 40mg/dl 27
LDL <100 210
LIPASE 0-50 U 25
ANA Postive
ANTI-THYROGLOBULIN Ab More than 110 132.9
ANTI-THYROID PEROXIDASE Ab More than 55 56.4

20. CXR

21. HospitalAdmission
Day1-2
A> Hashimotos Thyoiditis
> SLE  Lupus nephritis?
P> Continue Thyroxine
> Tab Itraconazole OD
> Tab Atorvastatin 10mg (0+0+1)
Tab Prednisolone 5mg (3+3+0)
> DsDNA, C-3, 24 hr Urinary Collection advised
Nephrotic range proteinuria: Warrant renal biopsy
Nephritic range proteinuria: ARB/ ACE

22. HospitalAdmission
Day3-4
S> Cough
O> Awake, Alert, swelling was improving
> Vitals: Stable
> Abd: distended, non tender, No visceromegaly
> Resp: Bases dec air entry, with crepts
> Throat: Improving
> Grade 2 Bi-pedal edema
INVESTIGATIONS
C-3 (90-180) 26.5
ANTI-dsDNA More than 1.1 IU/ML 3.31

23. A> Lupus nephritis with thyroiditis
P> Continue previous treatment
> Start Tab Azithromycin 500mg OD, then 250 mg from the following day
> Add INJ ALBUMIN 25% in 100ml 1+0+1
> Add INJ HEPARIN 500 Units 1+0+1
> Plan Renal biopsy
5th Postadmission day patient got LAMA

24. Lupus nephritis
Hahn BH, Mcmahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas
GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey‐Goldman R.
American College of Rheumatology guidelines for screening, treatment, and
management of lupus nephritis. Arthritis care & research. 2012 Jun 1;64(6):797-808.

25. Introduction
• Systemic lupus erythematosis is an autoimmune disease in
which organs and cells undergo damage initially mediated by
tissue binding autoantibodies and immune complexes.
• The term lupus means ‘Wolf’.
• The median age of onset in SLE is 24.5 years and the sex ratio
(F:M) is 9:1.

26. Etiopathogenesis
•
• Polymorphisms in
HLA locus on
chromosome 6
Inherited mutations
in:
• Complement
C1q,C2,C4
• Immunoglobulin
receptor FcyIIIb
• DNA Exonuclease
TREX1

27. Antibody & Prevalence Clinical Utility
Antinuclear
antibodies
98 Best screening test (May occurs years before overt disease)
Anti-dsDNA 70 SLE-specific and in some patients correlate with disease activity, nephritis,
vasculitis
Anti-Sm 25 Specific for SLE (Lupus nephritis)
Anti-RNP 40 Not specific for SLE (MCTD)
Anti-Ro (SS-A) 30 Not specific for SLE; associated with sicca syndrome, predisposes to
subacutecutaneous lupus, and to neonatal lupus with congenital heart block;
Sjogren syndrome, associated with decreased risk for nephritis
Anti-La (SS-B) 10 Usually associated with anti-Ro; associated with decreased risk for nephritis
Antihistone 70 More frequent in drug-induced lupus than in SLE
Antiplatelet 30 Associated with thrombocytopenia
Antineuronal 60 In some series a positive test in CSF correlates with active CNS lupus.
Antiribosomal P 20 In some series a positive test in serum correlates with depression or
psychosis due to CNS lupus

28. Clinical features
• At its onset, SLE may involve one or several organ systems; over time,
additional manifestations may occur .
• Most of the autoantibodies characteristic of each person are present at
the time clinical manifestations appear .
• Severity of SLE varies from mild and intermittent to severe and
fulminant.
Manifestation Prevalence, %
Systemic: Fatigue, malaise, fever, anorexia, weight loss 95
Musculoskeletal 95
Arthralgias/myalgias 95
Nonerosive polyarthritis 60
Myopathy/myositis 25/5
Ischemic necrosis of bone 15

29. Manifestation Prevalence, %
Cutaneous 80
Photosensitivity 70
Malar rash 50
Oral ulcers 40
Alopecia 40
Discoid rash 20
Vasculitis rash 20
Other (e.g., urticaria, subacute cutaneous lupus) 15
Hematologic 85
Anemia (chronic disease) 70
Leukopenia (<4000/L) 65
Lymphopenia (<1500/L) 50
Thrombocytopenia (100,000/L) 15
Lymphadenopathy 15
Splenomegaly 15
Hemolytic anemia 10

30. Manifestation Prevalence, %
Neurologic 60
Cognitive disorder 50
Mood disorder 40
Headache 25
Seizures 20
Mono-, polyneuropathy 15
Stroke, TIA 10
Acute confusional state or movement disorder 2–5
Aseptic meningitis <1
Cardiopulmonary 60
Pleurisy, pericarditis, effusions 30–50
Myocarditis, endocarditis 10
Lupus pneumonitis 10
Coronary artery disease 10
Interstitial fibrosis 5
Pulmonary hypertension, ARDS, hemorrhage <5

31. Manifestation Prevalence, %
Renal 30–50
Proteinuria 500 mg/24 h, cellular casts 30–50
Nephrotic syndrome 25
End-stage renal disease 5–10
Gastrointestinal 40
Nonspecific (nausea, mild pain, diarrhea) 30
Abnormal liver enzymes 40
Vasculitis 5
Thrombosis 15
Venous 10
Arterial 5
Ocular 15
Sicca syndrome 15
Conjunctivitis, episcleritis 10

32. Associations
• That once you have an autoimmune disease, you are more susceptible to
developing others!!
• Sjogren syndrome
• MCTD
• Hashimotos thyroiditis
• Myasthenia gravis
• ENDOCRINE INVOLVEMENT:
• Hypothyroidism(6%) > Hyperthyroidism (1%)
• Up to 35% of SLE patients have anti-thyroid antibodies, w/ 10-15% of
patients developing overt hypothyroidism
• Mechanism ?? Unknown
• AITD is secondary to the production of thyrotropin by activated
lymphocytes or auto antibodies against the thyroid, its hormones or
receptors
Pyne D, Isenberg DA. Autoimmune thyroid disease in systemic lupus erythematosus. Annals of
the rheumatic diseases. 2002 Jan 1;61(1):70-2.

33. 1997 ACR criteria
Malar rash Fixed erythema, flat or raised, over the malar eminences
Discoid rash Erythematous circular raised patches with adherent keratotic scaling
and follicular plugging; atrophic scarring may occur
Photosensitivity Exposure to ultraviolet light causes rash
Oral ulcers Includes oral and nasopharyngeal ulcers, observed by physician
Arthritis Nonerosive arthritis of two or more peripheral joints, with
tenderness, swelling, or effusion
Serositis Pleuritis or pericarditis documented by ECG or rub or evidence of
effusion
Renal disorder Proteinuria >0.5 g/d or 3+, or cellular casts
Neurologic disorder Seizures or psychosis without other causes
Hematologic disorder Hemolytic anemia or leukopenia (<4000/L) or lymphopenia (<1500/L)
or thrombocytopenia(<100,000/L) in the absence of offending drugs
Immunologic disorder Anti-dsDNA, anti-Sm, and/or anti-phospholipid
Antinuclear antibodies An abnormal titer of ANA by immunofluorescence or an equivalent
assay at any point in time in the absence of drugs known to induce
ANAs

34. Lupus nephritis
• Renal involvement is a major cause of morbidity and hospital
admissions in SLE patients and occurs in 40% to 70% of all patients.
• Generally, renal involvement tends to occur within the first 2 years
of SLE with its frequency decreasing significantly after the first 5
years of disease.
• Almost half of patients present with asymptomatic urine
abnormalities, such as hematuria and proteinuria.
• Nephrotic or nephritic syndrome or both also may be observed in
30% of patients.
• 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.

35. Features %
Proteinuria 100
Miroscopic hematuria 80
Tubular abnormalities 60-80
Reduced renal function 40-80
Nephrotic syndrome 45-65
Granular casts 30
Rapidly declining renal function 30
Hypertension 15-50
Hyperkalemia 15
Macroscopic hematuria 1-2
Acute renal failure 1-2
• Clinical features of patients with lupus.

36. American College of Rheumatology Guidelines for
Screening, Treatment, and Management of Lupus
Nephritis. 2012
Joint European League Against Rheumatism and European
Renal Association–European Dialysis and Transplant
Association (EULAR/ERA-EDTA) recommendations for the
management of adult and paediatric lupus nephritis.2012
KDIGO(Kidney disease improving global outcomes)
Clinical Practice Guideline for Glomerulonephritis.
2012

37. ACR definition:
• persistent proteinuria >0.5 g/d or >3+ by dipstick, and/or
• cellular casts including RBCs, Hb, granular, tubular, or mixed).
Additional recommendations by ACR:
• Spot urine protein/creatinine ratio of >0.5 can be
substituted for the 24-hour protein measurement.
• “active urinary sediment” (>5 RBCs/hpf, >5 WBCs/hpf in the
absence of infection, or cellular casts limited to RBC or WBC
casts) can be substituted for cellular casts.
• Optimal would be a histological demonstration.
• ACR Core Executive Panel- diagnosis of LN should also be
considered valid if based on the opinion of a rheumatologist
or nephrologist

38. 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
• Biopsies may identify additional or alternative causes of
renal disease, such as tubular necrosis related to
medications, hypovolemia, or hypotension.

39. Indications for renal biopsy in patients with systemic lupus
erythematosus
• Increasing serum creatinine without compelling alternative causes
(such as sepsis, hypovolemia, or medication)
• Confirmed proteinuria of 1.0 gm per 24 hours (either 24-hour urine
specimens or spot protein/creatinine ratios are acceptable)
• Combinations of the following, assuming the findings are
confirmed in at least 2 tests done within a short period of time and
in the absence of alternative causes:
a. Proteinuria 0.5 gm per 24 hours plus hematuria, defined as 5
RBCs per hpf
b. Proteinuria 0.5 gm per 24 hours plus cellular casts

40. • At least 8 glomeruli should be examined by LM with H&E, PAS
(Periodic acid–Schiff) , Masson’s Trichrome & Silver stains.
• IF for IgG, IgA, IgM, κ and λ.
• EM can be used(if possible) for recognition of proliferative and
membranous lesions.
• Chronicity and activity scoring to be done.

41. Pathology

43. WHO Classification of Lupus Nephritis

45. Class I (Minimal mesangiallupusnephritis)
Delicate mesangial positivity for
IgG.
No structural changes by light
microscopy. PAS stain

46. Class II (Mesangialproliferativelupus nephritis)
Mesangial cell proliferation,
mesangial matrix expansion.
Granular mesangial positivity of
all three immunoglobulins and
both complements (C1q and C3)
(“full house” pattern)

47. Focal-Involving <50% of glomeruli
Diffuse-Involving 50% or more of glomeruli
Segmental-Involving part of a glomerular tuft(<50%)
Global-Involving all of a glomerular tuft(>50%)
International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification

48. Active and chronic glomerular lesions
Active lesions
• Endocapillary hypercellularity with or without leukocyte
infiltration and with substantial luminal reduction
• Karyorrhexis
• Fibrinoid necrosis
• Rupture of glomerular basement membrane
• Subendothelial deposits identifiable by light microscopy
(wireloops)
• Intraluminal immune aggregates (hyaline thrombi)
Chronic lesions
• Glomerular sclerosis (segmental, global)
• Fibrous adhesions
• Fibrous crescents

49. ClassIII(Focallupusnephritis)
Focal-Involving <50% of glomeruli
Less than 50% of all glomeruli,
segmental or global, swelling and
proliferation of endothelial and
mesangial cells associated with
leukocyte accumulation, capillary
necrosis, extracapillary
proliferation,.

50. ClassIV (Diffuselupusnephritis)
Diffuse-Involving 50% or more of glomeruli
Lesions similar to Class III, but
involves > 50% of glomeruli

51. Wire loop lesions
• Wire loops, a classic sign of active lupus nephritis, are
segmental areas of refractile, eosinophilic, thickening of
the glomerular capillary seen by light microscopy in
haematoxylin and eosin stained sections.

52. CLASS V (MEMBRANOUS LUPUS NEPHRITIS)
Diffuse thickening of the capillary
walls due to deposition of
subepithelial immune complexes,
increased production of basement
membrane-like material. PAS stain

53. ClassVI
Advancedsclerosislupusnephritis
Sclerosis of more than 90% of the
glomeruli, end stage renal disease, severe
tubular atrophy, interstitial fibrosis,
inflammation.

54. Treatment of lupus nephritis
• Depends upon class of LN diagnosed on kidney biopsy
along with presence of extra-renal manifestations of SLE
• Goal of treatment is to normalize kidney function,
reduce proteinuria, and prevent progressive loss of
kidney function.
• Goals of immunosuppressive treatment:
• Long-term preservation of renal function,
• Prevention of flares,
• Avoidance of treatment-related harms, and
• Improved quality of life and survival.

55. Adjunctive TreatmentsDrugs Cause
Hydroxychloroquine
[Max 6–6.5 mg/kg body weight]
All SLE patients with; unless there is a
contraindication:
• Lower rates of Flare
• Reduced renal damage
• Less clotting events
ACEi/ARBs Patients with proteinuria >0.5 gm/day
• Reduces proteinuria by 30%, and
• Significantly delays doubling of serum
creatinine
• Delays progression to ESRD
Antihypertensive Target of ≤130/80 mmHg
• Significant delay in progression of
renal disease
Statin therapy Patients with LDL >100 mg/dl
• As GFR<60ml/min/1.73m2 & SLE itself
accelerated atherosclerosis
Calcium supplementation Prevent osteoporosis if the patient is on
long-term corticosteroid therapy

56. Class I and class II
• Conservative (Non-immunomodulatory) treatment is
appropriate for Class I and II LN
• RAAS Blockade with ACE/ARB delays progression of
Lupus Nephritis
• Spironolactone significantly reduces proteinuria and
lowers levels of anti ds DNA and anti ss DNA
• Class I and II LN be treated as dictated by the extrarenal
clinical manifestations of lupus
• EXCEPTION: II LN with proteinuria >3 g/d be treated
with corticosteroids or CNIs as described for MCD.

57. • At high risk of progressing to ESRD
• Require aggressive therapy.
• Therapy for class III and IV LN has 2 phases:
• Initial/Induction phase: to rapidly decrease
kidney inflammation/ to induce remission of
active disease
• Maintenance phase: to consolidate treatment
over a longer time/ Keeps patient in remission,
prevents relapse.
Class III and IV LN

58. Initial/Induction phase
• 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.

59. Glucocorticoids
• Pulse IV glucocorticoids (500–1000 mg
methylprednisolone daily for 3 doses) in
combination with immunosuppressive
therapy is recommended.
• Followed by daily oral glucocorticoids (0.5–1
mg/kg/day), followed by a taper to the
minimal amount necessary to control
disease.

61. MMF CYC
• Non Asian = 3gm/D
• Asian = 2 gm/D
• Class III/IV + crescents = 3gm/D
• Proteinuria + recent significant
rise in creatinine = 3gm/D
• In severe class III/IV LN
• In whites, low- and high-dose regimens were
equivalent in efficacy.
• Serious infections were less frequent with the lower
doses
• Low and high-dose regimens similar rates of LN
flares, end-stage renal disease, and doubling of the
serum creatinine.

62. Important considerations for CYC
• The use of sodium-2-mercaptoethane (mesna) will also
minimize the risk of hemorrhagic cystitis when
cyclophosphamide is given as i.v. pulses.
• Lifetime maximum of 36 g cyclophosphamide in patients with
systemic lupus as there is chance of hematologic malignancies
later in life.
• The dose of cyclophosphamide should be decreased by 20%
(CrCl 25-50ml/min) or 30% (10–25 ml/min)
• To minimize bladder toxicity with oral cyclophosphamide,
suggest instructing patients to take cyclophosphamide in the
morning, and to drink extra fluid.
• To protect fertility, women should be offered prophylaxis with
leuprolide and men testosterone. Ovarian tissue
cryopreservation/sperm banking are other options.

63. How can we predict outcome??
• After 8 week: ≥ 25% reduction in proteinuria
and/or normalization of C3 and/or C4 serum
levels = likely to show good clinical renal
responses
• After 6 months: decrease in serum creatinine
and in proteinuria to <1 gm/D predicts a good
long-term outcome

64. Definitions of response to therapy
• Complete response: Return of SCr to previous baseline, plus a
decline in the uPCR to <500 mg/g (<50 mg/mmol).
• Partial response: Stabilization (±25%), or improvement of SCr,
but not to normal, plus a ≥50% decrease in uPCR. If there was
nephrotic-range proteinuria (uPCR≥3000 mg/g [≥300
mg/mmol]), improvement requires a ≥50% reduction in uPCR,
and a uPCR <3000 mg/g [<300 mg/mmol].
• Deterioration: There is no definition of deterioration in LN to
define treatment failure. A sustained 25% increase in SCr is
widely used but has not been validated.
Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis:
reading between the (guide) lines—application to the individual patient. Kidney
international. 2012 Oct 1;82(8):840-56.

65. If the patients
not
improving??
Switch REGIMEN

68. Other Initial Regimens
Regimens
Rituximab • When treatment failed with MMF/CYC
Azathioprine • 2nd line protocol
• Less effective than CYC
MPA • Less nausea & diarrhea than MMF
Cyclosporine • (4–5 mg/ kg/d) was used for 9 months, and then
tapered over the next 9 months.
• No differences in responses, relapse rate, Infections and
leukopenia with CYC.
• ACR guideline preferred it for maintenance therapy.
Tacrolimus • Equivalent to high-dose IV CYC in inducing complete
and partial remissions of LN

69. maintenance therapy

72. • Azathioprine (1.5–2.5 mg/kg/d) or
• MMF (1–2 g/d in divided doses)
±
Low-dose oral corticosteroids
Calcineurin inhibitors with low-dose corticosteroids be
used for maintenance therapy in patients who are intolerant
of MMF and azathioprine.
maintenance therapy

73. Complete remission
is achieved
Repeat
kidney
biopsy
Change in
therapy
Continued for at
least 1 year
Consideration for
tapering
Kidney function
deteriorates and/or
proteinuria worsens
Treatment be increased
to the previous level of
immunosuppression
that controlled the LN
YESNO
After
1 year

74. 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.

75. Class V LN (membranous LN)
• Generally treated with prednisone for 1-3 months,
followed by tapering for 1-2 years if a response occurs. If
no response occurs, the drug is discontinued.
• Immunosuppressive drugs are generally not used unless
renal function worsens or a proliferative component is
present on renal biopsy samples.

76. Class VI LN (advanced sclerosis LN)
• Treated with corticosteroids and
immunosuppressives only as dictated by the
extrarenal manifestations of systemic lupus.
• Dialysis and
• Kidney transplantation

77. Lifestyle Changes for Lupus Nephritis
• Drink enough fluids to stay well hydrated.
• Eat a low-sodium diet, especially if hypertension is an
issue.
• Avoid smoking and drinking alcohol.
• Exercise regularly.
• Maintain a healthy blood pressure.
• Limit cholesterol.
• Avoid medications that can affect the kidneys, such as
nonsteroidal anti-inflammatory drugs (NSAIDs).

78. ESRD
• All methods of renal replacement treatment can be used in
patients with lupus, but there may be increased risk of
infections in patients on peritoneal dialysis still on
immunosuppressive agents and vascular access thrombosis
in patients with anti-phospholipid antibodies
• Transplantation should be performed when lupus activity has
been absent, or at a low level, for at least 3– 6 months, with
superior results obtained with living donor and pre-emptive
transplantation. Anti-phospholipid antibodies should be
sought during transplant preparation because they are
associated with an increased risk of vascular events in the
transplanted kidney.
• Treated with corticosteroids and immunosuppressives only
as dictated by the extrarenal manifestations of systemic
lupus.

79. Side effects

80. Prognostic Features- Lupus Nephritis
• Histological Predictors
• Class IV (diffuse proliferative LN)
• High activity and chronicity on Biopsy
• Crescents
• Interstitial fibrosis
• Clinical Predictors
• Hypertension
• Anemia
• High baseline serum creatinine
• Higher baseline proteinuria
• Delay in therapy
• Epidemiologic Predictors
• African American Race
• Gender
• Low socioeconomic status

81. References
• Harrison's Principles of Internal Medicine. 18th edition
• Kelley's Textbook of Rheumatology. 8th ed.
• American College of Rheumatology Guidelines for Screening,
Treatment, and Management of Lupus Nephritis. 2012
• Joint European League Against Rheumatism and European
Renal Association–European Dialysis and Transplant
Association (EULAR/ERA-EDTA) recommendations for the
management of adult and paediatric lupus nephritis.2012
• KDIGO Clinical Practice Guideline for Glomerulonephritis.
2012
• Derivation and Validation of the Systemic Lupus
International Collaborating Clinics Classification Criteria for
Systemic Lupus Erythematosus.2012

82. References
• Harrison's Principles of Internal Medicine. 18th edition
• Kelley's Textbook of Rheumatology. 8th ed.
• American College of Rheumatology Guidelines for Screening,
Treatment, and Management of Lupus Nephritis. 2012
• Joint European League Against Rheumatism and European
Renal Association–European Dialysis and Transplant
Association (EULAR/ERA-EDTA) recommendations for the
management of adult and paediatric lupus nephritis.2012
• KDIGO Clinical Practice Guideline for Glomerulonephritis.
2012
• Derivation and Validation of the Systemic Lupus
International Collaborating Clinics Classification Criteria for
Systemic Lupus Erythematosus.2012

83. Thank you