Transcript Slide 1

Makati Medical Center
Department of Medicine
Medical Grandrounds
July 12, 2007
8:15Am, Ledesma Hall
MARIZEN L. LIM, MD
Learning Objectives
 To present a case of SLE with lupus nephrtis
 To present updates on the treatment of lupus
nephritis
Idenifying Data
 ER
 43-y/0 female
 Chief Complaint: Persistently elevated BP
History of the Present Illness
 20 years PTA  malar rash
 photosensitivity
 polyarthralgia
 3x spontaneous abortions
 1 month PTA  severe throbbing headache,
vomiting, dizziness, dyspnea on
exertion
 BP: 200/100  consult  u/a: +3 alb, 60 rbc,
hyaline & coarse granular casts; crea 0.9
History of the Present Illness
 Metoprolol 50mg OD & Felodipine 2.5mg OD
 BP remained uncontrolled
 Beta blocker  calcium channel blocker 
ACE inhibitor  Angiotensin II receptor
blocker
 BP persistently elevated
History of the Present Illness
 1 week PTA  progressive dyspnea,
periorbital, facial, pitting bipedal edema ,
noted ↓ urine output
 Consult  Leukopenia w/ thrombocytopenia;
+3 albumin, 12 wbc, fine granular casts; crea
1.2 from 0.9; K 5.7
Nephrology
Admitted
Review of Systems
 (-) fever
 (-) pleurisy
 (+) headache
 (-) abdominal pain
 (+) nausea
 (-) dysuria
 (+) body malaise
 (-) depression/mania
 (+) anorexia
 (-) easy bruisability
 (-) chest
pain/palpitation
Past Medical, Social and
Personal, Family History
 (-) DM
 (+) HPN
 (-) BA
 (-) DM
 (-) allergies
 (-) connective tissue
disease
 Non smoker
 Non alcoholic
beverage drinker
 Officer worker
Physical Examination
 General Survey: conscious, coherent, oriented,
not in cardiorespiratory distress
 Vital Signs: BP: 160/100 CR: 68/min, regular
RR: 18/min
Temp: 36.2°C
 HEENT: no alopecia, no head lesions, anicteric
sclera, slightly pale palpebral conjunctivae, no
abnormal discharges, no oral or nasopharyngeal
ulcers, no tonsillopharyngeal wall congestion, no
cervical lymphadenopathy, flat neck veins
 Skin: no pallor, no jaundice, no rashes, (-)
petechiae/hematoma
Physical Examination
 Cardiovascular: adynamic precordium, distinct
S1 and S2, normal rate, regular rhythm, no
murmur
 Respiratory: symmetrical chest expansion, no
intercostals/subcostal retractions, clear breath
sounds
 Abdomen: flabby, normoactive bowel sounds,
soft, no tenderness, no organomegaly, no
palpable masses
 Extremities: (+) grade 3 pitting bipedal edema,
no cyanosis, full and equal pulses
Salient Features
 43 y/o female
 ↑ BP
 History of malar rash, photosensitivity,
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arthralgia, 3x miscarriages
Decreased urine output
Pitting bipedal edema
Proteinuria, hematuria, casts
Increasing creatinine 0.9  1.2
Differential Diagnoses
ARF
Prerenal
Renal
RPGN
Immune Complex GN
Postrenal
Low C3
Post infectious
GN
Normal C3
Lupus nephritis
Admitting Diagnosis
 Acute renal failure, probably rapidly
progressive glomerulonephritis, probably
immune-mediated
 Hypertension, poorly controlled, probably
secondary to a renal pathology
 Connective tissue disease t/c systemic lupus
erythematosus
Course in the Wards
 On admission
 CBC: H 11.6, H 33.6, wbc 5990 (s 65, L 22, M 11, E2)
 K: 6.6↑
 Crea: 1.7 ↑
 U/A: (protein +3, rbc 3.8, wbc 23.1, e.c. 20.3, bact 1784,
fine granular casts 5-10/lpf)
  Meropenem 500mg IV q 12hrs
Course in the Wards
 Elevated ESR: 74 (n.v. 0-20)
 ANA and C3 beta complement
 ABG: 100/7.36/34.1/18.8/97.5/+5.7/19.9
 Hyperkalemia regimen: (Furosemide 40mg IV q8;
Kalimate QID; Salbutamol neb q6; NaHCO3 drip)
 Methylprednisolone (Solumedrol) 1gm in
D5W 100cc slow IV push x 3 days
 Crea: 1.7  1.8
 K: 5.1  6.6
Course in the Wards
 2nd Hospital day:
 Hyponatremia: 134
 Crea: 1.3  1.7  1.8
 BUN: 49↑
 24-hour urine protein: 864.5mg/24hrs ↑
 24-hour urine crea: 551.85mg/24°
estimated crea clearance: 29.48 ml/min
 24 hour urine vol: 650 cc
Course in the Wards
 3rd Hospital Day: s/p utz-guided kidney biopsy
 Result: Lupus Nephritis Class III
RENAL BIOPSY
 Specimen consists of a strip of brown tissue
measuring 1.1 cm
 Block all
Scan X4
HPOX40
HPOX40
HPOX40
HPOX40
HPOX40
PAS
HPOX40
Trichrome
Scan X4
Trichrome
HPO X 40
Trichrome
HPO X 40
Final Diagnosis
RENAL BIOPSY:
Clinically diagnosed Systemic Lupus
Erythematosus (SLE) with proteinuria
Lupus Nephritis Class III
Course in the Wards
 Anemia  Hgb: 9.7 ↓
Hct: 27.4 ↓
 Kidney UTZ: no hematoma
 4th Hospital day:
 ANA: positive up to 1:320 serum dilution;
speckled pattern
 C3 beta complement: 23.80mg% ↓(N.V. 79-
152)
Course in the Wards
 Rheumatology
 Anti-cardiolipin Ab: 11 GPL (N.V. <15)
 Full Lupus Panel:
 ANA (+) up to 1:320 dilution, speckled pattern
anti-DNA: (+)
anti-Sm: (+)
anti-RNP: (-)
anti-SSA(Ro): (+)
anti-SSB(La): (+)
anti-Jo1: (-)
Course in the Wards
 Progression of anemia: Hgb: 9.4  9.7
Hct: 27.9
 EPO (Renogen) 8000 u IV OD
 Crea: 2  1.3
Course in the Wards
 Prednisone 30mg PO AM, 20mg PO PM (on
full stomach)
 CaCO3 500mg OD
 Urine CS: E.coli sensitive to Ertapenem &
Cefuroxime: Meropenem  Cefuroxime
250mg PO BID
 Losartan 50mg PO OD
Course in the Wards
 5th Hospital day:
 Cyclophosphamide (CYC) IV pulsed therapy
CYC 700mg in D5W 500cc x 2 hours
 Crea: 1.4  2
 Prednisone
Course in the Wards
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6th Hospital day:
Discharged stable and improved
THM:
EPO (Recormon) 5000U SC, T-Th-Sat
Esomeprazole 40mg OD
Clonidine 75mcg SL TID
Losartan 50mg OD
Cefuroxime 250mg BID x 7 days
Prednisone 5mg/tab, 30mg in AM, 20mg in PM w/
meals
7. CaCo3 500mg PO OD
Final Diagnoses
 Systemic lupus erythematosus, lupus
nephritis Class III, ARF 2°, s/p kidney biopsy
 Hypertension stage II, secondary to lupus
nephritis
 Urinary tract infection, on treatment
Discussion
Lupus Nephritis
 50% of lupus patients will develop clinically
relevant nephritis at some time in the course
of their illness1
 Varies from isolated abnormalities of the
urinary sediment to full-blown nephritic or
nephrotic syndrome or chronic renal failure
 Formation of immune complexes w/in
glomerular capillary wall
 Diagnosed by renal biopsy
1http://www.cerebrel.com/lupus/nephritis.php
ISN/RPS(2003)classification of LN
Class I
Minimal Mesangial LN
Class II
Mesangial Proliferative LN
Class III
Focal proliferative LN (<50% of glomeruli)
IIIA
Active lesions
IIIA/C
Active and chronic lesions
IIIC
Chronic lesions
Class IV
Diffuse proliferative LN (>50% of glomeruli)
Diffuse segmental (IV-S) or global(IV-G) LN
IVA
Active lesions
IVA/C
Active and chronic lesions
IVC
Chronic lesions
Class V
Membranous LN
Class VI
Advanced sclerosing LN
(>90% globally sclerosed glomeruli w/o residual activity)
Corticosteroids
 Mainstay of tx for any inflammatory life-
threatening or organ-threatening
manifestations of SLE (proliferative LN)
 High dose IV glucocorticoid pulses given
slowly over a 3-4 hour period, monthly for 6
months with 0.5 - 1mg of oral prednisone per
kg between pulses, to control both renal and
extrarenal manifestations
Pulse steroids: How much is enough?
Giovanni Franchin, and Betty Diamond
Columbia University, Department of Medicine, Division of
Rheumatology, 1130 St. Nicholas Ave., Audubon III Room 923,
New York, NY 10032, USA
Available online 29 August 2005.
 High dose pulse intravenous steroids with 1 g
of methylprednisolone (MEP) given daily,
usually for three days, is an accepted practice
to treat severe manifestations of systemic
lupus erythematosus (SLE) or systemic
vasculitides, despite the lack of definitive
data.
Adverse Effects of Steroids
 Weight gain
 Hirsutism
 Acne
 Infection
 Glucose intolerance
 Osteopenia/
osteonecrosis
 Glaucoma
 PUD
Cytotoxic drugs
 Used in severe corticosteroid-resistant
disease or in the context of unacceptable
steroid side effects
 Cyclophosphamide has been shown to reduce
progression of scarring in the kidney & reduce
risk for end-stage renal failure
Cyclophosphamide
 An alkylating agent; Cyclophosphamide given
intravenously for prolonged periods is the
current gold standard.
 National Institution of Health Protocol:
Cyclophosphamide 1gm/m2 every month for
6 months (Induction phase)
Cyclophosphamide 1gm/m2 every 3 months
for 2 years (Maintainance phase)
Adverse effects of Cyclophosphamide
 Nausea and vomiting
 Alopecia
 Ovarian failure or azoospermia
 Hemorrhagic cystitis, bladder fibrosis,
bladder transitional or squamous CA
Monitoring for patients on CTX
 Regular and frequent lab evaluations to
screen for:
 bone marrow toxicity: CBC
 monitor renal function: BUN, crea,
electrolytes
 avoid major drug-induced bladder
complications: urinalysis
Other treatment options
 Azathioprine
Long-term efficacy of azathioprine treatment
for proliferative lupus nephritis
H. C. Nossent and W. Koldingsnes Department of
Rheumatology, University Hospital Tromsø, Norway
 Plasmapheresis
 The Lupus Nephritis Collaborative Study: A
randomized, controlled, multicenter clinical trial (John M.
Lachin, Sc.D.)
Mycophenolate mofetil
 A new immunosuppressive drug
 May be more effective in inducing
remission than standard regimen of IV
cyclophosphamide
 Produces fewer complications than
Cyclophosphamide like the loss of childbearing ability
Updates
Long-Term Study of Mycophenolate Mofetil as Continuous Induction and
Maintenance Treatment for Diffuse Proliferative Lupus Nephritis (TakMao Chan, et al; Feb. 23,2005)
 Background: Mycophenolate mofetil (MMF) and the
sequential use of cyclophosphamide followed by
azathioprine (CTX-AZA) demonstrate similar short-term
efficacy in the treatment of diffuse proliferative lupus
nephritis (DPLN), but MMF is associated with less drug
toxicity
 Materials and Methods: Thirty-three patients were
randomized to receive MMF, and 31 were randomized to
the CTX-AZA treatment arm, both in combination with
prednisolone.
 RESULTS: >90% in each group responded
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favorably (complete or partial remission) to
induction treatment.
Serum creatinine in both groups remained stable
and comparable over time.
Creatinine clearance increased significantly in
the MMF group, but the between-group
difference was insignificant.
Improvements in serology and proteinuria were
comparable between the two groups.
A total of 6.3% in the MMF group and 10.0% of
CTX-AZA–treated patients showed doubling of
baseline creatinine during follow-up (P = 0.667).
 Both the relapse-free survival and the hazard
ratio for relapse were similar between MMFand CTX-AZA–treated patients (11 and nine
patients relapsed, respectively) and between
those with MMF treatment for 12 or 24 mo.
 MMF treatment was associated with fewer
infections and infections that required
hospitalization (P = 0.013 and 0.014,
respectively).
 Four patients in the CTX-AZA group but none
in the MMF group reached the composite end
point of end-stage renal failure or death (P =
0.062 by survival analysis).
 CONCLUSION: MMF and prednisolone
constitute an effective continuous inductionmaintenance treatment for DPLN in Chinese
patients.
 MMF-based induction-maintenance
regimen has comparable long-term
efficacy regarding renal preservation and
the prevention of relapse as the sequential
CTX-AZA regimen but is associated with
significantly reduced unfavorable
outcomes, in particular infection and
amenorrhea
Prognosis of Lupus Nephritis
 has dramatically increased over the last
several decades (40% at five years in the
1950s to current survival rates of approx. 90%
at 10 years)
Prognosis is Good due to:
 earlier and better disease recognition with
more sensitive diagnostic tests
 earlier treatment
 the inclusion of milder cases
 increasingly judicious therapy and prompt
treatment of complications
Prognosis
 Many patients go into remission and require
no treatment.
 In one study of 667 patients, approx. 25% had
remission lasting for at least a year.
Remission occurred in 50% of those with
disease over 18 years duration, and in 75 % of
those with disease over 30 years duration
 Remission was even seen in some patients
who had had severe kidney disease
http://patients.uptodate.com/topic.asp?file=arth_rhe/6415
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