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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

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makati medical center department of medicine medical grandrounds july 12 2007 8 15am ledesma hall
Makati Medical Center

Department of Medicine

Medical Grandrounds

July 12, 2007

8:15Am, Ledesma Hall

Marizen L. Lim, Md

learning objectives
Learning Objectives
  • To present a case of SLE with lupus nephrtis
  • To present updates on the treatment of lupus nephritis
idenifying data
Idenifying Data
  • ER
  • 43-y/0 female
  • Chief Complaint: Persistently elevated BP
history of the present illness
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 illness1
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 illness2
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
Review of Systems
  • (-) fever
  • (+) headache
  • (+) nausea
  • (+) body malaise
  • (+) anorexia
  • (-) easy bruisability
  • (-) chest pain/palpitation
  • (-) pleurisy
  • (-) abdominal pain
  • (-) dysuria
  • (-) depression/mania
past medical social and personal family history
Past Medical, Social and Personal, Family History
  • (-) DM
  • (-) BA
  • (-) allergies
  • Non smoker
  • Non alcoholic beverage drinker
  • Officer worker
  • (+) HPN
  • (-) DM
  • (-) connective tissue disease
physical examination
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 examination1
Physical Examination
  • Cardiovascular: adynamicprecordium, 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
Salient Features
  • 43 y/o female
  • ↑ BP
  • History of malar rash, photosensitivity, arthralgia, 3x miscarriages
  • Decreased urine output
  • Pitting bipedal edema
  • Proteinuria, hematuria, casts
  • Increasing creatinine 0.9  1.2
differential diagnoses
Differential Diagnoses

ARF

Prerenal

RenalRPGNImmune Complex GN

Postrenal Low C3 Normal C3

Post infectious Lupus nephritis

GN

admitting diagnosis
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
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 wards1
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 wards2
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 wards3
Course in the Wards
  • 3rd Hospital Day: s/p utz-guided kidney biopsy
  • Result: Lupus Nephritis Class III
renal biopsy
RENAL BIOPSY
  • Specimen consists of a strip of brown tissue measuring 1.1 cm
  • Block all
slide25

PAS

HPOX40

slide26

Trichrome

Scan X4

slide27

Trichrome

HPO X 40

slide28

Trichrome

HPO X 40

final diagnosis
Final Diagnosis

RENAL BIOPSY:

Clinically diagnosed Systemic Lupus Erythematosus (SLE) with proteinuria

Lupus Nephritis Class III

course in the wards4
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 wards5
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-SSA(Ro): (+)

anti-Sm: (+) anti-SSB(La): (+)

anti-RNP: (-) anti-Jo1: (-)

course in the wards6
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 wards7
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 wards8
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 wards9
Course in the Wards
  • 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
  • CaCo3 500mg PO OD
final diagnoses
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
lupus nephritis
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

corticosteroids
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
slide41

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
Adverse Effects of Steroids
  • Weight gain
  • Hirsutism
  • Acne
  • Infection
  • Glucose intolerance
  • Osteopenia/ osteonecrosis
  • Glaucoma
  • PUD
cytotoxic drugs
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
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
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
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
Other treatment options
  • Azathioprine

Long-term efficacy of azathioprine treatment for proliferative lupus nephritis

H. C. NossentandW. 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
Mycophenolatemofetil
  • 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 child-bearing ability
slide50

Long-Term Study of MycophenolateMofetil as Continuous Induction and Maintenance Treatment for Diffuse Proliferative Lupus Nephritis (Tak-Mao Chan, et al; Feb. 23,2005)

  • Background: Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamidefollowed by azathioprine (CTX-AZA) demonstrate similar short-termefficacy in the treatment of diffuse proliferative lupus nephritis(DPLN), but MMF is associated with less drug toxicity
  • Materials and Methods: Thirty-three patients wererandomized to receive MMF, and 31 were randomized to the CTX-AZAtreatment arm, both in combination with prednisolone.
slide51

RESULTS: >90% in each group responded favorably (complete or partial remission)to induction treatment.

  • Serum creatinine in both groups remainedstable and comparable over time.
  • Creatinine clearance increasedsignificantly in the MMF group, but the between-group differencewas insignificant.
  • Improvements in serology and proteinuriawere comparable between the two groups.
  • A total of 6.3% in theMMF group and 10.0% of CTX-AZA–treated patients showeddoubling of baseline creatinine during follow-up (P = 0.667).
slide52

Both the relapse-free survival and the hazard ratio for relapsewere similar between MMF- and CTX-AZA–treated patients(11 and nine patients relapsed, respectively) and between thosewith MMF treatment for 12 or 24 mo.

  • MMF treatment was associatedwith fewer infections and infections that required hospitalization(P = 0.013 and 0.014, respectively).
  • Four patients in the CTX-AZAgroup but none in the MMF group reached the composite end pointof end-stage renal failure or death (P = 0.062 by survival analysis).
slide53

CONCLUSION: MMF and prednisolone constitute an effectivecontinuous induction-maintenance treatment for DPLN in Chinesepatients.

  • MMF-basedinduction-maintenance regimen has comparable long-term efficacyregarding renal preservation and the prevention of relapse asthe sequential CTX-AZA regimen but is associated with significantlyreduced unfavorable outcomes, in particular infection and amenorrhea
prognosis of lupus nephritis
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
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
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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