Makati Medical Center Department of Medicine Medical Grandrounds July 12, 2007 8:15Am, Ledesma Hall.
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Transcript of Makati Medical Center Department of Medicine Medical Grandrounds July 12, 2007 8:15Am, Ledesma Hall.
Makati Medical CenterDepartment of Medicine
Medical GrandroundsJuly 12, 2007
8:15Am, Ledesma Hall
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
Past Medical, Social and Personal, Family History
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, 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 GNPostrenal Low C3 Normal C3
Post infectious Lupus nephritis GN
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
PASHPOX40
TrichromeScan X4
TrichromeHPO X 40
TrichromeHPO 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 patternanti-DNA: (+) anti-SSA(Ro): (+)anti-Sm: (+) anti-SSB(La): (+)anti-RNP: (-) 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
6th Hospital day: Discharged stable and improved THM:1.EPO (Recormon) 5000U SC, T-Th-Sat2.Esomeprazole 40mg OD3.Clonidine 75mcg SL TID4.Losartan 50mg OD5.Cefuroxime 250mg BID x 7 days6.Prednisone 5mg/tab, 30mg in AM, 20mg in
PM w/ meals7.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 biopsy1http://www.cerebrel.com/lupus/nephritis.php
ISN/RPS(2003)classification of LN
Class I Minimal Mesangial LN
Class II Mesangial Proliferative LN
Class IIIClass III Focal proliferative LN (<50% of Focal proliferative LN (<50% of glomeruli)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
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 drugA new immunosuppressive drug May be more effective in May be more effective in
inducing remission than inducing remission than standard regimen of IV standard regimen of IV cyclophosphamidecyclophosphamide
Produces fewer complications Produces fewer complications than Cyclophosphamide like the than Cyclophosphamide like the loss of child-bearing abilityloss of child-bearing ability
Updates
Long-Term Study of Mycophenolate Mofetil 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 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 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 MMF- and 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 induction-maintenance 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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