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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