LUPUS NEPHRITIS:AN UNDERDIAGNOSED CONDITION?

Dr Femi Adelowo, M.B.B.S(Ib), FMCP, FWACP, FACR, FRCP(Edin) FRCP(Lond)

Professor of Medicine/Consultant Rheumatologist Lagos University College of Med/LASUTH and Arthrimed Specialist Clinic Ikeja

INTRODUCTION

What manner of disease is Systemic Lupus Erythematosus (SLE)?

Multisystemic auto immune disease affecting mostly females

Incidence estimate – 1.8 – 7.6 cases per 100,000 person years – (USA) [1]

INTRODUCTION

3.3 – 4.8 per 100,00 person years (Europe) – [2] Few case reports from Africa Said to be rare – [3] Recent reports show that is not uncommon Constitutes 5.25% of rheumatological cases – [4]

– Fessel W. J. Arch. Int. Med 1974; 134: 1027-35– Gudnundsson S, Steinsson K. J. Rheumatol. 1990:17:1162-1167– Bae SC et al. Arthritis Rheum. 1999:41:2091-2099– Adelowo O. O, Oguntona S. Clin Rheumatol 2009: 28:6:699-703– Adelowo O. O, Bamgboye E L. Lupus Nephritis among Nigerians: Case Reports and Literature Review. In

EAMJ

PRESENTATION

Recurrent fever(Malaria-Typhoid-Malaria Syndrome!!), polyarthralgia, weight loss, extreme fatigue, loss of weight, seizures

Diagnosis by ACR criteria- Malar rash Discoid rash Photosensitivity

ACR CRITERIA

Non erosive arthritis Pleuritis or pericarditis Renal disorders Seizures or psychosis Hematologic disorder .Immunological disorder – anti DNA, Anti

Sm, ACA, false +ve VDRL Positive ANA

CRITERIA

Ref. Hochberg M C Arthritis Rheum 1997;40;1725

– FREQUENCY OF LUPUS NEPHRITIS

Very high among African Americans [1] Low prevalence among black Africans –[2] Prevalence may be high in black Africans Report of urinary abnormalities in 35 out of 44 –

Nigerian series – [3] Report from Dakar, Senegal – 13% with Histological features of lupus nephritis in a non

selective series of 115 kidney biopsies – [4]

CONTD

– 1.Tang S et al. Nephrology 2005; 10(2): 174-179– 2.McCarty D J et al. Arthritis Rheum: 38: 1260-70– 3.Adelowo O O, Oguntona S. Clin. Rheumatol 2009;28:699-703– 4.Diouf B et al. Dakar Med 2001:46(1):51-3

Kidney affectation is of prognostic importance 60% of Adults and 80% of SLE develop Lupus

Nephritis:STUDY OF 12,344 of ESRD from LN(1995-2006)

10-30% develop ESRD within 15 years

49.5% were blacks SLE and Lupus Nephritis commoner in

blacks

Costenbader KH. Arth Rheum on line Mar 28

RISK FACTORS FOR LUPUS NEPHRITIS

- High Serum Anti dsDNA– -Low serum C3/C4– High serum anti C1q Ab

SIGNS OF LUPUS NEPHRITIS– Nocturia( tubular dysfunction)– Foamy urine( glomerular dysfunction)– Nephrotic syndrome( 20%: oedema)– Hypertension

DIAGNOSIS

How is Lupus Nephritis diagnosed? Combination of clinical, laboratory and

possible biopsy results 24 hour proteinuria of more than 500mg or

Dipstick of 3+ Presence of casts (red blood cell, heme,

granular, tubular, mixed

Haematuria Pyuria in absence of infection Elevated creatinine

Ref. Rahman P et al. Lupus 2001:10:418-423

EARLY DETECTION CRITICAL– Regular urine analysis– Early morning concentrated urine– Microscopic examination– Regular assessment of proteinuria– Regular assessment of renal function

PROTEINURIA– Dipstick for screening purposes only– 24 hour proteinuria: timed urine collection often

inadequate(30% under-collection: 15% over-collection

– Urine protein-to-creatinine ratio preferred to creatinine clearance

MICROSCOPIC URINE ANALYSIS– Not during menstrual periods– Immediate processing of specimen(bacterial

overgrowth makes urine alkaline/disrupts casts– RBC morphology critical-dysmorphism glomerular

origin– WBCs, RBCs,mixed casts-

nephritic(inflammatory)– Granular/fatty casts- proteinuric states

HISTOLOGY

Renal biopsy controversial but perform if significant proteinuria

WHO classified based on changes on light, electron microscopy and immunofluorescence –

Class I – Normal histology on light, electron microscopy, immunoflourescence

Class II – Mesangial expansion and immune deposits Class III – Focal proliferative Class IV Diffuse Proliferative Class V – Membranous Class VI – Glomerulosclerosis

Golbus J, McCune W J. Rheum Dis North Am 1994;20:213-242

PROGNOSTIC FACTORS FOR ESRD– African American race– Poor socio economic status– Non compliance with medications– Severe clinical onset– Uncontrolled hypertension– Renal relapse– Poor initial response to therapy

Response rate to treatment- 80% Relapse rate- 35%(2-4years) ESRD- 10% at 10 years

TREATMENT

What is the treatment? Time is of essence especially among

Nigerians Delay will result in CKD Dialysis is mostly unaffordable or unavailable

in Nigeria Early immunosuppressive treatment critical Initiation

TREATMENT

1. NIH regimen:INITIATION Pulse IV .Cyclophosphamide – High dose Igm monthly X 6 months

MAINTENANCE 1GM three monthly to 2 years 2. EULAR REGIMEN : INITIATION Pulse IV Cyclophosphamide

Low Dose 500mg every 2 weeks X 3 Months MAINTENANCE- Azathioprine tablets( 1-2mg/Kg) Mycophenolate Mofetil

3 Mycophenolale Mofetil for both induction and maintenance

4. Rituximab+/- Cyclophosphamide- Induction. Maintenance- Azathioprine or Mycophenolate

– Maintenance – Azathioprine or Mycophenolate Mofetil or Leflunomide

– Pulse Methylprednisolone– Oral Corticosteroids

Other Biologics: Anti TNF alpha- Etanercept, Infliximab

Belumimab- approved by FDA for SLE

Rituximab in organ involvement of SLE CLINICAL RESPONSES( 188 SLE patients) Cardiopulmonary- 100% Haematological- 94% Renal 91% Articular 91% CNS 89% Mucocutaneous 89%

Rituximab and organs response contd(%)

Epilepsy 100 Type V nephropathy 100 Type IV nephropathy 98 Serositis 87 Type III nephropathy 82 Pericarditis 50

Ramos-Casals M, Soto MJ, Cuadrado MJ et. al Lupus 2009, 18: 767-776

TREATMENT

Newer agents – Tacrolimus, LPJ – 394 Ciclosporin – Membranous

Glomerulonephritis

PROGNOSIS

What is the prognosis? Good if immunosuppressives are

introduced early.Supportive management- renal replacement therapy

Adelowo O. O, Bamgboye E L. Lupus Nephritis among Nigerians: Case reports and Literature Review – EAMJ

THANK YOU