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Lupus Nephritis by TZA

Lupus Nephritis
Normal urinary protein excretion is 150 – 200 mg/24 hr/1.75π‘š2
Normal urinary creatinine excretion is 1000 mg/24hr/1.75π‘š2
Thus, normal urinary Protein-to-creatinine ratio (UPCR) is < 0.2.
CRP is generally not elevated in SLE even with disease activity.
But CRP is increased in significant arthritis or infection.
LN is present in 50% of SLE patients.
LN arises within 5 years of Dx.
Only 10% of LN will develop into ESRD.
HLA-DR2,3 is associated with LN,
HLA-DR4 is protective to LN. ( In RA, HLA-DR4 is associated with poor Px)
Ruminococcus gnavus (RG) : Gram(+)ve fecal bacteria is 5 times associated
with LN ( Azzouz et al.)
When does it called Lupus Nephritis?
Protein 3(+++) on urine dipstick
24 hour urinary protein > 500 mg/day
Urine PCR > 0.5
RBC or WBCs > 5 cells/HPF or cellular casts
D.Dx of LN
1. C.G.N
2. R.P.G.N ( Anti-GBM disease, IgA nephropathy, APSGN, Wegner`s )
3. PAN
Family History
50% chance
5% chance
So, environmental trigger must be present to develop Lupus
Classification of Lupus Nephritis
( 2003 International Society of Nephrology and Renal Pathology Society)
Class I
Minimal mesangial LN
---> No specific treatment, normal urinalysis
Normal on light microscopy.
Mesangial deposits only on Electron Microscpe
Class II
Mesangial Proliferative LN ---> If proteinuria > 1g/D, low to
moderate dose of prednisolone ( 20-40 mg/day) for 1-3 months
and subsequent taper)
Class III
Focal, proliferative , sclerosing LN
---> sclerotic lesion < 50% of glomeruli.
High risk of progression into ESRD
Class IV
Diffuse, proliferative, sclerosing LN (most severe & most common)
---> sclerotic lesions > 50% of glomeruli.
Renal failure common
Highest risk of progression into ESRD
Class V
Non-proliferative, membranous LN
---> subepithelial deposits. So it is called membranous.
Renal failure is uncommon.
Present with Nephrotic range proteinuria. Overt Nephrotic $
Marked oedema with venous thrombosis.
Class VI
Advanced glomerulosclerosis (ESRD stage) (renal transplant or HD)
--> Sclerotic lesions > 90% of glomeruli
Renal Biopsy
Should be considered in active LN.
Can determine prognosis and treatment.
Main pitfalls οƒ  Sampling errors and pathologist experience
Examples, LN with CNS manifestations οƒ  with or without Renal Bx --->
IV CYC must be given. So why should renal biopsy should be taken?
Yes ! renal biopsy can still predict renal outcome
Prednisolone tapering formula
Month 1
from Month 2 onwards
Firstly, tapered to 20 mg/day by 2 weekly reduction of 10 mg.
Then, tapered to 10 mg/day by 4 weekly reduction of 5mg.
Finally, tapered to 5mg/day by 4 weekly reduction of 2.5 mg.
The final 5 mg/day is maintained for at least 1 year.
Before CYC, 0% 5 years and 10 years survival.
After CYC, excellent 5 years and 10 years survival ( 80%)
Disease Activity
C3,C4 and CH 50 assays
Lupus and pregnancy
Need stable disease for at least 6 months to conceive pregnancy.
Some drugs are needed to stop before pregnancy
2 years for leflunomide ( Lefra is long)
6 months for MMF
3 months for MTX and CYC
Some drugs that can be used during pregnancy
HCA, Low dose prednisolone
Aspirin can reduce eclampsia
Lupus and Tuberculosis
Severe lupus activity οƒ  Aggressive Rx after 2 weeks of Anti-TB
Less severe LN
οƒ  Aggressive Rx after 2 months of anti-TB
Lowest side-effect Regimen οƒ  MMF + TAC f/b AZA maintenance
Asian population
African, American, Hispanics
TAC is beneficial
MMF is more superior than CYC
Aggressive Mx of HT
BP maintained at or below 130/80 mmHg
Efficacy in remission induction
MMF ( safer) = CYC + CS ( more SEs) > AZA ( less SEs)
MMF is the best drug for maintenance Tx.
CYC -induced Ovarian failure can be prevented by Gonadotrophin-Releasing
hormone analogue
β€œ leuprolide acetate”
Methylprednisolone has little mineralocorticoid activity. So it is useful in
oedematous patients
Class V patients
If subnephrotic range proteinuria
If nephrotic range proteinuria
οƒ  ACEIs or ARBs
οƒ  Aggressive Tx
All patients should be given HCQ.
Antiphospholipid Ab $ can cause Glomerular thrombosis. (Aspirin given)
Treatment algorithm
Induction for first 6 months
P.O Prednisolone as above
IV CYC for 1 day
P.O MMF 2-3 G/day
If improved
IV MP for 3 days or
IV MP for 3 days
οƒ  Both Rx are changed into MMF 1-2G/day
If not improved
οƒ  CYC Rx should be switched into MMF induction Rx
οƒ  MMF Rx should be switched into CYC induction Rx
Maintenance ( 6 months – 3 years)
MMF = 1-2 G/day or
AZA = 2 mg/kg/day or
Leflunomide 20 mg/day
Still not improved
Rituximab = 2 doses , 2 weeks apart and repeat 6 months later or
Rituximab = single dose f/b lefra or
Renal response to Tx
Complete response ( 100% response)
If UPCR < 50 mg/mmol or
23 hr Urinary Protein < 500 mg/day or
Near or near normal GFR
Partial response ( > 50% reduction to subnephrotic range proteinuria)
1. Nephritic flare ( if Crt > 30% rises or GFR decline > 10% or Hematuria
RBC > 10 cells/HPF)
2. Nephrotic flare ( if UPCR 100 mg/mmol if previously complete
responders, if UPCR 200 mg/mmol in partial responder)
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