Lupus Nephritis
Normal urinary protein excretion is 150 – 200 mg/24 hr/1.75𝑚2
Normal urinary creatinine excretion is 1000 mg/24hr/1.75𝑚2
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
or
24 hour urinary protein > 500 mg/day
Urine PCR > 0.5
or
or
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
Familial
Monozygotic
10%
50% chance
Dizygotic
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  Sampling errors and pathologist experience
Examples, LN with CNS manifestations  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
Tapered
1mg/kg/day
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.
Prognosis
Before CYC, 0% 5 years and 10 years survival.
After CYC, excellent 5 years and 10 years survival ( 80%)
Disease Activity
1.
2.
3.
4.
ds-DNA
C3,C4 and CH 50 assays
ESR
CRP
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
AZA, TAC
Aspirin can reduce eclampsia
Lupus and Tuberculosis
Severe lupus activity  Aggressive Rx after 2 weeks of Anti-TB
Less severe LN
 Aggressive Rx after 2 months of anti-TB
Treatment
Lowest side-effect Regimen  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
ACEIs or ARBs
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
“ 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
 ACEIs or ARBs
 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
 Both Rx are changed into MMF 1-2G/day
If not improved
 CYC Rx should be switched into MMF induction Rx
 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
MMF + TAC
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)
Flares
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)