Transcript Nair R.. Kidney International

Focal Segmental
Glomerulosclerosis
Jai Radhakrishnan, MD, MS, MRCP, FACC, FASN
Associate Professor of Clinical Medicine
Columbia University, New York
www.glomerularcenter.org
Objectives


Diagnosis and epidemiology of FSGS
Principles of therapy using a stepwise
approach.
Changing Epidemiology of FSGS
Prevalence of FSGS: Arkansas 2001-2005
Impact of Race
120
100
80
IgAN
FSGS
60
40
20
0
AA
Cau
Hisp
Asian
Other
Total
Nair R.. Kidney International (2006) 69, 1455–1458
Prevalence of FSGS
Impact of Age
Nair R.. Kidney International (2006) 69, 1455–1458
Changing Incidence of Glomerular Disease
in Olmsted County
Swaminathan S. Clin J Am Soc Nephrol 1: 483-487, 2006
Clinical history



A Caucasian female in her 30’s developed abrupt onset of
full nephrotic syndrome
July of 2002
 24 hr urine protein 13 g/day
 Renal biopsy: 8/8 normal glomeruli
100 % foot process effacement on EM
 Minimal change disease
 Rx: oral prednisone, resulting in thrush, skin
breakdown, cellulitis
September of 2002
 Cyclosporine 100 mg/day, leading to ARF
(creatinine=4.4 mg/dL, cyclosporine=107ng/ml).
 Cyclosporine stopped; creatinine declined to 1.7mg/dl
Clinical history

January 2003: Came to Columbia University
Medical Center for a 2nd opinion




Physical exam: emaciated, 3+ edema with ascites,
skin breakdown
24 hour urine protein= 17 g/day
Albumin=
1.9 mg/dL
Creatinine=
1.7 mg/dL
Focal Segmental Glomerulosclerosis
NOS (not otherwise specified)

Location:



The scar:





portion (segment)
some (focal), but not all
glomeruli.
increased mesangial matrix
collapsed glomerular
capillaries
adhesion between tuft and
Bowman’s capsule
Hyaline deposits.
Accompanying features:


mesangial hypercellularity
foam cells.
“ Columbia” Classification of FSGS





FSGS (NOS)
FSGS perihilar variant
FSGS cellular variant
FSGS tip variant
FSGS collapsing variant
D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Am J Kidney Dis. 2004 Feb;43(2):368-82.
FSGS collapsing variant

Only 1 glomerulus
showing


Segmental or global
obliteration of the
glomerular capillary
lumina by wrinkling and
collapse of glomerular
basement membranes
Hypertrophy and
hyperplasia of the
overlying podocytes
FSGS tip variant



Exclude collapsing
variant
At least 1 glomerulus
with a segmental
lesion of cellular or
sclerosing nature
involving the tip
domain.
Perihilar location
sclerosis rules out the
tip variant
FSGS cellular variant


Tip and collapsing
variants be excluded
At least 1 glomerulus
with endocapillary
hypercellularity
involving at least 25%
of the tuft and causing
occlusion of the
capillary lumen/lumina
FSGS- perihilar variant



At least 1 glomerulus
with perihilar hyalinosis,
with or without sclerosis
Greater than 50% of
segmental lesions
showing perihilar
sclerosis and hyalinosis
Cellular variant, tip
variant, and collapsing
variant be excluded.
Outcomes of FSGS Variants:
Columbia University
REMISSION
80
70
60
50
40
30
20
10
0
ALL FSGS
CELL
COLL
ESRD
TIP
LESION
NOS
Kidney International (2006) 70, 1783–1792.
Diffuse Mesangial Sclerosis




Postnatal proteinuria
ESRD by age 3
Steroid refractory
Autosomal recessive



PLCE1: DMS
WT-1
(Frasier syndrome and Denys-Drash syndrome )
LAMB2 (Pierson)
What is her prognosis?
Prognosis in Primary FSGS
Clinical Features
Troyanov.. J Am Soc Nephrol. 2005 Apr;16(4):1061-8
Focal and segmental glomerulosclerosis: definition
and relevance of a partial remission.
Troyanov S.. J Am Soc Nephrol. 2005 Apr;16(4):1061-8.
Survival from Renal Failure
No Remission vs. PR with a relapse
Troyanov S.. J Am Soc Nephrol. 2005 Apr;16(4):1061-8.
Treatment of FSGS
Stepwise Approach to FSGS Treatment




Step 1: Exclude Secondary FSGS
Step 2: Conservative therapy
Step 3: Immunosuppressive therapy
Recurrent FSGS after renal transplant
Secondary FSGS
1. Familial

α-actinin 4
nephrin
Podocin
TRPC6
INF2

Lmx1b




(Nail-Patella Syndrome)

Mitochondrial cytopathies
Molecular Biology of the Podocyte
JASN, 13:3005-3015, 2002
Genetic Screening in Steroid-Resistant
FSGS? Results of NPHS2 studies
AUTHORS
Weber S.
GROUP
FAMILIAL
NON FAMILIAL
SS
SR
Children
43%
(n=81, AR)
ND
10.5%
(n=172)
Adult
0%
(N=9)
13%
(N=15)
10%
(n=63)
Adult
27%
(n=33)
KI (2004) 66, 571–579;
He N.
CJASN 2: 31-37, 2007
Tsukaguchi H
JCI. 2002
Dec;110(11):1659-66.
Monteiro EJ.
J Nephrol. 2006 MayJun;19(3):366-71
Adult
6% (control 1.6-3.9%)
(n=91)
Only 1 mutation in familial
(n=39)
MYH9 is a Major Risk Gene for FSGS and
Hypertensive ESRD

PURPOSE: To identify genetic variants predisposing
to idiopathic and HIV associated FSGS

METHODS: Mapping by Admixture LinkageDisequilibrium (MALD) genome scans performed in
190 AA with FSGS and 222 controls.

RESULTS: A region was identified centered on MYH9
(Myosin Heavy Chain 9) Chrom 22.

MYH9 is a functional candidate gene expressed on
podocytes
Kopp et al, ASN 08, FC-254; Nature Genetics 40:1175, 27
2008
MYH9 is biologically plausible candidate gene
 MYH9 binds actin and has been
localized to podocytes and mesangium
 Actin/myosin cytoskeleton is enriched
in podocyte foot processes
 MYH9 mutations associated with
glomerulonephritis
Kopp et al, ASN 08, FC-254; Nature Genetics 40:1175, 200828
MYH9 alleles and Extended (E) Haplotypes:
Risk and Protection
Haplotype
Frequency
AA
EA
Odds ratio
iFSGS
AA
EA
E1
60%
4%
5
7.6
Increased Risk
E2
21%
69%
0.2
0.4
Reduced Risk
E3
12%
27%
NS
NS
E4
4%
<1%
NS
NS
E5
3%
<1%
NS
NS
Abbreviations: AA, African American; EA, European American
Kopp et al, Nature Genetics 40:1175, 2008
29
E1 Haplotype Predicts FSGS+HIVAN
35%
73%
Copies of alleles
Winkler, Kopp et al, ASN 09, FC 232, PO 1389
0
1
2
MYH9 Risk Variant is Strongly
Associated with Kidney Disease
Disease
Continental Cases/co
OR
origin
ntrols
(recessive model)
P
HIVAN
Africa
53/511
6.6
7 x 10-8
Idiopathic FSGS
Africa
188/511
4.1
9 x 10-16
Idiopathic FSGS
Europe
125/221
7.7
0.052
HTN- ESKD
Africa
241/192
2.2
7 x 10-5
DM-2 ESKD
Africa
284/192
1.3
0.02
Kopp, Nature Genetics 2008
(*In DM2 with larger cohort Freedman, NDT 2009)
Clinical Implications of MYH9
Lifetime risk estimates in AA Pts
0 risk alleles 1 risk allele 2 risk alleles
HIVAN
0%
5%
20%
1:20
1:5
FSGS
0.2%
0.4%
1.6%
1:500
1:250
1:62
HTN attributed1.4%
1.9%
3.1%
ESKD
1:71
1:53
1:32
Kopp, ASN 09
32
Hypothetical Pathways of MYH9-Associated FSGS
Cytokines
Viral infection
Environmental toxins
Medications
Fragile podocyte (footing)
- Reduced adhesion/mobility
- Altered proliferation
Sickle cell anemia
Obesity, HTN
HIV-1
FSGS
Kopp, ASN 09
33
Secondary FSGS
2. Virus-associated


Parvovirus B19
HIV-associated nephropathy
Association of parvovirus B19 infection with
idiopathic collapsing glomerulopathy
ISH
80.00%
78.26%
70.00%
60.00%
50.00%
40.00%
22.22%
30.00%
25.93%
15.79%
20.00%
10.00%
0.00%
CG
HIVAN
FSGS
Controls
Moudgil A. Kidney Int. 2001 Jun;59(6):2126-33.
Antiretroviral therapy in the treatment of
HIV-associated nephropathy
Atta M. Nephrology Dialysis Transplantation 2006 21(10):2809-2813
Secondary FSGS
3. Medications




Heroin nephropathy
Interferon-α
Lithium
Pamidronate / alendronate
Lithium nephrotoxicity:
A Progressive Combined Glomerular and
Tubulointerstitial Nephropathy (n=24)
Renal insufficiency
100%
Mean SCr initial (mg/dl)
2.8(range, 1.3 to 8.0)
Proteinuria (>1 g/24 h)
41.70%
24-h urine protein
0 to 0.5
0.5 to 1.0
1.0 to 3.0
> 3.0
41.70%
16.70%
16.70%
25%
Nephrotic syndrome
12.50%
Clinical evidence of NDI
87%
Markowitz GS, Radhakrishnan J.. J Am Soc Nephrol. 2000 Aug;11(8):1439-48
Lithium nephrotoxicity:
S Creatinine >2.5 mg/dl is a significant predictor of
progression to ESRD
(P = 0.008).
Markowitz GS, Radhakrishnan J.. J Am Soc Nephrol. 2000 Aug;11(8):1439-48
Collapsing FSGS following Treatment with
High-dose Pamidronate





7 White pts 49-77
Treated with pamidronate
90mg (usual dose) followed
by (180-360mg)
15-48 months later
developed full NS
4 pts reached ESRD
2 of 3 pts improved after
discontinuing Pamidronate
Markowitz GS…. J Am Soc Nephrol 2001 Jun;12(6):1164-72

11 patients (7F, 10 Black)

IFN-α: hepatitis C virus infection (n = 5),
malignant melanoma (n =1)





IFN-β for multiple sclerosis (n=3)
IFN-γ for idiopathic pulmonary fibrosis (n=2)
Duration: mean 4.0, median 12.6 months
AKI (Cr 3.5mg/dL), nephrotic proteinuria (9.7g)
After stopping IFN: 9/10 creat improved, prot 3.0g
1 complete remission
 2 partial
No benefit with immunosuppression (4/7)

Clin J Am Soc Nephrol. 2010 Mar 4. [Epub ahead of print]
Secondary FSGS
4. Adaptive structural-functional responses likely mediated by
glomerular hypertrophy or hyperfiltration





Reduced renal mass
Oligomeganephronia
Unilateral renal agenesis
Renal dysplasia
Cortical necrosis
Reflux nephropathy








Surgical renal ablation
Chronic allograft nephropathy
Any advanced renal disease
with reduction in functioning
nephrons
Initially normal renal
mass
Diabetes mellitus
Hypertension
Obesity, Body Builders
Cyanotic congenital heart
disease
Sickle cell anaemia
Obesity Trends* Among U.S. Adults
BRFSS, 1990, 1998, 2006
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
1998
1990
2006
No Data
<10%
10%–14
15%–19%
20%–24%
25%–29%
≥30%
Obesity-Glomerular “Stress”
Secondary FSGS
Obesity-related Glomerulopathy at Columbia
Obesity-related glomerulopathy: An
emerging epidemic
Definition:


Obesity BMI> 30 kg/m2.
Obesity-related glomerulopathy
(ORG)




FSGS + Glomerulomegaly (N = 57)
Glomerulomegaly alone (N = 14).
71 cases (mean age 43 y, 75%
White)
50 Controls with Classic FSGS
Kambham N, Markowitz GS, Valeri AM, Lin J, D'Agati VD.
Kidney Int. 2001 Apr;59(4):1498-509
Obesity-related glomerulopathy: An
emerging epidemic
Compared to Classic FSGS:
More Caucasians

(75% vs 52%)
Less

(48% vs 66%)
Less

nephrotic-range proteinuria
nephrotic syndrome
(5.6% vs 54%)
Kambham N, Markowitz GS, Valeri AM, Lin J, D'Agati VD.Kidney Int. 2001;59(4):1498-509
Obesity-related glomerulopathy: An
emerging epidemic


4 patients
lost wt:
proteinuria
reduced by
>50%
ACE-I
reduced
proteinuria
by 1g
Kambham N, Markowitz GS, Valeri AM, Lin J, D'Agati VD.Kidney Int. 2001
Apr;59(4):1498-509
FSGS Associated with Anabolic
Androgenic Steroid Use in Bodybuilders




10 pts (W-6, H-4), long-term AAS use, BMI-35 kg/m2
UPro-10 g/d (1-26 g/d), 5 pts with NS
SCr- 3 mg/dl (1.3-8)
FSGS-9 and/or glomerulomegaly-5


Follow-up in 8 pts of 2 yrs



Perihilar-4, collapsing-3, 7 had >40% interstitial fibrosis
1 progressed to ESRD rapidly
Off AAS, 7 had stable/improved SCr and UPro with ACEi
FSGS may result from post-adaptive glomerular
changes due to increased BMI and toxic effects of
AAS
Herlitz, D’Agati al, ASN 09, PO 163
51
Treatment Principles
Primary FSGS


Spontaneous remission is rare <5%
Any remission is better than no remission
Conservative Treatment
(In all cases of FSGS)
The Role of Blood Pressure Control
Progression of Non-Diabetic Proteinuric CKD
Metanalysis of 11 studies (1860 pts)
Ann Intern Med. 2003 Aug 19;139(4):244-52.
% of patients without
combined endpoint*
REIN Study: ACE Inhibition in Proteinuric
Non-Diabetic Nephropathy
100
80
Ramipril
60
40
P=0.02
20
0
Placebo
00
66
12
12
18
18
24
24
30
30
36
36
Baseline SBP
∆ SBP
Baseline DBP
∆ DBP
Ramipril
149.8
-5.8 mmHg
92.4
-4.2 mmHg
Placebo
148.0
-3.4 mmHg
91.3
-3.4 mmHg
*Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure
The GISEN Group. Lancet. 1997;349:1857–1863.
www.hypertensiononline.org
Combination ACE-i/ARB
COOPERATE (Non diabetic glomerular disease- 14% FSGS)Doubling of Serum Creatinine or Progression to ESRD
Proportion Reaching
Endpoint, %
30
Trandolapril
Losartan
Combination
25
20
15
10
5
P = 0.02
0
0
5
12
18
24
30
Months After Randomization
Nakao N et al. Lancet. 2003;361:117–124.
36
ACE-I in HIVAN
Wei A… Kidney Int. 2003 Oct;64(4):1462-71.
The nephrotic syndrome, lipids, and
risk factors for cardiovascular disease
100
90
80
70
60
ALL
Membranous
FSGS
50
40
30
20
10
0
>200mg/dl
>300mg/dl
>400mg/dl
Radhakrishnan J..Am J Kidney Dis. 1993 Jul;22(1):135-42.
The increased risk of CHD associated
with nephrotic syndrome
Ordonez J.. Kidney International (1993) 44, 638–642
Effects of Atorvastatin on Proteinuria and
Progression of Kidney Disease



N=56
idiopathic
N.S., (not
biopsied)
ACE &/or
ARB >1 year
Bianchi S.. Am J Kidney Dis. 2003 Mar;41(3):565-70.
Effects of Atorvastatin on Proteinuria and
Progression of Kidney Disease
Bianchi S.. Am J Kidney Dis. 2003 Mar;41(3):565-70.
Primary FSGS:
Treatment Options


Corticosteroids
Cytotoxic agents




Cyclophosphamide
Chlorambucil
Cyclosporine/Tacrolimus
Plasmapheresis
Steroid Treatment of FSGS
Response in Adults
Korbet S. Kidney International (2002) 62, 2301–2310
Steroid Treatment of FSGS
How long should I treat?

Studies before 1980, CR <20%


Duration < 2 months
Studies after 1980, CR > 40%

Average duration 5-9 months
Steroid “Resistance” is generally defined when
Prednisone 1mg/kg x 4 months fails.
Prognosis in FSGS
Response to Corticosteroids
100
90
PERCENTAGE
80
70
60
60
50
40
30
25
30
20
10
3
0
COMPLETE
PARTIAL
NONE
ALL
Korbet, S.. Nephrol Dial Transplant 1999;14 [Suppl 3]: 68–73
Steroid Resistant FSGS
Cyclophosphamide
Adult Pts. – 8 Studies
125 Pts.
CR 17%
PR 7%
Ped Pts. – 2 Studies
42 Pts.
CR 52%
PR 17%
Matalon A, Valeri A, Appel GB. Sem. Nephrol. 2001.
Steroid-resistant FSGS
Cyclosporine (North American Collaborative Trial)



49 patients with steroid-resistant FSGS
26 weeks of CYA + low-dose prednisone vs
placebo plus prednisone.
F/U 200 weeks
Cattran DC, Appel GB,.. Kidney Int. 1999 Dec;56(6):2220-6.
Steroid-resistant FSGS
Cyclosporine (North American Collaborative Trial)
Remission Rates
Cattran DC, Appel GB.. Kidney Int. 1999
Dec;56(6):2220-6.
Cyclosporine vs Chlorambucil in the
Treatment of FSGS
Heering P et al. AJKD 43:10-18, 2004
MMF for Steroid Resistant FSGS
16 Pts age 42 10B/4W/2O
All NS Uprot 9.4 g/d Screat. 0.8-3.1 mg/dl
All failed Pred. + others IS( 34 Course Rx Failed )
MMF 750-2g/d av. 9 months
50% Improved by 6 months
U prot decrease > 50% w/o NS = 4
U prot decrease > 50% w NS = 2
U prot decrease < 50% w/o NS = 2
Cattran , Appel, Briggs Clin Nephrol 2005
MMF Treatment for Primary
Glomerular Disease
18 Pts FSGS 16-65 yo 67% M 72% W / 22% B
Up/cr 2.7
Scr 1.8 mg/dl
9 / 17 Nephrotic
12 / 18 + STDS
6 / 18 MMF Alone
Up/cr 2.7 to 0.8 (2 CR, 6 PR)
9 NS Up/cr 7.5 to 3.9 (1 CR)
Choi MJ, Eustace JA, Gimenez LF, et al. Kidney Int 61:1098-1114, 2002.
MMF v Steroids in Primary FSGS
•
33 Nephrotic FSGS after ACEi/ ARBs for 6
months
•
Therapy:
• MMF 1 g BID x 6 mo + steroids 0.5
mg/kg/d x 2-3 months OR
• Steroids 1 mg/kg/d x 3-6 mo
Nayagam, et al, NDT 2007
MMF v Steroids in Primary FSGS
Remission
Pred
MMF= 71%
Pred= 60%
MMF
Nayagam, et al, NDT 2007
FSGS-NIH Sponsored Controlled Trial
Week
0
CYA
MMF + Dexamethasone
26
52
Failures Depart
12 Month Primary Outcome Assessment
Treatment Withdrawn (CYA/MMF/Dex)
6 months
78
ACEi
Secondary Outcome Assessment
Remission/Relapse Status at 18 months
Steroid-resistant FSGS
Cyclosporine (North American Collaborative Trial)
50% Decline in Creatinine Clearance
Cattran DC, Appel GB.. Kidney Int. 1999
Dec;56(6):2220-6.
Treatment of Steroid Refractory or
Relapsing Patients.
Response to Cytotoxic and Cyclosporine therapy
Steroid Refractory/Dependent
FSGS
Mycophenolate Mofetil (MMF)

N=18



CR: 2
PR: 6
Proteinuria reduction


Pre: 7.5 (2.7 to 20.3)
Post: 3.9 (0.1 to 8.2)
Choi M.. Kidney International (2002) 61, 1098–1114;
Steroid Refractory Patients n=21
Sirolimus (Rapamycin)
Tumlin J.. Clin J Am Soc Nephrol. 2006 Jan;1(1):109-16.
Acute Rapamycin Nephrotoxicity


11 Pts with GN and
progressive renal failure
(GFR decline >5ml/y)FSGS, IgAN, IMN, MPGN
were entered into a 12
month study.
Target rapa levels: 7-10
Nephrol Dial Transplant (2004) 19: 1288-1292
Phase I trial of adalimumab
FONT study group
56%: Stabilized
eGFR slopes
Dose: 24 mg/m2 SQ every 14 day (max 40 mg) x 16 weeks
Phase I trial of Rosiglitazone
FONT (Novel Therapies in Resistant FSGS)study group
3 mg/m2 /d twice a day (max 8 mg/d)
Clinical history

Developed ARF with low dose tacrolimus

No respond to oral cyclophosphamide

Renal replacement therapy started in June
of 2003 (12 months after onset)
Clinical History

The patient became progressively anuric
on dialysis after which she improved
clinically



Normal serum albumin
20 lb weight gain
Several family members offered her a
kidney including an HLA-identical sister
Post-transplant course



12/9/04: Zero-mismatch living donor transplant, 18 month after
the start of RRT
 Simulect (basiliximab) induction
 Sirolimus and tacrolimus maintenance
Rapid steroid taper
12/12/05: Creatinine decreased to 1.5mg/dL
12/13/05: Urine output dropped to 200ml/8 hours
• Wt gain 25 lbs / 1+ edema
• Creatinine increased to 1.8 mg/dL
• Hematocrit=27%; platelets= 300x 109/L
 Albumin=2.4 g/L(4.0 pre-transplant)
 Sirolimus 3.2ng/ml; tacrolimus 3.6 ng/ml
Post-transplant course
Urine protien (g/g creat.)
25
22.8
19.5
20
15
10
5
0
1.6
DEC 10
DEC 11
DEC 12
Renal allograft biopsy performed on 12/13/04
Diagnosis & findings

90% foot process effacement, highly suggestive of
early recurrent FSGS
What therapy would you recommend for this patient?
Recurrent FSGS in the allograft

Recurrence rate estimated at 30%


Probably higher when 20 FSGS excluded
Risk factors for recurrence:






Age < 20 years
Rapid progression to ESRD of < 3 yrs
Previous recurrence in a transplant
Caucasian
No difference in cadaveric versus living donor
transplantation
> 90% of recurrences occur in first 3 months posttransplant
Plasmapheresis with Recurrent FSGS
after Transplantation
50 kd
Savin V.. N Engl J Med 1996; 334: 878– 883.
Cardiotrophin-like Cytokine-1(CLC1):
Candidate for the FSGS Permeability Factor






CLC1 is a member of the IL-6 family
CLC1 was overexpressed in peripheral blood cells of 15
FSGS pts compared to controls (p <0.03).
Increasing doses of recombinant CLC1 incrementally
increased glomerular permeability (Palb)
Monoclonal Ab to CLC1 blocked the increase in Palb by
CLC1 and FSGS serum
Incubation of CLC1 with glomeruli decreased nephrin and
podocin expression
IV- CLC1 in rats increased UPCR by 3 fold
Savin et al, ASN 08, FC-26091
Cardiotrophin like cytokine-1: Candidate for the focal
glomerular sclerosis permeability factor

CONCLUSION: CLC1 is a strong candidate for
the permeability factor in FSGS.

Future studies will be required to:



Verify the clinical significance of CLC1.
Define the mechanism of action of CLC-1.
Develop specific therapies (antibodies, cytokine traps
or affinity based strategies) to prevent progression
and permit successful transplantation.
Savin et al, ASN 08, FC-26092
Plasmapheresis for Recurrent FSGS
The Columbia Experience

12/15 (80%) of the patients received 4 to 48 plasmapheresis
treatments.


Complete Remission: 3/12
Partial remission: 5/12

3 of these 8 patients who responded to PTE subsequently
experience a relapse after discontinuing PTE.

4 patients progressed to ESRD and 2 patients ultimately died with
graft failure.

Mean P. Creatinine at last follow for the other 11 patients was 1.9
mg/dl ( range 0.7 to 3.8 mg/dl ).
ASN 2007.
Post-transplant course




The patient rapidly
diuresed 30lbs
Creatinine peaked at
2.3mg/dL and then
declined to 1.3mg/dL on
1/5/05
Albumin improved to 3.6
g/dL
Proteinuria decreased
from peak 22.8 g/day to
7.6 g/day
25
22.8
19.5
20
PLASMAPHERESIS
15
13.4
9.7
10
5
0
1.6
7.6
3.9
DEC DEC DEC DEC DEC JAN JAN
10 11 12 16 27
3
10
Post Transplant Monitoring
Vincenti F, Am J Transplant. 2005 Jun;5(6):1179-85
Suggested Algorithm for Nephrotic FSGS
FSGS ON BIOPSY
Conservative
Therapy
PRIMARY
Prednisone 1mg/kg
Cytotoxics
Cyclosporine
Mycophenolate
Sirolimus
SECONDARY
Initial Treatment of patients with FSGS and
nephrotic syndrome

FSGS.2.1
We suggest prednisone or prednisolone be given as a daily
single dose of 1 mg/kg (maximum 80 mg) or alternative day dose of 2 mg/kg
(maximum 120 mg) (2C)

FSGS 2.2
We suggest the initial high dose of corticosteroids be given
for a minimum of 4 weeks up to a maximum period of 16 weeks, as
tolerated, if remission has not been achieved (2D).

FSGS 2.3
After achieving complete remission, we suggest
corticosteroids be tapered slowly over a total period of 6 months. (2D)

FSGS 2.4
For patients with relative contraindications or intolerance to
high dose corticosteroids (uncontrolled diabetes, psychiatric conditions,
severe osteoporosis), we suggest calcineurin inhibitors (CNI) (2D), as
discussed in steroid resistant FSGS.
Treatment for steroid-resistant FSGS


FSGS.4.2
We suggest that in steroid
resistant patients a CNI (cyclosporine at 3-5
mg/kg/day or tacrolimus at 0.1 mg/kg/day in
divided doses) should be given for at least 46 months (2B).
FSGS.4.3
In patients with at least a
partial remission, we suggest to continue CNI
treatment for at least 12 months and then
taper slowly (2D).
Conclusions




FSGS is a pathological diagnosis
Secondary causes need to be ruled out
Steroid responsiveness defines a better
prognostic subset of patients
Calcineurin inhibitors, cytotoxic agents and
mycophenolate are options in steroidrefractory/dependent pts