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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 2001-2005Impact of Race
0
20
40
60
80
100
120
AA Cau Hisp Asian Other Total
IgAN
FSGS
Nair R.. Kidney International (2006) 69, 1455–1458
Nair R.. Kidney International (2006) 69, 1455–1458
Prevalence of FSGSImpact of Age
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: portion (segment) some (focal), but not all
glomeruli. The scar:
increased mesangial matrix collapsed glomerular
capillaries adhesion between tuft and
Bowman’s capsule Hyaline deposits.
Accompanying features: mesangial hypercellularity foam cells.
FSGS (NOS) FSGS perihilar variant FSGS cellular variant FSGS tip variant FSGS collapsing variant
“ Columbia” Classification of FSGS
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
01020304050607080
ALL FSGS CELL COLL TIPLESION
NOS
REMISSION ESRD
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 FSGSClinical 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 FSGS1. Familial
α-actinin 4 nephrin Podocin TRPC6 INF2
Lmx1b(Nail-Patella Syndrome)
Mitochondrial cytopathies
JASN, 13:3005-3015, 2002
Molecular Biology of the Podocyte
Genetic Screening in Steroid-Resistant FSGS? Results of NPHS2 studies
AUTHORS GROUP FAMILIAL NON FAMILIAL
SS SRWeber S.KI (2004) 66, 571–579;
Children 43%
(n=81, AR)
ND 10.5%
(n=172)
He N.CJASN 2: 31-37, 2007
Adult 0%
(N=9)
13%
(N=15)
10%
(n=63)
Tsukaguchi HJCI. 2002 Dec;110(11):1659-66.
Adult 27%
(n=33)
6% (control 1.6-3.9%)
(n=91)
Monteiro EJ.J Nephrol. 2006 May-Jun;19(3):366-71
Adult Only 1 mutation in familial
(n=39)
27
PURPOSE: To identify genetic variants predisposing to idiopathic and HIV associated FSGS
METHODS: Mapping by Admixture Linkage-Disequilibrium (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, 2008
MYH9 is a Major Risk Gene for FSGS and Hypertensive ESRD
28
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, 2008
29
MYH9 alleles and Extended (E) Haplotypes: Risk and Protection
Haplotype Frequency Odds ratioiFSGS
AA EA AA EA
E1 60% 4% 5 7.6
E2 21% 69% 0.2 0.4
E3 12% 27% NS NS
E4 4% <1% NS NS
E5 3% <1% NS NS
Increased Risk
Reduced Risk
Abbreviations: AA, African American; EA, European American
Kopp et al, Nature Genetics 40:1175, 2008
E1 Haplotype Predicts FSGS+HIVAN
35% 73%
Winkler, Kopp et al, ASN 09, FC 232, PO 1389
Copies of alleles
0 1 2
Disease Continental origin
Cases/controls
OR
(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
MYH9 Risk Variant is Strongly Associated with Kidney Disease
Kopp, Nature Genetics 2008
(*In DM2 with larger cohort Freedman, NDT 2009)
32
Clinical Implications of MYH9
Lifetime risk estimates in AA Pts
0 risk alleles 1 risk allele 2 risk alleles
HIVAN 0% 5%1:20
20%1:5
FSGS 0.2%1:500
0.4%1:250
1.6%1:62
HTN attributed-ESKD
1.4%1:71
1.9%1:53
3.1%1:32
Kopp, ASN 09
33
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
FSGS
HIV-1
Kopp, ASN 09
Secondary FSGS2. Virus-associated
Parvovirus B19 HIV-associated nephropathy
Association of parvovirus B19 infection with idiopathic collapsing glomerulopathyISH
78.26%
15.79%22.22%
25.93%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
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 FSGS3. 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 1.01.0 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 FSGS4. 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
1998
Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1998, 2006
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2006
1990
No Data <10% 10%–14 15%–19% 20%–24% 25%–29% ≥30%
Obesity-Glomerular “Stress”
Secondary FSGSObesity-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
Compared to Classic FSGS:More Caucasians
(75% vs 52%)Less nephrotic-range proteinuria
(48% vs 66%)Less nephrotic syndrome
(5.6% vs 54%)
Obesity-related glomerulopathy: An emerging epidemic
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
51
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
Perihilar-4, collapsing-3, 7 had >40% interstitial fibrosis Follow-up in 8 pts of 2 yrs
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
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 CKDMetanalysis of 11 studies (1860 pts)
Ann Intern Med. 2003 Aug 19;139(4):244-52.
REIN Study: ACE I nhibition in REIN Study: ACE I nhibition in ProteinuricProteinuricNonNon--Diabetic NephropathyDiabetic Nephropathy
91.3
92.4
Baseline DBP
148.0
149.8
Baseline SBP
-3.4 mmHg-3.4 mmHgPlacebo
-4.2 mmHg-5.8 mmHgRamipril
∆ DBP∆ SBP
00 66 1212 1818 2424 3030 3636
100
80
60
40
20
0
100
80
60
40
20
0
RamiprilRamipril
PlaceboPlacebo
P=0.02P=0.02
The GISEN Group. Lancet. 1997;349:1857– 1863.
% o
f pa
tien
ts w
itho
utco
mbi
ned
endp
oint
*
* Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure
www.hypertensiononline.org
Combination ACE-i/ARBCOOPERATE (Non diabetic glomerular disease- 14% FSGS)-
Nakao N et al. Lancet. 2003;361:117–124.
Doubling of Serum Creatinine or Progression to ESRD
0
5
10
15
0 5 12 18 24 30 36
20
25
30
Pro
po
rtio
n R
eac
hin
g
En
dp
oin
t, %
Months After Randomization
Trandolapril
Losartan
Combination
P = 0.02
ACE-I in HIVAN
Wei A… Kidney Int. 2003 Oct;64(4):1462-71.
The nephrotic syndrome, lipids, and risk factors for cardiovascular disease
0
10
20
30
40
50
60
70
80
90
100
>200mg/dl >300mg/dl >400mg/dl
ALL
Membranous
FSGS
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.
Bianchi S.. Am J Kidney Dis. 2003 Mar;41(3):565-70.
Effects of Atorvastatin on Proteinuria and Progression of Kidney Disease
Primary FSGS: Treatment Options
Corticosteroids Cytotoxic agents
Cyclophosphamide Chlorambucil
Cyclosporine/Tacrolimus Plasmapheresis
Steroid Treatment of FSGSResponse in Adults
Korbet S. Kidney International (2002) 62, 2301–2310
Steroid Treatment of FSGSHow 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 FSGSResponse to Corticosteroids
3
25
60
30
0
10
20
30
40
50
60
70
80
90
100
PE
RC
EN
TA
GE
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 FSGSCyclosporine (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.
Cattran DC, Appel GB.. Kidney Int. 1999 Dec;56(6):2220-6.
Steroid-resistant FSGSCyclosporine (North American Collaborative Trial)Remission Rates
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/2OAll NS Uprot 9.4 g/d Screat. 0.8-3.1 mg/dlAll 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.
• 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
MMF v Steroids in Primary FSGS
Nayagam, et al, NDT 2007
MMF v Steroids in Primary FSGS
Nayagam, et al, NDT 2007
Remission
MMF= 71%
Pred= 60%
MMF
Pred
FSGS-NIH Sponsored Controlled Trial
12 Month Primary Outcome Assessment
Treatment Withdrawn (CYA/MMF/Dex)
6 months
Secondary Outcome AssessmentRemission/Relapse Status at 18 months
0
26
52
78
Week
CYA MMF + Dexamethasone
ACEi
Failures Depart
Cattran DC, Appel GB.. Kidney Int. 1999 Dec;56(6):2220-6.
Steroid-resistant FSGSCyclosporine (North American Collaborative Trial)50% Decline in Creatinine Clearance
Treatment of Steroid Refractory or Relapsing Patients.Response to Cytotoxic and Cyclosporine therapy
Steroid Refractory/Dependent FSGSMycophenolate 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=21Sirolimus (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
56%: Stabilized eGFR slopes
Phase I trial of adalimumab FONT study group
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
1.6
19.5
22.8
0
5
10
15
20
25
Uri
ne
pro
tien
(g
/g c
reat
.)
DEC 10 DEC 11 DEC 12
Post-transplant course
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 post-transplant
Plasmapheresis with Recurrent FSGS after Transplantation
Savin V.. N Engl J Med 1996; 334: 878– 883.
50 kd
91
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-260
92
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.
Cardiotrophin like cytokine-1: Candidate for the focal glomerular sclerosis permeability factor
Savin et al, ASN 08, FC-260
Plasmapheresis for Recurrent FSGSThe 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
1.6
19.5
22.8
3.9
9.7
13.4
7.6
0
5
10
15
20
25
DEC10
DEC11
DEC12
DEC16
DEC27
JAN3
JAN10
PLASMAPHERESIS
Post Transplant Monitoring
Vincenti F, Am J Transplant. 2005 Jun;5(6):1179-85
Suggested Algorithm for Nephrotic FSGS
FSGS ON BIOPSY
PRIMARY SECONDARY
Conservative Therapy
Prednisone 1mg/kg
Cyclosporine
Sirolimus
Mycophenolate
Cytotoxics
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 4-6 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 steroid-refractory/dependent pts
Recommended