anjali gupta 12/28/11 - nyu langone health · 2014-08-13 · anjali gupta . 12/28/11 ... all...

Anjali Gupta 12/28/11

FSGS most common cause( 57%) of nephrotoc syndrome in AA

FSGS is the most

common cause of GN related ESRD

Familial-Genetic Alpha-actin4 Podocin

Virus –Associated HIV associated Parvovirus B-19

Drug-med Heroin Pamidronate

Reduced Renal Mass Unilateral renal agenesis Reflux nephropathy

Initial normal renal mass Obesity Atheroembolic Sickle cell Anemia

Obesity Related 1. Low grade proteinuria 2. Slow progressive increase

in proteinuria 3. Usually asymptomatic

and not nephrotic 4. Obese with no family

history 5. Slow progression to ESRD 6. Glomerulomegaly on

biopsy 7. Do not have 100%

effacement of podocytes

Idiopathic 1. Massive proteinuria 2. Acute onset nephrotic

syndrome 3. Faster progression to

ESRD 4. No glomerulomegaly 5. 100% foot process

effacement

Foot process effacement In a systematic study of podocyte alterations mean

percentage of the glomerular surface area affected by foot process fusion was

42% +22% in obesity associated FSGS

compared with classic FSGS (65% + 23%) Although helpful, the semi-quantitative assessment of foot

process fusion thus does not provide an absolute means for distinguishing between these primary and secondary forms.

Mod Pathol 7:157A, 1994 Barasoni et all

17 patient with idiopathic and 12 patients with secondary causes of FSGS based on clinical criterion evaluated.

Kidney International (2008) 74, 1568–1576

Serum Albumin Retrospective study 37 pt with biopsy proven FSGS and persistent nephrotic

syndrome were dived base on albumin levels prior to biopsy Gp1 <3 gm/dl and Gp2 with >3.5gm/dl.

All patients in Gp 1 were diagnosed of i FSGS and all expect 2 patients were in Gp 2 were diagnosed of sec FSGS ( 44% Obese, 27% had vesicoureteral refkex and 13% had reduced renal mass.

Gp 2 patients had significant glomerulomegaly.

American Journal of Kidney Diseases, Vol 33, No 1 (January), 1999: pp 52-58

Renal survival in patients with obesity‐associated FSG (OB‐FSG) and idiopathic FSG (I‐FSG).

Praga M et al. Nephrol. Dial. Transplant. 2001;16:1790-1798

European Renal Association-European Dialysis and Transplant Association

Clinical Proteinuria/ Nephrotic syndrome AA race

Histopathology Interstitial fibrosis Tip lesion Collapsing FSGS

Course Remission of proteinuria

Toronto registry examined 281 FSGS patients

Median follow up of 5 years

J Am Soc Nephrol 16: 1061-1068, 2005.

• No randomized trials to guide the dose and duration of glucocorticoid

therapy

• Multiple retrospective studies showed Complete Remission form 32-47% and partial remission 20- 26 % ( Agarwal 1993, Pontechilli 1999, Chun 2004 ) • Dose 0.5-1 Kg/day. High dose usually 2-3 months with total duration of 6-

9 months • Median time to remission 3.7- 5months • In Pontechilli study if steroid duration was <16 weeks Remission was 16%

as compared to 61% if duration was >16 weeks

• 33 Nephrotic FSGS after 6

months of ACE n ARB • Therapy Gp A: MMF Ig BID * 6 months

+ Steroids 0.5mg/kg/day * 3months

Gp B: Steroids 1 mg/kg/day *

3-6 months Relapse rate 4 in each

patient

Response in 5-10 weeks Nayagam: NDT 2008 23: 1926-30

Steroid resistance : Children 8 weeks of therapy and adults 16 weeks of steroids. 40-70% of FSGS pts are steroid resistant

Steroids Calcineurin Inhibitors Cyclosporine Tacrolimus Cytotoxic agents Cyclophosphamide MMF

Cyclosporine

•RTC of 49 steroid resistance FSGS cases comparing 26 weeks of cyclosporine and low dose prednsione with placebo and prednsione

•Relapse was common after cyclosporine withdrawal (40 and 60 percent had worsening of proteinuria by week 52 and 78, respectively). •At four years, active therapy was associated with a lower risk of a 50 percent reduction in creatinine clearance (25 versus 52 percent).

MMF vs cyclosporine in FSGS

Prospective , randomized, multi-center, open label trial Compared MMF with cyclosporine Enrolled 138 pts (initial plan for 500) Age 2-40 years E GFR > 40 , u p/cr >1gm/g Corticosteroid resistant defined as >4 weeks of steroids

Cyclosporine 5-6 mg/kg to maintain levels

of 100-250 ng/ml

(max dose 250)

MMF + Dexa MMF 25-35 mg/kg (max 2gm/day)

Dexa 0.9mg/kg

Weekly , biweekly n then monthly

Total 46 doses

Both Groups: Prednisone 0.3mg/kg (max 15mg ) * 6 months Ace inhibitor for 18 months

MMF (N=66) Csa( n =72) O R CI

CR 26 2 (3.0) 4.0(5.6) 0.53 0.09-3

CR 52 4 (6.1) 10(13.9) 0.41 0.15-1.15

PR 16(24.2) 19(26.4) 0.59 0.30-1.18

CR+PR 22(33.3) 33(45.8) 0.59 0.30-1.18

Relapse rate at 78 weeks : 33% in Csa vs 17 % in MMF Adverse events: •Infections 13.6 in Csa Vs 9.7% in MMF •Both groups hospitalization 25-27% and Gi side affects ~ 70 %

Results

60% patients were less than <18 years Underpowered study Definition of corticosteroid resistant Pt with sub nephrotic proteinuria included

Thank you

Results

Chlorambucil