CLINICAL CASE CONFERENCE DANA ASSIS, MD

12.22.2015

CC: Dizziness

HPI: 45 year old male med hx as below presented from Kings County from HD hypotensive episode during HD BP 80/40s. Patient symptomatic dizzy and weak, no cp/sob/palpitations/diaphoresis. O/w was in USOH no f/c/nausea/vomiting/diarrhea.

PMHx: ESRD on HD for 15 years (unclear etiology of renal disease, never biopsied) severe aortic stenosis with insufficiency dx 2014, LVH EF 60-65% subclavian vein stenosis

PSHx: R AVF 2005

Subclavian stent placement bilateral 2006

All: NKMA

Meds: nephrovite, sevelamer, sensipar, aspirin, atorvastatin

FHx: Mother died of renal disease, Father died prostate cancer. Maternal grandfather also died of kidney disease. Sister started HD at age 52.

Social: Immigrated from Nigeria, one daughter, two grandchildren. No toxic habits.

• ROS: right sided hearing loss, left eye pain

• BP 97/40 HR 62 RR 18 O2 100% RA

• Gen: well appearing nad

• Heent: mmm, venous distension neck veins

• CV: 5/6 systolic murmur RUSB radiating to carotids, regular rhythm

• Pulm: CTA B/L

• Abd: bs positive, soft, nd, nt

• Ext: no pedal edema, distal pulses 2+ , right femoral HD catheter

• RUE fistula no thrill no bruit

• Neuro: aaox3, no facial droop, sensation intact, strength intact, decreased hearing in right

Labs

• BMP 139/3.8/102/26/39/7.6/97

• Ca 8.4 PTH 3224 P 2 vit D 13.7

• Troponin 1.05

• BNP

• Hb 10.3 plt 189 wbc 5

• Inr 1

• Alb 3.2 Tp 6.6; SPEP no abnl bands seen

• K/L 1.63 Kappa 161 Lambda 98

• Hep Panel negative HIV negative

• A1c 5.8

Hospital Course

• At OSH EKG reportedly NSTEMI with troponin peak 7.17. Cardiac cath with non obstructive disease. Transferred to BHC for evaluation AVR. Hospital course significant for telemetry showing third degree AVB. Tele intermittent 2:1 AVB and high degree AVB while sleeping.

• Deemed not to be surgical candidate 2/2 lack of symptoms and high operative risk. Patient was being considered for PPM given high grade AVB with escape rhythm <40 bmp, but patient deferred.

• Prev Hospitalization: 2014 presented from King’s County with decreased ET, progressive DOE, and feeling lightheaded. Found to have moderate to severe AS/AI but given no symptoms directly attributed to AS/AI surgery was deferred.

• Work up at that time significant for undetectable alpha-galactosidase levels

• Follow up NYU Medical Genetics 12/2015

Imaging

• TEE Nov 2015: concentric LVH no LV dilatation, hyperdynamic LV wall motion EF 80%. RVH. Severe AR, severe aortic valve thickening. No aneurysm or coarctation.

• TTE June 2014: Mod AS. Calculated AVR gradient 1.2cm2. Mod-Sev AR. Peak Pressure gradient AV is 80mmHg and mean pressure gradient is 46mmHg. No LV dilatation. Mod-sev concentric LVH, hyperdynamic left wall motion EF 75%.

• Brain MRI Nov 2015: multiple small acute or subacute infarcts in both cerebral hemispheres, predominantly in white matter, most likely related to patient hx of Fabry disease and small vessel disease. Extensive other chronic ischemic changes, small old infarcts and likely areas of deposition in bilateral cerebellum.

Outline

• What is Fabry disease

• Briefly pathology

• Disease progression

• Biomarkers disease detection

• Treatment Options

• Future Prospects

FABRY DISEASE

• First described in 1898

• William Anderson and Johannes Fabry

• Renal involvement described 50 years later autopsies of three brothers paper Pompen et al

• Lysosomal storage disease

• Deficiency α Gal A

• GLA gene

Clinical presentation

• Corneal opacities, vasculopathy

• Acroparesthesias, deafness, heat intolerance, tinnitus

• Angiokeratomas, hypohidrosis

• Renal proteinuria

• Cardiac conduction defects shortened PR, valvular insufficiency, LVH

• GI nausea vomiting diarrhea

• Stroke cerebrovascular disease

FABRY OUTCOME SURVEY

PODOCYTE INJURY AND GL-3 ACCUMULATION

PODOCYTE INJURY AND GL-3 ACCUMULATION

PODOCYTE INJURY AND GL-3 ACCUMULATION

DISCUSSION POINTS • Study correlating age with progressive accumulation of GL-3 in podocytes

• Patient absent or low grade proteinuria, normal renal function

• Longer term follow up, larger patient population

• Suggestive that UpUcr may not be sensitive enough to detect early kidney injury

DIALYSIS CHARACTERISTICS AND OUTCOMES

KIDNEY TRANSPLANT

REJECTION RATES

GRAFT AND PATIENT SURVIVAL

ENZYME REPLACEMENT THERAPY • Has been available since 2001

• Fabrazyme (agalsidase beta)

• Europe Replagal (agalsidase alpha)

• To date no direct comparison between two formulations

• Role patients with renal failure

• Role in transplant patients

ADDITIONAL RESEARCH

• Prevalance of Fabry disease CKD I to IV

• Evidence improved survival RRT patients on ERT

• Is ERT the same distribution across all tissues

• Cardiovascular Cerebrovascular complication

• Role of ACE-I long term benefit to stop progression CKD