1	Case Discussion Israel Society of Hypertension Dead Sea March, 2009
2	Recap relevant data Male, 37y, BMI 19.5, heavy smoker Admitted with: Hypertensive urgency (BP186/125,190/126) Hyponatremia (Na 121 mEq/L) Hypokalemia (K 2.0 mEq/L) Pure nephrotic syndrome (bland sediment) Normal renal function
3	On admission Per anamnesis – Right popliteal vein thrombosis (2001) Hypercoagulability workup Factor V Leiden heterozygote Primary APLA syndrome (APS) - lupus anticoagulant positive - APLA IgM, IgG markedly elevated
4	Patient’s hypertension Relatively recent onset – 6/12 history Not investigated Inadequately treated - atenolol only ? - patient compliance
5	Patient’s hypertension Per history – Left loin pain Renal sonography – LK 8.5cm, RK 12.5cm (compensatory growth) Doppler US – RI left 0.9, right 0.5 Renal scan – Non functioning LK (?1%) Abdo CT – Contracted LK, weak nephrographic effect 1998 – CT showed 2 normal sized kidneys
6	Patient’s hypertension Since 1998, probably as of 6/12 , developed contracted left kidney Thrombosed left main renal artery High renin hypertension Renovascular HTN (2 kidney, one clip Goldblatt)
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8	Patient’s course
9	Conclusions ACEI/spironolactone – BP well controlled Electrolyte abnormalities corrected Protein excretion reduced - ? parallel to BP reduction Patient incompliant
10	Electrolyte abnormalities and renovascular HTN Hypokalemia – secondary hyperaldosteronism Hyponatremia – Why?
11	Hyponatremia and RVHTN Not a reported textbook feature of RVHTN AII promotes Na reabsorption/ACEI natriuretic Our patient – lack of UNa, UOsm
12	Hyponatremia and RVHTN However, AII known dipsogenic (as is hypokalemia) Polydipsia/polyuria Increased ADH secretion Increased atrial β-type natriuretic peptides
13	In summary Hyponatremia Hypokalemia Polydipsia/polyuria RVHTN Hyponatremic hypertensive syndrome Sekkarie et al, AJKD 23;866-868,1994 Remuzzi et al ,AJKD 14;170-177, 1989 Acta Pediatr 1995;504-7, 2006
14	Nephrotic syndrome and RVHTN Proteinuria in RVHTN may be due to prolonged HTN Usually mild, non-nephrotic range Heavy proteinuria/NS Originates from non-ischemic kidney AII dependent Ameliorates/disappears on ACEI therapy (independent of BP lowering effect)
15	AII and proteinuria/NS Hemodynamic effect - ↑glomerular capillary pressure Increased glomerular permeability – increased size selective pore Effect abrogated by ACEI [Recent studies – normal glomerulus filters substantial amts of albumin, size/charge selectivity plays little or no role]
16	AII and proteinuria/NS Era of the podocyte Central role in glomerular disease Functions: Support glom.tuft/architecture Synthesis/maintenance of slit membrane Synthesis/maintenance of GBM Paracrine regulatory functions
17	AII and the podocyte Main players – VEGF,PDGF, TGFβ,AII Interaction podocyte (VEGF), mesangial cell (PDGF) and endothelial cell Podocyte damage – degenerative, inflammatory, dysregulative mechanisms Degenerative – high glom pressure model AII – stimulates VEGF, induces TGF, ↓nephrin expression, induces podocyte apoptosis
18	AII and the podocyte End result – Focal segmental glomerulosclerosis (FSGS) Renal artery stenosis and unilateral FSGS Alkhunaizi, AJKD 29; 936-941,1997
19	“Lest we forget” Our patient – primary APS Significance re renal manifestations ?
20	Renal disease in APS Occlusion of main renal artery/vein Thrombotic microangiopathy Associated with - membranous nephropathy - minimal change disease - pauci-immune GN Can mimic our patient’s presentation
21	Management options 1. Continue conservative treatment (based on RAS blockade) 2. Attempt revascularization 3. Selective renal vein renin 4. Renal biopsy non-stenosed kidney 5. Nephrectomy
22	Management options 1. Continue conservative treatment (based on RAS blockade) 2. Attempt revascularization 3. Selective renal vein renin 4. Renal biopsy non-stenosed kidney 5. Nephrectomy
23	Patient’s course Laparoscopic left nephrectomy Immediate post-op - normalized BP without medications - Na/K 139/3.9 - ACR 0.45 → 0.2 g/g 5 year FU (phone) – “everything’s alright” All’s well that ends well