HTN and Renal Disease

Question 1

arterionephrosclerosis - clinical history

Answer 1

*long-standing HTN (“benign” hypertension)
*+/- renal insufficiency

Question 2

arterionephrosclerosis - pathology

Answer 2

*smaller, shrunken kidneys grossly
*vascular medial wall thickening with hyaline deposits in the vascular walls
*distal ischemia results in:
-tubular atrophy
-interstitial fibrosis
-fibrosis/scarring in the glomerulus (either focal areas of scarring or global glomerulosclerosis)

Question 3

hypertensive emergency - clinical history

Answer 3

*BP >/= 180/120 WITH evidence of end-organ damage
*more common in middle-age white males
*patients may or may not have a history of HTN
*may be associated with thrombotic microangiopathy or microangiopathic hemolytic anemia

Question 4

hypertensive emergency - pathology

Answer 4

*gross examination shows petechial hemorrhages on the surfaces of the kidneys
*microscopically, endothelial swelling +/- complete occlusion of vessel lumen, fibrinoid necrosis of the vessel walls, RBC fragments lodged into vessel walls
*if chronic, can see “onion-skin” pattern of intimal fibrosis

Question 5

hypertensive emergency - pathogenesis

Answer 5

*significantly increased pressure in the vessel → endothelial damage
*fibrinoid material can enter vessel walls → fibrinoid necrosis (see image)
*smooth muscle layer hyperplasia → smaller vessel lumen
*intravascular thrombosis with associated distal ischemia
*with disease in the afferent arterioles → renal ischemia → RAAS system activated → increased renin → increased blood volume → further worsened HTN

Question 6

hypertensive emergency - treatment

Answer 6

*EMERGENCY → admit to hospital for IV anti-hypertensives (labetalol, nicardipine, sodium nitroprusside)
*lower BP gradually so that end-organs have time to auto-regulate to new pressure
*note - CKD often results, even if HTN emergency is treated

Question 7

thrombotic microangiopathy (TMA) - overview

Answer 7

*a group of diseases characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and renal failure
*the endothelial damage → shearing of RBCs → formation of schistocytes → clots → renal failure

Question 8

thrombotic microangiopathy (TMA) - pathogenesis

Answer 8

*many different causes (commonly associated with HUS and TTP)
*hypertensive emergency can also cause TMA
*endothelial damage that comes with HTN emergency → shearing of RBCs, creating schistocytes that can clump with fibrin & platelets and form clots
*occluded arteries → glomerulosclerosis → renal failure

Question 9

thrombotic microangiopathy (TMA) - pathology

Answer 9

*swollen endothelium → can close off vessel walls → distal ischemia → activates RAAS system
*schistocytes in vascular walls

note - histology similar to that of hypertensive emergency

Question 10

ddx for increased renin, increased aldosterone

Answer 10

*renal artery stenosis (RAS)
*renin-producing tumor
*hypertensive emergency

Question 11

ddx for decreased renin, increased aldosterone

Answer 11

*Conn’s Syndrome / Primary Hyperaldosteronism
*bilateral adrenal hyperplasias
*glucocorticoid remediable hyperaldosteronism

Question 12

ddx for decreased renin, decreased aldosterone

Answer 12

*Cushing’s Syndrome
*Liddle’s Syndrome
*SAME (Syndrome of Apparent Mineralocorticoid Excess)
*licorice ingestion

Question 13

renal artery stenosis (RAS) - overview

Answer 13

*a narrowing of the arteries that supply blood to one or both kidneys, which prevents normal supply of oxygen to the cells → impairment of renal function
*includes RAS related to :
-ATHEROSCLEROSIS of the renal arteries (usually older age, proximal renal artery)
-fibromuscular dysplasia (usually younger age, distal renal artery)

Question 14

renal artery stenosis (RAS) - clinical manifestations

Answer 14

*resistant hypertension
*renal failure
*acute rise in serum creatinine following administration of ACEi or ARB
*recurrent episodes of flash pulmonary edema
*RENAL ARTERY BRUITS may be heard on physical exam

Question 15

renal artery stenosis (RAS) due to atherosclerosis - pathogenesis & pathology

Answer 15

*narrowing at the origin of the renal artery by an atheromatous plaque
*ischemic kidney becomes smaller and show signs of diffuse ischemic atrophy with crowded glomeruli, atrophic tubules, interstitial fibrosis, focal inflammatory infiltrates

Question 16

renal artery stenosis (RAS) - diagnosis

Answer 16

*renal artery duplex (ultrasound)
*CT angiogram (gold standard)
*MR angiogram

Question 17

renal artery stenosis (RAS) due to fibromuscular dysplasia

Answer 17

*a noninflammatory, nonatherosclerotic condition characterized by abnormal cell growth in the walls of arteries that most commonly affects the renal arteries, causing hypertension

*younger to middle aged, usually females
*commonly affects the distal 2/3 of the renal artery
*HTN responds well to revascularization
*may have family hx
*may be bilateral
*may involve other arteries (cerebral arteries common)

Question 18

renal artery stenosis (RAS) due to atherosclerosis

Answer 18

*older adults (>50)
*evidence of other vascular disease (known PAD, CAD, history of CVA)
*other sx: headache, pulsatile tinnitus, neck pain, flank/abdominal pain
*hx of smoking, CKD common
*generally treated medically, as revascularization does not generally change outcomes
*may be bilateral

Question 19

treatment of UNILATERAL renal artery stenosis (RAS)

Answer 19

*over time, the non-affected kidney will show signs of HTN (arterionephrosclerosis)
*treat with RAAS blockade (ACE inhibitors or ARBs) protects the good kidney

Question 20

treatment of BILATERAL renal artery stenosis (RAS)

Answer 20

*do NOT use RAAS blockade (NO ACEi or ARBs) because these will cause renal failure
*instead, use diuretics

Question 21

treatment of renal artery stenosis (RAS) due to fibromuscular dysplasia

Answer 21

*REVASCULARIZATION (angioplasty, stent placement)
*ACEi/ARB is first-line medical therapy

Question 22

APOL1 nephropathy - overview

Answer 22

*APOL1 = gene that encodes apolipoprotein L1, located on chromosome 22
*G1 and G2 (i.e. 1 and 2 copies of the risk allele, respectively) are associated with earlier age and faster progression to ESRD
*almost exclusively seen in Black patients
*G1 and G2 are protective against Trypanosoma brucei, which is the parasite transmitted by the tsetse fly, that causes African sleeping sickness (trypanosomiasis)
*2-hit hypothesis where APOL1 gene variants are the first hit

Question 23

APOL1 nephropathy - pathology

Answer 23

*solidified glomerular tufts, often with “disappearing glomeruli”
*spectrum, with increased proteinuria and nephropathy progression rate: focal global glomerulosclerosis < focal segmental glomerulosclerosis < collapsing FSGS