Renal Vascular Disease

Benito K. Lim Hong III, M.D.

 Objectives

1. To know the various diseases affecting the blood

vessels of the kidney.
2. To understand the pathophysiology of the various
diseases affecting the blood vessels of the kidney.
3. To know the etiology affecting the blood vessels of
the kidney.
 Case Scenario

 A 87 year old male, hypertensive for 13 years with highest

BP=230/140 & usual BP=160/100 & poorly compliant to his
maintenance antihypertensive meds (Losartan), non-diabetic,
chronic smoker & alcoholic, was rushed to the ER due to
elevated BP, dizziness, gross hematuria, & nape pains 30 minutes
before he went to bed. V/S: BP=240/150, HR=60 bpm, RR=23
cpm, T=36˚C. Serum Crea=4.5 mg/dl (Normal Values=0.5-1.5
mg/dl)
 Diseases of the Blood Vessels

 Nearly all disease of the kidney & many systemic diseases

secondarily affects the blood vessels of the kidney.
 Hypertension has marked effects on the renal vessels &,
conversely, the vascular changes augment the hypertension.
 2 principal renovascular diseases:
1. Benign Nephrosclerosis (BNS)
2. Malignant Nephrosclerosis
 Benign Nephrosclerosis (BNS)

 Term used for abnormalities of the kidney induced by benign

hypertension, with associated hyaline arteriolosclerosis.
 Hyaline Arteriolosclerosis is characterized by narrowing of the
lumina of the arterioles, caused by thickening & hyalinization of
the walls.
 Larger muscular arteries show fibroelastic hyperplasia.
 The changes are more severe in patients with essential
hypertension &/or diabetes mellitus.
 Benign Nephrosclerosis (BNS)

 The vascular lesions cause diffuse ischemic atrophy of

nephrons, hence the small kidneys & granular surfaces
encountered in benign nephrosclerosis.
 BNS rarely causes renal failure, but mild proteinuria can occur &
up to 5% of patients develop CRF, usually after development of
malignant hypertension.
 Malignant Nephrosclerosis

 The kidney disease associated with an accelerated phase of

hypertension.
 Although occasionally developing in previously normotensive
people, most cases are superimposed on pre-exisiting benign
essential hypertension, chronic renal disease (particularly GN
or reflux nephropathy), or scleroderma.
 The condition occurs in 1% to 5% of patient with hypertension,
& in pure form is most frequent in black males.
 Malignant Nephrosclerosis

 Pathologic changes include fibrinoid necrosis of arterioles

(necrotizing arteriolitis), hyperplastic arteriolosclerosis (onion-
skinning), & necrotizing glomerulitis, often associated with a
thrombotic microangiopathy.
 Onset of diffuse intravascular coagulation may trigger
malignant hypertension, & there is markedly increase renin,
angiotensin, & aldosterone.
 Malignant Nephrosclerosis

 Patient have a diastolic pressure > 130 mmHg, marked

proteinuria, hematuria, papilledema, encephalopathy,
cardiovascular abnormalities, & eventually renal failure.
 Currently, 50% of patients with treatment survive 5 years.
Benign Nephrosclerosis (Gross)
Benign Nephrosclerosis (Histopathology)
Malignant Nephrosclerosis (Gross)
Malignant Nephrosclerosis (Histopathology)
 Case Scenario
 A 79 year old male, hypertensive for 23 years with highest
BP=200/120 & usual BP=150/100 & poorly compliant to his
maintenance antihypertensive meds (Losartan), non-diabetic,
chronic smoker & alcoholic, was rushed to the ER due to
elevated BP, dizziness, gross hematuria, & nape pains few
minutes after he wake up from bed. V/S: BP=240/130, HR=60
bpm, RR=25 cpm, T=36˚C. Physical Examination: (+) bruit on the
umbilical area of the abdomen upon auscultation. Serum Crea=5
mg/dl (Normal Values=0.5-1.5 mg/dl). Total Cholesterol=400
mg/dl (Normal Value=<200 mg/dl), Triglycerides=300 mg/dl
(Normal Value=<150 mg/dl), LDL=160 mg/dl (Normal
Value=<100 mg/dl), HDL=20 mg/dl (Normal Value=>50 mg/dl)
 Renal Atery Stenosis

 Renal artery stenosis (RAS) is the major cause of renovascular

hypertension and may account for 1-10% of the 50 million
people in the United States who have hypertension.
 Apart from its role in the pathogenesis of hypertension, renal
artery stenosis is also being increasingly recognized as an
important cause of chronic renal insufficiency and end-stage
renal disease.
 In older individuals, atherosclerosis is by far the most common
etiology of renal artery stenosis.
 Renal Atery Stenosis

 As the renal artery lumen progressively narrows, renal blood

flow decreases, eventually, the decreased perfusion
compromises renal function and structure.
 70% of stenosis are caused by obstructive atheromatous plaque
at the origin of the renal artery, the remainder by fibromuscular
dysplasia.
 Before arteriolosclerosis develops in the opposite kidney,
surgery cures about 80% in fibromuscular dysplasia & 60% in
atherosclerotic stenosis.
 Renal Atery Stenosis

 Pathophysiology:
 In patients with atherosclerosis, the initiator of endothelial
injury is not clear; however, dyslipidemia, hypertension,
cigarette smoking, diabetes mellitus, viral infection,
immune injury, and increased homocysteine levels may
contribute to endothelial injury.
 In the atherosclerotic lesion site, endothelium permeability
to plasma macromolecules (eg, low-density lipoprotein [LDL])
increases, turnover of endothelial cells and smooth muscle
cells increases, and intimal macrophages increase.
 Renal Atery Stenosis

 Pathophysiology:
 When atherogenic lipoproteins exceed certain critical levels,
the mechanical forces may enhance lipoprotein insudation in
these regions, leading to early atheromatous lesions.
 In patients with renal artery stenosis, the chronic ischemia
produced by the obstruction of renal blood flow leads to
adaptive changes in the kidney that are more pronounced in
the tubular tissue.
 Renal Atery Stenosis

 Pathophysiology:
 These changes include atrophy with decreased tubular cell
size, patchy inflammation and fibrosis, tubulosclerosis,
atrophy of the glomerular capillary tuft, thickening and
duplication of the Bowman capsule, and intrarenal arterial
medial thickening.
 Renal Atery Stenosis
 Etiology:
 Risk factors associated with ischemic renal disease (IRD) are
as follows:
1. Hypertension: Of patients with IRD, 35% can be
normotensive
2. Advanced age: Numerous cases occur in persons aged
60-69 years; incidence increases in persons older than
70 years
3. Renal insufficiency
4. Extrarenal atherosclerosis
5. Diabetes mellitus
6. Smoking
 Renal Atery Stenosis
 Signs & Symptoms:
1. Abdominal bruit
2. Azotemia
3. Sudden worsening of hypertension or renal function
4. Acute renal failure or decreased renal function after
antihypertensive therapy, especially with angiotensin-
converting enzyme (ACE) inhibitors or angiotensin receptor
blockers
5. Unexplained renal insufficiency, in elderly patients.
6. Congestive heart failure with poor control of hypertension
and renal insufficiency in the absence of a significant
decrease in ejection fraction (the so-called flash
pulmonary edema)
Renal Artery Stenosis (Angiogram)
Atherosclerotic Renal Disease (Angiogram)
Fibromuscular Dysplasia (Angiogram)
Atherosclerotic Renal Disease (Histopathology)
Fibromuscular Dysplasia (Histopathology)
 Case Scenario
 A 76 year old female, hypertensive for 20 years with highest
BP=190/100 & usual BP=120/80 & good compliant to his
maintenance antihypertensive meds (Losartan), non-diabetic,
non-smoker & non-alcoholic, was rushed to the ER due to
dysentery for 1 day then with undocumented fever & change in
sensorium. The stools are described to be watery, grossly
bloody, & mucoid. V/S: BP=70/30, HR=124 bpm, RR=45 cpm,
T=40˚C. Physical Examination: (+) Sunken eyeballs, Dry lips, Poor
skin turgor. Fluid Resuscitation was done & patient was admitted
to ICU. CBC & peripheral blood smear revealed normocytic,
normochromic RBC with marked anisopoikilocytosis & numerous
schistocytes, monocytosis (Mono=15), anemia (hgb=8 g/dl), &
thrombocytopenia (Plt=20 x 103/microliter), Serum Crea=2.0
mg/dl (Normal Values=0.5-1.5 mg/dl). Peripheral smear showed:
 Thrombotic Microangiopathies

 A group of diseases with overlapping clinical manifestations

(Microangiopathic Hemolytic Anemia, Thrombocytopenia,
Renal Failure, & manifestation of Intravascular Coagulation)
are all characterized morphologically by thrombosis in the
interlobular arteries, afferent arterioles, & glomeruli, together
with necrosis & thickening of the vessels walls.
 Thrombotic Microangiopathies
 The morphologic changes are similar to those in malignant
hypertension, but in this group the changes may precede the
development of hypertension or be seen in its absence. The
disease include:
1. Childhood & Adult Hemolytic Uremic Syndrome (HUS)
2. Thrombotic Thrombocytopenic Purpura
3. Scleroderma
 Although these diseases may have diverse causes, endothelial
injury & intravascular coagulation appear to be shared
pathogenetic mechanisms.
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Produces acute renal failure, usually after a GI or flu-like

prodrome of hematemesis &/or melena, oliguria, hematuria,
microangiopathic hemolytic anemia, & (in some patient)
neurologic signs.
 Up to 75% of patients are infected with verocytotoxin-producing
Escherichia coli (EHEC).
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Pathophysiology:
 Subsequent inflammation of the colon facilitates systemic
absorption of the Shiga Toxin and lipopolysaccharide from
the GI tract.
 The major toxins that cause hemolytic-uremic syndrome,
Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2).
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Pathophysiology:
 These toxins bind to globotriaosylceramide (Gb3), a
glycolipid receptor molecule on the surface of endothelial
cells in the gut, kidney, and, occasionally, other organs.
 Differential expression of Gb3 on glomerular capillaries
compared with other endothelial cells may explain the
predominance of renal injury.
 Classic (Childhood) Hemolytic-Uremic
Syndrome
 Pathophysiology:
 Damaged endothelial cells of the glomerular capillaries
release vasoactive and platelet-aggregating substances.
 The endothelial cells swell, and fibrin is deposited on the
injured vessel walls.
 Swelling and microthrombi formation within the glomerular
capillaries produce a localized intravascular coagulopathy.
 The glomerular filtration rate is reduced, and renal
insufficiency ensues.
 Classic (Childhood) Hemolytic-Uremic
Syndrome
 Pathophysiology:
 Erythrocytes are damaged and fragmented as they traverse
the narrowed glomerular capillaries leading to the
characteristic microangiopathic hemolytic anemia.
 Hemolysis may also be a result of lipid peroxidation.
 Thrombocytopenia is believed to result from a combination
of platelet destruction, increased consumption,
sequestration in the liver and spleen, and intrarenal
aggregation.
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Pathophysiology:
 Platelets are damaged as they pass through the affected
glomerular capillaries.
 Remaining platelets circulate in a degranulated form and
show impaired aggregation.
 Stx also binds to activated platelets.
 Classic (Childhood) Hemolytic-Uremic
Syndrome
 Pathophysiology:
 Abnormalities of anti–platelet-aggregating agents (eg,
prostaglandin I2 [PGI2]), platelet-aggregating agents
(thromboxane A2 [TXA2]) and von Willebrand factor (vWF)
multimers are also important factors that contribute to
thrombocytopenia.
 A decrease in PGI2 during the early stages of hemolytic-
uremic syndrome has been noted.
 Classic (Childhood) Hemolytic-Uremic
Syndrome
 Pathophysiology:
 TXA2 levels are increased during the acute stage of
hemolytic-uremic syndrome, leading to increased platelet
aggregation.
 Large vWF multimers, In vitro, have a greater ability to
aggregate platelets than the normal, smaller multimers.
 Normal plasma contains a vWF-cleaving metalloproteinase
(ADAMTS13) that rapidly degrades large vWF multimers.
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Pathophysiology:
 Many cases of TTP are associated with deficient function of
ADAMTS13.
 Abnormalities of ADAMTS13 may take the form of decreased
quantity or absence of the enzyme, a mutation resulting in
normal quantity of a defective enzyme, or an antibody
inhibitor of the enzyme.
 Classic (Childhood) Hemolytic-Uremic
Syndrome
 Pathophysiology:
 WBCs are usually elevated in the blood of patients with
hemolytic-uremic syndrome.
 Activated neutrophils are believed to damage endothelial
cells by releasing elastase (a catabolic enzyme that promotes
endothelial cell detachment) and by producing free radicals.
 Monocytes may be stimulated to release cytokines (ie,
interleukin 1 and tumor necrosis factor [TNF]) that also
damage endothelial cells.
 Classic (Childhood) Hemolytic-Uremic
Syndrome

 Morphology:
 Kidney show renal cortical necrosis, glomerular capillary
wall thickening (due to deposits of fibrin-related materials),
& arteriolar changes (fibrinoid necrosis, intimal hyperplasia,
& thrombi).
Childhood Hemolytic-Uremic Syndrome
(Peripheral Blood Smear)
Childhood Hemolytic-Uremic Syndrome
(Histopathology)
Adult Hemolytic-Uremic Syndrome

 A syndrome similar to that in children arises in adults under a

variety of settings:
 In association with infections, such as typhoid fever, E. coli
septicemia, viral infections, & shigellosis.
 In women with pregnancy complications, or in postpartum
women after an uneventful pregnancy (postpartum renal
failure).
Adult Hemolytic-Uremic Syndrome

 A syndrome similar to that in children arises in adults under a

variety of settings:
 Secondary HUS, associated with other vascular renal disease
(SLE, scleroderma, malignant hypertension), or drug therapy
(mitomycin, cyclosporine)
 Hereditary HUS, with recurrent attacks, similar to that in
children.
 Thrombotic Thrombocytopenic
Purpura

 The entity differs from HUS in that CNS involvement is the

dominant feature, whereas renal involvement occur in only 50%.
Platelet/fibrin thrombi are present in the terminal interlobular
arteries, afferent arterioles, & glomerular capillaries.