Vascular diseases of the kidney

1. Overview

Nearly all kidney diseases involve renal blood vessels secondarily.

2. Benign Nephrosclerosis

Definition

• Renal changes seen in benign hypertension.
• Always associated with hyaline arteriolosclerosis.
• Frequency & severity ↑ with age, HTN, DM.

Morphology

• Asymmetrically atrophic kidneys; diffuse fine granular surface.
• Histology:
  • Hyaline thickening of walls of small arteries + arterioles.
  • Homogeneous pink hyaline thickening at the expense of vessel lumina.
  • Loss of underlying cellular detail.
• Pathophysiology: ↑ wall thickness → ↓ luminal diameter → ↓ blood flow → ischemic atrophy.
• Advanced: global glomerular sclerosis.

3. Malignant Nephrosclerosis (Malignant Hypertension)

Definition

• Far less common than benign.
• Can arise without preexisting HTN or as sudden exacerbation of mild HTN.

Pathogenesis (vicious cycle)

1. Long-standing HTN → arteriolar wall injury → ↑ permeability → fibrinogen + plasma protein leak → endothelial injury + platelet deposition → fibrinoid necrosis.
2. Platelet-derived mitogens → intimal smooth muscle hyperplasia → hyperplastic arteriolosclerosis → further luminal narrowing.
3. Afferent arteriole injury → RAAS activation → ↑ BP → more ischemia (cycle repeats).

Morphology

• Normal or slightly shrunken kidney.
• Pinpoint petechial hemorrhages on cortical surface (“flea-bitten” kidney) from ruptured arterioles/capillaries.
• Histology:
  • Fibrinoid necrosis of arterioles.
  • Hyperplastic arteriolosclerosis — concentric “onion-skin” arrangement of intimal cells → luminal narrowing.

Clinical course

• Diastolic BP > 120 mmHg, encephalopathy, cardiac abnormalities, renal failure.
• Early symptoms from ↑ ICP: headache, nausea, vomiting, visual impairment (papilledema, retinal hemorrhages).
• As BP ↑ → marked proteinuria + hematuria without major renal function change initially.
• Deaths: 90 % uremia, 10 % cerebral hemorrhage or cardiac failure.

4. Thrombotic Microangiopathies (TMAs)

Definition

• Widespread microcirculatory thrombosis + microangiopathic hemolytic anemia + thrombocytopenia + renal failure.
• Diseases:
  • Childhood HUS
  • Adult HUS variants
  • TTP

HUS pathogenesis

• Endothelial injury + activation → intravascular thrombosis.
• 75 % follow intestinal infection with Shiga-toxin-producing E. coli (O157:H7) or Shigella.
• Shiga toxin carried by neutrophils; glomerular endothelial cells express receptors (Gb3) → cytotoxicity.
• Endothelial effects:
  • ↑ Leukocyte adhesion
  • ↑ Endothelin production
  • ↓ Endothelial NO
  • Direct endothelial damage / cell death
• Result: thrombosis + vasoconstriction → thrombotic microangiopathy.

TTP pathogenesis

• Acquired defect in proteolytic cleavage of von Willebrand factor (vWF).
• Cause: autoantibody against ADAMTS-13 (vWF-cleaving protease).
• Result: ultra-large vWF multimers → platelet aggregation → microthrombi.

HUS vs TTP — Clinical Pentads

Feature	HUS (childhood)	TTP
Trigger	Shiga toxin (E. coli O157:H7)	Anti-ADAMTS-13 Abs
Organ predominance	Kidney	Brain (CNS)
Hemolytic anemia (MAHA)	+	+
Thrombocytopenia	+	+
Acute renal failure	Prominent	Less common
Neurological Sx	Mild	Prominent (fluctuating)
Fever	Variable	+

Clinical course

• Childhood HUS: sudden onset → bleeding (hematemesis, melena), severe oliguria, hematuria, MAHA, neurologic changes.
• HUS is a main cause of acute renal failure in children.

💡 High-yield: Benign nephrosclerosis = benign HTN → hyaline arteriolosclerosis + granular kidneys + ischemic atrophy. Malignant nephrosclerosis = diastolic > 120, fibrinoid necrosis + “onion-skin” hyperplastic arteriolosclerosis, flea-bitten kidney, RAAS vicious cycle. TMA: MAHA + thrombocytopenia + renal failure. HUS = Shiga toxin (E. coli O157:H7), kidney-dominant, kids. TTP = anti-ADAMTS-13 → ↑ vWF multimers, CNS-dominant, fever pentad.