Hypertensive Renovascular Disease

Hypertensive Renovascular Disease

A. Brad Farris, III, MD

A nephrectomy in a case of hypertensive renovascular disease shows a characteristic coarsely granular, “fleabitten” surface with scattered petechial hemorrhages image.

This PAS stain shows arterioles image with plump endothelial cells and muscular hypertrophy in a case of hypertensive renovascular disease.



  • Hypertension (HTN)

  • Arterionephrosclerosis (ANS)


  • Arterio-/arteriolonephrosclerosis

  • Hypertensive nephrosclerosis

  • Benign nephrosclerosis

  • Malignant nephrosclerosis


  • Renal vascular and glomerular disease secondary to hypertension (blood pressure > 120/80 mmHg)

  • Accelerated hypertension, mean blood pressure > 140 mmHg, papilledema, retinal hemorrhage


Essential Hypertension

  • 95% of cases

  • Evidence for multigenic basis plus environmental factors

  • Risk factors include obesity, lack of exercise, salt intake, black race

  • Other factors: Low birth weight, decreased nephron number, dysmetabolic syndrome

Secondary Causes of Hypertension

  • 5% of cases

  • Renal artery stenosis

    • Atherosclerosis, dysplasia, vasculitis, dissection

    • Increased production of renin by ischemic kidney

  • Neoplasia

    • Pheochromocytoma

    • Adrenal cortical tumors

    • Renin-producing tumors

  • Chronic renal disease

  • Cocaine abuse

  • Hypercoagulable states

Malignant Hypertension

  • May be primary or secondary

  • Renin release causes a cycle of vascular injury followed by more renin release

  • Features of thrombotic microangiopathy

Effect of Hypertension on Arteries and Arterioles

  • Hypertension precedes renal vascular disease

    • Shown in early renal biopsy series of Castleman and Smithwick

    • The more severe the renal vascular disease, the more reduced the glomerular filtration rate and renal blood flow

    • Vascular disease is the result, rather than cause, of hypertension

  • Involves direct injury to endothelium

  • Plasma (and fibrin) insudates into vascular walls

  • Arterial stiffening and increased pulse pressure to afferent arteriolar level leading to hyalinosis

  • Severe hypertension causes renal vascular fibrinoid necrosis (Goldblatt)



  • Incidence

    • Approximately 30% of adult Americans have hypertension

    • Hypertension accounts for around 25% of end-stage renal disease (ESRD) cases

    • Malignant nephrosclerosis as result of malignant hypertension occurs at rate of 1-2 cases/100,000 per year

  • Age

    • Hypertension appears mostly between mid 40s and mid 50s

      • Renal damage and dysfunction take years to develop and manifest

  • Gender

    • Males have predisposition

  • Ethnicity

    • Disproportionately affects black race


  • Hypertension

  • Proteinuria, asymptomatic

    • Related to severity of hypertension

  • Renal dysfunction

  • Accelerated (malignant) hypertension if mean blood pressure > 160 mmHg

    • Papilledema

    • Retinal hemorrhage

    • Congestive heart failure

    • Stroke

    • Encephalopathy

    • Renal insufficiency

    • Microangiopathic hemolytic anemia (MAHA)


  • Drugs

    • Antihypertensive agents

      • Diuretics, mineralocorticoid receptor antagonists

      • ACE inhibitors, vasopeptidase inhibitors, renin inhibitors

      • Smooth muscle dilators, endothelin antagonists

      • β-adrenergic blockers, α-adrenoceptor blockers

    • Optimal blood pressure control reduces progression to renal insufficiency and may reverse hypertensive nephrosclerosis


  • ESRD develops in mean of 6 years from onset of azotemia

  • Factors that predispose to renal failure include

    • Increasing age

    • Poor serum glucose control in diabetic patients

    • Level of systolic blood pressure

    • Male gender

    • Black race

    • Elevated uric acid and triglycerides

    • High diastolic blood pressure

  • Malignant hypertension

    • If left untreated, survival is poor (20% 1-year survival)

    • Long-term survival is > 90% if blood pressure is controlled


General Features

  • May be normal in size or slightly reduced in size and weight

  • Capsular surface is usually finely granular

  • Cortical scars may be present

  • Simple cysts may be present

  • Cortex may be thinned

  • Malignant hypertension

    • May be normal or increased in weight to 400 g

    • Petechial hemorrhages secondary to arteriolar necrosis gives “flea-bitten” appearance

    • May be mottled yellow and red if infarcts arise


Histologic Features

  • Subcapsular scars

    • Composed of sclerotic glomeruli, thickened arterioles, and atrophic tubules

    • Result in granular surface of kidney

    • Bulging areas between depressed scars contain spared and hypertrophied nephrons

  • Medium-sized arteries

    • Intimal fibrosis

    • Internal elastic lamina becomes multilayered (fibroelastosis); best seen on elastic stains

    • Smooth muscle hyperplasia

    • Decreased vascular lumen

  • Arterioles

    • Hyaline arteriolosclerosis

      • Afferent arteriolar media is replaced by homogeneous eosinophilic material positive on PAS or Masson trichrome stains

      • Begins under endothelial layer and eventually replaces entire media

  • Glomeruli

    • May have swollen endothelial cells and may thus appear “bloodless” and consolidated

    • Glomerular basement membranes may be duplicated

    • Glomerular mesangial matrix may be increased

    • Global glomerulosclerosis

      • Solidified type: Global solidification without collagenous material in Bowman space

      • Obsolescent type: Glomerular tuft sclerosed and Bowman space filled with collagenous material

    • Segmental glomerulosclerosis

      • Secondary focal segmental glomerulosclerosis (FSGS) may occur, typically with GBM corrugation and periglomerular fibrosis and subtotal foot process effacement

    • Glomerular hypertrophy (compensatory) in spared areas

  • Interstitium and tubules

    • Interstitial fibrosis and mononuclear inflammation

    • Tubular atrophy

    • Tubular hypertrophy in spared areas

  • Histologic features of malignant hypertension

    • Small arteries

      • Mucoid (myxoid) intimal change and endothelial swelling in arterioles, a.k.a. “onion skinning”

      • Fibrinoid necrosis

      • Karyorrhectic debris

      • Occasional neutrophils within endothelium

      • Fibrin thrombi

    • Arterioles

      • Arteriolar occlusion by endothelial swelling/edema-type change

      • Fibrinoid necrosis

      • Fibrin thrombi

    • Glomeruli

      • Segmental necrosis of glomeruli

      • Ischemic retraction of glomeruli with corrugation of GBM

  • Treated hypertension

    • As shown by Pickering and Heptinstall

      • Acute lesions of fibrinoid necrosis and mucoid intimal thickening resolve with adequate treatment

      • Intima becomes fibrous with increased cellularity and elastic fibers

Predominant Cell/Compartment Type

  • Arterial intima



  • IgM and C3 may be present in hyaline layers of arterioles

  • C3 may be present in absence of immunoglobulins

  • Fibrinogen is most common reactant seen on IF in malignant hypertension (in areas of fibrinoid necrosis and glomerular capillary loops)

Electron Microscopy

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Hypertensive Renovascular Disease

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