Kidney Pathology 3 (Wolfgram) Flashcards Preview

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Flashcards in Kidney Pathology 3 (Wolfgram) Deck (33):
1

What is the leading cause of ESRD (in most western societies)?

Diabetic Nephropathy

2

Describe the pathogenesis of hyperfiltration in diabetic nephropathy

Early onset

  • GRF increases due to glucose-dependent dilation of the afferent arterioles (via vasoactive mediators)
  • Hyperfiltration increases colloid osmotic pressure in the post-glomerular capillaries, leading to increase sodium reabsorption in the proximal convoluted tubule
  • Increased angiotensin II causes hypertrophic PT growth

** can be corrected with good glycemic control

3

Describe the mesangial changes of diabetic nephropathy

  • mesangial expansion (increased cell number and size, increased deposition of ECM)
  • Nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson lesion)
  • mediated by glucose and glucose-dervice AGEs

4

What is a Kimmelstiel-Wilson lesion?

A type of acellular nodular diabetic glomerulosclerosis commonly seen in diabetic nephropathy

5

Describe the pathogenesis of the proteinuria seen in DN.

  • Widening of the GBM
    • accumulation of Type-IV collagen decreases the charge density (due negatively charged heparin sulfate) normally responsible for repelling serum proteins
  • Podocyte changes -> decreased coverage of the BM
    • Increased width of foot processes
    • Apoptosis triggered by AngII and TGF-beta
    • Migration suppressed by AngII

Serum proteins ultimately cross the basement membrane due to disruption in its texture, gaps, and holes.

6

Describe the pathogenesis of the fibrosis seen in DN

Early onset -> correlates with prognosis/progression

Triggered by growth factor release (TGF-beta and AngII) and glucose/AGEs

tubular cells change phenotype to fibroblasts

7

Describe the functional and structural characteristics of the following stages of DN

  1. Pre
  2. Incipient
  3. Overt

Functional

  1. Pre: increased GFR
  2. Incipient: microalbuminuria, hypertesion, reduced or normal GFR
  3. Overt: proteinuria, decreased GFR, nephrotic syndrome

Structural

  1. Pre: renal hypertrophy
  2. Incipient: mesangial expansion, GBM thickening, arteriolar hyalinosis
  3. Overt: mesangial nodules (Kimmelstiel-Wilson lesions), tubulointerstitial fibrosis

8

Name and describe the 5 major stanges of DN

  • Stage 1: onset of diabetes
    • increased GFR due to hyperfiltration
    • glomerular hypertrophy and increased renal size
    • reversible, transient albuminuria
  • Stage 2: biopsy-positive, asymptomatic
    • mesangial expansion
    • GBM thickening
  • Stage 3: early nephropathy
    • hypertension
    • persistent microalbuminuria (30-300mg/day)
  • Stage 4: overt proteinuria
    • urinary albumin >300mg/day
    • declining GFR -> ESRD within 7-10 years
    • Retinopathy (90-95% of patients)
  • Stage 5: end-stage renal disease
    • requires renal replacement
    • ~15 years after onset of T1DM with proteinuria

9

Describe the incidence of macrovascular complications in DN

5X more frequent, including stroke, CAD, PVD

10

What are some sequelae of autonomic polyneuropathy brought on by DN?

silent angina

gastroparesis

erectile impotence

detrusor paresis

11

Who is more likely to develop diabetic retinopathy in DN?

Almost all patients with type-1 develop DR

50%-60% of type-2 develop DR

12

True or false: increased albuminuria is associated with increased mortality in DN patients.

True

mortality is more or less proportional to level of proteinuria

13

Name (5) general treatment strategies for management of DN

  • hypertension therapy
  • glucose control
  • reduction of proteinuria
  • lipid-lowering therapy
  • lifestyle modification

14

What is the recommended blood pressure target for DN patients with hypertension (according to JNC8)?

JNC8 goal: 140/90 mmHg

JNC7 goal: 130/80 mmHg

15

How to ACE inhibitors reduce proteinuria in DN?

Blockade effects of AngII, including the hemodynamic and non-hemodynamic effects of AngII.

Long term renoprotective (despite significant decrease in GFR) -> reduces proteinuria

16

Describe the usual lipid profile of a DN patient

What drug family is used to manage this?

What are the lipid profile goals under this therapy?

Low HDL, high TGs, smaller LDL particles

manage with statins

LDL goal: <100mg/dL (or <70mg/dL for patients with CVD)

17

Name two major lifestyle modifications indicated for DN patients

  • smoking cessation
  • weight reduction

18

20% of cases of amyloidosis light chains affecting the kidney are caused by what?

Multiple myeloma (single clone of B-cells)

19

Deposition of lambda light chains are typically seen in what disease?

Amyloidosis

20

Describe the kidney manifestations of amyloidosis

enlarged kidney despite absent hypertension

albuminuria without hematuria

tubular defects due to amyloid deposits

Renal tubular acidosis (part of Fanconi syndrome)

Polyuria-polydipsia (defects in urine concentration)

21

What disease will show apple-green birefringence on congo-red stain?

amyloidosis

22

Name some other organ systems affected by amyloidosis

  • heart (restrictive cardiomyopathy)
  • GI motility disturbances, malabsorption, obstruction, hemorrhage
  • macroglossia
  • splenomegaly
  • peripheral neuropathies
  • skin purpura, papules, nodules, plauques (mostly face and upper trunk)
  • Joint pain and swelling (especially shoulder)

23

kappa light chains are typically seen with what?

This disease is also associated with what?

What are the general clinical features?

Light Chain Deposition Disease (LCDD)

Strongly associated with multiple myeloma (50%)

Clinical features: proteinuria, hematuria, chronic renal insufficiency

24

Describe the histological features of LCDD

  • LM: nodular glomerulosclerosis
  • IF: positive kappa staining, mostly confined to the mesagium
  • EM: granular light chain deposition in the TBM

25

Describe the general decision flow for differentiating amyloidosis, LHCDD/HCDD, and other immunoglobulin deposition diseases

  • Stain with congo red
  • If positive apple-green birefringence -> amyloid
  • If negative, stain IF with anti-kappa/lambda
  • If positive -> LHCDD/HCDD
  • If negative -> other

26

What is the inheritance pattern of Alport Syndrome?

What is the major defect?

X-linked recessive (80%)

may also be autosomal recessive

Defect in basement membrane, generally due to a mutation of the COL4A5 gene on Xq22 -> defect in type-IV collagen

27

Describe the major renal and extrarenal manifestations of Alport Syndrome

  • Hematuria
  • Gradually-developing proteinuria (all males with XLAS, all patients with ARAS)
  • Hypertension
  • ESRD (90% XLAS males by age 40, less prevalent in female XLAS)
  • Cochlear defects (adherance defect in organ of Corti -> 80% males)
  • Ocular defects (lenticonus, maculopathy, M > F)
  • Leiomyomatosis of the esophagus and tracheobronchial tree

28

If you encounter a male with hearing loss and kidney disease, what genetic disease should be considered in your differential?

Alport Syndrome

29

Describe Alport Syndrome histologically

  • LM: normal glomeruli, may see sclerosis or fibrosis later in disease
  • IF: negative or non-specific
  • EM: variable thickening/thinning ("Basket Weaving") and lamellation (splitting) of the GBM

30

What are the treatment options for Alport Syndrome

No disease-specific therapies, renal replacement ultimately necessary (all males)

Consider RAAS blockade

2-3% of renal transplants for Alport Syndrom will develop anti-GBM disease (immune system native to collagen Type-IV, will consider foreign)

31

Benign Familial Hematuria is also known by what name?

What is the inheritance pattern?

What are the major clinical features?

Thin Basement Membrane Disease (TBMD)

autosomal dominant

  • Continuous or intermittent microhematuria
  • Generally no renal insufficiency
  • Extra-renal involvement is rare

32

What are the morphologic features of TBMD?

  • LM: normal glomeruli
  • IF: negative
  • EM: thin GBM (<=200nm), no lamellation (splitting)

Remember: Alport Syndrome shows lamellation and 'woven' thinning. TBMD shows no lamellation and the thinning is uniform.

33

What is the treatment/clinical management of TBMD?

Reassurance

Follow closely (BMP, BP, and urinalysis every 1-2 years) to monitor for rare progression to ESRD

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