7 Systemic and hereditary glomerular diseases

Question 0

DN complications

Answer 0

Retinopathy
*100% DN with DM I
*50-60% DN with DM II
Polyneuropathy
*Peripheral
* auonomic
      *silent angina, gastroparesis, ED, urinary retention
Macrovascular (5X)  more common
*stroke
*CAD
*PVD

Question 1

Diabetic Nephropathy

Answer 1

30-40% of diabetes patients

1) Increase in GFR (stage 1)
* frequently caused by hyperfiltration 2/2 glucose dependant afferent arteriole dilation
* AnG II constriction of efferrent arteriole
2) Hypertrophy by 1-2cm (stage 2)
* increasing mesangium and capillary cells
* mesangial ECM deposition (PAS positive)
3) Proteinuria (stage 3-4 [overt albuminuria])
* IV collagen accumulation and loss of negative heparin
* Podocyte cchanges- foot process fusion, apoptosis, migration reduced, holes in podocyte covering
4) Fibrosis: Tubulointerstitial fibrosis from TGF-B and ANGII (stage 4)
* Tubular cells become fibroblasts

Stage 5 diabetic nephropathy= ESRD

Question 2

DM DN tratment

Answer 2

• HTN therapy/proteinuriatreatment
• Glucose control
• Lipid lowerng/statins (Substantial CV benefit if not in ESRD)
• Lifestle mods

Question 3

Non-Diabetic Nephrotic Syndromes

Answer 3

Amyloidosis

Light chain deposition

Question 4

Amyloidosis etiology and manifestations

Answer 4

• Light chains from a single B cell clone common(multiple myeloma 20%)
• Lamda chains common (AL)

Kidney manifestations

• Enlarged without HTN
• Proteinuria/ albuminuria without hematuria
• Tubular defects: Renal tubular acidosis, polyuria-polydipsia

Question 5

Amyloidosis histology

Answer 5

Deposits on LM
Congo red stain causes Apple green birefringence
IF stains deposets in mesangium

Question 6

Extrarenal amyloidosis symptoms

Answer 6

• restrictive CDM
• GI motility isuues, malabsorption, hemorrhage, obstruction
• macroglossia
• Splenomegaly
• polyneuropathy
• Purpura, papules, nodules, and plaques
• Shoulder joint pain and swelling

Question 7

Light chain deposition disease

Answer 7

• Kappa common
• 50% associated with multiple myeloma
• Proteinuria
• hemauria
• Chronic renal insufficiency

Question 8

Light chain deposition disease isto

Answer 8

LM: PAS weak, Nodular glomerulosclerosis
negative for congo red stain

IM: KAppa staining in mesangium

EM: Deposits and widening of BM

Question 9

Alport syndrome

Answer 9

1) X recessive in 80% of cases
2) COL4A5 gene on Xq22, alpha5 chain of IV collagen (BM)
3) Hematuria
* Males have persistent microscopic hematuria
* Gross hematuria with URI
* early onset
* females with ppersistent or iintermittent microscopic hematuria
4) Proteinuria later (especially males) All who are auosomal recessive
5) HTN
6) ESRD: M 90% by 40, F 12% by 40, 30 by 60, 40 by 80

Question 10

Extrarenal Alport manifestations

Answer 10

• Organ of corti/cochlear defects
• ocular defects- Anterior Lentioconus or Maculopathy (whitish uellowish flecks)
• Leiomyomatosis of esophageal and tracheobronchial tree

Question 11

Alport syndrome histo

Answer 11

LM: Early looks normal, later global or segmental glomerulosclerosis, interstitial fibrosis
IF:Negative or nonspecific IgM/C
EM: Basketweaving/ variable thickening and thinning of the GBM

Question 12

Alport treatment

Answer 12

• ACEi,ARB

* Transplant,

Question 13

Thin BM disease (benign familial hematuria)

Answer 13

• autosomal dominant
• continuous or intermittent micrro and gross hematuria
• NO RENAL INSUFFICIENCY
• ususally no other problems

Question 14

Thin BM disease histo and treatment

Answer 14

Normal except thin BM on EM

Monitor electrolytes, UA, and BP (will usually stay normal)