Renal Pathology (DN) Flashcards
Diabetic Nephropathy is the leading cause of _____ in most Western societies in both DM I and II
ESRD
*risk related to duration of disease
Diabetics will increase risk of developing diabetic nephropahty drastically ____ to ____ years after Dx with diabets and ____ to ____ years after onset of proteinuria
20-25 yrs
2-3 yrs
Pathology of DN: Hyperfiltration
See increased GFR due to:
glucose dependent afferent arteriolar dilation and Ang II mediated cnx of efferent arteriole
As a result of hyperfiltration in early DM we see increase ________ pressure post glom
This cause wht to the Na+
increases colloid osmotic P
increase Na reabsorption in PT
Besides increasing GFR, what other effect does Ang II have
causes hypertrophic PT growth
How can we control the hyperfiltration aspect of DN?
Glycemic control!
Pathogeneis of DN: HYpertrophy
Seen when:
Assoicated with:
early onset w/ size of kids increasing several cm
see increased number of mesangial cells and capillary loops–> increases SA
Pathogenesis of DN: Mesangial Cells
Results in:
Mesangial expansion with nodular diabetic glomerulosclerosis = Kmmelsteil Wilson lesion
- mediated by glucose and AGEs
- -> increased size and more ECM deposition
Pathogenesis DN: Proteinuria What happens to the 1. GBM 2. Podocytes 3. Serum proteins
- GBM accumulate type IV col and net reduction of (-) heparin sulfate
- Podocyte feet increase width and apoptosis trig by AngII and TGF-B, also decreaed migration from Ang II
- Serum pros cross BM from disrupted holes
Pathogeneis DN: Fibrosis
What do we see early on and what causes this
early on see tubulointerstitial fibrosis from GFs TGF-B and ANG II
In fibrosis seen in DN, tubular cells change phenotype to____
fibroblasts
What enhances the fibrosis process in DN
glucose concentration and AGEs
During Stage 1 and 2 we see ____ GFR and renal _____
Increased GFR (25-50%) Renal hypertrophy
What stage do we see mesangial expansion and GBM thickening in?
Stage 2 of DN; clinically asymptomatic but see on biopsy
What stage is there devo of HTN, persistent microalbuminuria and urinary albumin excretion of 30-300/day?
Stage 3: Early nephropathy
See GFR decline, urninary albumin >300 mg/day
50% pts reash ESRD w/in 7-10 yrs and retinopathy in 95%
Stage 4: Overt proteinuria
Renal replacement therapy necessary, seen about 15 ys after onset of Type I DM pts with proteinuria (30%)
Stage 5: ESRD
Co-morbidities of DN
- HTN
- Neuropathy
- Vascular changes
- Increased mortality
Diabetic retinopathy
• in almost all patients with______diabetes and nephropathy.
• In 50% to 60% of ______diabetes with nephropathy
type 1
type 2
What polyneuropathy issues do we see with DN?
- Polyneuropathy.
- Sensory polyneuropathy: Diabetic foot
- Autonomic polyneuropathy
- Silent angina
- Gastroparesis
- erectile impotence
- detrusor paresis
Macrovascular complications _____ x more frequent in DN
• Stroke
• coronary heart disease
• peripheral vascular disease
(5X more frequent)
Key Txs for DN
- HTN therapy
- Glucose control
- Reduction of proteinuria
- Lipid lowering therapy
- Life style modification
• In DM pts with DN, HTN is
almost always present
• Uncontrolled hypertension is
associated with:
• more rapid progression of DN
• increased risk of fatal and
nonfatal CV events.
Recommended BP for all diabetics pts
140/90 • antihypertensive therapies improve survival in both type 1 and type 2 diabetics with DN Control glucose levels! decreases progression from normo-microalbuminuria
What are ways to reduce proteinuria and
- Renin-angiotensin-aldosterone system blockade
- Renoprotective independent of BP
- May cause up to 30% decline in GFR but renoprotective in the longterm
RAAS works through renal hemodynamic changes
and blocking non-hemodyanmic effects of
Ang II
• Most patients with DN have: – Low HDL – High TGs – Smaller LDL particle • In type 2 diabetic patients with DN, treatment with\_\_\_\_\_\_ provides substantial CV benefit
statins
–seen in DN with ESRD
Current guidelines
– LDL _____mg/dl for diabetic patients in general and
____mg/dl for diabetic patients with CVD
<70
Lifestyle modifications • Smoking cessation – Decreases progression of \_\_\_\_\_ • weight reduction – Possibly improves renal outcome via reduction in \_\_\_\_
micro to macro albuminuria
proteinuria
• Amyloidosis affecting the kidney
– light chains, secreted by a _______
• 20% of cases associated with multiple myeloma
– Usually _________
single clone of B cells
lambda light chains (AL)
What kidney manifestations do we see with Amyloidosis?
enlarged and hypertension is absent even when renal function is impaired.
Proteinuria, mainly albuminuria, occurs in the absence of microscopic hematuria.
Tubular defects from amyloid deposits
What tubular defects from amyloid deposits do we see?
– Renal tubular acidosis (mostly as a part of Fanconi syndrome)
– polyuria-polydipsia (resulting from urinary concentration defect)
What do we see on LM and IM on amyloidosis?
LM: see deposits and Congo-red stain: apple green birefringence
IM: staining for light chain
What extra-renal manifestations do we see with amyloidosis?
restrictive cardiomyopathy GI issues Splenomegaly macroglossia Peripheral nerve damage skin joint
Light Chain Deposition disease is excess ________ in kidney and 50% of cases co-exsist with _____
immunoglobuin light chain, usually Kappa
multiple myeloma
Pts with Light chain deposition develop
proteinuria
hematuria
chronic renal insufficiency
Looking at LM we see nodular glomerulosclerosis
IF: is + for Kappa staining
EM: see granular deposits along the GBM
Light Chain deposition
Alport Syndrome
• Most commonly ______ (80%) but can be autosomal recessive as well
• Mutation of the ____ gene on chromosome Xq22 which encodes the alpha-5
chain of _________
X-linked recessive
COL4A5
type IV collagen
*–> defect in the basement membrane
– Affected males have persistent microscopic hematuria
– episodic gross hematuria, precipitated by URI
– Present in the first two decades of life.
Alport syndrome
Most females with _____ have persistant or intermittent microscropic hematuria while only 7% of _____ never manifest hematuria
XLAS
obligate heterozygotes
•______ is absent early but develops eventually in all males
with XLAS and in both males and females with ARAS.
Proteinuria
• ESRD develops in all affected males with XLAS (90% by age 40)– rate determined by the underlying _____
COL4A5 mutation.
What are the extra-renal manifestations in Alport
Cochlear defects
Ocular defects–yellowish flecks or granulations in perimacular distrubtion
Leiomyomatosis
Pathology of AS
• LM:
• IF:
EM:
• LM: Early =normal. Later global and segmental glomerulosclerosis, interstitial fibrosis
• IF: Negative or non-specific IgM, C
EM: variable thickening, thinning, basket weaving, and lamellation of the GBM
Tx for Alport
RAAS blockade
Renal replacement eventually necessary
Transplant: 2-3% get anti-GMB disease
Inheritance pattern of Thin Basement Membrane Disease (Benign familial Hematuria)
autosomal dominance
• Continuous or intermittent microhematuria, with or without gross hematuria, and
generally no renal insufficiency
Thin basement membrane disease (benign familial hematuria)
What do we see on EM in Thin Basement Membrane Disease
• EM: Thin GBM (usually < 200 nm)
Tx for Thin Basement Membrane Disease
-reassurance, very small risk for ESRD
– BMP, urinalysis and BP monitored every 1-2 years
