HTN Neuropathy Vascular changes Increased mortality

Renal Pathology (DN) Flashcards by Meghan May

Diabetic Nephropathy is the leading cause of _____ in most Western societies in both DM I and II

ESRD

*risk related to duration of disease

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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

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Pathology of DN: Hyperfiltration

See increased GFR due to:

glucose dependent afferent arteriolar dilation and Ang II mediated cnx of efferent arteriole

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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

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Besides increasing GFR, what other effect does Ang II have

causes hypertrophic PT growth

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How can we control the hyperfiltration aspect of DN?

Glycemic control!

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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

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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

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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

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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

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In fibrosis seen in DN, tubular cells change phenotype to____

fibroblasts

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What enhances the fibrosis process in DN

glucose concentration and AGEs

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During Stage 1 and 2 we see ____ GFR and renal _____

Increased GFR (25-50%)
Renal hypertrophy

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What stage do we see mesangial expansion and GBM thickening in?

Stage 2 of DN; clinically asymptomatic but see on biopsy

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What stage is there devo of HTN, persistent microalbuminuria and urinary albumin excretion of 30-300/day?

Stage 3: Early nephropathy

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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

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Renal replacement therapy necessary, seen about 15 ys after onset of Type I DM pts with proteinuria (30%)

Stage 5: ESRD

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Co-morbidities of DN

HTN
Neuropathy
Vascular changes
Increased mortality

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Diabetic retinopathy
• in almost all patients with______diabetes and nephropathy.
• In 50% to 60% of ______diabetes with nephropathy

type 1

type 2

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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