Kidney Pathology 3 (Wolfgram) Flashcards
What is the leading cause of ESRD (in most western societies)?
Diabetic Nephropathy
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
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
What is a Kimmelstiel-Wilson lesion?
A type of acellular nodular diabetic glomerulosclerosis commonly seen in diabetic nephropathy
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.
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
Describe the functional and structural characteristics of the following stages of DN
- Pre
- Incipient
- Overt
Functional
- Pre: increased GFR
- Incipient: microalbuminuria, hypertesion, reduced or normal GFR
- Overt: proteinuria, decreased GFR, nephrotic syndrome
Structural
- Pre: renal hypertrophy
- Incipient: mesangial expansion, GBM thickening, arteriolar hyalinosis
- Overt: mesangial nodules (Kimmelstiel-Wilson lesions), tubulointerstitial fibrosis
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
Describe the incidence of macrovascular complications in DN
5X more frequent, including stroke, CAD, PVD
What are some sequelae of autonomic polyneuropathy brought on by DN?
silent angina
gastroparesis
erectile impotence
detrusor paresis
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
True or false: increased albuminuria is associated with increased mortality in DN patients.
True
mortality is more or less proportional to level of proteinuria
Name (5) general treatment strategies for management of DN
- hypertension therapy
- glucose control
- reduction of proteinuria
- lipid-lowering therapy
- lifestyle modification
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
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
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)
Name two major lifestyle modifications indicated for DN patients
- smoking cessation
- weight reduction
20% of cases of amyloidosis light chains affecting the kidney are caused by what?
Multiple myeloma (single clone of B-cells)
Deposition of lambda light chains are typically seen in what disease?
Amyloidosis
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)
What disease will show apple-green birefringence on congo-red stain?
amyloidosis
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)
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
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
