Renal Pathology 3 Flashcards Preview

Renal > Renal Pathology 3 > Flashcards

Flashcards in Renal Pathology 3 Deck (13):

What disease association is caused by diabetic nephropathy?

What causes diabetic nephropathy?

What is the risk of developing it?

Leading cause of ESRd in most Western societies

Occurs in both T1DM and T2DM

Risk is multifactorial, related to duration of disease, 30-40% of diabetic patients


What is the pathogenesis of diabetic nephropathy?

Hyperfiltration common in early diabetes
Increased GFR due to glucose-dependent afferent arteriolar dilation
AT II Mediated constriction of the efferent arteriole
Hyperfiltration increases colloid osmotic pressure in the post-glomerular capillaries (results in increased Na absorption in the PT)
Angiotensin II


What is the pathogenesis of hypertrophy in DN?

What is pathogenesis of mesangial changes?


Early in onset
Size of kidney may increase by several cm
Associated with an increase in the number of mesangial cells and of capillary loops (increasing filtration surface area)

Mesangial Changes

Hallmarks of DN: Mesangial expansion, nodular diabetic glumerulosclerosis
Early mesangial lesion is characterized by increase in cell number and size and increased deposition of ECM
Mesangial expansion is mediated by both glucose and glucose-derived AGEs


What is the pathogenesis of proteinuria in DN?

What is the pathogenesis of fibrosis?


Widening of the GbM due to accumulation of type IV collagen and net reduction in negatively charged heparin sulfate
Podocyte changes due to increased width of the foot processes, apoptosis triggered by Ang II and TGF-B, migration reduced by Ang II preventing coverage
Serum proteins cross the bm due to disrupted texture, gaps, and holes


Tubulointerstitial fibrosis is seen early in DN (correlates with prognosis)
Caused by release of growth factors: TGFB, Ang II
Tubular cells change their phenotype and become fibroblasts
High glucose concentration and AGEs further stimulate this process


What are the stages of DN?

Stage 1: Onset of diabetes

  • GFR due to glomerular hyperfiltration
  • Glomerular hypertrophy seen on biopsy
  • Renal size
  • Reversible transient albuminuria

Stage 2: Clinically asymptomatic, but biopsy shows

  • Mesangial expansion
  • GbM thickening

Stage 3: Early nephropathy

  • Development of HTN
  • Persistent microalbuminuria by 24-hr collection
  • Urinary albumin excretion 30-300 mg/day

Stage 4: Overt proteinuria

  • Urinary albumin > 300 mg/day
  • GFR starts to decline
  • 50% of patients will reach ESRD within 7-10 years
  • Retinopathy present in 90-95% of patients

Stage 5: ESRD

  • Renal replacement therapy necessary
  • Occurs a mean of 15 years after onsets of Type 1 DM in patients who develop proteinuria (30%)



What co-morbidities are there of DM?

What are the complications of DN?

What is the biggest factor in determining DN mortality?

HTN, Neuropathy, Vascular changes, Increased mortality

Diabetic retinopathy (almost all of T1DM/DN 50-60% of T2DM/DN)
Polyneuropathy: Sensory (foot) or autonomic (silent angina, gastroparesis, erectile impotence, detrusor paresis)
Macrovascular complications (stroke, Coronary HD, PVD)



What is treatment of DN? What does each treatment do in protecting against sequelae?

HTN Therapy - Target of <140/90
If uncontrolled risk for more rapid progression of DN and CV events

 Glucose control - Decreases risk of progression
Reduction in reaching normoalbuminuria, microvascular complications, retinopathy, CV sequelae

Reduction of proteinuria - Blocking RAAS
Renoprotective (despite 30% decline in GFR), independent of BP

Lipid lowering therapy - Statins help in T2DM patients (not seen with ESRD)
LDL < 100 in general and <70 for diabetics with CVD

Life style modification - Smoking cessation (blocks proteinuria progression)
Weight reduction (improved renal outcome with reduction in proteinuria)


What is amyloidosis?

How does amyloidosis affect the kidney?

Characterized by the deposition of a proteinaceous material in extracellular spaces

Light chain amyloidosis (secreted by a single clone of B cells) typically lambda light chains (AL), 20% associated with multiple myeloma
Systemic amyloidosis from chronic inflammation


What are the effects of kidney amyloidosis?

What is seen on LM?

What stain is used and what is the characteristic finding?

What is the finding on IM?

What are the extra-renal manifestations?

Kidney enlargement and renal function impariment (but no hypertension)
Proteinuria, primarily albuminuria, occurs in the absence of microscopic hematuria
Tubular defects from amyloid deposits
Renal tubular acidosis (Fanconi syndrome), polyuria-polydipsia (urinary concentration defect

Deposits on LM

Congo-red stain with apple green birefringence

Light chain staining on IM

Restrictive cardiomyopathy, GI tract, Macroglossia, Splenomegaly, Peripheral nerve, Skin, Joint


What is light chain deposition disease?

What do patients develop?

What is the LM, IF, EM findings?

Deposition of excess immunoglobulin light chains in the kidney, usually K and 50% of cases coexist with multiple myeloma

Proteinuria, hematuria, chronic renal insufficiency

LM: Nodular glomerulosclerosis
IF: Light chain staining (Kappa staining)
EM: Granular deposits along GBM


What is Alport syndrome?
What is the genetic pattern?
What are the renal manifestations?

Mutation of the COL4A5 gene on Xq22 encoding alpha-5 chain of type IV collagen resulting in a defect in the basement membrane

Most commonly X-linked recessive (80%) but also can be autosomal recessive

Hematuria - Affected males have persistent microscopic hematuria with episodic gross hematuria, precipitated by URI
Proteinuria is absent early but eventually develops in all patients
Hypertension, ESRD eventually develops


What are the extra-renal manifestiatons of Alport syndrome?

What are the findings on LM and IF?

What are the treatment options?

Cochlear defects - adherence defect of the organ of Corti to the basilar membrane, 80% of males, 20-30% of female
Occular defects - 30-40% of XLAS, 15% of XLAS females, Anterior lenticonus, pathognomic (15% of males, associated with ESRD by 30 years, maculopathy
Leiomyomatosis (less common) - esophagus and tracheobronchial tree

LM: Early in disease , glomeruli may appear normal. Later global and segmental glomerulosclerosis, interstitial fibrosis

IF: Negative or non-specific IgM

Treatment: Not disease specific but can use RAAS blcockade, eventually will need replacement
2-3% of transplants will get anti-GMB disease


What is thin basement membrane disease? (Benign familial hematuria)
What is the genetic pattern of inheritance?
What is the morphology on LM/IF/EM?
What is treatment?

Continous or intermittent microhematuria with or without gross hematuria and generally no renal insufficiency, previously considered benign (rare proteinuria, HTN, and ESRD); Extra renal features are rare

Autosomal dominant inheritance

LM: Normal glomeruli
IF: Negative
EM: [Blocked by picture, if anyone knows feel free to tell me]

Treatment: Reassurance and follow up to monitor chance of ESRD
BMP, urinalysis and BP monitored every 1-2 years