CVPR First Aid: Renal pathology Flashcards
Are there urine casts in acute cystitis with pyuria
No casts
RBC casts indicate
Glomerulonephritis
Hypertensive emergency
WBC casts are indicative of?
3 listed
- Tubulointerstitial inflammation
- Acute pyelonephritis
- Transplant rejection
Fatty casts are indicative of?
Nephrotic syndrome
Associated with “maltese cross” sign
Granular (“muddy brown”) casts are associated with?
Acute tubular necrosis
Acute tubular necrosis AKA
ATN
Waxy casts are indicative of?
End-stage renal disease/chronic renal failure
Hyaline casts are indicative of?
Nonspecific
Can be a normal finding
Often seen in concentrated urine samples
Pictures of casts
578
Nomenclature of glomerular disorders
Focal
Diffuse
Proliferative
Membranous
Primary glomerular disease
Secondary glomerular disease
Characteristics of focal glomerular disease
< 50% of glomeruli are involved
Characteristics of diffuse glomerular disease
>50% of glomeruli are involved
Characteristics of proliferative glomerular disease
Hypercellular glomeruli
Characteristics of membranous glomerular disease
Thickening of glomerular basement membrane (GBM)
Characteristics of primary glomerular disease
1° disease of the kidney specifically impacting the glomeruli
Characteristics of secondary glomerular disease
Systemic disease or disease of another organ system that also impacts the glomeruli
Examples of focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis
Examples of diffuse glomerular disorders
Diffuse proliferative glomerulonephritis
Examples of proliferative glomerular disorders
Membranoproliferative glomerulosclerosis
Examples of membranous glomerular disorders
Membranous nephropathy
Examples of primary glomerular disease
Minimal change disease
Examples of secondary glomerular disease
SLE
Diabetic nephropathy
Describe nephritic syndrome
Due to GBM disruption
HTN
↑ BUN
↑ creatinine
Oliguria
Hematuria
RBC casts in urine
Proteinuria often in the subnephrotic range (<3.5g/day) but in severe cases can be in the nephrotic range
Examples of nephritic syndrome
5 listed
Acute poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
IgA nephropathy (Berger disease)
Alport syndrome
Membranoproliferative glomerulonephritis
Examples of nephritic-nephrotic syndrome
Diffuse proliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Examples of nephrotic syndrome
Focal segmental glomerulosclerosis (1° or 2°)
Minimal change disease (1°or 2°)
Membranous nephropathy (1° or 2°)
Amyloidosis (2°)
Diabetic glomerulonephropathy (2°)
Describe nephrotic syndrome
Podocyte disruption → charge barrier impaired
Massive proteinuria (>3.5g/day)
Hypoalbuminemia
Hyperlipidemia
Edema
May be 1°(direct podocyte damage) or 2° (podocyte damage from systemic process [eg, diabetes))
Describe nephritic-nephrotic syndrome
Severe nephritic syndrome with profound GBM damage that damages the glomerular filtration charge barrier → nephrotic-range proteinuria (>3.5 g/day) and concomitant features of nephrotic syndrome
Can occur wuth any form of nephritic syndrome but is most commonly seen with
Diffuse proliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Describe the features of nephrotic syndrome
Nephrotic syndrome - massive proteinuria (> 3.5 g/day) with hypoalbuminemia, resulting edema, hyperlipidemia
Frothy urine with fatty casts
Disruption of glomerilar filtration charge barrier may be 1° or (eg,direct sclerosis of podocytes) or 2°(systemic process [eg diabetes] secondarily damages podocytes)
Describe the features of severe nephritic syndrome
May present with nephrotic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage the charge barrier
Nephrotic syndrome associated complications
Associated with hypercoaguable state due to antithrombin III (AT III) loss in urine and ↑ risk of infection (loss of immunoglobulins in urine and soft tissssue compromise by edema)
What is the most common type of nephrotic syndrome in children?
Minimal change disease
Minimal change disease AKA
Lipoid nephrosis
Most common causes of minimal change disease
Often 1° idiopathic and may be triggered by recent infection, immunization, immune stimulus
Rarely 2° to lymphoma (eg, cytokine-mediated damage)
Treatment of minimal change disease
1° disease has excellent response to corticosteroids
Minimal change disease features under Light microscopy
normal glomeruli (lipid may be seen in PCT cells)
Minimal change disease features under immunofluorescence
(-)
Minimal change disease features under Electron microscope
Effacement of podocyte foot processes
Focal segmental glomerulosclerosis prevalence
Most common cause of nephrotic syndrome in African-Americans and Hispanics
Causes of Focal segmental glomerulosclerosis
Can be 1° idiopathic or 2° to other conditions (eg, HIV, Sickle Cell disease, heroin abuse, massive obesity, interferon treatment or congenital malformations)
Treatment of focal segmental glomerulosclerosis
1° disease has inconsistent responses to steroids
What is IF?
immunofluorescence
Complications of Focal segmental glomerulosclerosis
Can progress to CKD
Focal segmental glomerulosclerosis under light microscopy
Segmental sclerosis and hyalinosis
Focal segmental glomerulosclerosis under immunofluoresence
Often (-) but may be positive for non-specific focal deposits of IgM, C3 and C1
Focal segmental glomerulosclerosis under EM
Effacement of podocyte foot processes similar to minimal change disease
What is the most common cause of nephrotic syndrome in African-Americans and Hispanics?
Focal segmental glomerulosclerosis
Membranous nephropathy AKA
Membranous glomerulonephritis
Membranous glomerulonephritis AKA
Membranous nephropathy
Causes of Membranous nephropathy
Can be 1° (eg, antibodies to phospholipase A2 receptor) or 2° to drugs (eg, NSAIDs, penicillamine, gold)
Infections (eg, HBV, HCV and syphilis), SLE or solid tumors
Treatment of Membranous nephropathy
1° disease has poor response to steroids
Complications of membranous nephropathy
Can progress to CKD
Membranous nephropathy under light microscopy
Diffuse capillary and GBM thickening
Membranous nephropathy under IF
Granular due to IC deposition
Membranous nephropathy under EM
“spike and dome” appearance of subepithelial deposits
Amyloidosis
Kidney is the most commonly involved organ (systemic amyloidoisis)
Amyloidosis associations
Associated with chronic conditions that predispose amyloid deposition (eg, AL amyloid, AA amyloid)
Amyloidosis under LM
Congo red stain shows apple-green bifringence under polarized light due to amyloid deposition in the mesangium
What is ESRD?
End-stage renal disease
What is the most common cause of ESRD in the US?
Diabetic glomerulonephropathy
Diabetic glomerulonephropathy
Most common cause of ESRD in the U.S
Causes of Diabetic glomerulonephropathy
Hyperglycemia → nonenzymatic glycation of tissue proteins → mesangial expansion;
GBM thickening and ↑ permeability
Hyperfiltation (glomerular HTN and ↑GFR) → glomerular hypertrophy and glomerular scarring (glomerulosclerosis) leading to further progression of nephropathy
Features of Diabetic glomerulonephropathy under LM
4 listed
Mesangial expansion
GBM thickening
Eosinophilic nodular glomerulosclerosis
Kimmelstiel-Wilson lesions picture 580
Nephritic syndrome
Nephritic syndrome = inflammatory process
When glomeruli are involved, leads to hematuria and RBC casts in urine
Nephritic syndrome is associated with?
Azotemia
Oliguria
HTN (due to salt retention)
Proteinuria
Hypercellular/inflamed glomeruli on biopsy
Acute poststreptococcal glomerulonephritis most commonly occurs in?
Most frequently seen in children
Causes of Acute poststreptococcal glomerulonephritis
2-4 weeks after group A streptococcal infection of pharynx or skinn
Type III hypersensitivity reaction
Prognosis of Acute poststreptococcal glomerulonephritis
- Resolves spontaneously in most children
- May progress to renal insufficiency in adults
Presentation of acute post-streptococcal glomerulonephritis
5 listed
Presents with
- peripheral and periorbital edema
- cola-colored urine,
- HTN,
- (+) strep titers/serologies
- ↓ complement levels (C3) due to consumption
LM features of Acute poststreptococcal glomerulonephritis
Glomeruli enlarged and hypercellular
Features of Acute poststreptococcal glomerulonephritis under IF
(Starry sky) granular appearance (“lumpy-bumpy”) due to IgG, IgM and C3 deposition along GBM and mesangium
Pesentation of Acute post-streptococcal glomerulonephritis
Presents with peripheral and periorbital edema, cola-colored urine, HTN, (+) strep titers/serologies, ↓ complement levels (C3) due to consumption
Features of Acute post-streptococcal glomerulonephritis under EM
Subepithelial immune complex IC humps
Causes of Rapidly progressive (crescentic) glomerulonephritis
Poor prognosis
Rapidly deteriorating renal function (days to weeks)
Several disease processes may result in this pattern which may be delineated via IF pattern
Linear IF due to antibodies to GBM and alveolar basement membrane:
Goodpasture syndrome- hematuria and hemoptysis; type II hypersensitivity reaction
Negative IF/Pauci-immune (no Ig/C3 deposition):
granulomatosis with polyangiitis (Wegner) - PR3-ANCA/c-ANCA
Or
Microscopic polyangiitis- MPO-ANCA/p-ANCA
Granular IF-PSGN or DPGN
Features of Acute post-streptococcal glomerulonephritis under LM
Glomeruli enlarged and hypercellular
Features of Acute poststreptococcal glomerulonephritis under IF
(Starry sky) granular appearance (“lumpy-bumpy”) due to IgG, IgM and C3 deposition along GBM and mesangium
Features of Acute poststreptococcal glomerulonephritis under EM
Subepithelial immune complex IC humps
How to distinguish causes of Rapidly progressive (crescentic) glomerulonephritis
Several disease processes may result in this pattern which may be delineated via IF pattern
Goodpasture syndrome - linear IF
Granulomatosis with polyangiitis (Wegner) - pauci-immune
Microscopic polyangiitis - granular
Linear IF due to antibodies to GBM and alveolar basement membrane in RPG
Goodpasture syndrome- hematuria and hemoptysis; type II hypersensitivity reaction
Pauci-immune IF in RPG
Granulomatosis with polyangiitis (Wegner) - PR3-ANCA/c-ANCA
Granular IF-PSGN or DPGN in RPG
Microscopic polyangiitis- MPO-ANCA/p-ANCA
Treatment of Goodpasture syndrome
plasmapheresis
Features of rapidly progressive (crescentic) glomerulonephritis under LM
Crescent moon shape
Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes and macrophages
Course of rapidly progressing glomerulonephritis
Poor prognosis
Rapidly deteriorating renal function (days to weeks)
Crescentic AKA
Rapidly progressing glomerulonephritis
Diffuse proliferative glomerulonephritis
Often due to SLE (think “wire lupus”)
DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently
Features of diffuse proliferative glomerulonephritis under LM
“wire looping” of capillaries
Features of diffuse proliferative glomerulonephritis under IF
Granular
Features of diffuse proliferative glomerulonephritis under EM
Subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IgA nephropathy AKA
Berger disease
Describe the presentation of IgA nephropathy
Episodic hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings)
Renal pathology of IgA vasculitis (HSP)
Features of IgA nephropathy under LM
Mesangial proliferation
Features of IgA nephropathy under IF
IgA-based IC deposits in mesangium
Features of IgA nephropathy under EM
Mesangial IC deposition
Causes of Alport syndrome
Most commonly X-linked dominant mutation in Type IV collagen → thinning and splitting of glomerular basement membrane
Alport syndrome symptoms
Eye problems (eg, retinopathy, lens dislocation)
Glomerulonephritis
Sensorineural deafness
“can’t see, can’t pee, cant hear a bee”
Features of Alport syndrome under LM
Mutation in Type IV collagen → thinning and splitting of glomerular basement membrane
Features of Alport syndrome under EM
“Basketweave”
Membranoproliferative glomerulonephritis
MPGN is a nephritis syndrome that often co-presents with nephrotic syndrome
Type I may be 2° to hepatitis B or C infection
May also be idiopathic
Subendothelial IC deposits with granular IF
Type II is associated with C3 nephritic factory (IgG antibody that stabilizes C3 convertase → persistent complement activation → ↓ C3 levels
Intramembranous deposits, also called dense deposit disease
In both types mesangial outgrowth → GBM splitting → “tram-track” appearance on H&E and PAS stains
Types of kidney stones
Calcium
Ammonium magnesium phosphate
Uric acid
Cystine
Complications of Kidney stones
Can lead to severe complications such as hydronephrosis, pyelonephritis
Presentation of obstructed kidney stone
Obstructed stone presents with unilateral flank tenderness, colicky pain radiating to groin, hematuria
Kidney stone treatment and prevention
Encouraging fluid intake
What is the most commmon kidney stone presentation
Calcium oxalate stone in patient with hypercalciuria and normocalcemia
Focal segmental glomerulosclerosis nephritic or neprotic?
nephrotic
Minimal change disease nephritic or nephrotic
nephrotic
Membranous nephropathy nephritic or nephrotic
nephrotic
Amyloidosis nephritic or nephrotic?
nephrotic
Diabetic glomerulonephropathy nephritic or nephrotic
nephrotic
Acute post-streptococcal glomerulonephritis nephritic or nephrotic
nephritic
Rapidly progressive glomerulonephritis nephritic or nephrotic
nephritic
IgA nephropathy (Berger disease) nephritic or nephrotic
nephritic
Alport syndrome nephritic or nephrotic
nephritic
Membranoproliferative glomerulonephritis nephritic or nephrotic
nephritic
Most common types of nephritic-nephrotic syndromes
Can occur wuth any form of nephritic syndrome but is most commonly seen with
Diffuse proliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Describe the pathophysiology of Alport syndrome
Mutation in Type IV collagen → thinning and splitting of glomerular basement membrane
