Renal Path 1 Flashcards
Most common cause of chronic renal failure/end stage renal disease
Diabetes
[second most common is HTN]
A daily dose of _____ may slow the decline of renal function in people with CKD
Folic acid
[people with CKD have a high prevalence of hyperhomocysteinemia which is associated with folate deficiency and increased risk for stroke/ASCVD]
More than 50% of those over 50 have ____ in the renal parenchyma
Cysts
[often small and asymptomatic, generally incidental findings; most common are simple cysts, but can be multilocular, may represent dysplastic kidney, polycystic disease, or a cystic tumor]
What is the most likely mechanism of edema present with renal disease?
Loss of plasma proteins (proteinuria) d/t glomerular damage —> loss of plasma oncotic pressure in vessels —> edema
Techniques utilized on renal biopsy include light microscopy, fluorescence microscopy, and electron microscopy
What test are these methods usually correlated with?
Urinalysis
What has the largest spike and lies closest to the positive pole in serum protein electrophoresis?
Albumin
Thin layer chromatography is used to look for what in serum?
Serum protein
IgG, IgA, IgM
Kappa and lambda light changes
4 major compartments/components of kidney used to categorize renal disease
Glomeruli (e.g., glomerulonephritis)
Tubules (e.g., Bence-Jones proteinuria)
Interstitium (e.g., fibrosis, inflammation, or edema)
Vessels (e.g., vasculitis, nephrosclerosis)
The general category of glomerular disorders is considered predominantly due to ______ disease; primary or secondary
Immunologic
What is azotemia?
Biochemical abnormality indicating an elevation of BUN and creatinine levels; usually related to decreased GFR
Azotemia is generally a result of renal disorders but may arise from 2 categories of extra-renal insults — what are they?
Prerenal azotemia — occurs after hypoperfusion of kidneys (hemorrhage, shock, volume depletion, and CHF) that impairs renal function in the absence of primary renal parenchymal damage
Postrenal azotemia — seen whenever urine flow is obstructed distal to calyces and renal pelvis; removal of obstruction corrects the azotemia
____ = azotemia + a constellation of clinical findings and biochemical abnormalities resulting from renal damage
Uremia
[generally a manifestation of chronic renal failure]
What are some clinical signs/symptoms that may be included in uremia of chronic renal failure?
N/V, weight loss, fatigue, anorexia
Pruritis
Polydipsia
Electrolyte abnormalities, muscle cramping
Encephalopathy
Bleeding manifestations d/t platelet dysfunction and anemia
Pericarditis
Pleuritis/pleural effusion
Normal GFR
Range from 90-120
Rule of thumb = 100 mL/min
Clinical manifestations of AKI
- Rapid decline in GFR
- Most severe forms exhibit oliguria or anuria
- May result from glomerular, interstitial, vascular, or acute tubular injury (most common pattern is acute tubular necrosis)
- Can be reversible, or progress to CKD
Clinical manifestations of chronic kidney disease
When mild, it is clinically silent
When more severe, exhibits uremia
Defined by persistently diminished GFR <60ml/min for at least 3 months from any cause, OR persistent albuminuria
CKD is generally irreversible
Clinical manifestations of ESRD
- GFR < 5% of normal
2. End stage of uremia
Major clinical manifestations of Nephrotic syndrome
Characterized by severe proteinuria (> 3.5g/day but may be less in children)
Hypoalbuminemia (plasma levels <3g/dL)
Severe edema
Hyperlipidemia
Lipiduria
Major clinical manifestations of nephritic syndrome
Dominated by acute onset of grossly visible hematuria
Azotemia and oliguria
Mild to moderate proteinuria
Hypertension
[proteinuria and edema are common, but not as severe as in nephrotic syndrome]
Clinical manifestations of rapidly progressive glomerulonephritis include signs of _____ syndrome with rapid decline in GFR; implies severe gomerular injury
Nephritic
General Pathologic responses of the glomerulus to injury
Hypercellularity of native cell populations, inflammatory cell infiltration, or crescent formation
Basement membrane thickening or deposits
Hyalinosis and sclerosis
[note that native cells include mesangial, endothelial, visceral epithelial (podocytes), etc.]
Examples of primary glomerulonephropathies
Acute proliferative (diffuse) glomerulonephritis
Rapidly progressive glomerulonephritis
Membranous glomerulopathy
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis; dense deposit disease
IgA nephropathy
Chronic glomerulonephritis - end stage
Systemic diseases with glomerular involvement
SLE
DM
Amyloidosis Goodpasture Microscopic polyarteritis/angiitis Wegener granulomatosis Henoch-schonlein purpura Bacterial endocarditis
Hereditary disorders with renal involvement
Alport syndrome (x-linked)
Thin Basement Membrane disease
Fabry disease
Diseases associated with glomerular subepithelial humps seen on microscopy
Acute glomerulonephritis
Diseases associated with epimembranous glomerular deposits on microscopy
Membranous nephropathy
Heymann glomerulonephritis
Diseases associated with subendothelial glomerular deposits seen on microscopy
Lupus nephritis
Membranoproliferative glomerulonephritis
Disease associated with mesangial deposits on microscopy
IgA nephropathy
Immune mechanisms of glomerular injury
Ab-mediated:
In-situ immune complex deposition—fixed, intrinsic tissue Ags (Goodpasture), or plated Ags (infectious etiology); Circulating immune complex deposition (SLE) — can be endogenous or exogenous
Cell-mediated immune injury
Activation of alternative complement
Descriptive patterns/distributions in categorization of glomerular disorders
Diffuse = involves all glomeruli
Focal = involves only subset of glomeruli
Segmental = of affected glomeruli, only portions are affected
Global = involves entire glomerulus
Once any renal disease, glomerular or otherwise, destroys functional nephrons and reduces the GFR to 30-50% of the normal rate, progression to end stage renal failure proceeds at a steady rate, independent of original stimulus or activity of the underlying disease.
The 2 major histologic features of such a progression are _____ and _____
Focal segmental glomerulosclerosis (FSGS); tubulointerstitial fibrosis
Most frequent clinical presentation and pathogenesis of postinfectious glomerulonephritis
Most frequent clinical presentation = nephritic syndrome
Pathogenesis = immune complex mediated; circulating or plated antigen
Glomerular pathology of postinfectious glomerulonephritis seen on light microscopy, fluorescence microscopy, and electron microscopy
Light: diffuse endocapillary proliferation, leukocytic infiltration
Fluorescence: granular IgG and C3 in GBM and mesangium; granular IgA in some cases
Electron: primarily subepithelial humps; subendothelial deposits in early stages
Most frequent clinical presentation and pathogenesis of Goodpasture syndrome
Presents as rapidly progressive glomerulonephritis
Pathogenesis: anti-GBM COL4-A3 antigen
Goodpasture syndrome findings on microscopy
Light: extracapillary proliferation with crescents; necrosis
Fluorescence: linear IgG and C3; fibrin in crescents
Electron: no deposits; GBM disruptions; fibrin
Most frequent clinical presentation and pathogenesis of chronic glomerulonephritis
Presents as chronic renal failure; pathogenesis is variable
Chronic glomerulonephritis findings on microscopy
Hyalinized glomeruli
Fluorescence microscopy may be granular or negative
Most frequent clinical presentation and pathogenesis of membranous nephropathy
Presents as nephrotic syndrome
Pathogenesis: in-situ immune complex formation; PLA2R antigen — in most cases of primary disease
Microscopy findings with membranous nephropathy
Light: diffuse capillary wall thickening
Fluorescence: granular IgG and C3; diffuse
Electron: subepithelial deposits
Most frequent clinical presentation and pathogenesis of minimal change disease
Presents as nephrotic syndrome
Pathogenesis unknown (possibly podocyte injury)
Minimal change disease findings on microscopy
Light: normal; lipid in tubules
Fluorescence: negative
Electron: loss of foot processes; no deposits
Most frequent clinical presentation and pathogenesis of focal segmental glomerulosclerosis
Presents as nephrotic syndrome; nonnephrotic proteinuria
Pathogenesis unknown
FSGS findings on microscopy
Light: focal and segmental sclerosis and hyalinosis
Fluorescence: IgM + C3 in many cases
Electron: loss of foot processes, epithelial denudation
Most frequent clinical presentation and pathogenesis of membranoproliferative glomerulonephritis (MPGN) type I
Presents with mixed pattern of nephritic/nephrotic syndrome
Pathogenesis = immue complex
MPGN type I findings on microscopy
Light: mesangial proliferative or membranoproliferative patterns of proliferation; GBM thickening; splitting
Fluorescence: IgG++ C3; C1q ++C4
Electron: subendothelial deposits
Most frequent clinical presentation and pathogenesis of dense deposit disease (MPGN type II)
Presents as hematuria and chronic renal failure
Pathogenesis: autoantibody; alternative complement pathway activation
MPGN type II findings on microscopy
Light: mesangial proliferative or membranoproliferative patterns of proliferation; GBM thickening; splitting
Fluorescence: C3 [no C1q or C4]
Electron: dense deposits (intramembranous)
Most frequent clinical presentation and pathogenesis of IgA nephropathy
Presents as recurrent hematuria or proteinuria
Unknown pathogenesis
IgA nephropathy findings on microscopy
Light: focal mesangial proliferative glomerulonephritis; mesangial widening
Fluorescence: IgA +/- IgG, IgM, and C3 in mesangium
Electron: Mesangial and paramesangial dense deposits
Pathogenesis of acute proliferative glomerulonephritis (diffuse)
Immune complex injury triggered by exogenous bacterial, viral, or fungal Ag
Historically antecedent infection by beta-hemolytic strep — specific nephritogenic strains of Lancefield Group A
Microscopic findings in pts with acute proliferative glomerulonephritis
Marked hypercellularity — ranges from simple mesangial to complex endocapillary cell infiltrate
Leukocyte infiltration: exudative within glomerular tuft
[subepithelial humps, granular deposits of IgG, IgM, C3 along GBM]
Describe presentation of acute proliferative glomerulonephritis (post-strep) in children
Generally ages 6-10
Typically 1-4 wks after pharyngitis or skin infection
Often SpeB (streptococcal pyogenic exotoxin B)
Often presents with malaise, fever, nausea, oliguria, and hematuria 1-2 weeks after recovery from sore throat
Dysmorphic red cells or RBC casts; mild proteinuria, periorbital edema, and mild/moderate HTN
Describe presentation of acute proliferative glomerulonephritis (post-strep) in adults
More atypical and aggressive course
May exhibit sudden HTN or edema, frequently with elevated BUN
Clinical course of acute proliferatieve glomerulonephritis (post-strep) in children vs. adults
Children tend to clear in 6-8 weeks; renal biopsy generally not indicated. Most recover completely with conservative therapy and no long term sequelae
Only 60% of adults recover completely with no sequelae; higher percentage than children progress to rapidly progressive GN, prolonged time to resolution, and progress to chronic glomerulonephritis
Describe microscopic findings of crescentic glomerulonephritis (RPGN)
Collapsed, compacted glomerular tufts
Crescent-shaped mass of proliferating visceral and parietal epithelial cells
Rather rapid obliteration of urinary space
Infiltrates of macrophages and leukocytes
Characteristic wrinkling and disruption of GBM
Types of RPGN
Type I = Anti-GBM Ab (renal-limited)
Type II = immune complex (idiopathic or post-infectious glomerulonephritis)
Type III = pauci-immune (ANCA-associated or idiopathic)
What condition is associated with type I RPGN?
Goodpasture syndrome
What conditions are associated with type II RPGN?
Lupus nephritis
Henoch-schonlein purpura
IgA nephropathy
What conditions are associated with type III RPGN?
Granulomatosis with polyangiitis
Microscopic polyangiitis
[50% of primary renal diseases associated with RPGN have a type III pauci-immune pattern on immunofluorescence studies]
what renal diseases are treated with plasmapheresis?
Goodpasture
TTP
Most common cause of nephrotic syndrome (in primary glomerular disease) in children
Minimal-change disease
What is the difference in pathogenesis of nephrotic syndrome in primary vs. secondary renal disease?
Primary:
Characteristic kidney pathologic changes in the absence of associated systemic disease — so ONLY the kidney is affected. Primary kidney disease is by far the most common cause of nephrotic syndrome in children (usually MCD)
Secondary:
Systemic diseases causing nephrotic disease (e.g., DM, SLE); with characteristic alterations in histomorphology. Secondary causes are more frequent in ADULTS
Leading etiologies of nephrotic syndrome in systemic disease
DM and SLE are most common
Others: amyloidosis, drugs (NSAIDs, penicillamine), infection (malaria, syphilis, hep B and C, HIV), malignant disease, bee-sting allergy, hereditary nephritis
About 75% of cases of membranous glomerulopathy are ______
Primary or secondary?
Primary!
[secondary causes include certain drugs, underlying malignancy, SLE, infection, other autoimmune dz,etc]
Multiple proteins are found in the urine of people with membranous glomerulopathy, in other words the proteinuria is said to be _____
Nonselective
Clinical course of membranous glomerulopathy
Proteinuria persists in 60% of pts
40% of these develop renal insufficiency
10% progress to ESRF
Is MCD usually associated with selective or nonselective proteinuria?
Selective! Meaning primarily albuminuria
A characteristic feature of MCD is a dramatic response to _____ therapy
Corticosteroid
Most common overall cause of nephrotic syndrome in US adults
Primary FSGS
[note greater incidence in Hispanic and African-American pts]
The 5-10% of MCD cases in children that does not respond to corticosteroid therapy generally exhibits ____ upon biopsy
FSGS
How does the clinical presentation of idiopathic FSGS differ from MCD and other podocytopathies?
Higher incidence of hematuria, reduced GFR, and HTN
Proteinuria tends to be nonselective
Generally there is poor response to corticosteroids
Significant progression to CKD with at least 50% developing ESRD within 10 years
Patients with HIV that are found to have a glomerulopathy are most likely to have _____
FSGS
Which types of MPGN are most common in kids vs. adults?
MPGN type I Primary = most cases present in children or young adults; common presentation is nephrotic syndrome
MPGN type I Secondary = almost exclusively in adults; frequently associated with chronic antigenemia
MPGN type I secondary has notably been a reflection of renal glomerular disease in patients with what other conditions?
Hepatitis C with cryoglobulinemia
Chronic immune complex disorders such as SLE endocarditis
Certain malignancies (CLL, lymphomas, melanoma)
Which is more common, MPGN I or II?
MPGN I is more common
___ is a more dominant clinical finding in MPGN type II, in contrast to the proteinuria seen in MPGN type I
Hematuria
Which disease is associated with alternative pathway complement activation?
MPGN II (dense deposit disease)
C3NeF (nephritic factor) IgG autoantibody binds C3 convertase, leading to continuous activation of alternative pathway
Would see low levels of circulating complement
Most common type of glomerulonephritis worldwide (Not in US!!)
IgA nephropathy
More common in Caucasians and Asians > African Americans
Male predominance
Renal IgA nephropathy not associated with systemic disease
Berger disease
IgA nephropathy associated with systemic disease, often exhibiting skin manifestations and involvement of abdominal viscera other than the kidney
Henoch-Schonlein purpura (HSP)
IgA nephropathy has known associations with ____ enteropathy and ____ disease
Gluten; liver
Clinical outcomes of IgA nephropathy
Recurrent episodes of hematuria without progression of renal disease in a majority of pts
Acute nephritic syndrome with HTN in 5-10%
Acute renal failure in 1-2%, associated wtih HTN, edema, oliguria, and crescenteric glomerulonephritis (RPGN)
Chronic renal failure in 15-40% as a slowly progressive disease over 20 year period
What condition is MOST likely to progress to chronic glomerulonephritis?
Crescentic glomerulonephritis (RPGN) — 90%
[others include FSGS, membranoproliferative, IgAN, membranous nephropathy]
