Clinical manifestations of renal diseases
- azotemia = BUN + creatinine
o usually related to GFR
- pre-renal azotemia = hypoperfusion of
kidneys
- post-renal azotemia = obstruction to urine
flow
- uremia = azotemia + other metabolic &
endocrine alterations
o resulting from renal damage
- nephritic syndrome = glomerular dz +
hematuria
o RBC casts
o mild-moderate proteinuria
o HTN
o ex = acute poststrep GN
- rapidly progressive GN = nephritic
syndrome w/ rapid  in GFR (hours to
days)
- nephrotic syndrome = glomerular dz +
proteinuria >3.5 gm/day
o hypoalbuminemia  severe edema
o hyperlipidemia, lipiduria
o  risk of inf.
o  risk of thrombosis, renal v.
thrombosis
- acute renal failure = rapid & frequently
reversible deterioration of renal function
o oliguria or anuria
o recent onset of azotemia
o ex = acute kidney injury or acute
tubular necrosis
Chronic renal failure
- prolonged symptoms + signs of uremia
- end result of all chronic renal parenchymal
dz
- progresses thru 4 stages that merge into
one another:
- 1. diminished renal reserve
o GFR is 50% of normal
o BUN and Cr are normal
o asymptomatic
- 2. renal insufficiency
o GFR si 20%-50% of normal
o azotemia, anemia, HTN
o polyuria & nocturia appears
- 3. chronic renal failure
o GFR <20% of normal
o volume & solute composition can’t be
regulated
o edema, metabolic acidosis,
hyperkalemia
o overt uremia
- 4. end-stage renal disease
o GFR <5% of normal
o terminal stage of uremia
Glomerular diseases
- systemic disorders assoc w/ glomerular
dz: SLE, DM, vasculitis, amyloidosis
The Glomerular Syndromes
Syndrome
Manifestations
Nephritic
Hematuria, RBC casts in
syndrome
urine
Azotemia
Variable proteinuria
Oliguria
Edema
HTN
Rapidly
Acute nephritis
progressive
Proteinuria
GN
ARF
Nephrotic
>3.5gm/day proteinuria
syndrome
Hypoalbuminemia
Hyperlipidemia
Lipiduria
Chronic renal Azotemia  uremia
failure
progressing for months to
years
Isolated
Glomerular hematuria
urinary
Subnephrotic proteinura
abnormalities
Systemic manifestations of chronic
kidney disease & uremia
Fluid &
Dehydration
electrolytes
Edema
Hyperkalemia (peaked
T waves)
Metabolic acidosis
Calcium
Hyperphosphatemia
phosphate &
Hypocalcemia
bone
2
hyperparathyroidism
Renal osteodystrophy
Hematologic
Anemia
Bleeding diasthesis
Cardiopulmonary HTN
Congestive heart
failure
Cardiomyopathy
Pulmonary edema
Uremic pericarditis
GI
N/V
Bleeding
Esophagitis, gastritis,
colitis
Neuromuscular
Myopathy
Peripheral neuropathy
Encephalopathy
Dermatologic
Sallow color
Pruritus
Dermatitis
Heymann nephritis
- induced by immunizing animals w/ an
antigen contained w/in preparations of
proximal tubular brush border
- rats develop Abs to this antigen 
membranous nephropathy
- electron-dense deposits along
subepithelial aspect of BM
- granular lumpy pattern
Anti-GBM Ab-induced GN
- Abs are directed against intrinsic fixed
antigens that are normal components of
GBM proper
- diffuse linear pattern of staining
- Goodpasture syndrome = anti-GBM also
react w/ lung alveoli BM
- GBM antigen responsible for classic antiGBM Ab-induced GN & Goodpoasture
syndrome is component of the NC1
domain of the α3 chain of collagen type IV
- severe crescentic glomerular damage
- rapidly progressive GN
Circulating immune complex GN
- glomerular injury is caused by the
trapping of circulating antigen-Ab
complexes within glomeruli
- subendothelial & subepithelial deposits
- granular deposits along BM, mesangium,
or both
- molecules of neutral charge tend to
accumulate in mesangium
2 major histologic characteristics of
progressive renal damage:
1) Focal segmental glomerulosclerosis
(FSGS)
- develop proteinuria
- glomerulosclerosis initiated by adaptive
change that occurs in the unaffected
glomeruli
- compensatory hypertrophy of remaining
glomeruli  proteinuria + segmental
glomerular sclerosis & uremia
- glomerular hypertrophy  hemodynamic
changes ( blood flow, filtration,
glomerular HTN)
2) Tubulointerstitial fibrosis
- may be caused by ischemia of tubule
segmentsacute/chronic inflammation in
adjacent interstitium, and damage or loss
of peritubular capillary blood supply
- proteinuria can cause direct injury to and
activation of tubular cells
Acute proliferative poststreptococcal GN
- immune complex mediated
- strep = MC underlying inf.
- 1-4 weeks after strep inf. of skin or
pharynx
- MC in 6-10 years of age
- serum complement 
- ASO & other anti-strep Abs 
- granular immune deposits in glomeruli
- morphology:
o enlarged, hypercellular glomeruli
o crescent formation
o diffuse leukocyte infiltration of all
lobules of all glomeruli
o tubules contain red cell casts
o immunofluorescence = granular
deposits of IgG, IgM, & C3 in GBM &
mesangium
o EM = subepithelial humps
- clinical:
o abrupt malaise, fever nausea, oliguria,
hematuria (smoky or cola-color
urine)
o 1-2 weeks after sore throat recovery
o RBC cast in urine, mild proteinuria
o periorbital edema
o mild-mod HTN
- adults have less benign course:
o present w/ sudden HTN, edema, 
BUN
o many develop chronic or rapidly
progressive GN
Rapidly progressive (crescentic) GN
(RPGN)
- severe oliguria + nephritic syndrome
- untreated  death from renal failure in
wks-months
- crescent formation in glomeruli
- 3 types:
o Type I (anti-GBM)
 linear deposits of IgG
 ex = Goodpasture syndrome
 tx = plasmapheresis
o Type II (immune complex deposition)
 granular staining pattern
 ex = post-infectious GN, lupus
nephritis, Henoch-Schonlein
purpura
 tx underlying dz
o Type III (pauci-immune)
 p-ANCA or c-ANCA +
 ex = Wegener granulomatosis,
microscopic polyangiitis,
idiopathic
- morphology:
o distinctive crescent formation
o fibrin strands prominent between
cellular layers in crescents
o rupture in GBM
o crescents undergo sclerosis in time
o immune complex = granular deposits
o Goodpasture’s = linear fluorescence
o pauci-immune = little or no
deposition
- clinical:
o hematuria w/ RBC cast in urine
o moderate proteinuria
o variable HTN & edema
o eventually severe oliguria
o Goodpasture’s = recurrent
hemoptysis
Nephrotic syndrome
- massive proteinuria
- sodium & water retention
- soft pitting edema
o marked in periorbital region
o possible pleural effusion & ascites
- hyperlipidemia  lipiuria (oval fat bodies)
- vulnerable to inf.
- thrombotic & thromboembolic
complications
o renal v. thrombosis
- systemic causes:
o DM
o amyloidosis
o SLE
- primary glomerular lesions:
o membranous nephropathy
o minimal-change
o focal segmental glomerulosclerosis
o membrano-proliferative
Membranous nephropathy
- common cause of nephrotic syndrome in
adults
- may occur due to 2 cause of systemic
disease:
o drugs (penicillamine, NSAIDS,
captopril, gold)
o malignancy
o SLE
o inf. (chronic HBV, HCV, syphilis,
shistosomiasis, malaria)
o autoimmune dz (thyroiditis)
- chronic immune complex mediated dz
- linked to susceptibility genes
- morphology:
o diffuse uniform thickening of
glomerular capillary wall (accum. of Ig
deposits along subepithelial side of
BM)
o EM = spike and dome pattern
(irregular spikes protruding from GBM
 thicken to domelike protrusions)
o spikes best seen in silver stains
- generally indolent course
- nonselective proteinuria
- doesn’t respond well to corticosteroid
therapy
- progressive sclerosis of glomeruli  
serum creatinine  HTN
Minimal change disease
- MC cause of nephrotic syndrome in
children (peak 2-6 yo)
- morphology:
o primary visceral epithelial cell injury
o loss of glomerular polyanions
o diffuse effacement of foot process of
visceral epithelial cells
o appear normal by light microscopy &
EM
o proximal tubule cells lipid & protein
laden (lipoid nephrosis)
- clinical:
o highly selective proteinuria (mostly
albumin)
o dramatic response to corticosteroid
therapy (completely reversible)
o 2 dz may follow NSAID therapy
o assoc w/ Hodgkin lymphoma
o assoc w/ respiratory inf. &
prophylactic immunization
o assoc w/ other atopid disorders
o  prevalence in certain HLA types
Focal segmental glomerulosclerosis
(FSGS)
- MC form of nephrotic syndrome in adults
- sclerosis of some but not all glomeruli
(focal)
- only portions of affected glomeruli
involved (segmental)
- more common in Hispanic and blacks
- epithelial damage is hallmark of FSGS
- causes:
o idiopathic (10-35%)
o HIV-associated, heroin addiction,
obesity
o inherited mutations in slight
diaphgram proteins (podocin)
- morphology:
o collapse of capillary loops,  in
matrix, hyalinosis
o lipid droplets & foam cells present
o EM = loss of foot processes &
denudation of underlying GBM
o immunofluorescence = IgM & C3 may
be present
- clinical:
o hematuria,  GFR, HTN
o nonselective proteinuria
o poor response to corticosteroid
therapy
o progression to chronic kidney dz
o 50%  end-stage renal dz
o children have better prognosis
HIV-associated nephropathy
- MC causes severe form of collapsing
variant of FSGS
- striking focal cystic dilation of tubule
segments
- EM = many tubuloreticular inclusions
within endothelial cells
Slit diaphragm mutation diseases
- Congenital nephrotic syndrome of Finnish
type
o mutation of NPHS1 gene (encodes slit
diaphragm protein nephrin)
o produces minimal-change diseaselike glomerulopathy
o extensive foot process effacement
- AR FSGS
o from mutation in NPHS2 (codes for
podocin)
o steroid-resistant nephrotic syndrome
o childhood onset
Membranoproliferatve
glomerulonephritis
- aka mesangiocapillary glomerulonephritis
- characterized by:
o alterations in GBM
o proliferation of glomerular cells
o leukocyte infiltration
- Type I MPGN (MC)
o immune complexes & activation of
classical & alternative complement
o HBV and HCV associated
- Type II MPGN (rare)
o dense-deposit disease
o activation of alternative complement
o  serum C3
o circulating Ab C3 nephritic factor
(C3NeF) binds C3 convertase 
persistent C3 activation and
hypocomplementemia
- morphology:
o glomeruli large & hypercellular
o lobular appearance of glomeruli
o “double contour” or “tram track”
appearance due to duplication of the
BM (splitting)
o Type I = discrete subendothelial
electron dense deposits; C3 deposited
in granular pattern
o Type II = lamina densa ofGBM 
irregular ribbon-like extremely
electron-dense ; deposition of dense
material; C3 present in mesangium in
mesangial rings
- clinical:
o young adults with nephrotic
syndrome + nephritic component
o hematuria, mild proteinuria
o steroids, immunosuppressives,
antiplatelets not effective
IgA nephropathy (Berger disease)
- presence of prominent IgA deposits in
mesangial regions
- frequent cause of recurrent gross or
microscopic hematuria
- MC cause of GN worldwide
- Henoch-Schönlein purpura
o systemic disorder in children
o many overlapping features of IgA
neph.
- only IgA1 forms deposits in this dz
- activation of alternative complement
- abnormal immune regulation  increased
IgA synthesis in response to respiratory or
GI exposure to environmental agents
- assoc w/ Celiac dz and liver dz
- morphology:
o mesangial deposition of IgA
o often w/ C3 and properdin
o EM = electron dense deposits in
mesangium
- clinical:
o older children and young adults
o gross hematuria after respiratory, GI,
urinary tract inf
o hematuria lasts several days 
subsides  returns every few months
o may progress slowly to chronic renal
failure (higher risk in old age)
Hereditary nephritis
- group of heterogenous familial renal dzes
assoc w/ glomerular injury
- Alport syndrome and thin BM lesion
Alport syndrome
- hematuria w/ progression to chronic renal
failure accompanied by:
o nerve deafness
o various eye disorders (lens
dislocation, post. cataracts, corneal
dystrophy)
- X-linked in 85% of cases
o males express full syndrome
o females are carriers w/ only
hematuria
- abnormal α chains in type IV collagen
(crucial for function of GBM, lens of eye,
and cochlea)
- morphology:
o EM = basket-weave appearance
(irregular thickening and attenuation
of GBM and splitting and lamination
of the lamina densa)
- clinical:
o gross or microscopic hematuria
o red cell casts
o symptoms begin at age 5-20
o subtle auditory defects
Thin BM lesion (benign familial
hematuria)
- asymptomatic hematuria
- diffuse thinning of GBM
- renal function normal
- prognosis excellent
Dialysis changes
- arterial intimal thickening from
accumulation of smooth muscle-like cells
- loose proteoglycan-rich stroma
- focal calcification within residual tubular
segments
- extensive deposition of calcium oxalate
crystals in tubules & interstitium
- acquired cystic dz
Henoch-Schönlein purpura
- syndrome w/ purpuric skin lesions on
extensor surfaces of arms, legs, butt
- abdominal pain, vomiting, intestinal
bleeding
- arthralgia & renal abnormalities
- IgA nephropathy & this disease are
manifestations of same disease
- MC in children 3-8 years old
- deposition of IgA in mesangium
Diabetic nephropathy
- one of the leading causes of chronic kidney
failure in US
- 2 main processes involved:
o metabolic defect (glycosylation end
products  thickened GBM)
o hemodynamic effects (glomerular
hypertrophy  glomerulosclerosis)
- MC lesions involve glomeruli
- assoc w/ 3 glomerular syndromes:
o non-nephrotic proteinuria
o nephrotic syndrome
o chronic renal failure
- also causes hyalinizing arteriolar sclerosis
-  susceptibility to develop papillary
necrosis
- morphology:
o capillary BM thickening
o diffuse mesangial sclerosis
o nodular glomerulosclerosis
Amyloidosis
- most types are assoc w/ deposits of
amyloid within glomeruli
- MC renal amyloid = light chain (AL) or AA
type
- stain with Congo red
Fibillary glomerulonephritis
- characteristic fibrillar deposits in
mesangium and glomerular capillary walls
- resemble amyloid fibrils bud don’t stain
w/ Congo red
Other systemic disorders
- Goodpasture syndrome, microscopic
polyangiitis, Wegener granulomatosis
o characterized by foci of glomerular
necrosis + crescent formation
o hematuria
o mild  in GFR
- Essential mixed cryoglobulinemia
o deposits of cryoglobulins (mainly
IgG-IgM complexes
o cutaneous vasculitis, synovitis, MPGN
o most cases assoc w/ HCV
- Plasma cell dyscrasias
o multiple myeloma
o light-chain or monoclonal Ig
deposition dz
Tubular and interstitial diseases
Acute kidney injury (AKI)/Acute tubular
necrosis (ATN)
- acute diminution of renal function and
often morphologic evidence of tubular
injury
- MC cause of acute renal failure
- ischemic AKI = inadequate blood flow to
the peripheral organs
- toxic AKI = caused by drugs (gentamicin,
other antibiotics), radiographic contrast
agents, poisons & heavy metals (mercury),
carbon tetrachloride
- pathogenesis:
o tubule cell injury
 loss of cell polarity
 luminal obstruction
o disturbance in blood flow
 intrarenal vasoconstriction
  GFR, ischemic renal injury
- morphology in ischemic AKI:
o focal tubular epithelial necrosis at
multiple points along nephron w/
large skip areas in between
o rupture of BM (tubulorrhexis)
o occlusion of tubular lumens by casts
o straight prox. tubule & TAL esp.
vulnerable
o eosinophilic hyaline casts &
pigmented granular casts
o casts have Tamm-Horsfall protein
(urinary glycoprotein secreted by
cells of TAL and distal tubules)
- morphology in toxic AKI:
o acute tubular injury
o most obvious in PCT
o distinct poisoning w/ certain agents
- clinical course:
o initiation phase
 lasts 36 hours
 inciting medical, surgical, or OB
event in ischemic form
 slight  urine output;  BUN
o maintenance phase
 oliguria
 salt & water overload
 rising BUN
 hyperkalemia
 metabolic acidosis
 uremia
o recovery phase
 steady  in urine vol.
 hypokalemia becomes problem
  risk of inf.
 BUN + Cr begin to return to
normal
- non-oliguric AKI occurs often w/
nephrotoxins and has more benign clinical
course
Tubulointerstitial nephritis
- acute
o interstitial edema
o eosinophils & neutrophils
- chronic
o interstitial fibrosis
o widespread tubular atrophy
Pyelonephritis & UTI
- affects tubules, interstitium, renal pelvis
- acute and chronic forms
- serious complicating of UTI that affect
bladder, kidneys, and collecting systems
- more than 85% of UTIs are from gram-neg
bacilli from GI flora
o MC = E. coli
- ascending inf. = MC cause
- acquired VUR can result from persistent
bladder atony from spinal cord injury
Acute pyelonephritis
- acute suppurative inflammation of kidney
- usually bacterial; sometimes viral
(Polyomavirus)
- morphology:
o patchy interstitial suppurative
inflammation
o intratubular aggregates of
neutrophils
o tubular necrosis
o if assoc w/ reflux, damage is mostly
in upper & lower poles
o glomeruli characteristically resistant
to inf.
o fungal pyelonephritis often affects
glomeruli
- complications:
o papillary necrosis = mainly seen in
diabetics and urinary tract obst.
o pyonephrosis = total obstruction
o perinephric abscess = extension of
suppurative inflammation thru the
renal capsule into the perinephric
tissue
- healing:
o irregular scars
o patchy, jigsaw pattern
o almost always assoc w/
inflammation, fibrosis, & deformation
of the underlying calyx & pelvis
- clinical:
o sudden pain at CVA
o fever, malaise
o dysuria, frequency, urgency, pyuria
o leukocyte cast = renal involvement
- polyomavirus nephropathy
o seen in kidney allografts
o inf. of tubular epithelial cell nuclei
o intranuclear inclusions (viral
cytopathic effect)
o virions arryed in crystalline-like
lattices
Chronic pyelonephritis
- chronic tubulointerstitial inflammation &
renal scarring; involve calyces & pelvis
- important cause of kidney destruction in
children w/ severe lower urinary tract
abnormalities
- 2 forms:
o reflux nephropathy (MC)
o chronic obstructive pyelonephritis
(recurrent inf.)
- morphology:
o irregularly scarred; asymmetric
o coarse, discrete, corticomedullary
scars overlying dilated, blunted, or
deformed calyces, and flattening of
papillae
o mostly in upper/lower poles
o tubules show atrophy in some areas
and hypertrophy/dilation in others
o dilated tubules filled w/ colloid casts
(thyroidization)
- xanthogranulomatous pyelonephritis
o rare form of chronic pyelo.
o accum. of foamy macrophages w/
plasma cells, lymphocytes,
polymorphonuclear leukocytes, giant
cells
o assoc w/ Proteus inf. & obstruction
o large yellow-orange nodules
o confused w/ RCC
- clinical:
o chronic obstructive
 may be insidious
 may present like acute recurrent
pyelo.
o reflux nephropathy
 may have silent onset
 HTN in children
 loss of conc. ability  polyuria +
nocturia
o some develop 2 FSGS w/ significant
proteinuria years after scarring
Acute drug-induced interstitial nephritis
- sulfonamides, synthetic penicillins,
rifampin, thazies, NSAIDS, allopurinol,
cimetidine
- beings 15 days after exposure
- fever, eosinophilia, rash, renal
abnormalities (hematuria, mild
proteinuria, leukocyturia)
- 50% have rising serum Cr or ARF w/
oliguria
- type I and IV hypersensitivity
- morphology:
o interstitial edema & infiltration by
mononuclear cells
o tubulitis = infiltration of tubules by
lymphocytes
- tx = withdrawal
Analgesic nephropathy
- excessive intake of analgesic mixtures
- phenacetin, aspirin, caffeine,
acetaminophen, codeine
- most cases consume phenacetincontaining mix
- papillary necrosis  cortical
tubulointerstitial nephritis  impeded
urine outflow
- morphology:
o papillae show various stages of
necrosis, calcification, fragmentation,
sloughing
o patchy necrosis  complete papillary
necrosis  ghosts of tubules
o cortical columns of Bertin
characteristically spared
- clinical:
o MC in women
o prevalent in pts w/ recurrent HAs &
muscle pain, psychoneurotic pts,
factory workers
o accompanied by HA, anemia, GI
symptoms, HTN
o UTI inf. in 50%
o drug withdrawal may improve Sx
o small % develop transitional
papillary carcinoma of renal pelvis
Urate nephropathy
- Acute uric acid nephropathy
o precipitation of uric acid crystals in
renal tubules/collecting ducts
o lead to obstruction of nephrons &
ARF
o leukemia & lymphoma pts
undergoing chemo
- Chronic urate nephropathy (gouty
uropathy)
o deposition of monosodium urate
crystals in acidic milieu of distal
tubules, collecting duct, interstitium
o birefringent needle-like crystals in
tubular lumens or interstitium
o urates induce tophus
o may have  exposure to lead (from
drinking contaminated moonshine)
- Nephrolithiasis
o uric acid stones
o pts with gout and hyperurecemia
Light-chain cast nephropathy
- several factors contribute to renal damage:
o Bence Jones (light-chain) proteinuria
& cast nephropathy
 main cause of renal dysfunction
 proteins toxic to epithelial cells
 combine w/ Tamm-Horsfall
protein, form large tubular
casts  obstruct lumen cast
nephropathy
o amyloidosis
 AL type
 formed from free light chains
o light-chain deposition disease
 light chains deposit in GBMs
and mesangium 
glomerulopathy
 may deposit in tubular BMs 
tubulointerstitial nephritis
o hypercalcemia & hyperurecemia
- morphology:
o Bence Jones tubular casts are pink to
blue amorphous masses
o some casts surrounded by
multinucleate giant cells
- clinical:
o chronic renal failure develops
insidiously
o precipitating factors = dehydration,
hypercalcemia, acute inf., nephrotoxic
antibiotics
o Bence Jones proteinuria in 70% of
multiple myeloma pts
o significant non-light-chain
proteinuria = AL amyloidosis or lightchain deposition dz
Vascular diseases
Benign nephrosclerosis
- sclerosis of renal arterioles & small
arteries
- results in focal ischemia of parenchyma
- MC in blacks than whites
- HTN & DM  incidence & severity of
lesions
- 2 processes participate in arterial lesions:
o medial & intimal thickening
o hyaline deposition in arterioles
- morphology:
o cortical surface resemble grain
leather
o loss of mass from cortical scarring &
shrinking
o hyaline arteriolosclerosis
o interlobular & arcuate arteries
fibroelastic hyperplasia
o patchy ischemic atrophy
- clinical:
o moderate  in renal blood flow
o GFR normal or slightly 
o 3 groups of pts w/ HTN at risk:
 African descent
 severe BP elevations
 2nd underlying dz (DM)
Renal artery stenosis
- potentially curable form of HTN w/
surgical tx
- elevated plasma or renal vein renin lvls
- show reduction in BP when given
angiotensin II blockers
- causes:
o atheromatous plaque origin of renal
a.
 MC in men, elderly, DM
o fibromuscular dysplasia of renal a.
 MC = medial type
 MC in women, 3-4th decades
- morphology
o ischemic kidney reduced in size
o diffuse ischemic atrophy
o arterioles in ischemic kidney
protected from effects of HTN
o nonischemic kidney shows more
arteriolosclerosis
- clinical:
o bruit may be heard on auscultation of
affected kidneys
o  plasma renin or renal v. renin
o response to ACE inhibitors
Malignant HTN & accelerated
nephrosclerosis
- often superimposed on preexisting HTN or
underlying chronic renal dz
- MC in younger, men, blacks
- initial insult = vascular damage to kidney
- activation of RAS
- pts w/ malignant HTN have markedly 
renin
- morphology:
o small, pinpoint petechial
hemorrhages (flea-bitten
appearance)
o fibrinoid necrosis of arterioles
(eosinophilic granular change in BV
wall)
o onion-skinning in interlobular
arteries & arterioles
- clinical:
o BP > 200/120 mmHg
o papilledema, retinal hemorrhages,
encephalopathy, CV abnormalities,
renal failure, loss of consciousness
o medical emergency
Renal infarction
- most infarcts are due to embolism
- major source of emobli = left atrium &
ventricle from MI
- morphology:
o most infarcts are “white” anemic type
o ringed by zone of intense hyperemia
o wedge shaped
o eventually scar  depressed, pale,
gray-white scars that assume V shape
on section
- many infarcts clinically silent
- sometimes CVA tenderness
- showers of red cells in urine
Thrombotic microangiopathies
- characterized clinically by:
o microangiopathic hemolytic anemia
o thrombocytopenia
o renal failure
- characterized morphologically by:
o thrombotic lesions in capillaries &
arterioles in various tissue beds
(kidney)
o schistocytes in peripheral blood
smears
Typical HUS (epidemic, classic, diarrhea +)
- cause by Shiga-like toxin from E. coli
0157:H7
- affect children preferentially
- after diarrhea, sudden onset of bleeding
(hematemesis & melena), severe oliguria,
and hematuria
- assoc w/ hemolytic anemia,
thrombocytopenia, and some cases neuro
changes
Atypical HUS (non-epidemic, diarrhea – )
- mutations in complement-regulatory
factors
o MC = factor H; protects from
uncontrolled complement activation
- antiphospholipid syndrome
- postpartum renal failure
- vascular renal dzes
- drugs (chemo, immunosuppressives)
- irradiation
TTP
- pentad = fever, neuro Sx, microangiopathic
hemolytic anemia, thrombocytopenia,
renal failure
- caused by Abs or genetic def. of
ADAMST13
- occur in age <40
- CNS involvement = major feature
Congenital anomalies
Agenesis of the kidney
- b/l agenesis is incompatible w/ life
- assoc w/ other congenital disorders
- unilateral agenesis is compatible w/ life
but uncommon
- develops progressive glomerulosclerosis
from adaptive hypertrophic changes
Hypoplasia
- failure of the kidneys to develop a normal
size
- MC unilateral
- true hypoplastic kidney has no scars &
fewer renal lobes and pyramids
- oligomeganephronia = kidney is small w/
fewer nephrons that are markedly
hypertrophied
Ectopic kidneys
- usually at abnormally low levels
- may cause kinking or tortuosity of ureters
and cause obstruction of urinary flow
Horseshoe kidneys
- fusion of upper or lower poles of kidneys
- continuous across the midline anterior to
great vessels; trapped below IMA
- 90% fused at lower pole
- assoc w/ Turner syndrome
Multicystic renal dysplasia
- sporadic disorder (not inherited)
- abnormal metanephric differentiation 
abnormal structures in kidney
- abnormal lobar organization
- assoc w/ other anomalies
- MC unilateral
- enlarged, extremely irregular, multicystic
- characteristic = presence of islands of
undifferentiated mesenchyme (often
cartilage) & immature collecting ducts
- discovered as a flank mass
Cystic diseases of the Kidney
ADPKD (adult)
- multiple expanding cysts of both kidneys
- ultimately destroy renal parenchyma &
cause renal failure
- all B/L
- renal function retained until 40-50 yo
- PKD1 or PKD2 mutation
o PKD1 = polycystin1 (85%)
o PKD2 = polycystin2 (later onset)
- mutations PKD1 or 2 cause problems in
primary cilium of tubular epithelial cells
o may cause aberrant regulation in
intracellular Ca levels
o changes in proliferation, apoptosis,
interactions w/ ECM, secretory
functions of epithelia   # of cells
and abnormal secretions  cyst
formation & enlargement
- morphology:
o B/L enlarged
o external surface composed of cysts
o cysts filled with clear serous fluid or
MC turbid red to brown hemorrhagic
fluid
o cysts arise from the tubules
throughout the nephron
- clinical:
o begins w/ insidious onset of
hematuria
o progressive chronic kidney disease
o PKD2 have later onset and later
development of renal failure
o progression accelerated in blacks,
males, and sickle-cell trait
o assoc w/
 berry aneurysm
iver cysts/polycystic liver dz
(40%)
Simple cysts
- translucent, filled with clear fluid
- common postmortem findings without
clinical significance
- occasionally, hemorrhage may cause
sudden distention and pain
- calcification may give bizzare radiographic
shadows
- in contrast to tumors: smooth contours,
avascular, fluid signals on US
ARPKD (childhood)
- MC = perinatal & neonatal forms
- mutation of PKHD1 gene
o encodes fibrocystin
o in primary cilium of tubular cells
- morphology:
o enlarged kidneys
o smooth external appearance
o spongelike appearance (numerous
small cysts in cortex & medulla)
o dilated elongated channels at right
angles to the cortical surface
o cylindrical dilation of all CTs
o liver cysts usually present 
proliferation of portal bile ducts
- clinical:
o pts who survive infancy  congenital
hepatic fibrosis
Medullary sponge kidney
- multiple cystic dilations of collecting ducts
in the medulla
- occurs in adults
- discovered radiographically incidentally
- calcifications in dilated ducts, hematuria,
inf., urinary calculi
- renal function normal
- small cysts present in medulla
Nephronopththisis & adult-onset
medullary cystic dz
- variable # of cysts in medulla; usually
conc. at corticomedullary junction
- cortical tubulointerstitial damage is cause
of eventual renal insufficiency
- 3 variants:
o sporadic, nonfamilial
o familial juvenile nephronophthisis
(MC)
 AR; presents in childhood
o renal-retinal dysplasia
- MC genetic cause of end-stage renal dz in
children & young adults
- adult onset medullary cystic dz = AD
- morphology:
o small kidneys
o contracted granular surfaces
o cysts in medulla (corticomedullary
junction)
- clinical:
o affected children present w/ polyuria
& polydipsia
o Na wasting and tubular acidosis
o mutations in NPH1, NPH2, NPH3
Acquired (dialysis-associated) cystic dz
- pts who have undergone prolonged
dialysis sometimes show numerous
cortical & medullary cysts
- cysts contain clear fluid, lined by
hyperplastic tubular epithelium, often
contain calcium oxalate crystals
- most are asymptomatic
- sometimes cysts bleed  hematuria
- RCC may develop in walls of cysts (7%)
Urinary tract obstruction
- obstruction  susceptibility to inf. & stone
formation
- unrelieved obstruction almost always
leads to permanent renal atrophy
(hydronephrosis) or obstructive uropathy
- common causes:
o congenital anomalies
o BPH
o inflammation
o pregnancy
o functional (neurogenic)
o urinary calculi
o tumors
o sloughed papillae or blood clots
o uterine prolapse & cystocele
- hydronephrosis = dilation of the renal
pelvis & calyces assoc w/ progressive
atrophy of the kidney due to obstruction to
the outflow of urine
- obstruction also triggers interstitial
inflammatory rxn  interstitial fibrosis
- morphology:
o kidney may be slightly to massively
enlarged
o significant interstitial inflammation
o blunting of apices of pyramids 
cupped
o far advanced cases
 kidneys become thin-walled cystic
structure
 parenchymal atrophy
 total obliteration of pyramids
 thinning of cortex
- clinical:
o acute obstruction
 painful
 calculi lodged in ureter  renal colic
 prostatic enlargement  bladder Sx
o U/L complete or partial
hydronephrosis
 may remain silent for long
periods
o B/L partial obstruction
 earliest sign = polyuria +
nocturia
 chronic tubulointerstitial
nephritis
 HTN common
o complete B/L obstruction
 oliguria or anuria
 must be relieved
 postobstructive diuresis
Urolithiasis
- men > women
- peak age at onset = 20-30 years
- calcium stones
o 70% (MC)
o oxalate and/or phosphate; radiopaque
o may occur in hypercalcemia
(hyperparathyroidism)
o 20% associated w/  uric acid
secretion
- triple stones (struvite stones)
o magnesium ammonium phosphate
o staghorn calculi (very large)
o bacterial inf.
- uric acid stones
o gout, leukemia
o acidic urine  risk
o radiolucent
- cystine stones
o genetic defects in renal absorption of
AAs (cysteine)
- stone formation due to  urinary conc. of
stones’ constituents
- low urinary vol. may favor supersaturation
- morphology:
o stones are unilateral in 80%
o favored sites = renal calyces, pelvis,
bladder
o may have smooth contours, or may be
irregular, jagged mass of spicules
o many stones often found in 1 kidney
o progressive accretion of salts may
create branching structures 
staghorn calculi
- clinical:
o smaller stones are most hazardous
because they may pass into ureters
and cause colic and obstruction
o larger stones more likely to remain
silent in the kidney
o larger stones first manifest as
hematuria
o predispose to infection
Tumors of the kidney
Renal papillary adenoma
- small discrete adenoma in cortex
- arise from renal tubular epithelium
- commonly found on autopsy
- MC = papillary adenomas
- pale yellow-gray, discrete, wellcircumscribed nodules
- <3cm rarely metastasize; >3cm will
metastasize
Angiomyolipoma
- benign tumor of BVs, smooth muscle, fat
- tuberous sclerosis
o 25% have angiomyolipoma
o lesions in cerebral cortex, skin
abnormalities, unusual benign tumors
at other sites
- susceptibility to spontaneous hemorrhage
Oncocytoma
- benign epithelial tumor
- composed of large eosinophilic cells w/
numerous mitochondria
- tumors are tan or mahogany brown
- well encapsulated
- may achieve large size
Urothelial carcinoma of the renal pelvis
- produce noticeable hematuria
- small when discovered
- may block urinary outflow 
hydronephrosis + flank pain
- increased incidence in individuals w/
analgesic nephropathy and Balkan
nephropathy
- infiltration of wall of pelvis and calyces is
common
- prognosis is not good
Renal cell carcinoma (Adenocarcinoma of
the kidney)
- MC renal cancer in adults
- risk factors:
o old age (6-7th decades)
o males
o SMOKERS
o obesity
o HTN
o unopposed estrogen therapy
o asbestos, petroleum & heavy metal
exposure
-  incidence in pts w/:
o chronic renal failure
o acquired cystic dz
o tuberous sclerosis
- arise from tubular epithelium
- most cases are sporadic
- familial variants:
o von Hippel-Lindau
 ½-⅔ develop renal cysts
 bilateral RCC
o hereditary clear cell carcinoma
o hereditary papillary carcinoma
 AD
 multiple B/L tumors w/ papillary
histology
 mutations in MET
- clear cell carcinoma
o MC variant
o nonpapillary
o most sporadic
o loss of sequences on short arm of
chromosome 3 (harbors VHL gene)
- papillary carcinoma
o papillary growth pattern
o not assoc w/ 3p deletions
o MET mutation
o frequently multifocal
- morphology:
o MC affects poles
o clear cell carcinoma
 arise from prox. tubular
epithelium
 usually solitary unilateral lesions
 bright yellow-gray-white tissue
 confined within capsule
 abundant clear or granular
cytoplasm; contains glycogen &
lipids
 delicate branching vasculature
o papillary tumors
 arise from DCT
 multifocal & B/L
 typically hemorrhagic & cystic
 MC renal cancer in dialysis assoc
cystic dz
 interstitial foam cells common in
papillary cones
o tendency to invade renal vein; may
produce continuous cord of tumor in
IVC and extend into the right heart
- clinical:
o CVA pain, palpable mass, hematuria
o hematuria is most reliable
(intermittent and microscopic)
o paraneoplastic syndromes:
 polycythemia
 hypercalcemia
 HTN
 hepatic dysfunction
 feminization/masculinization
 Cushing syndrome
 eosinophilia
 leukemoid rxns
 amyloidosis
o tendency to metastasize widely (MC
to lungs; also to bones)
-