Renal Neoplasms

- Mostly occur in the urinary tract, lower urinary tract most common
#1 renal cell carcinoma
#2 nephroblastoma (Wilm’s tumor)
- Imaging CT: nephrogenic phase is the most sensitive for detection of abnormal contrast enhancement
- Rapid increased enhancement and rapid washout is characteristic of renal cell
- Mas may be heterogeneous with areas of necrosis, cystic changes, and hemorrhage
- MRI: BEST for kidney imaging
Most common metastatic cancers TO kidney = melanomas, solid tumors - lung, breast, stomach, gyno, intestinal,
pancreatic

Renal Cortical ● <1.5cm, in the cortex

Adenoma ● Pale, yellow-gray, discrete,
well-circumscribed nodules
● Found in 40% of autopsies
● Made of complex, branching, papillomatous
structures with complex fronds. Cells are
cuboidal to polygonal and have regular, small
nuclei, scanty cytoplasm and no atypia
● Psammomatous calcifications seen

Angiomyolipoma ● BENIGN - made of vessels, smooth muscle

and fat
● Originates from perivascular epithelioid cells
● Seen in patients with tuberous sclerosis
● Susceptible to spontaneous hemorrhage
Oncocytoma BENIGN - arise from intercalated cells of collecting
ducts
● Associated with loss of chromosomes 1
and Y
● Plethora of mitochondria
● Central stellate scar proves a characteristic
appearance on imaging (central area of white
stroma)

Renal Cell Carcinoma In cortex → made from renal tubular epithelium

MOST COMMON KIDNEY CANCER
● 3 forms: clear cell carcinoma, papillary renal
cell carcinoma, chromophobe renal
carcinoma

TRIAD: painless hematuria, dull flank pain,

palpable abdominal mass
- Fever, polycythemia (b/c of production of
erythropoietin by cancer cells), weight loss,
anemia, left sided varicocele

Risk Factors: Cigarette smoking, HTN, obesity, cystic

disease of the kidney associated with end stage
renal disease

Paraneoplastic syndromes:polycythemia,
erythrocytosis, hypercalcemia, stauffer syndrome,
acquired dysfibrinogenemia,
feminization/masculinization due to gonadotropin

Clear Cell Carcinoma ● Most common

● Composed of cells with clear cytoplasm
● Often invades renal vein
● Associated with von-hippel-lindau disease
- deletion on chromosome 3p
○ Loss of VHL gene → VHL protein
normally causes degradation of
hypoxia induced factors -> if not
degraded, can lead to carcinogenesis
by stimulating VEGF
VHL: AD
 ● Hemangioblastomas of brain and spine
● retinal hemangioblastomas Stage 1: <7cm
● pancreatic tumors Stage 2: >7 cm
● Pheochromocytoma Stage 3: tumor involves veins or LN -
● papillary cystadenomas of the epididymis and within Gerota fascia
broad ligament Stage 4: Tumor extends past the
● endolymphatic sac tumors of the middle ear Gerota fascia or adrenal gland
involvement
Tx: surgery, radiation, chemotherapy (antiangiogenic
- inhibit receptor tyrosine kinase through VEGF and
PDGF receptors), immunotherapy

Papillary Renal Cell Multifocal and bilateral often

Carcinoma ● Associated with MET proto-oncogenes
located on chromosome 7q
● Gain the C7 and 17 (trisomy) and loss of Y

See: papillae and foamy macrophages in the stalk

Chromophobe Renal From intercalated cells of collecting ducts

Carcinoma ● Multiple losses of entire chromosomes seen
● Have favorable prognosis

Uncommonly - produce hormone like substances

- Can metastasis to lungs and bones

Urothelial Carcinoma ● Foci of atypia or carcinoma in situ in grossly

normal urothelium remote from the pelvic
tumor are seen
Wilms tumor ● Kidney is showing a claw sign around the
(nephroblastoma) mass on imaging - indicates renal origin
○ Well-encapsulated and well
circumscribed - necrotic
● Derived from primitive metanephric
blastema (small round blue cell tumor) -
have epithelial, blastemal and stromal
components
● MOST COMMON renal tumor of
CHILDHOOD
● Peak incidence between 2-4 (<5most
common)
● Most common sxn: Abdominal mass
○ Abdominal pain, fever, painless
hematuria, loss of appetite
○ HTN, anemia
● Less common - polycythemia, acquired von
willebrand disease
● Other genes: TP53, FWTT1
Associated with congenital syndromes:
● WAGR syndrome
○ Wilms tumor, aniridia (loss of iris),
genial abnormalities, range of
developmental delays Nephrogenic Rests = persistent
○ WT1 - tumor suppressor genes → embryonic tissue in kidney that
critical role in development of represent precursors to Wilms tumor.
kidneys and gonads transcription Will regress or differentiate but can
factor become cancerous if they persist.
● Denys-Drash syndrome - Imply increased risk of wilms in
○ Renal mesangial sclerosis, early contralateral kidney
onset renal failure, gonadal dysplasia **anaplasia (lack of
○ WT1 maturation/specialization of cells) =
● Beckwith-Wiedemann Syndrome indicative of poor prognosis and
○ Hemihyperplasia, organomegaly, associated with resistance to
macroglossia, omphalocele chemotherapy, linked to TP53 mutation
○ Neonatal hypoglycemia - Mitotic figures w/
○ Chromosome 11p15.5, WT2 → loss hypersegmented nuclei
of material imprinting or
uniparental disomy of IGF2

Tx: Surgery (total nephrectomy), chemotherapy,

radiation

Tubular and Interstitial Diseases: ATN, AIN

 Acute Tubular Injury/Necrosis (ATN)

Characterized by acute renal failure + tubular cell necrosis.

2 events: tubular injury + persistent, interrupted BF
Causes:
● Ischemia: decreased or interrupted BF
○ malignant HTN, thrombo angiopathies, hypovolemic shock
○ Loss of cell polarity due to redistribution of membrane proteins
in tubular cells → abnormal ion transport → increased Na to
distal tubules → aff. VC via tubulo-glomerular feedback →
decreased GFR
○ Weakened cell to cell adhesion → cast obstruction and leak of
tubular fluid
○ Ischemic tubular cells = express cytokines → recruit
See muddy brown, granular casts in
leukocytes → more injury
urine
○ Injured cells detach from BM → luminal obstruction, increased
intratubular P = decreases GFR
Nephrotoxic: continuous PCT necrosis
■ Lethal injury = necrosis and inflammation
■ Sublethal injury = endothelial cell injury, tubular
Ischemic: patchy PCT and ascending
obstruction
limb necrosis
● Direct toxic injury to tubules = nephrotoxic
○ light chains, bile, drugs, heavy metals, myo/hemoglobin

Recovery: repair dependent on capacity of injury cells to proliferate

Tubulointerstitial Nephritis (TIN=AIN)

Group of inflammatory kidney disease that involve interstitium and tubules
● When cause is bacterial infection = pyelonephritis
● Acute Interstitial nephritis = drug induced, metabolic disorder,
irradiation, viral infection, immune rxn
○ Can progress to renal papillary necrosis
○ Eosinophils in urine
○ Oliguria, fever, rash day to weeks after starting drug
○ Hypersensitivity rxn
● Acute TIN
○ Rapid clinical onset
○ Interstitial edema, leukocytic infiltration of interstitium and
tubules, tubular injury See inflammatory infiltrate in interstitial
● Chronic TIN nephritis
○ Mononuclear leukocyte infiltrate, interstitial fibrosis, tubular
atrophy
** Sxn: No proteinuria or hematuria BUT
- Have imapired ability to concentrate urine: polyuria or nocturia
- Salt washing
- Metabolic acidosis - can’t excrete acids
- Isolated reabsorption and secretion deficits
Drug Induced Due to adverse reaction
Acute Interstitial ○ Penicillins, rifampin
Nephritis (AIN) ○ Diuretics (furosemide)
○ PPI, NSAIDs
○ phenin-ion, cimetidine, immune
checkpoint inhibitors
Pathology:
● Drug acts as haptan → covalently bind to
some cytoplasmis or extracellular component
of tubular cells and become immunogenic
when secreted by tubules Prominent eosinophilic and
○ Injury caused by IgE or T cell mononuclear cell infiltrate
mediated reactions to tubular cells or
BM
○ Pronounced edema and mononuclear
cell infiltrate

Urate nephropathy ● Urate deposits evoke mononuclear response

that contains foreign body giant cells (tophus)
● Tubular obstruction by urate = cortical
atrophy and scarring

Hypercalcemia and ● Deposition of calcium phosphate within renal

Nephrocalcinosis tubules and interstitium usually b/c of chronic
hypercalcemia
(Kidney stones) ● Causes: primary parathyroidism, sarcoidosis,
milk-alkali syndrome, malignancy associated
hypercalcemia
● SXN
○ Chronic renal failure with inability
to concentrate urine - polyuria,
nocturia
○ Calculi within collecting system -
associated with secondary infection
and obstruction
Light Chain ● Excessive production of monoclonal light
Nephropathy chains by malignant plasma cells → high
levels of free light chain in glomerular filtrate
● Accumulation of lights chains with uromodulin
in distal tubules = tubular obstruction
● Tubular casts have hard, fractured appeared
with associated inflammation and tubular
injury
● Some casts are surrounding by
multinucleated giant cells → cast rupturing
can lead to granulomatous inflammatory Tubular cast surrounding by
reaction macrophages

Tx: underlying plasma cell cancer

Pyelonephritis Inflammation of tubules, interstitium, and renal pelvis

● Acute pyelonephritis
○ Bacterial UTI
○ See yellow, raised abscesses on renal
surface - liquefactive necrosis
○ Pus formation

● Chronic pyelonephritis
○ Bacterial infection +
○ Vesicoureteral reflux or obstruction
○ Types: chronic obstructive, chronic Neutrophilic infiltrate of interstitium and
reflux associated, tubules
Xanthogranulomatous,
Complications: Chronic pyelonephritis
● Papillary necrosis
● Pyonephrosis = suppurative
inflammation can’t drain
● Perinephric abscess = extension of
suppurative inflammation through
renal capsule into perinephric tissue
Pathology:
● Can lead to chronic kidney disease
● One or both kidneys, diffuse or patchy
○ Kidney are not equally Thyroidization: dilated tubules with
 damaged flattened epithelium filled with casts
○ See uneven scarring that look like thyroid colloid
○ Scarring = papillary blunting
● See tubular atrophy, thyroidization,
interstitial inflammation and fibrosis

● Neutrophilic infiltrate of interstitium and

tubules
● Virus induced pyelonephritis = most
commonly polyomavirus
○ See enlarged tubular epithelial cells
and nuclear inclusions and interstitial
inflammation Renal scarring, cortical thinning,
calyceal clubbing due to necrosis

Renal Abscess Needs to be drained

Decreased density = area of infection

Emphysematous Infection or abscess with gas formation around the

Pyelonephritis kidney → can lead to fulminant sepsis
Tx: drainage and antibiotics

Papillary Necrosis Complication of Chronic pyelonephritis (AIN)

● See loss of structure within renal papilla due
to necrosis and focal calcifications
● Distal ⅔ and tips of pyramids are necrotic w/
focal calcifications

Sxn: gross hematuria and colicky flank pain

Causes:
● Chronic analgesic use (aspirin/NSAIDs)
● DM, urinary tract obstruction
● Sickle cell
● Chronic pyelonephritis
Chronic obstructive Obstruction predisposes the kidney to infection
pyelonephritis ● Bilateral - congenital anomalies
● Unilateral - kidney stones or obstructive
ureteral lesions

Inflammation and dilation of cavities

Chronic Most common cause of chronic pyelonephritis

reflux-associated ● Due to superimposition of UTI on congenital
pyelonephritis vesicoureteral reflux and intrarenal reflux
(Reflux nephropathy) ● Can lead to chronic renal insufficiency if
bilateral
Pathology
● Course scars that are polar and
associated with underlying blunted
calyces → seen in vesicoureteral reflux

Xanthogranulomatous Rare form of chronic pyelonephritis →

pyelonephritis non-functioning kidney
● Increased UTI, staghorn calculi, DM
● Accumulation of foamy macrophages
intermingles with plasma cells, lymphocytes,
PML, and giant cells
● Hydronephrosis
● Associated with E.coli and Proteus
infections and obstruction - produce large
orange nodules that may be confused with
renal cell carcinoma
Sxn: malaise, weight loss, low grade fever,
hematuria, pain

Tx: nephrectomy + antibiotics

Bear paw sign - multiple stones

Renal Vascular Disorders

Benign Kidney changed induced by chronic mild to
Nephrosclerosis moderate HTN (<220/120)
● Patho
○ Kidney may be reduced in size and
weight
○ Capsular surface is usually granular
with some deep scars
○ Cortex is thinned and simple cysts
may be present
● Histo: focal global glomerulosclerosis,
tubular atrophy and interstitial fibrosis
○ Arteries show intimal fibrosis, SM
hyperplasia, and reduction of lumen Hyaline atherosclerosis = uniform wall
size thickening
○ Internal elastic lamina becomes
multilayered
○ Afferent arterioles and small arteries
show subendothelial deposition of
eosinophils = hyaline
arteriosclerosis (hyalinosis)

Malignant ● Severe HTN >220/120

Nephrosclerosis ● Kidneys may show same signs as benign
nephrosclerosis + petechial hemorrhages
Histo:
● Interlobular arteries have mucoid thickening
with erythrocytes in intima
● Reduced lumen - occluded by fibrin thrombi
● Wall of arterioles replaced by eosinophilic
material (fibrinoid necrosis)
● Glomeruli may have fibrinoid necrosis
● Onion skin appearance = proliferation of
intimal cells after acute injury
○ Lesion called hyperplastic
arteriosclerosis = marked narrowing
of arterioles and small arteries - can
obstruct
Renal artery stenosis Hypertension secondary to renal artery stenosis
caused by increased renin production from ischemic
kidney
● Tx - surgery
● Most common cause
1. atheromatous plaque at the origin of
the renal artery (men)
2. fibromuscular dysplasia of renal
artery = thickening that may involve all
parts of artery (women)

● Ischemic kidney reduced in size and shows

signs of diffuse ischemic atrophy w/ fibrosis Fibromuscular dysplasia
and inflammatory infiltrate
● Arterioles are protected from high BP thus
only see mild atherosclerosis there

+ Rim sign = if rim is enhancing, it’s infarction

Don’t see rim sign in infection

Thrombotic Microangiopathies

Microvascular thrombosis accompanied by microangiopathic hemolytic

anemia, thrombocytopenia, and sometimes renal failure

● Vascular compromise results in ischemic injury and organ dysfxn

● Patho: endothelial injury, platelet activation and aggregation
● Labs: thrombocytopenia, microangiopathic hemolytic anemia

Morphology
● Thrombi in glomerular capillaries, arterioles, and even larger
arteries
 ● Glomerular changes = widening of subendothelial space, duplication
of GBM, lysis of mesangial cells
● Cortical necrosis

Thrombotic microangiopathy
associated with malignant HTN

Typical Shiga like toxin produced by bacteria (E.Coli) →

hemolyetic-remic platelet activation and thrombosis
syndrome (HUS) ● Hemolytic anemia: pallor and anemia
● Uremic - renal failure (elevated BUN)
● CNs: lethargy, coma, seizures
● Thrombocytopenia: purpura and ecchymosis

Shiga like toxin enters blood stream → destroy RBC

and damage linings of blood vessels, including
glomeruli

Sxn: abdominal pain, bloody diarrhea, decreased

urine output, HTN, schistocytes - helmet cells on
peripheral smear

*contracted from contaminated water, uncooked

See schistocytes and bite cells on
meat, unpasteurized apple cider, cow or goat
smear
milk
Pathology:
Tx: supportive, NO antimicrobials (can make it
● Endothelial complement
worse), may need transfusion of RBC - some will
deposition
need dialysis for short time
● Hyperplasia of renal arteria
● Occlusion and firbin deposits
● Hemorrhagic colitis
● Hemolytic anemia

Atypical HUS Associated w/:

● Inherited mutations of autoantibodies targeting complement regulatory proteins
● Acquired causes of endothelial injury:
○ Antiphospholipid antibodies
○ Pregnancy or BC pill complications
○ Scleroderma, malignant HTN
○ Chemotherapy, immunosuppressants
○ Radiation

Thrombotic Deficiencies of ADAMTS13

thrombocytopenic ● Can’t cleave vWF → overactive → promote adhesion
purpura (TTP) ● In body: excessive clotting in body
 ● Can be secondary to cancer, pregnancy, or bone marrow transplant
● Tx: plasma exchange, corticosteroids

SXN: fever, thrombocytopenia, microangiopathic hemolytic anemia, renal failure, altered

mental status

Other Renal Vascular Disorders

Atherosclerotic ● Unilateral renal artery stenosis - HTN

Ischemic Renal ● Bilateral renal artery - chronic ischemia with
Disease renal insufficiency
Surgery can prevent further dysfunction and decline
in renal function

Atheroembolic Renal Embolization of fragments of atheromatous plaques

Disease from the aorta or renal artery
● Recognized in lumen of arcuate and
interlobular arteries - cholesterol clefts
● Large emboli can cause infarcts

Sickle Cell Leads to Hematuria and Hyposthenuria - diminished

Nephropathy concentrating ability
● Patchy papillary necrosis
● Proteinuria is common

Renal Infarcts ● Kidney common site b/c ¼ of cardiac output

goes to kidney + limited collateral circulation
● Most infarcts are due to embolism
● Major source → mural thrombosis in left
atrium and ventricle as a result of myocardial
infarction
● Vegatative endocarditis, aortic aneurysms,
and aortic atherosclerosis less common
sources

Congenital & Cystic Renal Disorders

Birth defects ● Renal agenesis: children with 1 kidney

○ Bilateral incompatible with life
● Renal dysplasia: children born with both kidneys, but one doesn’t function
 ●Hypoplasia: failure to develop to normal size
○ Unilateral
● Ectopic kidney: children born with kidney in wrong place
○ I.e. pelvic kidney due to abnormal migration
○ Predisposed to bacterial infections if there is kinking in ureters → obstruction
● Accessory renal arteries: extra supply to kidney
● Horseshoe kidney: fused at inferior poles
○ IMA gets caught during ascension
Normal lives but agenesis and dysplasia can increase risk of developing kidney disease

Potter Syndrome “If can’t pee, develop Potter”

● Present before birth
Causes: AR polycystic kidney disease, bilateral renal agenesis

Oligohydraminors (can’t urinate) → increased atmospheric pressure/compression of

developing fetus
● Facial anomalies: flattened nose, low set ears, micrognathia
● Limb deformities
Amniotic fluid is not bathing the lungs & compression of chest: pulmonary hypoplasia is
usually COD

Polycystic Kidney AR
Disease ● Infancy - bilateral flank masses, History of
oligohydramnios (Potter syndrome)1
○ If they survive develop liver cirrhosis
● Older children - bilateral kidney mass, signs
of chronic portal HTN (hematemesis, palpable
liver, thrombocytopenia, splenomegaly)
● Mutation in PKHD1 gene → fibrocystin
○ Cell surface receptor with role in
collecting duct and biliary differentiation
● Elongated channel perpendicular to cortical
surface
● Also see liver cysts

AD
● Adults - should include renal ultrasound
● Multiple, bilateral cysts
● Associated with intracranial aneurysms
(berry aneurysms), liver cysts AD - PKD
○ Mitral valve prolapse
● Have FH of died of renal disease or cerebral
aneurysms
● PKD1 gene → Chromosome 16 - polycystin 1
○ 2 hits - second is acquired in somatic cells in
kidney
○ Polycystin-1 localizes to non-motile cilium of
tubular cells → serve as mechanosensors of
fluid flow
○ Mutations = defects in mechanosensing →
disrupts downstream signaling of calcium
 influx → increased intracellular Ca →
stimulates secretion of tubular epithelial cells
→ cyst formation
● PKD2 gene → chromosome 4 - polycystin 2
○ Integral membrane protein in renal tubule →
function as Ca channel
○ Also localizes to cilia but slower rate of
disease
● Pressure of expanding cysts → ischemic atrophy of
intervening renal substance
Sxn: dull flank pain, abdominal flank mass, AR - PKD
hematuria, HTN, renal failure

*Monitor BP and proteinuria in child of family

member

Multicystic Dysplastic Non-inherited

Kidney ● Non functioning kidneys composed of cysts
and connective tissue
○ Often associated with ureteropelvic
obstruction or agenesis
● Islands of undifferentiated mesenchyme,
often with cartilage, and immature CD
● Potter syndrome

Dx: Ultrasound
- See atrophy with compensatory
hypertrophy on the other side

Due to failure of ureteric bud formation or lack of

interaction/induction of ureteric bud and metanephric
mesoderm

Medullary Sponge Multiple cystic dilations of the collecting ducts in the

Kidney medulla
(tubular ectasia) ● Enlarged tortuous collecting ducts, tiny cysts
in pyramids
● Complications: infection, stones, distal renal
tubular acidosis, hematuria

Nephronophthisis CKD that starts in childhood - cysts in medulla

(medullary cystic ● BM disruption → tubular atrophy involving medulla and cortex, interstitial fibrosis
disease complex) ● Cortical tubulointerstitial damage → renal insufficiency

Sxn: polyuria, polydipsia (impaired ability to concentrate urine), sodium wasting, tubular
acidosis

Acquired Cystic Patients with ESRD + under gone dialysis = show cortical and medullary cysts
Disease ● Increased risk of renal cell carcinoma
Simple cysts Have smooth contours, avascular on ultrasound
- Need to differentiate from tumors
Uncomplicated :
- Anechoic lesions with thin walls
- Sharply defined smooth wall
- Back wall visible
- Posterior acoustic enhancement
Complicated: require follow up US/CT
- Small amount of intracystic
hemorrhage/debris
- Small septum
- Too small for posterior enhancement
- Thickened or irregular walls
**suspect malignancy (RCC) especially if septa is
vascular on doppler

● Bosniak 1: no enhancement
● Bosniak 2: enhancement, septa/thin
calcification
● Bosniak 3: thickened irregular septa w/
enhancement
● Bosniak 4: clearly malignant, enhancing soft
tissue

Obstructive Uropathy Causes of obstructive hydronephrosis:

(UT obstruction) → ● Stones, UPJ obstruction, filling defects due to tumor, clot, infection, cervical or ovarian
Hydronephrosis cancer, retroperitoneal fibrosis

→ dilation of renal pelvis and calyces associated with progressive atrophy of kidney due to
obstructed urine outflow
● Obstruction triggers interstitial inflammatory reaction → interstitial fibrosis
● Pyramids get flattened, ureters can get dilated
● Start with tubular dilation → then atrophy and fibrous replacement
● Complete and sudden obstruction = coagulative necrosis of renal papilla

*Obstructive nephrosis mimics:

- Pregnancy related hydronephrosis
- Pregnant women have asymptomatic dilation b/c of mechanical compression of
ureter between uterus and iliopsoas
- Parapelvic cysts
- Get non-contrast CT
- Primary megaureters
- Isolated ureter dilation (w/o calyceal dilation or cortical atrophy as would be
seen in obstruction)
- Vesicoureteral reflux
- Abnormal flow of urine from bladder into upper urinary tract
Retroperitoneal Fibrosis around the aorta in the retroperitoneum that
fibrosis (chronic presents with ureteric obstruction
periaortitis)

Urolithiasis Hereditary predisposition

4 types:
● Calcium stones: calcium oxalate and/or calcium phosphate
● Triple stones or struvite stones: Mg ammonium phosphate
● Uric acid stones
● Cystine stones

See crystals of stone in urine, commonly in renal pelvis and calyces

● Staghorn calculi: Made of Mg ammonium phosphate

*Assume filling defects are malignant until proven otherwise (most common in stones though)

Glomerular = immune mediated, tubular/interstitial = toxic or infectious agents

Glomerular Disease

End Stage Renal Renal Failure = condition in which the kidneys lose the ability to remove waste and balance
Disease fluids
● Requires dialysis or kidney transplant
● Ages 0-4: birth defects and hereditary disease
● Ages 5-14: hereditary diseases, nephrotic syndrome, systemic disease
● Ages 15-19: Diseases that affect the glomeruli

● Trauma
○ Burns, dehydration, bleeding, surgery → decreased BF to kidney
● Lupus: autoimmune
● Diabetes
○ Elevated blood glucose scar kidneys
○ Thickening of efferent arteriole cause increase in filtration and leakage of protein and eventually cause
renal failure
○ Faster blood flow strains glomeruli, decreasing their ability to filter blood and raise BP
○ Screen for albuminuria in Type 1: 3-5 years after initial dx
○ #1 cause of kidney failure in adults
● HTN
○ If true HTN in children, heart and kidney are main suspects

Nephrotic Syndromes

Proteinuria
● >1+ dipstick or 30mg/dL protein
● If persistent proteinuria = glomerular disease that can progress to ESRD
 ● Nephrotic range: >3+ or 3-3.5 grams protein/24 hours
● See lipid casts, oval fat bodies in urine
Triad: Proteinuria, hypoproteinemia, edema

Podocyte damage → impairs change barrier → proteinuria

● Spilling of protein into the urine → low serum protein (hypoalbuminemia) → low oncotic pressure in vessels →
resulting edema
○ Important proteins are lost:
■ Immunoglobulins → complement level decreases = immunodeficiency
■ Albumin → low albumin decreased bound and available Ca → hypocalcemia,
hypoalbuminemia
■ Thyroxine binding globulin → resulting functional hypothyroidism
○ Body starts trying to make up for lost proteins
■ Hyperlipidemia: VLDL production increases: high LDL/HDL ratio
■ Fibrinogen, Factor V and VII + decreased vessel volume and increased platelet count →
hypercoagulability

SXN: swelling, edema, ascites, foamy urine, loose skin around eyes = puffy eyes

Minimal change ● Most common nephrotic syndrome Diffuse effacement and fusion of the
disease ● Loss of polyanions in GBM majority of podocyte foot processes
● Incidence 2-8

(Lipoid Nephrosis) Histo:

● H&E: Normal
● IF: No staining
● EM: Defining feature is diffuse effacement
and fusion of the majority of podocyte foot
processes without electron dense deposits on
electron microscopy

Tx: corticosteroids, good prognosis

● Associated with Hodgkin’s lymphoma

SXN: Abdominal pain, decreased urine output,

diarrhea, weight gain

Tx: salt restriction (decrease edema), steroids →

decrease swelling and reduce immune system
activity
Focal Segmental Histo:
Glomerulosclerosis ● H&E: Scarring in scattered regions of the
kidney, typically limited to small number of
glomeruli
● EM: Effacement of foot processes
● IF: No staining usually, but can have
non-specific IgM deposits
SXN:
● Can present as nephrotic syndrome
○ Proteinuria, hypoproteinemia, edema
● Typically seen in teenagers

● Normal C3 levels Segmental solidification of the

● Resistant to steroids and cyclophosphamide glomerular tuft with loss of capillary
lumens in the sclerosed segment
*Most common cause of nephrotic syndrome in
African Americans and Hispanics Scarring in scattered regions of the
● Associated with HIV, heroin, sickle cell, kidney
renal transplant

Membranous Due to antibodies to podocyte autoantigen (PLA2R - Spikes + subepithelial deposits

Nephropathy podocyte M-type phospholipase A2)

Histo:
● H&E: Diffuse thickening of glomerular
capillary wall due to accumulation of
subepithelial deposits
○ With intervening membrane spikes
● EM: Foot processes are effaced
● IF: Granular

Secondary causes:
● Drugs (penicillin, NSAIDs)
● Malignant tumors (lung, colon, melanoma) -
need to do cancer screening
● SLE
● Infections - Hep B, Hep C

*Seen in Caucasions

Membranoproliferative Can present nephrotic or nephritic (HTN, hematuria,

Glomerulonephritis asymptomatic proteinuria)
● Autoimmune disease
○ Inflammation via immune complexes
= proliferation of mesangial and
endothelial cells + recruitment of
inflammatory cells
○ Immune complex mediated and
 complement mediated
○ Tx: dipyridamole, aspirin
○ Slow progression to renal failure
● Child and young adults
● Type 1 - Hepatitis C

Histo:
1. H&E Fused podocytes = tram track
a. Diffuse global capillary wall thickening appearance
b. Increased mesangial matrix
c. Mesangial and endocapillary
hypercellularity
d. Subendothelial deposits
2. EM: global capillary thickening, increased
mesangial matrix, hypercellularity,
subendothelial deposits
a. Tram track appearance
3. IF: Granular for IgG and C3

Low C3 levels
● Steroids less effective in treating this
compared to MCD

Diabetic ● Most common cause of ESRD

Glomerulopathy
***Accumulation of extracellular matrix

● Lesions:
○ Glomerular lesions
■ Capillary BM thickening
■ Mesangial sclerosis
● Kimmelsteirl-Wilson
nodules Nodular glomerulosclerosis:
○ Vascular lesions Kimmelsteirl-Wilson nodules)
○ Pyelonephritis

Amyloidosis ● Seen in pts with plasma cell dyscrasia or

history of chronic inflammation = multiple
myeloma

● Antibodies against amyloid fibril protein

deposits in mesangium
● H&E: Amorphous eosinophilic deposition
● EM: fibrillar appearance
Stain: Congo red is + w/ classic birefringence
 Nephritic Syndrome

Hematuria
● If urine dipstick is positive for blood, obtain UA with microscopy b/c it could also be: hemoglobin, myoglobin,
porphyrias, urate crystals

0-4 RBC: not hematuria

>5: microscopic hematuria, urine not discolored
Gross hematuria: finding of RBC, urine is discolored

● Confirmed 3 disticks measured at different times

● Painless tea or cola colored urine (no casts or clots) = glomerular disease
○ Post-infectious nephritis, IgA nephropathy, Lupus nephritis, alport disease, MPGN, henoch schonlein
purpura, HUS
● Bright red urine w/ clots = non-glomerular disease
○ UTI - very common
○ Trauma sickle cell anemia, Wilms tumor, polycystic kidney disease, hypercalciuria, kidney stones

H - henoch Schoenlein Purpura and Hereditary Nephritis

E - easy benign familial
M - membranoproliferative
A - alport, IgA
T - trauma
U - ureteropelvic junction obstruction
R - renal stones
I - infectious
A - abnormal RBC
 Nephritic
Inflammation & Hematuria & HTN
● Azotemia - higher than normal blood level of urea or other nitrogen containing compounds: serum BUN level
● Proteinuria (<3.5 g/day)
● Edema
● RBC casts

Low complement: PMS → post strep GN, membranoproliferative, SLE

Normal complement: HSP, idiopathic vasculitis, RPGN, IgA

Alport Syndrome Inherited X-linked dominant; more frequent in males

● Mutation in gene for Type 4 collagen that
makes up glomeruli → scarring of kidney

Sxn:
● Hematuria
● Bilateral sensorineural hearing loss
● Ocular defects
● Ultimate renal failure

*thinning and splitting of BM (basket weave)

Post-Strep Caused by nephrogenic strain of GAS

Glomerulonephritis ● Skin and throat infections → PSGN
(PSGN) ○ Throat infection: 1-3 weeks later
(positive ASO)
○ Impetigo: 3-6 weeks later (positive
anti-DNAase)
● Infection stimulated overproduction of
antibodies that deposit in the glomeruli →
kidney damage
● Typically does not lead to renal failure See Sub-epithelial dense deposits =
humps
Histo:
● Glomerular hypercellularity
● IF: granular - C3, IgG, IgM
● EM: See Sub-epithelial dense deposits =
humps

Triad: HTN, edema (esp eyelids or face), hematuria

- cola colored urine

Low C3 levels for up to 2 months

Sxn: hematuria, pyuria, RBC casts, edema, HTN

- Headache, malaise, anorexia, flank pain
Tx: fluid restriction, BP control
- Can progress into rapidly progressing GN
 - Tx w/ penicillin decreases rheumatic fever
and peritonsillar abscess but NOT GN

IgA nephropathy IgA deposits in the mesangium

(Berger disease)
***related to defective mucosal immunity

● EM: Immune complex deposits → activate

alternate pathway
● IF: granular, IgA, C3
● Rarely see in <10 years

Hematuria during or 1-2 days after URI/GI tract

infection; episodic hematuria
- Mild abdominal pain
- Worsening disease indication by persistent IgA deposits in the mesangium
proteinuria → can turn into crescentic
glomerulonephritis

Tx: ACE -

Crescentic Associated with severe glomerular injury

glomerulonephritis ● Characterized by rapid and progressive loss of
renal function w/ oliguria and signs of nephritic
(rapidly progressing) syndrome

Histo:
● Crescents in glomeruli → produced by the
proliferation of epithelial cells lining the Bowman
capsule and by monocyte/macrophage infiltration
● IF: granular or linear - Ig, C3

Types: Crescent shaped mass of proliferating

● Immune complex deposition epithelial cells and leukocytes in
○ Granular antibody and complement Bowman capsule
deposition
○ Complication of deposition diseases: Crescents in glomeruli
PSGN, lupus nephritis, IgA
nephropathy
● Anti-GBM antibody mediated
○ Linear deposits of IgG and C3 in GBM
○ Goodpasture syndrome - anti-GBM
antibodies cross react with pulmonary BM
○ Tx: plasmapheresis,
immunosuppressants
● Pauci-immune crescentic (ANCA)
○ Lack of detectable anti-GBM or
immune complexes, idiopathic

● ANCA: spectrum of glomerular and vascular disease reaction

 ○ Can cause necrotizing and crescentic glomerulonephritis
○ Wegner’s granulomatosis, microscopic polyangiitis, churg-strauss syndrome
● C3 glomerulonephropathy
○ Intense C3 straining with no Ig staining

Lupus Nephritis ● Seen in ½ SLE patients

● Immune complexes deposition → activates complement → complement mediated
damage
● Granular pattern of staining
● Can also see tram track sign, wire loop appearance of glomerular capillaries

Pediatric Renal Disorders

Benign Orthostatic Benign, normal variant

Proteinuria ● Proteinuria during the daytime, but disappears when patient has been lying down
● Common during growth spurt
● Use first morning urine specimen for diagnosis
● Check serum creatinine
○ If there is still morning proteinuria - check urine protein/creatinine. If >0.2 need
to further investigate

Transient Proteinuria F = fever

E = Exercise
(benign, goes away) D = dehydration

Urate Crystals ● Precipitation of uric acid crystals in the diaper (secondary to increased urinary uric acid
excretion in infants) may be misidentified as blood
● Orange or red, brick dust color, in a newborn baby’s diaper
● More common in breastfed infants
○ Made of uric acid - if baby is not making enough urine, they will be very
concentrated and easy to see
○ Urate crystals in baby’s diaper in the first 3 days of life are normal in
breastfeeding infant
● Urate crystals >3 days - sign of dehydration or that baby is not getting enough
milk
● If persist beyond first week - could be serious condition

Henoch Schoenlein ● Most common systemic vasculitis in children

Purpura Involves kidneys, joints, skin, GI tract
● After an URI a week ago
SXN: Palpable purpura: rash on buttocks, abdomen, and lower extremities
● NO thrombocytopenia - normal platelet count
● Abdominal Pain: colicky - can have intussusception as cause of abdominal pain
○ Small blood vessels in intestine → heme positive stools
● Arthralgias, arthritis
● Renal Disease: hematuria, proteinuria, azotemia, HTN, cola colored urine. Elevated
BUN and creatinine
Histo: IgA in mesangium (similar biopsy to IgA nephropathy)
Tx: supportive only, most cases resolve on own
UTIs ● Common pathogens:
○ E.Coli, Staph Saprophyticus,
Klebsiella, Serratia, Enterococcus,
Proteus, Pseudomonas, Candida
● Risk Factors
○ Catheters, antibiotic use
○ Voiding dysfunction, frequent or
recent sex
○ Vesciulouretal reflux, females
○ Pregnancy - progesterone indices SM
relaxation in bladders and ureters =
less peristalsis = not clearing out
tubes
○ Genetics, susceptible uroepithelial
cells, vaginal mucous properties
● SXN:
○ Uncomplicated:
■ Dysuria, frequency, hematuria,
suprapubic pain
○ Complicated:
■ Fever, chills, leukocytosis,
CVA tenderness
○ Nausea, vomiting, pyuria Vesicoureteral reflux
● Dx: urinalysis and urine culture, dipstick
○ Leukocyte esterase = WBC activity
○ + Nitrite (gram neg)
○ +urease (sapro, proteus, klebsiella)
● Tx:
○ Outpatient: Cipro, TMP-SMX
(Bactrim), Amox-Clav (Augmentin)
○ Inpatient: Ceftriaxone, Pip-Tazo,
Meropenem + Vancomycin

Renal Tuberculosis Hematuria, flank pain, constitutional sxn

● Due to hematogenous spread at the time of
primary pulmonary infection → small inactive
granulomas travel to kidney
Patho:
● Pyelonephritis-hypoperfusion and swelling
● Pseudotumoral - single or multiple nodules

Dx: culture first thing in the morning

TB autonephrectomy = Whole kidney
gets calcified