• Excretes harmful waste products:
• ex. Urea, Creatinine, Uric Acid
• Maintains acid-base hemeostasis
• Controls the synthesis and excretion of bicarbonate and hydrogen ions
• Reabsorbs essential substances
• Ex. Sodium, Glucose, Amino Acids
• Regulates water and soidum metabolism
• Control water by concentrating and diluting urine
• Controls sodium reabsorption in the proximal and distal collecting tubule
• Maintains vascular tone
• Angiotensin II (ATII)
• Vasoconstricts peripheral resistance arterioles and efferent arterioles
• Stimulates the synthesis and release of aldosterone
• Renal-derived prostaglandin (PGE₂)
• Vasodilates the afferent arterioles 
• Produces erythropoietin 
• Synthesized in the renal cortex by interstitial cells in peritubular capillary bed
• Maintains calcium homeostasis 
• Second hydroxylation of vitamin D
• 1-α-Hydroxylase is synthesized in the proximal renal tubule cells 
• Converts 25-hydroxycholecalciferol to  1,25-dihydroxycholecalciferol 
• Functions of Vitamin D
• Increases GI reabsorption of calcium and phosphorus
• Promotes bone mineralization, maintians serum Ca levels
• Promontes bone mineralization by stimulating the release of alkaline phosphatase from osteoblasts.  Alkaline phosphatase hydrolyzes pyrophosphateand other inhibitors of Ca-phosphate crystallization
• Increases monocytic stem cells to become osteoclasts

• Upper urinary tract (Kidneys, ureter) causes of hematuria
• Renal stone
• Glomerulonephritis
• Characterized by dysmorphic RBCs (irregualr membrane)
• Renal Cell Carcinoma
• Lower urinary tract (Bladder, urethra, prostate) causes of hematuria
•  Infecton
• Transitional Cell Carcinoma
• MCC of gross hematuria in tha absence of infection
• Benign Prostatic Hyperplasia
• MCC of microscopic hematuria in adult males
• Drugs associated with hematuria
• Anticoagulants (warfarin, heparin)
• Cyclophosphamide
• Hemorrhagic cystitis
• Risk factor for transitional cell carcinoma

• Protein > 150mg/24 hrs OR 30 mg/dL (dipstick)
• Presistent proteinuria usually indicates renal diease
• Qualitative tests include dipsticks and sulfosalicyclic acid (SSA)
• Dipsticks are specific for albumin
• SSA detects albumin and globulins
• Quantitaive tests is a 24 hr urine collection  

• Protein < 2g/24 hrs
• NOT associated renal disease  
• Fever, exercise, congestive heart failure
• Orthostatic (postural): Occurs with standing and is absent in the recumbent state. Urine protein is absentin the first morning void. No progression to renal disease.

• Protein loss is variable
• LMW proteinuria
• Amount filtered> tubular reabsorption
• Multiple Myeloma with BJ proteinuria
• Hemoglobinuria: intravascular hemolysis
• Myoglobinuria: Crash injuries, McArdles glyconeosis (deficient muscle phosphorylast). Increase in serum CK  

• Nephritic syndrome: Protein > 150 mg/24 hr , but < 3.5 g/24 hr
• Nephrotic syndrome: Protein > 3.5 g/ 24 hrs
• Damage to GBM:nonselective proteinuria with loss of albumin and globulins. ex. Post streptococcal glomerulonephritis
• Loss of negative charge on GMB: Selective proteinuria with loss of albumin and NOT globulins. Ex. minimal change disease (lipoid nephrosis) 

• Protein < 2g/24 hrs
• Defect in proximal tubule reabsorption of LMW proteins (amino acids at normal filter loads)
• Heavy metal poisoning (lad and mercury poisoning)
• Fanconi syndrome: Inability to reabsorb glucose, amino acids, uric acid, phosphate, and bicarbonate
• Hartnup disease: Defects in reabsorption of neutral amino acids (tryptophan) in the GI tract and kidneys  

Serum Blood Urea Nitrogen

BUN

• Normal BUN is 7-18 mg/dL
• End-product of amino acid and pyrimidine metabolism
• Produced by the liver urea cycle
• Filtered at the kidneys
• Partly reabsorbed in the proximal tubule
• Amount reabsorbed is flow dependent
• Decreased glomerular filtration rate: More reabsorbed
• Increased glomerular filtration rate: Less reabsorbed  
• Extrarenal loss with very high serum concentrations
• Serum levels depend on the following
• GFR
• Protein content in the diet
• Proximal tubul reabsorption
• Functional status of the urea cycle

• Decreased Cardiac Output
• CHF, shock
• ↓Cardiac Output → ↓GFR → ↑ Proximal tubule reabsorption of urea → ↑ serum BUN
• Increased Protein intake
• High protein diet, blood in GI tract
• ↑ Amino acid degradation → ↑ serum BUN
• Increased tissue catabolism
• 3rd degree burns, postoperative state
•  ↓GFR → ↑ serum BUN
• Acute or Chronic renal failure
• Acute tubular necrosis, diabetic glomerulopathy
• ↓GFR → ↑ serum BUN
• Postrenal disease
• Urinary tract obstruction (urinary stones, BPH)
• ↓GFR back diffusion of urea  → ↑ serum BUN

• Increased plasma volume:
• Normal Pregnancy, SIADH
• ↑ Plasma Volume → ↑ GFR → ↓ serum BUN
• Decreased Urea Synthesis:
• Cirrhosis, Reye Syndrome, Fulminant Liver Failure
• Dysfuntional urea cycle → ↓ serum BUN 
• Decreased Protein Intake
• Kwashiorkor (↑  CHO is protein sparer), starvation gluconeogenesis in kidneys
• ↓ Amino acid degradtion → ↓ serum BUN

• Normal serum creatinine is 0.6-1.2 mg/dL
• Metabolic end product of creatine in muscle
• Creatine binds phosphate in muscle for ATP synthesis
• Creatinine is filtered in the kidneys and not reabsorbed or secreted
• Excellent metabolite for renal clearance testing
• Serum concentration varies with age and muscle mass
• Increased with age, decreased in muscle wasting
• Increase in serum BUN and creatinine is called azotemia
• Causes of increased and decreased serum creatinine are similar to those of BUN  

• Normal ratio is 15
• Creatinine is filtered and is not reabsorbed or secreted
• Urea is filtered and partly reabsorbed in the proximal tubule
• BUN:Cr ratio depends on changes at several time
• Before the kidneys (prerenal)
• Within the kidneys parenchyma (renal)
• After the kidneys (postrenal)
• Azotemia refers to an increase in serum BUN and creatinine
• Prerenal azotemia
• Caused by a decreased in CO
• Hypoperfusion of the kidneys decreased GFR
• There is no intrinsic renal parenchymal disease
• Serum BUN:Cr > 15
• Decreased GFR causes creatinine to back up in the blood
• Ratio remains unchanged because of proportionate increase
• After filtration proportionately more urea is reabsorbed back into the blood due to the decreased flow rate
• All of the creatinine is excreted in the urine  
• Addition of proportionately more urea to the blood increases the ratio to > 15
• Ex. BUN 80 mg/dL, creatinine is 4 mg/dL so BUN:Cr is 20
• Renal azotemia (uremia)
• Caused by parenchymal damage to the kidneys
• Ex. Acute tubular necrosis, chronic renal failure
• Serum BUN: Cr ratio is ≤ 15
• Decreased GFR causes creatinine and urea to back up in the blood; increased extrarenal loss of urea
• Ratio is already < 15 due to extrarenal loss or urea
• After filtration, both urea and creatinine are lost in the urine
• Proximal tubule cells are sloughed off in renal failure
• Serum BUN:Cr ratio remains ≤ 15
• Postrenal Azotemia
• Caused by urinary tract obstruction below the kidneys
• No intrinsic parenchymal disease
• Prostate hyperplasia, blockage of ureters by stones/cancer
• Serum BUN:Cr ratio > 15
• Obstruction to urine flow decreases the GFR
• Backup of urea and creatinine in the blood
• Proportionate increase at this point: ratio unchanged
• Increased tubular pressure cause back-diffusion of urea (not creatinine) into blood
• Disproportionate increase in urea increases ratio > 15
• Presistent obstruction damages tubular epithelium causing renal azotemia (ratio ≤ 15)

• Normal Pregnancy:
• Normal increase in plasma volume causes in increase in GFR leading to an increase in creatinine clearance (CCr) 
• Highest at the end of the first trimester
• Early Diabetic Glomerulopathy
• Efferent arterioles becomes constricted due to hyaline arterioclerosis  causing an increase in the GFR and CCr
• Increased GFR damages the glomerulus (hyperfiltration injury)

• Elderly people:
• GFR normally decreases with age causing a corresponding decrease in the CCr
• Danger when using nephrotoxic drugs
• Acute and Chronic Renal Disease
• ARF due to acute tubular necrosis
• CFR due to diabetic glomerulopathy

• Renal Cortex receives (90%) of the blood supply
• Renal Medulla is relatively ischemic due to reduced blood supply
• Renal vessels are end-arteries
• No collateral circulation
• Occlusion of any branch of a renal artery produces infarction
• Afferent arterioles
• Contain Juxtaglomerular aparatus
• Produced renin
•  Blood flow is controled by renal-derived PGE₂ (vasodilator of afferent arteriole)
• Direct blood into the glomerular capillaries
• Efferent arterioles
• Drain the glomerular capillaries
• Blood flow controlled by ATII (vasoconstrictor)
• Eventually become the peritubular capillaries
• NSAIDS inhibit production PGE₂ therefore intrarenal blood flow is controlled by the efferent arterioles whose blood flow is maintained by ATII, a vasoconstrictor. This increases the risk of ischemic damage to the medulla.

• Glomerular capillaries contain fenestrated epithelium
• Holes in the endothelial surface are important in the filtration process
• Glomerular basement membrane (GBM)
• Composed of Type IV collagen
• Size and charge are the priamry determinants of protein filtration
•  Heparan sulfate produces the negative charge of the GMB
• Cationic proteins of low molecular weight (LMW) are permeable
• Albumin has a strong negative charge and it not permeable
• Loss of the negative charge causes loss albumin in the urine
• Called selective proteinuri (minimal change disease)
• GBM is permeable to water and LWM (<70,000 daltons) proteins (amino acids)
• Causes of GBM thickening
• Deposition of immunocomplexes
• Ex. Membranous glomerulopathy
• Increased synthesis of type IV collagen
• Diabetes mellitus
• Visceral Epitelial cells (VEC)
• Primarily responsible for production of GBM
• Contain podocytes (foot like processes) and slit pores between the podocytes
• Serve as a distal barrier for preventing proetin loss in urine
• Fusion of the podocytes is present in any cause of the nephrotic syndrome
• Mesangial Cells
• Support the glomerular capillaries
• Can release inflammatory mediators and proliferate
• IgA glomerulopathy has mesangial immunocomplex deposits
• Parietal epithelial cells
• Lining cells of Bowman's capsule
• Proliferation causes "crescents" that encroach upon and destroy te glomerulus

• Conjoined kidneys usually connected at the lower pole
• MC congenital renal anomaly
• Kidney is abnormally located in the lower abdomen
• Horseshoe kidney gets caught on the infereior mesenteric artery root during its ascent from the pelvis to the abdomen
• Increased incidence wiht Turners Syndrome
• Danger of stone formation and infection  

• Absent kidney formation
• May be unilateral or bilateral
• Unilateral agenesis leads to hypertrophy of the existing kidney
• Hyperfiltration increases risk of renal failure later in life
• Bilateral agenesis leads to oligohydramnios with lung hypoplasia, flat face with low set easrs, and developmental defects of the extremities (Potter sequence)
•  Incompatible of life

• Noninherited congenital malformation of the renal parenchyma
• Enlarged, irregular, cystic, unilateral flank mass
• Usually unilateral but when bilateral must be distniquished from inherited polycystic kidney disease
• MC cystic diease in children  

Juvenile Polycystic Kidney Disease

• Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla
• AR
• Newborns may present with Potter sequence
• Enlarged kidneys at birth- most serious types are incomptable with life  
• Associated with congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts
• Maternal oligohydraminos (decreased amniotic fluid)

• AD
• Presents in young adults as hypertension due to increased renin, hematuria, and worsening renal failure
• Due to mutation in APKD1 or APKD2 gene
• Cysts develop over time
• Associated with berry aneurysm, hepatic cysts, and mitral valve prolapse  

• MCC is renal dialysis
• Tubules are obstructed by interstitial fibrosis or oxalate crystals
• Small risk for developing renal cell carcinoma  

• MC adult renal cysts
• Derived from tubular obstruction
• May produce hematuria
• Requires needle aspiration to distniguish it from renal cell carcinoma  

• AD according to Pathoma- Goljan says there is no inheritance pattern. Online it seems as if it is AD
• Cysts in the medullary collecting ducts
•  Parenchymal fibrosis results in shruken kidneys and worsening renal failure
• Recurrent UTI's, hematuria, and renal stones are complications

• Acute, severe disease in renal function
• Develops within days
• Hallmark is azotemia (Increased BUN and Increased Creatinine) often with oliguria
• Divided into preranal, postrenal and intrarenal azotemia  

• Injury and necrosis of tubular epithelial cells
• MCC of acute renal failure (intrarenal azotemia)
• Necrotic cells plug tubules, obstruction plugs GFR
• Brown granular casts are seen in the urine
• Dysfunctional tubular epithelium results in decreased reabsorption of BUN
• BUN:Cr < 15
• Decreased reabsorption of sodium
• Inability to concentrate urine (urine osm < 500 mOsm/kg)
• Etiology may be ischemic or nephrotoxic
• Ischemia-Decreased blood supply results in necrosis of tubules
• Often preceded by prerenal azotemia
• Proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage
• Nephrotoxic- Toxic agents result in necrosis of tubules
• Proximal tubule is particularly susceptible
• Causes include aminoglycosides (MC), heavy metals (lead), myogloburia (crush injury to muscle), radiocontrast dye, and urate (tumor lysis syndrome)
• Hydration and allopurinol are used prior to initiaton of chemotherapy to decrease the risk of urate-incduced acute tubular necrosis
• Oliguria with brown, granular casts
• Elevated BUN and Creatinine
• Hyperkalemia (due to decreased renal excretion) with metabolic acidosis
• Reversible but often requires supportive dialysis since electrolyte imbalances can be fatal
• Oliguria can persist for 2-3 weeks before recovery
• Tubular cells (stable cells) take time to reenter the cell cycle and regenerate  

• Drug induced hypersensitivity involving the interstitium and tubules results in acute renal failure (intrarenal azotemia)
• Causes include NSAIDs, penicillin, and diuretics
• Presents as oliguria, fever and rash days to weeks after starting a drug 
• Eosinophils may be seen in urine
• Resolved with cessation of drugs
• May Progress to papillary necrosis

• Necrosis of renal papillae
• Presents with gross hematuria and flank pain
• Causes include:
• Chronic analgesic abuse (long tern phenacetin or asprin use) 
• Diabetes mellitus
• Sickle cell trait or disease
• Severe acute pyelonephritis

• Glomerular disorders characterized by proteinuria (>3.5 g/day)
• Hypertension may be present in some types
• Hyoalbuminemia-pitting edema, due to Na retention
• Hypogammaglobulinemia- increased risk of infection (S. pneumoniae) due to loss of γ-globulins in urine
• Hypercoagulable state-due to loss of antithrombin III potential for renal vein thrombosis
• Hyperlipidemia and hyperholesterolemia-may result in fatty casts in the urine
• Glomerular injury is due to cytokines not neutrophils
• Cytokines destroy the (-) charge of GBM

Minimal Change Disease

MCD

• Most common causes nephrotic syndrome in children
• Girls > boys
• Usually idiopathic but may be associated with Hodgkins lymphoma
• Normal glomeruli on H&E stain
• Lipid may be seen in proximal tubule cells
• Fusion of Podocytes
• No immune deposits
• Negative immunofluorescence
• Selective proteinuria (loss of albumin but no immunoglobulin)
• (+) fat stains in glomerulus and tubules
• Often preceded by respiratory infectio nor routine immunization
• Usually normotensive
• Chronic renal failure is rare
• Excellent response to steroids (damage is mediated by cytokines from T cells)  

• MCC of nephrotic syndrome in adults (Hispanics and African Americans)
• Usually idiopathic, may be associated with HIV, heroin use, and sickle cell disease
• Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis on H&E stain
• Visceral epithelial cells damaged
• Effacement of foot processes on EM
• No immune complex deposits
• Negative immunofluorescence  
• Hypertensio nearly
• Poor response to steriods
• Porgress to chronic renal failure
• Poor Prognosis

• MCC of nephrotic syndrome in Caucasian adults
• Usualy idiopathic may be associated with HBV, HCV, solid tumors SLE, or drugs
• Diffuse thick glomerular basement membrane on H&E
• Due to immune complex deposition, granular immunofluorescence, suepithelial deposits with spike and dome appearance on EM
• Poor response to steroids
• Progress to chronic renal failure

• Thick glomerular basement membrane on H&E
• Tram Track appearnce due to splitting of the Glomerular basement membrane by ingrowth ofthe mesangium
• Type I:
• Subendothelial
• MC association wiht HBV but also associated with HCV
• Subendothelial immunocomplexes with granular immunofluorescence
• Immunocomplexes activate classical and alternative compliment pathways
• Hyper tension
• Type II: 
• Dense deposit disease
• Intramembranous
• Associated with C3 nephritic factor (autoantibody that stabalize C3 convertase leading to overactivation of complement, inflammation, and low levels of circulating C3)
• Hypertension
• Hematuria
• Poor response to steroids
• Progresses to chronic renal failure

• High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting in hyaline arteriolosclerosis
• Glomerular efferent arteriole is more affected than the afferent arteriole leading to high glomerular filtration pressure
• Eventually progresses to nephrotic syndrome
•  Characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules
• ACE inhibitors slow progression of hypertension induced damage

• Kidney is the MC involved organ in systemic amyloidosis
• Amyloid deposits in the mesangium resulting in nephrotic syndrome
• Characterized by apple-green birefringence under polarized light after staining with congored  

• Glomerular disorders characterized by glomerular inflamamtion and bleeding
• Limited proteinuria < 3.5 g/day
• Oliguria and azotemia, BUN:Cr > 15 
• Salt retention with periorbital edema and hypertension
• RBC casts and hematuria (dysmorphic RBCs) in urine
• Key Finding
• Biopsy reveals hypercellular inflammed glomeruli
• Immune-complex deposition activation complement
• C5a attracts neutrophils which mediate damage

• Nephritic syndrome that arises after Group A Streptococcal infection
• Skin or Pharynx
• Occurs with nephrogenic stains that carry the M protein virulence factor
• May occur after infection as hematuria, olguria, hypertension, and perioribital edema (due to Na retention not hypoalbuminemia)
• Usually seen in children but can occur in adults
• Hypercellular, inflamed glomeruli on H&E stain
• Mediated by immune complex deposition, granular immunofluorescence
• Subepithelial "humps" on EM
• Treatment is supportive:
• Children (1%) rarely progress to renal failure
• Some adults (25%) develop rapidly progressive glomerulonephritis

• Immunocomplex deposits with granular immunofluorescence
• Anti-DNA immune complexes activate classical complement pathway
• "wire looping" of capillaries
• Neutrophils infiltration with hyaline throbi in capillary lumens
• Evolves to CRF
• MCC of death in SLE
• Treatment is corticosteroids and cyclophosphamide  

• Nephritic syndrome that progresses to renal failure in weeks to months
• Characterized by crescents in Bowman space of glomeruli on H&E stains
• Crescents are comprised of fibrin and macrophages
• Linear (anti-basement membrane antibody)
• Goodpasture syndrome
• Antibody against collagen in glomerular and aveolar basement membranes.
• Presents as hematuria and hemoptysis
• Classically in young adult males
• Granular (Immune Complex Deposition)
• Diffuse Proliferative Glomerulonephritis
• Due to diffuse antigen-antibody complexes depostion
• Usually sub-endothelial
• Most common type of renal disease in SLE
• Negative IF (pauci-immune)
• Wegener Granulomatosis-ass with c-ANCA
• Microscopic polyangitis-p-ANCA
• Churg-Strauss syndrome-p-ANCA
• Granulomatous inflammtion, Eosinophilia, Asthma distniguish Churg-strauss from microscopic polyangitis

IgA nephropathy

Bergers Disease

• IgA immune complex depostion in mesangium of glomeruli
• MC nephropahty worldwide
• Presents during childhoos as episodic gross or microscopic hematuria with RBC casts, usually following a mucosal infection
• Increased IgA production and decreased IgA clearance
• IgA immune complex deposition in the mesangium is seen in immunofluorescence  
• May slowly progress to renal failure  

• Inherited defect in type IV collagen
• MC X-linked
• Results in thinning and splitting of the glomerular basement membrane
• Presents as isolated hematuria, sensory hearing loss, and ocular disturbances  

• Infection of urethra, bladder, or kidney
• MC arises due to ascending infection 
• F>M
• Risk factors include: sexual intercourse, urinary stasis, and catheters  

• Infection of the bladder
• Presents as dysuria, urinary frequency, urgency, and suprapubic pain
• Systemic signs such as fever are usally absent
• UA: Cloudy urine with > 10 WBCs/high power field
• Dipstick: Positive leukocyte esterase and nitrites (bacteria converts nitrates to nitrites  
• Culture:Greater than 100,000 colonies forming units
• Gold Standard
• E. Coli (80%)
• S. saprophytics: increased incidence in young, sexually active women
• Klebsiella pneumoniae
• P. mirabilis: Urine with ammonia scent
• E. faecalis
• Sterile pyuria is the presence of pyuria wtih a negative urine culture
• Suggests urethritis due to C. trachomatis or N. gonorrhoeae
• Dominant presenting sign of urethritis is dysuria

• Infection of the kidney
• Usually due to ascending infection: increased risk with vesicoureteral reflux 
• Presents with fever, flank pain, WBC casts, and leukocytosis in addition to symptoms of cystitis
• MC pathogens are:
• E. coli (90%)
• Klebsiella species
• E. faecalis

• Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
• Due to vesicouretal reflux (children) or obstruction (BPH or cervical carcinoma)
• Leads to cortial  scarring with blunted calyces scaring at upper and lower poles is characteristic vesicoureteral reflux
• Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles
• Waxy casts may be seen in urine

• Precipitation of a urinary solute as a stone
• Risk Factors include: 
• High concentration of solute in the urinary filtrate
• low urine volume
• Presents as colicky pain with hematuria and unilateral flank tenderness
• Stone is usually passed within hours, if not surgical intervention may be required

• End-stage kidney failure:
• May result from glomerular, tubular, inflammatory, or vascular insults
• MCC are diabetes mellitus, hypertension, and glomerular disease
• Uremia-increased nitrogenous waste products in blood (azotemia) results in nausea, anorexia, pericarditis, platlet dysfunction, encephalopathy with asterixis, and deposition or urea crystals in skin
• Salt and water retention with resultant hypertension
• Hyperkalemia with metabolic acidosis  
• Anemia due to decreased erythropoietin production by renal peritubular interstitial cells
• Hypocalcemia due to decreased 1-α-hydroxylation of vitamin D by proximal renal tubule cells and hyperphosphatemia
• Renal osteodystrophy due secondary hyperparathyroidism, osteomalacia, and osteoporosis
• Treatment involves dialysis or renal transplant
• Cysts often develop with shrunken end-stage kidneys during dialysis increasing risk for renal cell carcinoma

• Hamartoma comprised of blood vessels, smooth vessels, and adipose tissue
• Increased frequency in tuberous sclerosis

• Malignant epithelial tumor arising from kidney tubules
• Presents with classic triad of hematuria, palpable mass, and flank pain
• All three symptoms rarely occur together
• Hematuria is the most common symptom
• Fever, weight loss, or paraneoplastic syndrome (EPO, renin, PTHrP, or ACTH) may also be present
• Rarely may present with left-sided varicocele
• Involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein leading to varicocele
• Right spermatic vein drains directly into the IVC, hence right sided varicocele is not seen
• Gross exam reveals a yellow mass, microscopically the MC variant exhibits clear cyoplasm (clear cell type)
• Pathogenesis involves loss of VHI (3p) tumor supressor gene which leads increasd IGF-1 (promotes growth) and increased HIF transcription factor  (increased VEGF and PDGF)
• Sporadic Tumors classically arise in adult males (avg age is 60) as a single tumor in the upper pole of the kidney
• Major risk factor for sporadic tumors is cigarette smoke
• Hereditary Tumors arise in younger adults and are often bilateral.
• Von Hippel-Lindau disease is an AD disorder associated with inactivation of the VHL gene leading to increased risk for hemangioblastoma  of the cerebellum and renal cell carcinoma
• Staging:
• T: Based on size and involvement of the renal vein (occurs commonly and increases risk of hematogenous spread to the lungs and bone)
• N: Spread to retroperitoneal lymph nodes

• Malignant kidney tumor comprised of balstema (immature kidney mesenchyme), primitive glomeruli, tubules, and stromal cells
• Most common malignant renal tumor in children
• Avg age is 3
• Presents as large, unilateral flank mass with hematuria and hypertension (due to renin secretion)
• Associated with WT1 mutation, chromosome 11 p13
• WAGR syndrome:
• Wilms tumor
• Aniridia-lack or iris
• Genital abnormalities
• Mental and motor retardation
• Beckwith-Wiedemann syndrome:
• Wilms tumor
• Neonatal hypoglycemia
• Muscular hemihypertrophy
• Organomegaly (including tongue)  

• Malignant tumor arising from the urothelial lining of the renal pelivs, ureter, bladder, or urethra
• Most common type of lower urinary tract cancer
• Usually arises in the bladder
• Major risk factor is cigarette smoke
• Minor risk factors: naphthylamine, dyes, and long-term cyclophosphamide or phenacetin use
• Generally seen in older adults
• Classically presents with painless hematuria
• Arises via two distnict pathways
• Flat-Develops as a high grade flat tumor and then invades.  Associated with early p53 mutations
• Papillary- Develops as a low grade papillary tumor that progresses to a high-grade papillary and then invades. Not associated with early p53 mutations
• Tumors are often multifocal and recur (field detect)  

• Malignant proliferation of SC usually involving the bladder
• Arises is a background of squamous metaplasia (normal bladder surface is not lined by squamous epithelium)
• Risk factors
• Include chronic cystitis (older woman)
• Schistosoma hematobium infection (Egyptian male)
•  Long-standing nephrolithiasis

• Malignant proliferation of glands usually involving the bladder
• Arises from a urachal remnant (tumor develops at the dome of the bladder), cystitis, glandularis, or exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls)