1. Renal Agenesis

• Due to:
  
  • Lack of metanephric primordial
  • Failure of ureteric bud formation
  • Failure of contact of ureteric bud and metanephros
• Bilateral renal agenesis:
  
  • Incompatible with life, rare
  • Male:female = 25.1:1
  • Stillborn
• Unilateral renal agenesis:
  
  • Male: female = 2:1
  • Opp kidney usu enlarged due to compensatory hypertrophy
  • Some eventually develop progressive glomerulosclerosis in the remaining kidney due to adaptive changes in hypertrophied nephrons

4. Horseshoe kidney

• Fusion of lower (90%) or upper (10%) poles
• 1 in 500 to 1 in 1000 incidence
• Complications - Urolithiasis

4. Microscopic Hematuria

• Characteristics:
  
  • Hematuria not visible to the naked eye (detectable only by urinanalysis)
  • Some degree of proteinuria (below nephrotic range)
  • No change in urine volume
  • No HTN
  • No azotemia
• Causes:
  
  • Usually milder forms of proliferative GNs
  • IgA nephropathy
  • Thin basement membrane syndrome
• Clinical Features:
  
  • Always exclude lower urinary tract causes of hematuria in differential diagnosis (Trauma, tumour, infections, stones)

5. Chronic Renal Failure

• Stage 1: Diminished renal reserve
  
  • GFR = 50% of normal
  • Normal serum creatinine and blood urea nitrogen
  • Asymptomatic
• Stage 2: Renal Insufficiency
  
  • GFR = 20-50% of normal
  • Azotemia appears
  • Anemia, HTN, polyuria, nocturia
• Stage 3: Chronic renal failure
  
  • GFR < 20-25% of normal
  • Overt uremia (azotemia + GI, neurological and cardiovascular complications)
  • Edema, metabolic acidosis, hyperkalemia
• Stage 4: End-stage renal diseases
  
  • GFR < 5% normal
• Characteristics:
  
  • Change in urine volume:
    
    • Initial polyuria as tubules cannot concentrate glomerular filtrate
    • Terminal oliguria when little functioning nephrons are left
  • Consequences of decreased filtration
    
    • HTN and edema
    • Uremia
    • Metabolic derangements (hyperkalemia, metabolic acidosis)
  • Decreased endocrine functions of kidney:
    
    • Anemia (decreased EPO production)
    • Secondary hyperparathyroidism (due to decreased vit D activation by renal tubules leading to hypocalcemia)
• Causes of chronic renal failure:
  
  • Chronic glomerulonephritis
  • Tubulointerstitial diseases
  • Chronic pyelonephritis

Pathogenesis of Glomerular Injury

• Antibody-Mediated Mechanisms
  
  • In-situ formation of immune complexes
    
    • Against native antigen - Goodpasture disease
    • Against planted antigen that localises in glomerulus - HBV, HCV, Streptococcus, syphillis, malaria
  • Circulating immune complex deposition in glomerulus eg. Lupus nephritis
  • Anti-Neutrophil Cytoplasmic Antibodies (ANCA) - interacts with neutrophils within glomeruli
• Other pathogenic factors:
  
  • Activation of alternative complement pathway (no Abs required)
    
    • Seen in membranoproliferative glomerulonephritis type II
  • Platelet
    
    • Aggregate in glomeruli during immune-mediated injury, can subsequently release eicosanoids and growth factors which promotes inflammation and cellular proliferation
  • Coagulation system
    
    • Leakage of fibrin through damaged GBM into Bowman's space induces proliferation of the parietal layer of Bowman's capsule (forms crescents)
  • Cytokines
    
    • Angiotensin
    • Podocyte-released cytokines

Minimal Change Disease

• Nephrotic syndrome:
  
  • Postulated immune-mediated podocyte injury
  • Usually selective proteinuria (mostly albumin)
  • Most common cause of childhood nephrotic syndrome (good prognosis, typically responsive to steroid Tx)
• Renal Biopsy:
  
  • LM - normal
  • IF - no immune deposits
  • EM - fusion of foot processes and occasionally detachment from basement membrane

Focal Segmental Glomerulosclerosis

• Nephrotic syndrome:
  
  • Due to podocyte injury with loss of podocytes
  • Non-selective proteinuria
  • Poor response to steroid Tx
  • Many progress to chronic renal failure
• Renal Biopsy:
  
  • LM - Focal segmental glomerular sclerosis and hyalinosis
  • IF - Sclerotic lesions stain with IgM and C3
  • EM - effacement of podocyte foot processes

Membranous Glomerulopathy

• Nephrotic syndrome:
  
  • Idiopathic primary cause, secondary cause (10-20%)
  • Non-selective proteinuria
  • Most common cause of nephrotic syndrome in adults (resistant to steroid Tx)
  • Unpredictable clinical behaviour (less than half progress to renal failure)
• Renal Biopsy:
  
  • LM - Diffuse basement membrane thickening. Spikes or string of pearl appearance with silver stain (due to protrusions of growth of GBM between sub epithelial deposits)
  • IF - Granular IgG and C3
  • EM - Subepithelial deposits

Membranoproliferative Glomerulonephritis

• Nephrotic/Nephritic
• Asc with decreased serum C3
• LM - Proliferative changes involving mesangium + thickening of basement membrane

IgA Nephropathy (Berger Disease)

• Most common cause of glomerulonephritis
• Asc with pharyngitis
• Clinical Presentation:
  
  • Microscopic proteinuria with hematuria
  • Clinical course waxes and wanes, often asc with URTI
  • Less than half progress to renal failure
• Renal Biopsy
  
  • LM - Focal mesangial proliferation
  • IF - IgA in mesangium
  • EM - Mesangial dense deposits

Amyloidosis

• In the kidney, usu occurs in patients with:
  
  • Plasma cell dyscrasia (AL amyloid)
  • Chronic inflammatory diseases or neoplasms (AA amyloid)
• Clinical presentation:
  
  • Proteinuria, often nephrotic range
• Renal Biopsy:
  
  • LM -
    
    • Extracellular accumulation of fibrillary proteins (with Congo red stain)
    • Apple green birefringence under polarised light microscopy
  • IF - No immune complex deposition
  • EM - variable
    
    

Hypertensive Nephrosclerosis

• May present with proteinuria and/or impaired renal function
• Proteinuria usu low grade, but if secondary FSGS develops, may be in nephrotic range
• Arterioles show hyalinosis +/- muscular thickening
• Arteries show arteriosclerosis
• In malignant HTN, there may be fibrinoid necrosis of arterioles and glomeruli and mucoid intimal thickening of arteries

Diabetic Nephropathy

• AGEs in long-standing hyperglycaemia
• Clinical presentation:
  
  • Proteinuria - often ends up in chronic renal failure
• Glomeruli:
  
  • GMB thickening (seen on EM)
  • Mesangial widening (increase in matrix and cells) which becomes nodular as disease progresses (Kimmelstiel-Wilson nodules)
  • Hyalinosis lesions
  • Microaneurysms of glomerular capillary loops
  • Eventually, glomerular sclerosis
• Tubules:
  
  • Thickened tubular basement membranes
  • Tubular atrophy
• Interstitium:
  
  • Interstitial fibrosis as the disease progresses
• Vessels:
  
  • Arteriolar hyalinosis
  • Arteriosclerosis (often asc with HTN)

• Other findings - predispose to pyelonephritis

  
  

• Renal Biopsy:

  
  
  • LM - Kimmelstiel-Wilson lesions (nodular glomerulosclerosis)
  • IF - No immune complex deposition
  • EM - Increased basement membrane thickness, increase in mesangial matrix

Xanthogranulomatous Pyelonephritis

• Rare form of chronic pyelonephritis caused by Proteus spp. often in the setting of urinary tract infection
• Mimics renal carcinoma
• Gross:
  
  • Enlarged kidney, replaced by yellow nodules with firm greyish white tissue
• Histologically:
  
  • Macrophages with vacuolated cytoplasm (foam cells)
  • Giant cells, lymphocytes, plasma cells

Renal Tuberculosis

• Due to hematogenous spread from pulmonary TB (5% of cases)
• Gross:
  
  • Initial: Lesions in the medulla and papillae
  • Later on: Caseous foci enlarged in medulla and cortex to destroy the entire kidney
• Histologically:
  
  • Caseating granulomatous inflammation
• Pathological effects and complications:
  
  • Renal destruction and renal failure
  • Spread to ureter with subsequent fibrosis and obstruction
  • Spread to bladder (TB cystitis) and epididymis

Benign Nephrosclerosis

• Renal pathology asc with sclerosis of renal arterioles and small arteries, due to longstanding or poorly controlled diabetes
• Morphology:
  
  • Arteries: atherosclerosis
  • Arterioles: hyaline arteriolosclerosis
  • Patchy ischemic atrophy (interstitial fibrosis, glomerular changes, tubular atrophy)
• Pathological effects and complications:
  
  • Proteinuria (may be nephrotic range)
  • Mild reduction in GFR

Accelerated Nephrosclerosis

• Renal pathology due to malignant hypertension
• Initiating stimuli results in increased renal vascular permeability and increased release of PDGF
  
  • Causes fibrinoid necrosis and hyper plastic arteriolosclerosis
• Changes in arterioles narrow lumen of afferent arteriole
  
  • Decrease GFR and salt delivery to distal tubules - triggers renin production - in turn constricts renal vessels (Vicious cycle)
• Morphology:
  
  • Hyperplastic arteriolosclerosis (onion-skin appearance)
  • Fibrinoid necrosis
• Pathological Effects and Complications:
  
  • Renal failure (after initial proteinuria and hematuria)
  • Associated lesions in malignant HTN:
    
    • Papilledema
    • Retinal hemorrhages
    • Encephalopathy
      

Anatomical Changes:

• Hydroureter
  
  • Dilated ureter upstream of obstruction
• Hydronephrosis
  
  • Dilation of renal pelvis and calyces with progressive enlargement of the kidney with parenchymal atrophy due to ops of urine outflow
  • Unilateral hydronephrosis typically clinically silent - other kidney can compensate
  • Bilateral hydronephrosis
    
    • Oliguria, anuria
    • After relief of obstruction, post-obstructive diuresis occurs
• Pyonephrosis
  
  • Infected hydronephrosis with frank pus in the dilated calyces and pelvis

Urolithiasis

• Primary causes:
  
  • Supersaturation of stone components
  • Low urine volume
• Secondary causes:
  
  • UTI (crystalline material able to encrust on a necrosis focus on the mucosa)
  • Indwelling catheter or foreign body in the bladder
  • Vit A deficiency producing squamous metaplasia of the upper urinary tract mucosa
  • Altered urinary pH
    
    • Low pH - predispose to uric acid stones
    • High pH - predispose to triple stones
• Calcium stones (65-70%)
  
  • Composed of calcium oxalate +/- calcium phosphate
  • Radio-opaque
  • Predisposing factors:
    
    • Hypercalciuria (hyperparathyroidism, diffuse bone disease, Vit D intoxication, milk-alkali syndrome, sarcoidosis, renal tubular acidosis of Cushing syndrome, idiopathic)
    • Hyperoxaluria (hereditary, vegetarians due to high oxalate content in diet)
    • Hypocitraturia (asc with acidosis and chronic diarrhoea)
    • Hyperuricosuria (promotes nucleation of calcium oxalate)
• Magnesium ammonium phosphate stones (15%)
  
  • Aka triple stones or struvite stones
  • Predisposing factors:
    
    • Typically follows infection by urea-splitting bacteria (eg. Proteus) which converts urea to ammonia --> raise urine pH which promote precipitation
    • Such infections usu give rise to large stones/Staghorn calculi (lodged in renal pelvis) due to high urea content in urine
• Uric acid stones (6%)
  
  • Radiolucent
  • Predisposing factors:
    
    • Hyperuricemia (gout, leukemia)
    • Low urinary pH (<5.5)
• Cystine stones (3%)
  
  • Predisposing factors:
    
    • AR genetic defect in the transport of dibasic amino acids (cystine, ornithine, arginine, lysine)
• Indinavir stones
• Pathological effects and complications:
  
  • Urinary tract obs
  • Ulceration, bleeding and fistula formation
  • Urinary colic
• Treatment:
  
  • Extracorporeal shockwave lithotripsy (ESWL)
  • Percutaneous nephrolithotripsy (PCNL)
  • Ureteroscopic lithotripsy

2. Renal Cell Carcinoma

• Malignant tumour arising from the renal tubular epithelium
• Epidemiology:
  
  • Accounts for 85% of malignant renal tumours in adults
  • Accounts for 1% of all visceral cancers
  • Mostly occurs in the 6th and 7th decades of life
  • Male:female = 2:1
• Most common types of RCC:
  
  • 1. Clear cell RCC (70-80%)
    
    • Arises from proximal tubules
    • Gross:
      
      • Solitary, unilateral, with a circumscribed appearance
      • Yellowish cut surfaces with foci of necrosis and haemorrhage
      • Invasion of renal vein not uncommon
      • Tendency to metastasise widely, may be late
    • Histology:
      
      • Polygonal cells with clear cytoplasm
    • Delicate branching vasculature
    • Invasion of renal vein and its branches may be seen
  • 2. Papillary RCC (10-15%)
    
    • Arises from distal tubules
  • 3. Chromophobe RCC (5%)
    
    • Arises from the intercalated cells of collecting tubules
• Clinical Features:
  
  • Painless haematuria
  • Mass in flank
  • Fever due to necrosis
  • Costovertebral pain
  • Paraneoplastic syndromes (polycythaemia, HTN, hypercalcemia, Cushing syndrome, amyloidosis etc)

3. Urothelial Carcinoma

• Arises from the urothelium (transitional cell epithelium) lining the renal calyces, pelvis, ureter and bladder
• Patients are at risk of synchronous or subsequent urothelial tumours anywhere in the urothelial tract, as well as recurrent tumours
• Types:
  
  • Papillary urothelial carcinoma (non-invasive)
  • Invasive urothelial carcinoma - may arise from previously non-invasive papillary UC or from UC in-situ (flat, high grade dysplasia)
• Morphology:
  
  • Identical to urothelial carcinoma of the bladder
  • Exophytic mass
  • Usu asc with urothelial carcinoma of the ureter and bladder
• Clinical features:
  
  • Usually discovered early
    
    • Fragmentation causes noticeable haematuria
    • Blockage of urinary outflow gives rise to hydronephrosis and flank pain

4. Wilms Tumour (Nephroblastoma)

• Paediatric renal tumour
• Epidemiology:
  
  • Usually diagnosed between ages 2-5
  • Asc with congenital malformation syndromes:
    
    • WAGR sundrome, Denys-Drash syndrome, Beckwith-Wiedemann syndrome
• Gross:
  
  • Well circumscribed greyish soft mass
  • Begins in renal cortex and replaces entire kidney
• Histology:
  
  • Sheets of small blue cells (blastemal component)
  • Abortive tubular and glomeruloid structures (epithelial component)
  • Spindle-shaped cells (stromal component)
  • Heterogenous elements such as striated/smooth muscle and cartilage may be found
• Clinical features:
  
  • Large abdominal mass
  • Fever due to necrosis and haemorrhage
  • Haematogenous and lymphatic spread to lungs, liver, brain and lymph nodes
• Treatment:
  
  • Combination nephrectomy and chemotherapy
  • Generally good prognosis even for tumours which have spread beyond the kidney

Benign Prostate Hypertrophy/Nodular Hyperplasia

• Extremely common condition in men over age 50
• Pathogenesis:
  
  • Conversion of testosterone in prostate stromal cells into DHT by 5-alpha reductase (type 2)
  • DHT binds to androgen receptors in the epithelial and stromal cells --> induces the production of growth factors that increase growth rate, decrease death rate of these cells
  • Leads to progressive hyperplasia of the stromal and epithelial cells, forming nodules
  • Prostatic smooth muscle tone (mediated via alpha-1 adrenergic receptors) worsens the lower urinary tract obstruction
  • Most prominent in transitional zone - region surrounding prostatic urethra
• Complications:
  
  • Urinary tract obstruction due to compression of prostatic urethra, leading to:
    
    • Bladder distention and hypertrophy (yields a distended bladder with a trabeculated wall)
    • Bladder hypotonia, diverticulum
    • Hydronephrosis and hydroureter
  • UTI
    
    • Urolithiasis
    • Chronic kidney disease
• Treatment: Transurethral resection of the prostate (TURP)

Orchitis and Epididymitis

• Inflammation of the testes/epididymitis
• Tuberculosis
  
  • Begins in the epididymis, spreads to rest of testes
  • Typical caveating granulomas
• Mumps
  
  • Primarily cause inflammation and swelling of the parotid glands
  • Complication in post-pubertal males include orchitis and acute pancreatitis
• Gonorrhea
  
  • Typically cause orchitis as an extension from infection of the urethra, which first affects the epididymis
  • Produces frank abscesses
• Syphilis
  
  • Usually affects testes without affecting epididymis
  • May produce gummas

Seminomatous germ cell tumours

• Remain localised for a long time
• Very radiosensitive
• Spread by lymphatics to para-aortic nodes
• Examples:
  
  • Seminoma (commonest germ cell tumour, peak in 4th decade)

Non-seminomatous germ cell tumours (NSGCT)

• Metastasise relatively earlier
• Radioresistant
• Spreads via hematogenous route
• Examples:
  
  • Yolk sac tumour
    
    • Aka infantile embryonal carcinoma or endodermal sinus tumour
    • Most common testicular tumour in infants
    • Good prognosis
    • Usu occurs in mixed tumours when in adults
  • Choriocarcinoma
    
    • Highly malignant tumour
  • Teratoma
    
    • Contains a variety of mature and/or immature tissue types, most often from more than one germ layer
    • Common in females (benign), always malignant in males
    • May exist in combination with other germ cell tumours (mixed germ cell tumour)
  • Embryonic carcinoma
    
    • More aggressive than seminomas
    • Peak between ages 20-30

Mixed tumours:

• Seminoma + any NSGCT (one or more types)
• Teratoma + embryonal carcinoma
• Seminoma + embryonal carcinoma
• Teratoma + choriocarcinoma
• Other combinations