Chapter 12: Kidney and Urinary Tract Pathology

Question 1

Horseshoe kidney

Answer 1

Conjoined kidneys usually connected at the lower pole: most common congenital renal anomaly
Kidney is abnormally located in the lower abdomen; horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from teh pelvis to the abdomen.

Question 2

Renal agenesis

Answer 2

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 ears, and developmental defects of the extremities (Potter sequence), incompatible with life.

Question 3

Dysplastic kidney

Answer 3

Noninherited, congenital malformation of the renal parenchyma characterized by cysts and abnormal tissue (e.g. cartilage)
Usually unilateral; when bilateral, must be distinguished from inherited polycystic kidney disease.

Question 4

Polycystic Kidney Disease (PKD)

Answer 4

Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla.
Autosomal recessive form presents in infants as worsening renal failure and hypertension; newborns may present with Potter sequence.
- Associated with congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts.
Autosomal dominant form presents in young adults as hypertension (due to increased renin), hematuria, and worsening renal failure.
- Due to mutation in the APKD1 or APKD2 gene; cysts develop over time.
- Associated with berry aneurysm, hepatic cysts, and mitral valve prolaps.

Question 5

Medullary cystic kidney disease

Answer 5

Inherited (autosomal dominant) defect leding to cysts in the medullary collecting ducts.
Parenchymal fibrosis results in shrunken kidneys and worsening renal failure.

Question 6

Acute Renal Failure Basic Principles

Answer 6

Acute, severe decrease in renal function (develops within days)
Hallmark is azotemia (increased BU and creatinine, often with oliguria.
Divided into prerenal, postrenal, and intrarenal azotemia based on etiology

Question 7

Prerenal azotemia

Answer 7

Due to decreased blood flow to kidneys (e.g. cardiac failure); common cause of ARF.
Decreased blood flow results in decreased GFR, azotemia, and oliguria.
Reabsorption of fluid and BUN ensues (serum BUN:Cr ratio greater than 15) tubular function remains intact (fractional excretion of sodium less than 1% and urine osmolality greater than 500 mOsm/kg.

Question 8

Postrenal azotemia

Answer 8

Due to obstruction of urinary tract downstream from the kidney (e.g. ureters)
decreased outflow results in decreased GFR, azotemia, and oliguria.
During early stage of obstruction, increased tubular pressure “forces” BUN into the blood (serum BUN:Cr ratio greater than 15); tubular function remains intact (FENa less than 1% and urine osm greater than 500 mOsm/kg)
With long-standing obstruction, tubular damage ensues, resulting in decreased reabsorption of BUN (serum BUN:Cr ratio less than 15), decreased reabsorption of sodium (FENa greater than 2%) and inability to concentrate urine (urine osm less than 500 mOsm/kg)

Question 9

Acute tubular necrosis

Answer 9

Injury and necrosis of tubular epithelial cells; most common cause of acute renal failure.
Necrotic cells plug tubules; obstruction decreases GFR.
- brown, granular casts are seen in the urine.
Cysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN Cr ratio less than 15), decreased reabsorption of sodium (FENa greater than 2%) and inability to concentrate urine (urine osm less than 500 Osm/kg)

Question 10

Etiology of acute tubulular necrosis

Answer 10

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 (most common), heavy metals (e.g. lead), myoglobinuria (e.g. from crush injury to muscle), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, and urate (e.g. tumor lysis syndrome)
• Hydration and allopurinol are used prior to initation of chemothaerapy to decrease risk of urate-induced ATN.

Question 11

Clinical features of acute tubular necrosis

Answer 11

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 electrollyte imbalances can be fatal.
- oliguria can persist for 2-3 weeks before reovery; tubular cells (stable cells) take time to reenter the cell cycle and regenerate.

Question 12

Acute interstitial nehritis

Answer 12

Drug-induced hypersensitivity involving the interstitium and tubules.
Causes include NSAIDs, Penicillin, and diuretics
Presents as oliguria, fever, and rash days to weeks after starting a drug; eosinophils my be seen in urine.
Resolves with cessation of drug
May progess to renal papillary necrosis

Question 13

Renal papillary necrosis

Answer 13

Necrosis of renal papillae
Presents with gross hematuria and flank pain
Causes include
- chronic analgesic abuse (e.g. long-term phenacetin or aspirin use)
- diabetes mellitus
- sickle cell trait or disease
- severe acute pyelonephritis

Question 14

Nephrotic Syndrome Basic principles

Answer 14

Glomerular disorders characterized by proteinuria (greater than 3.5 g/day) resulting in

• hypoalbuminemia- pitting edema
• hypogammaglobulinemia- increased risk of infection
• hypercoagulable state- due to loss of antithrombin III
• hyperlipidemia and hypercholesterolemia - may result in fatty casts in urine

Question 15

Minimal change disease (MCD)

Answer 15

Most common cause of nephrotic syndrome in children
Usually idiopathic; may be associated with Hodgkin lymphoma
Normal glomeruli on H&E stain; lipid may be seen in proximal tubule cells
Effacement of food processes on electron microscopy
No immune complex deposits; negative immunofluorescence (IF)
Selective proteinuria (loss of albumin, but not immunoglobulin)
Excellent response to steroids (damage ismediated by cytokines from T cels)

Question 16

Focal Segmental Glomeruloscrlerosis

Answer 16

Most common cause of nephrotic syndrome in 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 glmerulus) sclerosis on H&E stain
Efffacement of foodt processes on EM
No immune complex deposits; negative IF
Poor response to steroids; progresses to chronic renal failure

Question 17

Membranoproliferative Glomerulonephritis

Answer 17

Thick glomerular basement membrane on H&E, often with “tram-track’ appearance
Due to immune complex deposition (granular IF)
Divided into two types based on location of deposits
- Type I- subendothelial associated with HBV and HCV
- Type II (dense deposit disease)- intramembranous; associated with C3 nephritic factor (autoantibody that stabilizes C3 convertase, leadint to overactivation of complement, inflammation, and low levels of circulating C3)
Poor response to steroids; progresses to chronic renal failure.

Question 18

Diabetes mellitus

Answer 18

High serum glucose leads to nonenzymatic glycosylation of the vascular basement membraen resulting in hyaline arteriolosclerosis.
Glomerular efferent arteriole is more affected than the afferent arteriole, leading to high flomerular filtration pressure.
- Hyperfiltration infury leads to microalbuminuria
Eventually proresses to nephrotic syndrome.
- Characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules.
ACE inhibitors slow progression of hyperfilatration-induced damage.

Question 19

Systemic amyloidosis

Answer 19

Kidney is the most commonly 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 Congo red.

Question 20

Nephritic syndrome Basic principles

Answer 20

Glomerular disorders characterized by glomerular inflammation and bleeding.

• limited proteinuria (less than 3.5 g/day)
• oliguria and azotemia
• Salt retention with periorbital edema and hypertension
• RBC casts and dysmorphic RBcs in urine

Biopsy reveals hypercellular, inflamed glomeruli.

Immune-complex deposition activates complement; C5a attracts neutrophils, which mediate damage.

Question 21

Post Streptococcal Glomerulonephritis

Answer 21

Nephritic syndrome that arises after group A beta-hemolytic streptococcal infetion of the skin (impetigo) or pharynx.

• Occurs with nephritogenic strains
• may occur after infection with nonstreptococcal organisms as well

Presents 2-3 weeks after infection as hematuria (cola-colored urine), oliguria, hypertension, and periorbital edema.
- usually seen in children, but may occur in adults.
Hypercellular, inflamed glomeruli on H&E
Mediated by imune complex deposition (granular IF); subepithelial ‘humps’ on EM
Treatment is supportive.
- Children rarely (1%) progress to renal fialure.
- some adults (25%) develop RPGN.

Question 22

Rapidly Progressive Glomerulonephritis

Answer 22

Nephritic syndrome that progresses to renal filure in weeks to months.
Characerized by crescents in Bowman space (of glomeruli) on H&E stain; crescents are comprised of fibrin and macrophages (not collagen!)
clinical picture and IF help resolve etiology

Question 23

IgA Nephropathy (Berger Disease)

Answer 23

IgA immune complex deposition in mesangium of glomeruli; most common nephropathy worldwide
Presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following mucosal infections (e.g. gastroenteritis)
- IgA production is increased during infection
IgA immune coplex deposition in the mesangium is seen on IF
May slowly progress to renal failure.

Question 24

Alport Syndrome

Answer 24

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