Renal Pathology

Question 1

Horseshoe Kidney

Answer 1

Connected at lower pole

Located in lower abdomen; Gets caught on inferior mesenteric artery

Question 2

Unilateral Renal Agenesis

Answer 2

Leads to hypertrophy of existing kidney; hyperfiltration leads to increased risk of renal failure later in life

Question 3

Bilateral Renal Agenesis

Answer 3

Leads to oligohydramnios (low amniotic fluid), flat face with low set ears, developmental defects in extremities, lung hypoplasia (potter sequence); incompatible with life

Question 4

Autosomal Recessive Polycystic Kidney Disease

Answer 4

Cysts in renal cortex and medulla; presents in infancy with worsening renal failure and hypertension in newborns; Associated with congenital hepatic fibrosis (leads to portal hypertension and hepatic cysts)

Question 5

Autosomal Dominant Polycystic Kidney Disease

Answer 5

Presents in young adults as hypertension (due to increased renin), hematuria, worsening renal failure
Due to mutations in the APKD1/APKD2 gene; Cysts develop over time
Associated with berry aneurysms, hepatic cysts and mitral valve prolapse

Question 6

Medullary Cystic Kidney Disease

Answer 6

Inherited defect leading to cysts in the medullary collecting ducts; Parenchymal fibrosis –> shrunken kidney and worsening renal failure

Question 7

Prerenal Azotemia

Answer 7

Due to decreased blood flow to kidneys –> decreased GFR, azotemia, oliguria
Reabsorption of fluid and BUN at all costs due to increased aldo/renin -
BUN:Cr ratio > 15
FENa 500 mOsm/kg

Question 8

Postrenal Azotemia

Answer 8

Due to obstruction of urinary tract downstream of kidneys
Decreased outflow results in decreased GFR, axotemia and oliguria
During early stage increased tubular pressure, forces BUN into the blood (serum BUN:Cr ratio >15), intact tubular function (FENa 500 mOsm/kg
With longstanding obstruction tubular damage ensues and get decreases reabsorption of BUN (BUN:Cr ratio 2%) and inability to concentrate urine (urine osm <500mOsm/kg)

Question 9

Acute Tubular Necrosis

Answer 9

necrosis of tubular epithelial cells; most common cause of intrarenal azotemia
Necrotic cells plug tubules and decrease GFR
Due to ischemia or nephrotoxic causes -
– Ischemic (proximal tubule and medullary thick ascending limb are particularly susceptible): preceded by prerenal azotemia
– Nephrotoxic (proximal tubule is particularly susceptible): aminoglycosides, heavy metals, myoglobinuria (from crush injury), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, urate (from tumor lysis syndrome)
Clinical Features:
- brown, granular casts in urine
- oliguria
- BUN:Cr < 15 (increased BUN and Cr)
- FENa >2%
- Urine osm < 500 mOsm/kg
- hyperkalemia with metabolic acidosis
Reversible but often requires supportive dialysis

Question 10

Acute Interstitial Neprhitis

Answer 10

Drug-induced hypersensitivity involving interstitium and tubules –> intrarenal azotemia
Causes: NSAIDs, penicillin, diuretics
Clinical Features: fever, oliguria and rash days to weeks after starting drug; eosinophils in urine
Resolves with cessation of drug; may progress to renal papillary necrosis

Question 11

Renal Papillary Necrosis

Answer 11

Necrosis of renal papillae
Presents with gross hematuria and flank pain
Causes: chronic analgesic abuse, diabetes mellitus, sickle cell, severe acute pyelonephritis

Question 12

Nephrotic Syndrome

Answer 12

Proteinuria > 3.4 g/day
Hypoalbuminemia - pitting edema
Hypogammaglobulinemia - increased infection risk
Hypercoag state - due to loss of antithrombin III
Hyperlipidemia and hypercholesterolemia - may cause fatty casts in urine (liver throws out fat to make blood thicker)

Question 13

Minimal Change Disease

Answer 13

Most common cause of nephrotic syndrome in children
May be associated with Hodgkin lymphoma
Normal glomeruli on H&E (lipid may be seen in PCT)
Effacement of foot processes on EM
No immune complex deposition (neg. IF)
Selective proteinuria (loss of albumin)
Excellent response to steroids

Question 14

Focal Segmental Glomerulosclerosis

Answer 14

Most comon cause of nephrotic syndrome in Hispanics and African Americans
Usu. idiopathic, but may be associated with HIV, heroin and sickle cell
Focal (some glomeruli) and segmental (part of glomerulus) sclerosis on H&E stains
Effacement of foot processes on EM
Negative IF (no immune complexes)
Poor response to steroids –> chronic renal failure

Question 15

Membranous Nephropathy

Answer 15

Most common cause of nephrotic syndrome in caucasian adults
May be associated with Hep. B or C, solid tumors SLE or drugs
Thick glomerular BM on H&E
Due to immune complex deposition (granular IF); Subepithelial deposits with ‘spike and dome’ appearance on EM
Poor response to steroids

Question 16

Membranoproliferative Glomerulonephritis

Answer 16

Thick glomerular basement membrane on H&E with tram-track appearance
Due to immune complex deposition (granular IF)
Divided into two types based on location of deposits:
- Type I - subendothelial deposits; associated with HBV and HCV
- Type II (dense deposit disease) - intramembranous, associated with C3 nephritic factor (autoantibodies that stabilize C3 convertase, leading to overactivation of complement, inflammation and low levels of circulating C3)

Question 17

Immune Complex Deposition

Answer 17

Beneath epithelium - membranous nephropathy
Beneath endothelium - Type I MPGN
In BM - Type II MPGN

Question 18

Diabetes Mellitus

Answer 18

High serum leads to nonenzymatic glycosylation of vascular BM –> hyalin arteriosclerosis
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 mesangium with formation of Kimmelstiel-Wilson nodules
ACE inhibitors slow progression

Question 19

Systemic Amyloidosis

Answer 19

Amyloid deposits in mesangium –> nephrotic syndrome

Characterized by apple-green birefringence under polarized light after staining with Congo Red

Question 20

Nephritic Syndrome

Answer 20

Char. by glomerular inflammation and bleeding
Limited proteinuria <3.5g/day
Oliguria and azotemia
Salt retention with periorbital edema and HTN
RBC casts and dysmorphic RBCs in urine
Hypercellular inflamed glomeruli (C5a mediated) - immune complex deposition activates complement, which attracts neutrophils and mediates damage

Question 21

Postreptococcal Glomerulonephritis

Answer 21

Arises 2-3 weeks after skin or pharynx infection with Group A beta-hemolytic streptococcal infection
Presents with coca-cola colored urine, oliguria, hypertension, periorbital edema
Hypercellular glomeruli on H&E
Mediated by granular immune complex deposition and subepithelial humps on EM

Question 22

Rapidly Progressive Glomerulonephritis

Answer 22

Characterized by crescents in Bowman’s space that are comprised of fibrin and macrophages
Nephritic syndrome that progresses to renal failure in weeks to months
Can be characterized as linear, granular or pauci-immune depending on immunofluorescence pattern

Question 23

Linear Immunofluorescense

Answer 23

Goodpasture syndrome - antibody against glomerular and alveolar basement membranes
Presents with hematuria, hemoptysis classically in young adult males

Question 24

Granular Immunofluorescence

Answer 24

PSGN or diffuse proliferative glomerulonephritis
DPGN - is due to diffuse antigen-antibody complex depositions usually sub-endothelial, most common type of renal disease in SLE

Question 25

Pauci-Immune

Answer 25

Wegners granulomatosis - cANCA; lung, kidney, pharynx/nasal passages (sinusitis)
Churg Strauss - pANCA; granulomatous inflammation, eosinophilia and asthma
Microscopic Polyangiitis - pANCA

Question 26

IgA Nephropathy

Answer 26

Berger Disease; Very common
IgA immune complex deposition in the mesangium of glomeruli
Presents during childhood as episodic gross or microscopic hematuria with RBC casts, usu following mucosal infection (eg. gastroenteritis)
IgA deposition in mesangium seen in IF

Question 27

Alport Syndrome

Answer 27

Inherited defect in type IV collagen; mostly X linked
Results in thinning and splitting of the BM
Presents as isolated hematuria, sensory hearing loss and ocular disturbances

Question 28

Cystitis

Answer 28

Infection of bladder; presents as dysuria, urinary frequency and suprapubic pain without systemic signs
Lab findings:
- cloudy urine with >10 WBCs/hpf
- + leukocyte esterase and nitrites
- >100,000 colony forming units
Most commonly due to: E coli, staph saprophyticus, klebsiella, proteus (alkaline urine with ammonia scent), enterococcus faecalis
Sterile pyuria with negative urine culture - think Chlamydia or Neisseria

Question 29

Pyelonephritis

Answer 29

Infection of the kidneys usually due to ascending infection; increased with vesicoureteral reflux
Presents with fever, flank pain, WBC casts and leukocytosis
Most commonly due to E. coli, enterococcus faecalis, klebsiella

Question 30

Chronic Pyelonephritis

Answer 30

Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
Due to VUR or obstruction due to BPH or carcinoma
Leads to cortical scarring with blunted calyces (upper and lower poles are char. of reflux)
Atrophic tubules contain eosinophilic proteinaceous material resembling thyroid follices
Waxy casts may be seen in urine