Kidney (COMPLETE)

What is anuria?

No urine output

What is oliguria?

Less than 1 L per day of urine

What should be the normal levels of urine?

1-2 L per day

What is polyuria?

>2 L per day of urine

What is azotemia?

Biochemical elevation of:

• BUN

• Creatinine

In response to a decreased GFR

Why do BUN and creatinine levels increase in azotemia?

The increased levels reflect a decreased GFR

What causes prerenal azotemia?

Hypoperfusion

• Hemorrhage

• Shock

• Volume depletion

• CHF

What causes postrenal azotemia?

Obstruction of urine flow distal to the kidney

• Ex. Kidney stones

What is uremia?

Azotemia + systemic metabolic/endocrine effects

• GI

• Heart

• Peripheral nerves

How does uremia affect other organs/structures?

GI — Uremic gastroenteritis

Peripheral nerves — Peripheral neuropathy

Heart — Uremic fibrinous pericarditis

What is the normal excretion amount in proteinuria?

40-150 mg/day

What amount is usually asymptomatic in proteinuria?

1-3 g/day

What contributes to asymptomatic proteinuria?

Reflects increased glomerular permeability

Impaired tubular reabsorption contributes to low-level proteinuria

What is nephrotic-range proteinuria?

≥3.5 g protein/day

• Massive proteinuria

What are the 4 classic features of nephrotic syndrome?

Massive proteinuria

Hypoalbuminemia — plasma albumin <3 g/dL

Generalized edema

Hyperlipidemia and lipiduria

What are major complications of nephrotic syndrome?

Increased susceptibility to:

• Infection (staphylococcus and pneumococcus)

• Thrombotic and thromboembolic complications

What classifies hematuria?

>5 RBC/HPF

• Glomerular bleeding often shows dysmorphic RBCs and RBC cast

What characterizes nephritic syndrome?

Hematuria with RBC casts

Mild-to-moderate proteinuria (usually <1 g/day)

Elevated creatinine

Oliguria

Hypertension

Mild-to-moderate edema → Periorbital edema

What do dysmorphic RBCs indicate?

Glomerular hematuria

What are key features of rapidly progressive GN (RPGN)?

Rapid decrease in renal function (≥50% in 3 months)

Crescents on bx

What are key features of isolated hematuria/proteinuria?

Asymptomatic

No other renal findings

What are key features of chronic renal failure?

Prolonged azotemia/uremia

Uremic symptoms

What is Tamm-Horsefall protein?

A renal glycoprotein secreted in the tubules that forms the essential gel matrix (backbone) that traps red blood cells to create RBC casts

• A key sign of glomerular bleeding

What are the macroscopic tests on urinalysis?

Color

• Red/brown urine:

  • Hematuria vs hemoglobinuria/myogloinuria vs. drugs/foods

What is the purpose of a dipstick in urinalysis?

Tests for:

• pH

• Protein

• Blood

• Leukocyte esterase

• Nitrates

• Glucose

• Ketones

in the urine

What are the microscopic tests on urinalysis?

Tests for:

• Cells

• Casts

• Crystals

  • Some are normal; Certain ones are NOT

in the urine

What type of tests are used for renal and urinary tract disease?

Major noninvasive diagnostic tools

What do fatty urinary casts indicate?

Nephrotic syndrome (lipiduria)

What do hylaine urinary casts indicate?

Nonspecific

• Concentrated urine

• Exercise

What do RBC urinary casts indicate?

Glomerulonephritis — Specific for glomerular bleeding

What do WBC urinary casts indicate?

Polynephritis

Interstitial nephritis

What do granular urinary casts indicate?

Nonspecific tubular injury

What do waxy urinary casts indicate?

Chronic renal failure

Urinary stasis

What crystal types are normally seen in urinary analysis?

Uric acid

Calcium oxalate

Triple phosphate

(Usually no pathologic significance)

What are some drug-induced crystal types seen in urinary analysis?

Sulfonamides

Indinavir

(Usually benign)

What are some pathologic crystal types seen in urinary analysis?

Cystine (cystinuria)

Calcium oxalate (ethylene glycol toxicity)

What crystals are these pictures microscopically showing?

A. Uric acid

B. Uric acid stone disease

C. Calcium oxalate

D. Cystine crystals

E. Wheat-like

F. Calcium phosphate

What causes nephrotic syndrome?

Excessive glomerular permeability to plasma proteins

What is the most common cause of nephrotic syndrome in children?

Minimal change disease

What is the typical age for minimal change disease?

Children

• Peak incidences — Ages 2–6

What does minimal change disease look like on LM?

Glomeruli appear normal

What does minimal change disease show on EM?

Diffuse podocyte foot-process effacement

• No immune deposits

How does minimal change disease respond to steroids?

Excellent response → Excellent prognosis

[Selective proteinuria (albumin only)]

What can minimal change disease sometimes follow?

Respiratory infection

Routine prophylactic immunization

What does FSGS mean?

Focal segmental glomerulosclerosis

• Focal = Some glomeruli affected

• Segmental = Only subset of glomeruli is affected by sclerosis

  • Not global/diffuse

What is the most common cause of nephrotic syndrome in adults?

Focal segmental glomerulosclerosis (FSGS)

• 10-35%

Membranous nephropathy

What are primary cases of FSGS?

Idiopathic

Podocyte injury

What are secondary cases of focal segmental glomerulosclerosis (FSGS)?

HIV

Heroin use

Obesity

Reflux nephropathy

What is the LM finding in FSGS?

Segmental sclerosis

Hyalinosis

What is the EM finding in FSGS?

Foot process effacement

What FSGS variant is associated with HIV?

Collapsing glomerulopathy

(An aggressive variant)

How does FSGS respond to steroids?

Less responsive than minimal change disease → Progress to chronic kidney disease

What are the primary causes of membranous nephropathy?

85% idiopathic

• Anti-PLA2R antibodies

What are the secondary causes of membranous nephropathy?

15% secondary

• SLE

• Hepatitis B/C

• Drugs

• Malignancy

What is the LM finding in membranous nephropathy?

Diffuse thickening of glomerular capillary walls

What are IF findings in membranous nephropathy?

Granular IgG and C3 deposits

Where are the granular IgG and C3 deposits locally seen on EM for membranous nephropathy?

Subepithelial deposits

• “Spikes” on silver stain

What is the overall prognosis for membranous nephropathy?

Variable course

NOT steroid-responsive

What causes membranoproliferative glomerulonephritis (MPGN)?

Combination of:

• Nephrotic features

• Nephritic features

A pattern of immune-mediated injury rather than a specific disease

What is the classic LM finding in MPGN?

Hypercellularity

Thickened GBM w/ tram-track/double-contour appearance

What causes Type I MPGN?

Immune-complex-mediated injury with subendothelial deposits

What is Type II MPGN called?

Dense deposit disease

What causes Type II MPGN?

Dysregulation of the alternative complement pathway

Where are the deposits in Type II membranoproliferative glomeurlonephritis (MPGN)?

Intramembranous dense deposits

What demographic typically presents MPGN?

Adolescence and young adults

How is MPGN treated?

Steroid treatments typically NOT helpful

• With 10 years → 50% of pts develop chronic kidney failure

Disease follows a slow progressive but unremitting course

What is diabetic nephropathy role in the US?

Leading cause of:

• Nephrotic syndrome

• End-stage renal disease

What are the major renal lesions in diabetic nephropathy?

Diffuse and nodular (Kimmelstgiel-Wilson) glomerulosclerosis

What is Kimmelstiel-Wilson disease?

Nodular glomerulosclerosis caused by diabetic nephropathy

Shows up on PAS+ stain

What happens to the renal arterioles in diabetic nephropathy?

Hyaline arteriolosclerosis affects both afferent and efferent arterioles

What happens microscopically in diabetic nephropathy?

Thickened GBM

Mesangial matrix expansion

What can diabetic nephropathy led to?

Increases susceptibility to pyelonephritis

What is acute proliferative (poststreptococcal) GN?

Immune complex-mediated

Occurs 1–4 weeks AFTER streptococcal pharyngitis or impetigo

What is the classic urine appearance in acute proliferative (poststreptococcal) GN?

Cola-colored/Brown urine

What demographic is most commonly susceptible to acute proliferative (poststreptococcal) GN?

Child 6-10 y/o

What are common symptoms of acute proliferative (poststreptococcal) GN?

Periorbital edema

Oligura

What is the LM findings of acute proliferative (poststreptococcal) GN?

Enlarged, hypercellular glomeruli with neutrophils

What are the IF findings of acute proliferative (poststreptococcal) GN?

Granular IgG, IgM, and C3

What are the EM findings of acute proliferative (poststreptococcal) GN?

Subepithelial humps

What is the prognosis of acute proliferative (poststreptococcal) GN?

>95% of children recover fully

What conditions can cause acute proliferative (poststreptococcal) GN?

Nonstreptococcal causes include:

• Endocarditis

• Hepatitis B/C

• Malaria

What defines rapidly progressive (crescentic) GN (RPGN)?

Severe glomerular injury

Rapid decline in renal function (≥50% within 3 months)

• With crescents in >50% of glomeruli

What is a histological hallmark of RPGN?

Crescents in >50% of glomeruli

What forms the crescents in RPGN?

Parietal epithelial cells + Macrophages/monocytes + Fibrin in Bowman space (compressed the space)

What are the 3 mechanical types of RPGN?

1. Anti-GBM

2. Immune-complex

3. Pauci-immune

What is the IF pattern in anti-GBM disease?

Linear IgG and C3 along the GBM

What is Goodpasture syndrome?

Anti-GBM disease involving both kidneys and lungs

• Causes pulmonary hemorrhage

What is the target antigen in Goodpasture syndrome?

α3 chain of type IV collagen (NC1 domain)

How is anti-GBM disease treated?

Plasmapheresis + immunosuppression

What is the IF pattern in type II: immune-complex RPGN?

Granular/"lumpy-bumpy" deposits

What diseases can cause type II: immune-complex RPGN?

Poststreptococcal GN

Lupus nephritis

IgA nephropathy

Henoch-Schönlein purpura

What characterizes type III: pauci-immune RPGN?

Little or no immune deposition

• Commonly ANCA-associated

What diseases are associated with type III: pauci-immune RPGN?

Wegener granulomatosis with polyangiitis

Microscopic polyangiitis

What can cause type III: pauci-immune RPGN?

Many cases are idiopathic

What is IgA nephropathy also called?

Berger disease

What are two types of hematuria groups?

IgA nephropathy (Berger disease)

Alport syndrome and thin basement membrane disease

What is the most common GN worldwide?

IgA nephropathy

When does hematuria occur in IgA nephropathy?

Shortly AFTER a mucosal respiratory or GI infection

• Infection → increased IgA circulation

What is a symptom of IgA nephropathy?

Recurrent gross or microscopic hematuria

Where are the immune deposits in IgA nephropathy?

Mesangium