B&B Renal: Nephron Disorders Flashcards
Capillary Endothelium
Structure & Function
- 1st barrier to filtration
- Fenestrated –> only small (<40 nm) particles pass through
- Repels RBCs, WBCs, platelets
Glomerular Basement Membrane (GBM)
Structure & Function
- Composed of negatively charged molecules
* Type IV collegen
* Heparan sulfate (-) - Repels (-) molecules (e.g., albumin)
- Also a size barrier: only small (<4 nm) molecules pass through
Podocytes
Structure & Function
- Epithelial cells
- Long foot process wrap around capillaries
- Slits between foot processes filter blood
* Further size barrier: only very small molecules pass through
Glomerular Diseases
Features
Characterized by breakdown of filtration barrier components
* Results in aberrant filtration of particles
* Findings: RBCs, proteins (albumin) in urine
Hematuria
Diagnosis
- Urinalysis
- Dipstick: test for presence of heme
* Heme has peroxidase activity –> reacts with strip
* Heme positive = hemoglobin or myoglobin - Microscopy: RBCs visualized
Glomerular Bleeding
Hematuria
- RBC casts: RBCs aggregate in nephron once they squeeze past damaged filtration barrier
- Dysmorphic RBCs: abnormally shaped RBCs resulting from squeezing past damaged filtration barrier
- Acanthocytes: RBCs with spiked cell membrane
- Proteinuria
- Urine appearance: red, smoky brown
Proteinuria
Diagnosis
- Urine dipstick
- Color change indicates amount of protein
- Primarily detects albumin (helpful for glomerular disease)
* Glomerular disease: usually 4+ protein - Affected by urine concentration
* Dehydration can increase concentration of normal amount of protein and produce false-positive
- Urine protein-to-creatinine ratio: “spot urine”
- 1st or 2nd morning urine sample after avoiding exercise
- Normal ratio: < 0.2 mg/mng
Gold Standard Test for Proteinuria
Diagnosis
24-hour urine collection
* Measures grams/day of protein excretion
* Normal: <150 mg/day
* Disadvantages:
* Cumbersome for patients
* Errors in collection are common
Glomerular Disease Spectrum
Spectrum of diseases ranging from nephritic to nephrotic
* Nephritic syndrome
* RBC casts
* Mild proteinuria
* Renal failure
* Nephrotic syndrome
* Massive proteinuria
* Hyperlipidemia
Nephrotic Syndrome
Glomerular Diseases
Loss of protein filtration barrier (GBM)
* RBC filtration barrier remains intact
* Massive proteinuria
* Dipstick: 4+
* 24-hr urine: >3.5 g/day
* Triggers pathological cascade
- Proteinuria / Frothy urine
- Edema
- Hyperlipidemia
- Fatty casts / Oval fat bodies
- Thrombosis
- Recurrent infections
Clinical Features
Nephrotic Syndrome
Proteinuria
Nephrotic Syndrome
Loss of GBM results in filtration of proteins into urine
* Appearance: frothy urine
Edema
Nephrotic Syndrome
- Loss of GBM results in loss of serum proteins via filtration into urine
- Loss of serum albumin lowers plasma oncotic pressure
- Low plasma oncotic pressure decreases ECV & GFR
* Low ECV & GFR activate RAAS increasing Na+ / H2O retention & plasma hydrostatic pressure - Low plasma oncotic pressure results in edema via osmotic diffusion of H2O into interstitium
- Low plasma oncotic pressure decreases ECV & GFR
Hyperlipidemia
Nephrotic Syndrome
- Loss of GBM results in loss of serum proteins via filtration into urine
- Low serum albumin increases liver metabolic activity
- Increased fatty acid production by liver causes hyperlipidemia
- Serum lipids are filitered into urine producing fatty casts & oval fat bodies
Thrombosis
Nephrotic Syndrome
- Loss of GBM results in loss of serum proteins via filtration into urine
- Low antithrombin III (clotting factor) increases risk of thrombosis
Hypercoagulable state
Infections
Nephrotic Syndrome
- Loss of GBM results in loss of serum proteins via filtration into urine
- Loss of immunoglobulins increases risk of infections
Urine
Nephrotic Syndrome
Urinary lipid may be present
Urine
Nephrotic Syndrome
Urinary lipid may be present
* Can be trapped in casts: fatty casts
* Can be enclosed by plasma membrane of degenerative epithelial cells (oval fat bodies)
* Under polarized light: “Maltese cross” appearance
Maltese cross = characteristic finding
- Frothy urine
- Swelling of ankles
- Periorbital edema
- Often mistaken for allergic reaction
- Serum total cholesterol: >300 mg/dL
- Proteinuria: >3.5 mg/day
Classic Presentation
Nephrotic Damage
Nephritic Syndrome
Glomerular Disease
Inflammatory process damages entire glomeruli and results in loss of both RBC & protein filtration barriers
* Glomerular damage: decreased GFR
* RBCs in urine: RBC casts, dysmorphic DBCs
* Protein in urine: <3.5 g/day
* Less than nephrotic syndrome due to lower GFR
Nephritic = nephritis; inflammatory
- Proteinuria
- Oliguria
- Edema
- Hypertension
- Increased BUN / Cr ratio
- RBC casts & dysmorphic RBCs
Clinical Features
Nephritic Syndrome
Proteinuria
Nephritic Syndrome
Loss of GBM results in filtration of proteins into urine
RBC Casts, Dysmorphic RBCs
Nephritic Syndrome
Damaged capillary endothelium results in filtration of RBCs into urine
Oliguria
Decreased GFR due to glomerular damage
* Decreased urine production results in oliguria
Increased BUN / Cr Ratio
Nephritic Syndrome
Glomerular damage results in increased BUN / Cr ratio
Hypertension
Decreased GFR due to glomerular damage results in increased plasma hydrostatic pressure
Edema
Nephritic Syndrome
- Decreased GFR due to glomerular damage results in increased plasma hydrostatic pressure
- Increased hydrostatic pressure drives fluid into extracellular space
- Dark urine (due to RBCs)
- Swellnig / edema
- Fatigue (due to uremia)
- Proteinuria: <3.5 g/day
Presentation
Nephritic Syndrome
- Dark urine (due to RBCs)
- Swellnig / edema
- Fatigue (due to uremia)
- Proteinuria: <3.5 g/day
Presentation
Nephritic Syndrome
Sites of Glomerular Injury
Nephritic/Nephrotic
Major determinant of whether a disease process leads to nephritic or nephrotic syndrome is the site of injury
* Podocyte injury –> nephrotic syndrome
* Podocytes are separated from blood by GBM
* Injury does not lead to inflammation
* Results in loss of protein in urine only
* Endothelial & mesangial cells –> nephritic syndrome
* Cells are exposed to blood elements
* Injury causes inflammation (nephritis)
* Influx of inflammatory cells
* Results in loss of RBCs & protein in urine
- Post-streptococcal glomerulonephritis
- Berger’s (IgA) nephropathy
- Diffuse proliferative glomerulonephritis
- Rapidly progressive glomerulonephritis (RPGN)
- Alport syndrome
- Membranoproliferative glomerulonephritis
Etiology
Nephritic Syndrome
Post-Streptococcal GN
Etiology
- Occurs following group A strep infection
- Impetigo (skin)
- Pharyngitis
- Nephritogenic strains of GAS carry specific subtypes of M protein virulence factor
- Immune complex deposit in glomeruli
* Circulating ATG-AB complexes
* In situ immune complex formation - Complexes fix complement & attract PMNs
* Inflammatory response –> nephritic syndrome
* Response depletes serum complement levels, results in hypocomplementemia
* Also seen in SLE nephritis, MPGN
- Child
- Nephritic syndrome
- 2-3 weeks following strep throat infection (pharyngitis)
Classic Case
Post-Streptococcal GN
* Takes 2-3 weeks for antibodies / immune complexes to form and deposit in kidneys
- LM: enlarged, hypercellular glomeruli
- Granular IF: stained for IgG, C3
- EM: subepithelial “humps”
Microscopy
Post-Streptococcal GN
Post-Streptococcal GN
Prognosis
Depends on age
* Children: good prognosis
* 95% recover completely
* Adults: moderate prognosis
* About 60% recover
* Patients at risk for renal insufficiency
* Can occur decades after initial illness
* Patients at risk of RPGN
Most common form of glomerulonephritis worldwide
Epidemiology
IgA Nephropathy / Berger’s Disease
IgA Nephropathy / Berger’s Disease
- Overactive immune system resulting in IgA overproduction in response to triggers
- Respiratory infection
- GI infection
- IgA immune complex deposit in mesangium
* Disease processes involving mesangium will trigger inflammation in glomeruli
* IgA complexes activate complement via alternative & lectin pathways
* No hypocomplementemia - Results in glomerular injury
Granular IF: stained for IgA
Microscopy
IgA Nephropathy / Berger’s Disease
- Recurrent episodes of hematuria since childhood
- Episodes follow URI or diarrheal illness
- Slow decline in renal function (BUN/Cr) over time
- Possible progression to ESRD & dialysis (>20 yrs)
Classic Case
IgA Nephropathy / Berger’s Disease
Most common childhood systemic vasculitis
Epidemiology
Henoch-Schonlein Purpura
IgA nephropathy with extra-renal involvement
* Diffuse IgA deposition
* Tissue biopsy: demonstrates IgA
* Skin: palpable purpura on buttocks, legs
* GI: abdominal pain; melena
* Joints: arthritis
Henoch-Schonlein Purpura
Nephritic Syndrome
Diffuse Proliferative GN (DPGN)
Nephritic Syndrome
- Most common & severe subtype of SLE renal disease
- Type IV Lupus Nephritis
- Often presents with other SLE features:
- Fever
- Rash
- Arthritis
- Diffuse: > 50% of glomeruli are affected
* < 50%: focal - Proliferative: increased glomerular cellularity
- Endotheial & mesangial cell prolfieration
- Monocyte / PMN infiltration
- Immune complex deposition in glomeruli
- Subendoethelial deposits trigger inflammatory response
- Immune complexes are formed by anti-dsDNA Abs & other SLE Abs
- ICs activate complement –> hypocomplementemia
- LM: thickened capillary loops (“wire looping”)
- Granular IF: stained for IgG, IgA, IgM, C3, or C1q
* “Full house” pattern
Microscopy
Diffuse Proliferative GN
- Wire looping = classic finding
- Mixed clinical presentation
- Proteinuria (sometimes nephrotic)
- Hematuria
- Reduced GFR
- Severe, often leads to ESRD
Presentation
Diffuse Proliferative GN
Rapidly Progressive GN (RPGN)
- Hallmark = presence of crescents within glomeruli
- Also called “crescentic” GN
- Crescents formed by inflammation:
* Monocytes / macrophages
* Fibrin - Pathologic description, not a cause of glomerulonephritis
* Common pattern of inflammation that results from various diseases - Severe form of glomerulonephritis
- Progressive loss of renal function
- Rapid onset; often presents as acute renal failure
- Non-specific symptoms: fatigue, anorexia, etc.
RPGN
Diagnosis
Causes are distinguished based on immunofluoresence
* Type I: Linear IF
* Type II: Granular IF
* Type III: Negative IF
Antibody-mediated destruction of GBM
* Type II HSR: autoimmune production of anti-GBM Abs
* Linear IF: linear patter of IgG antibodies
RPGN
Type I RPGN
- Caused by production of anti-collagen antibodies
- Antibodies to alpha-3 chain of type IV collagen
- Found in GBM & alveoli
- Presentation: hemoptysis & nephritic syndrome
- Typically in young adult male
Type I RPGN
Goodpasture’s Syndrome
Immune complex deposition
* Type III HSR
* Granular IF: “lumpy bumpy” appearance
RPGN
RPGN Type II
Immune complex kidney disorders
RPGN Type II
- Post-streptococcal GN
- Can progress to RPGN
- Diffuse proliferative GN (type IV SLE nephritis)
- Can progress to RPGN
Most common cause of rapidly progressive GN
Epidemiology
Post-Streptococcal GN
- Negative IF: no staining for IgG, IgA, etc.
- “Pauci-immune” pattern
- Most patients are ANCA-positive
- c-ANCA or p-ANCA
- Most patients have a vasculitic syndrome
RPGN
RPGN Type III
ANCA Diseases
RPGN Type III
All can lead to pauci-immune nephritis
1. Wegener’s Granulomatosis: c-ANCA
2. Microscopic Polyangiitis: p-ANCA
3. Churg-Strauss Syndrome: p-ANCA
ANCA: anti-neutrophil cytoplasmic antibodies
Alport Syndrome
Nephritic Syndrome
Hereditary Nephritis
* Genetic type IV collage defect
* Mutations in alpha-3, alpha-4, or alpha-5 chains
* Chains found in basement membranes of the kidneys, eyes, ears
* Inheritance: X-linked
* Classic triad:
* Hematuria
* Hearing loss
* Ocular disturbances
Disruption of podocytes / GBM; capillary endothelium is intact
1. Minimal change disease <— cytokines
2. FSGS <— podocyte damage
3. Membranous nephropathy <— immune complexes
4. Diabetic nephropathy <— glucose
5. Amyloidosis <— amyloid
6. Membranoproliferative glomerulonephritis
Etiology
Nephrotic Syndrome
FSGS: focal segmental glomerulosclerosis
Effacement (flattening) of podocyte foot processes
* Loss of GBM anion charge barrier
* Effacement of podocytes impairs function
* Inflammation triggered by cytokines damages podocytes
* Usually idiopathic
* Associated with Hodgkin Lymphoma
* May involve immunological trigger days before onset
* Viral infection (URI)
* Allergic reaction
* Recent immunization
* Presents as “selective” proteinuria
* Only albumin in urine, not immunoglobulins
Nephrotic Syndrome
Minimal Change Disease
Selective proteinuria = distinctive feature
EM: effacement of foot processes
Microscopy
Minimal Change Disease
Most common cause of nephrotic syndrome in children
Epidemiology
Minimal Change Disease
Minimal Change Disease
Prognosis & Treatment
- Responds well to steroids
- Disease mediated by cytokines
- Steroids are anti-inflammatory agents
- Favorable prognosis
Prognosis & treatment are unique among nephrotic syndromes
Focal Segmental Glomerulosclerosis (FSGS)
Nephrotic Syndrome
- Glomerulosclerosis: pink/dense glomerular deposition of collagen
- Segmental: only portion of glomerulus is involved
- Focal: only some glomeruli are involved
Features
Involves GBM & podocytes, but not capillary endothelium
* LM: focal, segmental sclerotic lesions
* Collapse of basement membranes
* Hyaline deposition (hyalinosis)
* IF: usually negative (no ICs)
* Sometimes IgM, C3, C1 (non-specific
* EM: effacement of foot processes
Microscopy
FSGS
Most common cause of nephrotic syndrome in African-Americans
Epidemiology
FSGS
FSGS
Epidemiology
- Often progresses to chronic renal failure
- 40-60% within 10-20 years
- Severe form of Minimal Change Disease
- Does not respond to steroids
- Usually idiopathic (primary)
FSGS
Associations
- HIV
- Sickle cell patients
- Heroin users
- Morbid obesity
- Interferon treatment
- Used to treat HCV & HBV
- Some leukemias & lymphomas, melanoma
- Loss of nephrons
- Congenital single kidney
- Surgical kidney removal
FSGS
Associations
- HIV
- Sickle cell patients
- Heroin users
- Morbid obesity
- Interferon treatment
- Used to treat HCV & HBV
- Some leukemias & lymphomas, melanoma
- Loss of nephrons
- Congenital single kidney
- Surgical kidney removal
Thick GBM w/o hypercellularity
* Thickening occurs due to immune complex deposition
* Caused by production of anti-PLA2R autoantibodies
* PLA2R is expressed on podocytes
* Typically idiopathic
Nephrotic Syndrome
Membranous Nephropathy
“Membranous” = thick membrane
PLA2R: phospholipase A2 receptor
- LM: thickening of capillary/GBM interface
- “Spike & dome” membrane with silver stain
- Granular IF: stained for IgG, C3
- EM: supepithelial deposits; “electron-dense” deposits
Microscopy
Membranous Nephropathy
Characteristic finding: “electron-dense” deposits; “spike & dome”
Membranous Nephropathy
Secondary Causes
- SLE
* Most lupus nephropathy is nephritic: DPGN
* 10-15% of SLE patients develop nephrotic syndrome via membranous nephropathy - Solid tumors
- Clon canxer
- Lung cancer
- Melanoma
- Infections
* HBV
* HCV - Rheumatoid arthritis drugs
* Penicillamine
* Gold
* NAIDs
Most common nephrotic syndrome in adults
Epidemiology
Membranous Nepropathy
Caucasians > African-Americans
Membranous Nephropathy
Prognosis
Depends on age
* Children: excellent prognosis
* Adults: may progress to ESRD
Autoimmune Nephropathy
- Most autoantibody-mediated disorders are nephritic
- Auto-Abs form ICs & trigger inflammation
- Nephritis –> nephritic syndrome
- Membranous nephropathy is nephrotic
- Subendothelial deposits –> podocyte disruption
- No inflammatory response
- Nephrotic syndrome
- Subendothelial deposits –> podocyte disruption
Non-enzymatic glycosylation of GBM results in protein leakage
* Long-term effect: glomerulosclerosus
* Proteinuria
* Can progress to nephrotic syndrome
Nephrotic Syndromes
Diabetic Nephropathy
Extracellular buildup of amyloid proteins
* Classic histological findings:
* Congo red stain: positive
* Apple-green birefringence
Nephrotic Syndromes
Amyloidosis
Most commonly involved organ in systemic amyloidosis
Epidemiology
Kidneys
Membranoproliferative GN (MPGN)
Nephritic / Nephrotic
- Rare glomerular disorders
- Can cause nephritic or nephrotic syndromes
- Result in varying degrees of renal dysfunction
- Proteinuria: +/- nephrotic rane
- Hematuria
- Renal failure: elevated BUN/Cr
MPGN
Features
Thick GBM & hypercellular
* * “Membrano-“ = thick membrane
* Proliferative = proliferation of mesangial cells & matrix
MPGN
Features
Thick GBM & hypercellular
* * “Membrano-“ = thick membrane
* Proliferative = proliferation of mesangial cells & matrix
Subendoethelial IC deposition
* IgG –> complement activation
* Induces inflammation
* IC deposits trigger mesangial ingrowth
* Mesangium splits BM
MPGN
MPGN Type I
- LM: “tram track” appearance; common (80%)
- “Tram track” = split GBM
- Glandular IF: stained for IgG, C3
- Subendothelial antibodies / immune complexes
Microscopy
MPGN Type I
Assoiated with HBV & HCV infection
Etiology
MPGN Type I
“Electron dense” deposits within GBM
* Mediated by complement overactivation
* IgG usually absent
MPGN
MPGN Type II
Dense Deposit Disease
“Electron dense” deposits within GBM
* Mediated by complement overactivation
* IgG usually absent
MPGN
MPGN Type II
Dense Deposit Disease
IF: stains for C3, not IgG
Microscopy
MPGN Type II
IF: stains for C3, not IgG
Microscopy
MPGN Type II
C3 Nephritic Factor (C3NF)
MPGN Type II
C3 Convertase Stabiliing Antibody
* Found in >80% of patients with MPGN Type II
* Overactivation of complement system
* C3 convertase activates alternative pathway
* Convertase is stabilized by C3NF
* Results in hypocomplementemia: low C3
C3 Nephritic Factor (C3NF)
MPGN Type II
C3 Convertase Stabiliing Antibody
* Found in >80% of patients with MPGN Type II
* Overactivation of complement system
* C3 convertase activates alternative pathway
* Convertase is stabilized by C3NF
* Results in hypocomplementemia: low serum C3
MPGN Type II
Epidemiology
- Primarily affects children
- Usually between ages 5-15
- 50% develop ESRD within 10 years
Summary
MPGN Type I
- Pathology: immune complexes
- Location: subendothelium
- Microscopy: tram tracks (LM)
- Associations: hepatits (HBV, HCV)
Summary
MPGN Type I
- Pathology: complement (C3)
- Location: GBM
- Microscopy: dense deposits (EM)
- Associations: children
Summary
MPGN Type II
Acute Kidney Injury (AKI)
Tubulointerstitial Diseases
Acute fall in GFR
* Rise in serum BUN & creatinine
* Usually reversible
* Comon problem in hospitalized patients
- Poor renal perfusion
- Acute tubular necrosis
Etiology
AKI
- Ischemia
- Drugs
- Toxins
AKI
Acute Tubular Necrosis (ATN)
Ischemia –> vasoconstriction –> decreased GFR
* Ischemia results in loss of tubular cell polarity
* Na+/K+-ATPase migrates to apical membrane
* Pumps Na+ from cells into urine
* Macula densa senses increased urinary [Na]
* MD induces vasoconstriction of afferent arterioles
ATN
Ischemic ATN
Affects proximal tubule, TAL
Causes of decreased renal perfusion
1. Hypovolemia
2. Cardiogenic shock
3. Massive hemorrhage
Etiology
Ischemic ATN
Toxin / Drug-Induced ATN
Etiology
- Aminoglycosides
- Contrast dye (i.e., for CT scans)
- Uric acid (tumor lysis syndrome)
- Myoglobin (rhabdomyolysis)
- Lead
- Cisplatin
- Ethylene glycol (antifreeze)
Affects proximal tubule
ATN
Pathology
Sudden damage to tubular epithelial cells
* Tubular epithelial cells necrosis –> cells shed into urine
* Patchy, focal necrosis of nephron
* Epithelial cells form casts in urine
* Granular / “muddy brown” casts
* Casts occlude tubular lumen
* Urinary obstruction –> intrinsic renal failure
* GFR falls
* BUN & Cr rise
ATN
Disease Course
- Phase 1: Injury
- Slight decline in urine output
- Phase 2: Maintenance
- Longest phase: may last weeks
* Rising BUN / Cr - Oliguria
- Hyperkalemia –> can be fatal if severe
- AG metabolic acidosis
- Longest phase: may last weeks
- Phase 3: Recovery
- Polyuria
- Hypokalemia
Acute Interstitial Nephritis
Tubulointerstitial Diseases
Inflammation of renal tubules & interstitium
* Caused by Type I HSR (allergic reaction)
* Mediated by eosinophils & neutrophils
* Main clinical feature: intrinsic renal failure
* No nephritic / nephrotic syndrome
* Usually resolves with removal of offending agent
* Rarely progresses to papillary necrosis
- Drugs: 75% of cases
- Sulfonamides: TMP-SMX
- Rifampin
- Penicillin
- Diuretics: loop, TZ
- NSAIDs
- Infections: 5-10% of cases
- Legionella
- Leptospira
- CMV
- TB
- Systemic disease: 5-10% of cases
- Sarcoidosis
- Sjögren’s syndrome
- SLE
Etiology
Acute Interstital Nephritis
Drugs act as haptens; bind to BM / epithelium & illicit immune response
- Prior exposure to trigger
- Sx: fever, rash, malaise
- Urine: WBC casts; eosinophilia
- Sterile pyuria: WBCs w/o symptoms of cystitis
- Blood: increased BUN / Cr; peripheral eosinophilia
- ARF: increased BUN / Cr
Presentation
Acute Interstitial Nephritis
Chronic Interstital Nephritis
Tubulointerstital Diseases
Mononuclear cell infiltration leads to fibrosis & atrophy of tubules
* Seen with longstanding NSAID use
* Presents with mild elevation of BUN / Cr
* Resolves with discontinuation of drugs
NSAID Nephrotoxicity
Tubulointerstitial Diseases
- Acute interstitial nephritis: fever, renal failure
- Chronic interstitial nephritis: renal failure
- ATN:
- Blocks PG vasodilation of afferent arteriole
- Results in ischemia
- Membranous GN: nephrotic syndrome
- Papillary necrosis
NSAID Nephrotoxicity
Tubulointerstitial Diseases
- Acute interstitial nephritis: fever, renal failure
- Chronic interstitial nephritis: renal failure
- ATN:
- Blocks PG vasodilation of afferent arteriole
- Results in ischemia
- Membranous GN: nephrotic syndrome
- Papillary necrosis
Coagulative necrosis of renal papillae
* Sloughing of tissue
* Gross hematuria
* May obstruct urine flow
* Often painless
* In isolation, does not cause intrinsic renal failure or produce WBC casts
Tubulointerstitial Diseases
Papillary Necrosis
- Chronice phenacetin use
- Diabetes
- Acute pyelonephritis
- Sickle cell anemia
Etiology
Papillary Necrosis
Cortical Necrosis
Tubulointerstitial Diseases
Acute-onset severe renal failure due to ischemic renal cortex
* Seen in very sick patients
* Septic shock
* Major obstetric complications: abruptio placentae; fetal demise
* Cortex = location of glomeruli
* Glomerular destruction –> no filtration
* Oliguria / anuria
Acute Renal Failure (ARF)
Definition
Decreased Cr clearance over days
* Often with associated symptoms
* Many causes
Chronic Kidney Disease (CKD)
Definition
Slow, gradual deterioration of renal function over years
* Usually due to DM, HTN
* Symptoms only present in most severe stages
- Anorexia
- Nausea, vomiting
- Platelet dysfunction (bleeding)
- Pericarditis
- Asterixis
- Encephalopathy
Signs & Symptoms
Uremia
Asterixis: tremor / flap when patients hold their hands out
ARF Classification
ARF
Elevated BUN / Cr
* Pre-renal ARF: insufficient blood flow to kidneys
* Dehydration
* Shock
* Heart failure
* Post-renal ARF: bilateral urine outflow obstruction
* Kidney stones
* BPH
* Tumors
* Congenital anomalies
* Intrinsic ARF: renal dysfunction
* ATN
* Glomerulonephritis
ARF: Key Labs
Diagnosis
- Creatinine
- Freely flitered
- Small amount secreted
- Blood urea nitrogen (BUN)
* Freely filtered
* Reabsorbed when kidney reabsorbs H2O - ARF: GFR falls –> BUN & Cr rise
* Dehydration BUN rises more than Cr; resorption
ARF Workup
Diagnosis
Detection of BUN / Cr elevation
1. History: medications, co-morbidities, hydration
2. Physical: low BP, dehydration, CHF, etc.
3. Urinalysis: protein, blood, casts
4. Ultrasound: hydronephrosis
ARF Measurements
Diagnosis
Determine cause based on blood & urine testing
* BUN: rises in ARF
* Cr: rises in ARF
* BUN / Cr ratio –> normal = 20:1
* Urine [Na]
* Urine [Fe]
* uOsm
ARF Measurements
Diagnosis
Determine cause based on blood & urine testing
* BUN: rises in ARF
* Cr: rises in ARF
* BUN / Cr ratio –> normal = 20:1
* Urine [Na]
* Fractional excretion of Na
* uOsm
Urinary [Na]
ARF Measurements
Varies based on intake of Na+ & H2O
* Very low (<20 mEq/L) in Na+ / H2O retention
Fractional Excretion of Na (F-Na)
ARF Measurements
Percentage of filtered Na+ that is excreted
* Very low (< 1%) during Na+ / H2O retention
Urinary Osmolarity (uOsm)
ARF Measurements
Measure of urine concentration
* Very high (>550 mOsm/kg) in H20 retention
Pre-Renal ARF
BUN / Cr
Decreased blood flow to kidneys
* GFR falls –> reduced BUN / Cr filtration
* Serum BUN & Cr increases
* Increased H2O resorption
* BUN is resorbed with H2O
* BUN rise > Cr rise
* Result: elevated BUN / Cr ratio
Pre-Renal ARF
Urinary Findings
- Significant H2O resorption
- Concentrated urine –> high uOsm
- Significant Na+ resorption
- Low urine [Na]
- Low F-Na
Intrinsic ARF
BUN / Cr
Kidney cannot filter blood
* GFR falls –> reduced BUN / Cr filtration
* Serum BUN & Cr increases
* No additional rise in BUN from H2O resorption
* No change in BUN / Cr ratio
Intrinsic ARF
Urinary Findings
- Kidney cannot reabsorb water –> low uOsm
- Cannot concentrate urine
- Cannot reabsorb Na+ –> high urine [Na]; high F-Na
Post-Renal ARF
Obstruction to urine outflow
* Urine backs up in kidneys
* Causes high pressure tubules:
* Impairs filtration: high hydrostatic pressure pushes blood out
* Impaired resorption: channels damaged / destroyed by high pressure
* Key features:
* Anuria
* Hydronephrosis
* Diagnostic test: ultrasound
* Shows enlarged, dilated kidneys
Chronic Kidney Disease (CKD)
Renal Failure
Slow, steady fall in Cr clearance
* Blood tests show rise in BUN / Cr
* Eventually progresses to dialysis for many patients
* Most common causes:
* Hypertensive nephrosclerosis
* Diabetic nephropathy
Stages of CKD
CKD
- Stage 1: GFR >90
- Stage 2: GFR 60-89
- Stage 3: GFR 30-59
- Stage 4: GFR 15-29 (approaching dialysis)
- Stage 5 (ESRD): GFR <15 (dialysis)
- Acidemia
- Hyperkalemia
- Intoxication (overdose of dialyzable substance)
- Volume overload (CHF)
- Uremic symptoms
Treatment
Indications for Dialysis
Mnemonic: AEIOU
Dialysis Methods
Treatment
- Hemodialysis
- Requires vascular access
- Blood pumped from body through filter & back
- Done in sessions of few hours at a time
- Peritoneal dialysis
- Fluid is cycled through peritoneal cavity
- Peritoneum used as dialysis membrane
- Hemofiltration
- Constant filtering of blood
- Usually done at bedside for critically ill patients
q
Vascular Access
Dialysis
For acute dialysis, central line can be placed
* Ideal method is fistula
* Connection between artery & vein
* Placed surgically, usually in arm
* Lowest rates of thrombosis, infection
* Fistula must “mature” for use
* Ideally placed several months before dialysis
CKD
Complications
- Anemia: due to loss of EPO production
- Dyslipidemia: mostly triglycerides
* Protein loss in urine –> stimulation of liver synthesis
* Impaired clearance of chylomicrons & VLDL - Renal osteodystrophy
- Growth failure (children)
CKD
Complications
- Anemia: due to loss of EPO production
- Dyslipidemia: mostly triglycerides
* Protein loss in urine –> stimulation of liver synthesis
* Impaired clearance of chylomicrons & VLDL - Renal osteodystrophy
- Growth failure (children)
