MODULE 5: RENAL DISEASE

CLASSIFICATION OF RENAL DISEASES

- Glomerular Disorders
- Tubular disorders
- Interstitial disorders

GLOMERULAR DISORDERS TYPES

IMMUNOLOGIC • majority of glomerular disorders
DISORDERS • Immune complexes from immunologic reactions throughout the body
• Increased serum immunoglobulins (such as immunoglobulin A, IgA) are
deposited on the glomerular membranes
• Immune system mediators: complement
migrate and produce change and damage to membranes
NONIMMUNOLOGIC • Chemicals and toxins, deposition of amyloid
material and acute phase reactants, electrical charge interference, membrane
thickening
GLOMERULONEPHRITIS • General term for sterile, inflammatory process affecting the glomerulus
• Causes blood, protein, and casts in urine

• Types of glomerulonephritis progress through various disorders

Acute glomerulonephritis → chronic glomerulonephritis → nephrotic syndrome → renal failure

Respiratory complications first -> good pasture syndrome

Pulmonary first -> Wegener granulomatosis

GLOMERULAR DISORDERS ETIOLOGY CLINICAL PRIMARY OTHER

COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
GLOMERULONEPHRITIS
• acute -Immune - Fever, edema • Hematuria, • Rapid anti–
glomerulonephritis complexes deposit around the eyes, proteinuria, group A
(AGN) on glomerular oliguria, fatigue, oliguria streptococcal
membranes hypertension and enzyme tests
hematuria
- is a disease marked by - Group A - Rapid onset of • Red blood cell • Ease in
the sudden onset of streptococcal hematuria and (RBC) casts, diagnosis
symptoms consistent infections from edema, permanent dysmorphic RBCs • Decline in
with damage to the organisms with M renal damage • Hyaline and incidence
glomerular membrane. protein in the cell seldom occurs granular casts
- Symptoms usually wall • White blood cells
occur in children and
young adults following
respiratory infections
• Rapidly Progressive • More serious • Rapid onset with • Macroscopic BUN
(Crescentic) acute glomerular damage hematuria Creatinine
Glomerulonephritis glomerulonephritis and possible • Proteinuria eGFR
→ renal failure progression to • RBC casts
• Systemic end-stage renal • Urinalysis
immune disorders failure similar to AGN
• Macrophages progresses to more
damage capillary abnormal,
walls elevated
• Fibrin = protein, low
permanent damage glomerular
to capillary tufts filtration rate
• Deposition of (GFR)
immune complexes • May have
from systemic increased fibrin
immune disorders degradation
on the glomerular products (FDP),
membrane cryoglobulins and
IgA immune
complex
depositions
• Goodpasture •Attachment of a •Hemoptysis and • Macroscopic • Cytotoxic
Syndrome cytotoxic antibody dyspnea followed hematuria antibody
- Morphological changes formed during viral by hematuria Proteinuria following viral
resembling crescentric respiratory • progression to RBC casts respiratory
GN infections to Chronic diseases
- Autoimmune disorder glomerular and glomerulonephritis •
against glomerular and alveolar basement to end-stage renal Antiglomerular
alveolar basement membranes failure is common basement
membranes membrane
antibody
• Wegener Antineutrophilic Pulmonary Macroscopic Antineutrophilic
Granulomatosis cytoplasmic symptoms hematuria peripheral or
autoantibody including Proteinuria cytoplasmic
binds to hemoptysis RBC casts antibody
neutrophils in develop first -
vascular walls followed by renal (elevated serum Antineutrophilic
producing involvement and creatinine and cytoplasmic
granulomas, possible BUN) antibody
damage to small progression to end- (ANCA)
vessels in the stage renal failure *p-ANCA = fixed
lungs and in ethanol;
glomerulus perinuclear
pattern
*c-ANCA = fixed
with
formaldehyde;
granular
throughout the
cytoplasm
• Henoch-Schönlein Occurs primarily Initial appearance Macroscopic Stool occult
Purpura in children of purpura (raised, hematuria blood
following viral red patches on the Proteinuria
respiratory skin) RBC casts
infections; a followed by blood
decrease in in sputum
platelets disrupts and stools and
vascular integrity eventual renal
involvement (mild
to heavy
proteinuria with
 RBC cast), the
most serious
complications

Complete recovery
is common, but
may progress to
renal failure
• Membranous Thickening of the Slow progression Microscopic Antinuclear
Glomerulonephritis glomerular to the nephrotic hematuria antibody
membrane syndrome or Proteinuria (very Hepatitis B
following IgG possible remission high protein) surface antigen
immune complex Fluorescent
deposition treponemal
associated with antibody-
systemic disorders absorption test
(FTA-ABS)
• Membranoproliferative Cellular Slow progression Hematuria Serum
glomerulonephritis proliferation to chronic Proteinuria complement
(MPGN) affecting the Glomerulonephritis levels
capillary walls or or nephrotic (decreased)
the glomerular syndrome
basement →Association
membrane, • Type 1: with
possibly immune- increased Autoimmune
mediated cellularity in the disorders,
subendothelial infections,
cells of the malignancies
mesangium
→Thickening of
capillary walls
→progress to
nephrotic
syndrome
 • Type 2:
extremely dense
deposits in the
glomerular
basement
membrane
→Poor prognosis
→experience
symptoms of
chronic
glomerulonephritis
• Chronic Marked decrease Noticeable Hematuria Increased BUN
Glomerulonephritis in renal function decrease in renal Proteinuria and Serum
→Progression from resulting from function Glucosuria creatinine
previous glomerular damage progressing to Cellular and eGFR (markedly
disorders precipitated by renal failure granular casts decreased)
other renal →Fatigue, anemia, Waxy and broad Electrolytes
disorders hypertension, casts (imbalanced)
edema, oliguria
gradually
worsening
• Immunoglobulin A Deposition of IgA Recurrent (early stages) Serum IgA
Nephropathy (Berger’s (complexes) on the macroscopic Macroscopic or (increase)
Disease) glomerular hematuria microscopic
→Most common cause of membrane following exercise Hematuria
glomerulonephritis resulting from with slow → from exercise or
→children and young increased levels of progression infection with
adults serum IgA to chronic spontaneous
glomerulonephritis recovery
(late stages)
See Chronic
glomerulonephritis
→20 years later,
gradual
progression
 →Granular and
disintegrating
RBC casts
NEPHROTIC SYNDROME Disruption of the Acute onset Heavy proteinuria Serum albumin
shield of negativity following systemic ( Marked (depleted)
and damage to the Shock (low blood proteinuria >3.5 Lipids
tightly fitting pressure to the g/day) increased:
podocyte barrier kidney) Microscopic Cholesterol
resulting in Gradual hematuria Triglycerides
massive loss of progression from Renal tubular
protein and lipids other glomerular cells
disorders and then Oval fat bodies
to renal failure Fat droplets
Fatty and waxy
Edema from loss of casts
oncotic pressure

Tubular damage
Minimal Change Disease Disruption of the allergic reactions, Heavy proteinuria Serum albumin
podocytes recent Transient Cholesterol
→aka. Lipid nephrosis occurring primarily immunization, and hematuria Triglycerides
in children with possession Fat droplets
edema following of the human normal BUN
allergic reactions leukocyte and
and antigen-B12 creatinine levels
immunizations (HLA-B12) antigen
Frequent complete
remission following
corticosteroid
treatment
Good prognosis,
steroids, remission
Focal Segmental Disruption of May resemble Proteinuria Drugs abuse
Glomerulosclerosis podocytes in nephrotic (moderate to (Heroin and
certain areas of syndrome heavy) analgesic)
glomeruli or minimal change Microscopic HIV tests
associated with disease but affects hematuria IgM and C3
heroin and only certain Macroscopic or immune
analgesic numbers and microscopic deposits
abuse and AIDS areas hematuria
of glomeruli;
Alport syndrome Genetic disorder Slow progression (early stages) Genetic testing
➔ Males more severely (Inherited sex- to nephrotic See Nephrotic
affected linked and syndrome syndrome
autosomal and end-stage (late stages)
disorder) showing renal disease Microalbuminuria
lamellated and
Thinning Macroscopic
glomerular hematuria with
basement respiratory
membrane infections by age 6
years

Mild to persistent
hematuria, later
nephrotic
syndrome, renal
failure for
some
Diabetic nephropathy • Glomerular (late stages) Blood Glucose
→Most common cause of basement See Chronic
end-stage renal disease membrane glomerulonephritis Reason for early
thickening microalbumin
• Increased testing
proliferation of
mesangial cells
 • Increased
deposition of
cellular and
acellular material
within matrix of
Bowman’s capsule
and around
capillary tufts
• Deposition
associated with
glycosylated
proteins from
poorly controlled
diet
• Sclerosis of
vascular structure

TUBULAR ETIOLOGY CLINICAL PRIMARY OTHER

DISORDERS COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
• Acute Tubular Damage to renal Acute onset of Microscopic Hemoglobin
Necrosis tubular cells renal dysfunction hematuria Hematocrit
caused by usually Proteinuria Cardiac enzymes
Ischemia resolved when Renal tubular
(Ischemia: severe underlying cause is epithelial cells
decrease in blood corrected Renal tubular
flow epithelial cell casts
• Trauma, surgery, Hyaline, granular,
cardiac failure, waxy, broad casts
electricity,
toxogenic bacteria,
anaphylaxis) or
nephrotoxic
 agents:
aminoglycosides,
amphotericin B,
ethylene glycol,
heavy metals,
mushroom
poisoning,
hemoglobin,
myoglobin
HEREDITARY AND
METABOLIC
TUBULAR
DISORDERS
• Fanconi Inherited in Generalized defect Glucosuria w/ Serum and urine
Syndrome association with in renal tubular Blood glucose electrolytes
➔ The disorder most cystinosis and (Generalized (normal) (electrolyte
frequently Hartnup disease or proximal Possible cystine imbalance)
associated with acquired through convoluted tubule crystals Amino acid
tubular exposure to toxic reabsorption chromatography
dysfunction agents failure) Mild proteinuria
requiring Low urinary pH
supportive therapy

Complication of
multiple myeloma,
renal transplant
• Alport Syndrome
• Uromodulin- Inherited defect in Continual (early stages) Serum uric acid
Associated the production of monitoring of renal Renal tubular
Kidney Disease normal function epithelial cells
uromodulin by the for progression to
renal tubules and renal failure and (late stages)
increased uric acid possible kidney See chronic
causing gout transplantation glomerulonephritis
• Diabetic
Nephropathy
→Most common
cause of end-stage
renal disease
• Nephrogenic Inherited defect of Requires Pale yellow, Low ADH testing
Diabetes tubular response to supportive therapy specific gravity,
Insipidus ADH to prevent polyuria, possible
or acquired from dehydration negative results
medications for other tests

Two types
1. Nephrogenic:
failure of tubules to
respond to
antidiuretic
hormone
(ADH), inherited
sex-linked recessive
or lithium and
amphotericin
B exposure,
polycystic kidneys
and sickle cell
anemia
2. Neurogenic:
failure to produce
ADH
• Renal Glycosuria Inherited Benign disorder Glycosuria w/ Blood glucose
➔ affects only the autosomal Blood glucose
reabsorption of recessive trait (normal)
glucose
• Decreased
number of glucose
 transporters in
tubules
• Decreased affinity
of transporters for
glucose

INTERSTITIAL • Infections and inflammations affecting the interstitium and the tubules
DISORDERS • Most common renal disease is urinary tract infection (UTI)
• Cystitis (bladder infection) is very common
• Untreated: progresses to upper urinary tract
• Many WBCs, bacteria, increased pH, mild proteinuria, hematuria
• WBCs in urine called pyuria
ETIOLOGY CLINICAL PRIMARY OTHER
COURSE URINALYSIS SIGNIFICANT
RESULT TESTS
Cystitis Ascending bacterial Acute onset of Leukocyturia Urine culture
infection of the bladder urinary frequency Bacteriuria
and burning Microscopic
resolved with hematuria
antibiotics Mild proteinuria
Increased pH
Acute Pyelonephritis Infection of the renal Acute or rapid Leukocyturia Urine culture
tubules and onset of urinary Bacteriuria
interstitium related to frequency, WBC casts
interference of urine burning, and Bacterial casts
flow to the bladder, lower back pain Microscopic
reflux of urine from the resolved with hematuria
bladder, and untreated antibiotics Proteinuria
cystitis
• Ascending movement Urinalysis: similar
of bacteria to cystitis with
• Conditions affecting one
emptying of bladder exception:
• Calculi, pregnancy, presence of WBC
reflux of urine from casts
 bladder to ureters
Chronic Recurrent infection of Frequently Leukocyturia Urine culture
Pyelonephritis the renal tubules diagnosed in Bacteriuria BUN
and interstitium children; requires WBC casts Creatinine
caused by structural correction of the Bacterial casts eGFR
abnormalities affecting underlying Granular, waxy,
the flow of urine structural broad casts
• Damage to tubules, defect Hematuria
possible renal failure Possible Proteinuria
• Congenital structural progression to
defects causing reflux renal failure • Early urinalysis
are most common similar to acute
cause pyelonephritis
• Can affect emptying • Later granular,
of collecting ducts waxy, and broad
casts; increased
protein,
hematuria, ↓ SG
Acute Interstitial Allergic inflammation of Acute onset of Hematuria Urine eosinophils
Nephritis (AIN) the renal interstitium renal dysfunction Proteinuria BUN
and tubules often Leukocyturia Creatinine
in response to certain accompanied WBC casts eGFR
medications (penicillin, by a skin rash
methicillin, Resolves following WBC (increased,
ampicillin, discontinuation of eosinophils)
cephalosporins, medication No bacteria
NSAIDs, thiazide and treatment
diuretics) with
corticosteroids
RENAL FAILURE

ACUTE RENAL FAILURE CHRONIC RENAL FAILURE

• Sudden onset, often reversible • Progression from original disorders to end-stage
• Decreased blood flow (prerenal), acute disease renal disease
(renal), renal calculi and • GFR <25 mL/min, ↑↑ BUN and creatinine levels
tumors (postrenal) (azotemia), electrolyte
• Urinalysis related to cause imbalance, isosthenuria, proteinuria, renal gycosuria;
• RTE cells = decreased blood flow ↑ granular,
• RBCs = glomerular damage waxy, broad casts
• WBCs and casts = infection/inflammation
• Urothelial cells = possible bladder tumor

CAUSES OF ACUTE RENAL FAILURE

PRERENAL Decreased blood pressure/cardiac output
Hemorrhage
Burns
Surgery
Septicemia
RENAL Acute glomerulonephritis
Acute tubular necrosis
Acute pyelonephritis
Acute interstitial nephritis
POSTRENAL Renal calculi
Tumors
RENAL LITHIASIS
• Renal calculi (kidney stones) in calyces and pelvis of kidney, ureters, bladder
• Staghorn, round and smooth, barely seen
• Severe back pain radiating from lower back to legs when passing
*microscopic hematuria = primary urnalysis finding in renal calculi
• Lithotripsy: high-energy shock waves break up stones
• Also surgical removal

• Formation conditions similar to crystals

• pH, concentration, urine stasis
• No exact cause of formation known
• Increased in the summer, dehydration
• Types of stones
• 75% calcium oxalate or phosphate
• Magnesium ammonium phosphate (stuvite)
• UTI and ↑ pH, like triple phosphate crystals
• Uric acid: increased purine diet
• Cystine: hereditary cystinosis
STUDY QUESTIONS
1. Most glomerular disorders are caused by:
- B. Immunologic disorders
2. Dysmorphic RBC casts would be a
significant finding with:
- A. Goodpasture syndrome
- B. Acute glomerulonephritis
- D. Henoch-Schönlein purpura
*C. Chronic pyelonephritis = WBC cast
3. Occasional episodes of macroscopic
hematuria over periods of 20 or more years
are seen with:
- B. IgA nephropathy
4. Antiglomerular basement membrane
antibody is seen with:
- C. Goodpasture syndrome
5. Antineutrophilic cytoplasmic antibody is
diagnostic for:
- B. Wegener granulomatosis
6. Respiratory and renal symptoms are
associated with:
- B. Wegener granulomatosis
- C. Henoch-Schönlein purpura
- D. Goodpasture syndrome
- * A. IgA nephropathy = only renal
7. The presence of fatty casts is associated
with all of the following:
- A. Nephrotic syndrome
- B. Focal segmental glomerulosclerosis
- D. Minimal change disease
- * C. Nephrogenic diabetes insipidus = no cast
8. The highest levels of proteinuria are seen with:
Nephrotic syndrome
9. Ischemia frequently produces: Acute renal
tubular necrosis
10. A disorder associated with polyuria and
low specific gravity is: Nephrogenic diabetes
insipidus
11. An inherited disorder producing a
generalized defect in tubular reabsorption is:
Fanconi syndrome
12. A teenage boy who develops gout in his
big toe and has a high serum uric acid should
be monitored for: Uromodulin-associated
kidney disease
13. The only protein produced by the kidney
is: Uromodulin
14. The presence of renal tubular epithelial
cells and casts is an indication of: Acute
tubular necrosis
15. Differentiation between cystitis and
pyelonephritis is aided by the presence of: WBC
casts
16. The presence of WBCs and WBC casts
with no bacteria is indicative of: Acute
interstitial nephritis
17. End-stage renal disease is characterized
by all of the following:
- Isosthenuria, Azotemia, Electrolyte
imbalance; Except: A. Hypersthenuria
18. Prerenal acute renal failure could be
caused by: Massive hemorrhage
19. The most common composition of renal
calculi is: Calcium oxalate
20. Urinalysis on a patient with severe back
pain being evaluated for renal calculi would be
most beneficial if it showed: Microscopic
hematuria