Science Medicine Nephrology

Renal- Glomerular diseases

Leave the first rating

Terms in this set (69)

A heterogeneous collection insults to the filtering

unit of the kidney (the glomerulus)

Hallmark: alteration in glomerular permeability and

Glomerular diseases
selectivity→proteinuria ±hematuria

Disease may be PRIMARY or part of a systemic

disease such as DM, systemic lupus or vasculitis

Proteinuria
Hematuria
Clinical manifestations of
Pyuria
glomerular disease
Vascular disease
Reduction of GFR

Acute developing over days

Time Span of glomerular disease Subacute developing over weeks
Chronic developing over months or years

Two main immune mechanisms of injury

-Humoral immunity: immunoglobulins
-Cell-mediated immune injury

Deposition of deposits of immunoglobulins &

Mechanisms of Glomerular Injury complement seen on immunofluorescent staining

Infiltration with neutrophils, platelets, macrophages

Antibodies to the GBM develop in certain forms of

Glomerulonephritis.
 Hyaline:
-Strenuous exercise
-Congestive heart failure
-Diabetic nephropathy
-Chronic renal failure

WBC
-Acute pyelonephritis
-Interstitial nephritis

Waxy
-Severe tubular atrophy
-Renal failure
Casts Found in Various -Transplant rejection
Conditions
RBC
-Acute glomerulonephritis
-Lupus nephritis
-Goodpasture syndrome

SBE
-Renal infarct
-Granular
-Nephrotic syndrome
-Pyelonephritis
-Glomerulonephritis
-Transplant rejection
-Lead toxicity

Glomerular inflammation with leakage of RBC's to

produce a RBC Cast

Most matrix or "glue" that cements urinary casts

Red Blood Cell Casts together is Tamm-Horsfall mucoprotein, although
albumin & some globulins are also incorporated.

Indicative of glomerulonephritis, with leakage of

RBC's from glomeruli, or severe tubular damage.
 Casts which persist may break down, so that cells
forming it are degenerated into granular debris, as
Granular Casts has occurred in this granular cast.

Roughly rectangular shape.

Nephritic
-Active urine sediment, often with RBC casts
-Proteinuria, variable degree
-Patient often has azotemia, edema, hypertension
-Common causes: glomerulonephritis, vasculitis (SLE,
Wegener's)
"Nephritic" vs "Nephrotic" Urine
Nephrotic
-Benign urine sediment, with heavy proteinuria as the
main finding
-Patient may have azotemia, edema, hypertension
-Causes: idiopathic glomerular lesions, systemic
illness (diabetes, amyloidosis)
 Isolated proteinuria
-Presence of greater than 150 mg or urinary protein/
day

Isolated hematuria: > 2-3 RBC per hpf in spun urine,

or painless, nonclotting, visible blood in urine
(macroscopic)
-Glomerular hematuria: confirmed by presence of
deformed or dysmorphic RBCs and RBC casts in
urine; supported by proteinuria.

Clinical Presentations of Nephrotic syndrome: clinical triad of:

Glomerular Disease -Proteinuria > 3.5 g/day
-Hyperlipidemia
-Hypoalbuminemia

Acute Nephritic Syndrome

-"Nephritic Urinary Sediment": hematuria, pyuria,
cellular & granular casts, & varying degrees of
proteinuria (usually non-nephrotic range)
-Renal Function: may have oliguria with rising BUN
and creatinine
-Laboratory evaluation should include measurement
of serum complement levels
 Detailed H/PE
-Onset & timing
-Associated PE Findings

Urine microscopy to r/o hematuria, RBC casts, oval

fat bodies or fatty casts

Evaluation of Glomerular
24 hr CC and proteinuria
Disease

BUN -Creatinine-lytes

Assessment for anemia, thrombocytopenia,

eosinophilia, microangiopathic hemolysis

Untimely a specific dx may rely on a renal biopsy

always includes three components

-Light microscopy
Renal Biopsy -Electron microscopy
-Immunofluorescent staining for immunoglobulins &
complement components
 Definition: Proteinuria > 3.5 g/24 h

Frequently accompanied by low albumin, edema,

hyperlipidemia, lipiduria

"Bland" vs. "Active" urinary sediment

"Bland": pure nephrotic syndrome
"Active" shows evidence of inflammation: RBC's, casts,
WBC's

Nephrotic Syndrome
1/3 of patients have a systemic disease
-DM
-SLE
-Amyloidosis

Remainder have primary renal disease

-Adults: most common is membranous nephropathy
-Children: "minimal change disease"(nil disease)

Renal Biopsy often required for diagnosis

Increased risk of atherosclerosis

Increased risk of thromboembolic events

Risks of nephrotic syndrome

Increased risk of infection

In long standing nephrotic syndrome decreased GFR

and HTN often develop
 Primary Glomerular Disease:
-Membranous Glomerulonephritis
-Minimal change disease (Synonyms: "nil" disease;
lipoid nephrosis; MCD)
-Focal segmental glomerulosclerosis (FSGS)
-Membranoproliferative GN
-Other proliferative GN (focal, "pure mesangial", IgA
nephropathy)

Causes of Nephrotic Syndrome

Systemic Disease:
-Diabetes Mellitus
-Systemic lupus erythematous(SLE)
-Drugs (gold, penicillamine, "street heroin")
-Infections (malaria, syphilis, hepatitis B, AIDS
-Malignancy (carcinoma, melanoma)
-Miscellaneous (bee-sting allergy, hereditary
nephritis)
-ANCA-associated vasculitis

Diet 1 g/kg high biologic value protein

-Consumption of large amounts of protein may
aggravate proteinuria through renal hemodynamic
effects and paradoxically cause more severe
hypoalbuminemia

Reduced cholesterol and saturated fat

General Principles of Treatment
Nephrotic Syndrome Sodium chloride 2-4 g/day

Bed rest will mobilize edema fluid

Diuretics

Thomboembolic event: patient treated with

anticoagulation according to standard practices
 Thickening of GBM on light microscopy

Subepithelial immune deposits of IgG & complement

on EM

Membranous Nephropathy
**Most common cause of nephrotic syndrome in
-pathology
adults > 60 years, & 2nd most common cause (after
-prevalence/epidemiology
focal sclerosing GN) in all adults

Uncommon in children & adolescents

M:F 2-3:1

I. Primary (idiopathic)
II. Secondary: hepatitis B, syphilis, carcinomas, gold
therapy, D-penicillamine, captopril; collagen vascular
Membranous Nephropathy
diseases
causes

About 50% progress to end-stage renal disease by

5-10 years; may have spontaneous remissions

Associated with underlying malignancy

-Lung, stomach, breast, colon, prostate
-Nephrotic syndrome may precede clinical evidence
Membranous Nephropathy of cancer by up to 1 year
associated with...
Associated with certain drugs or other agents
-Gold, penicillamine, hydrocarbons, mercury,
formaldehyde, captopril

85-90% of nephrotic syndrome in children 2-8 y/o

Minimum Change Nephrotic
M:F 2:1
Syndrome epidemiology
20% of nephrotic syndrome in adults

Bland urinary sediment

Bx: light microscopy normal; EM shows fusion of

Minimum Change Nephrotic
podocyte (visceral epithelial cell) foot processes
Syndrome dx

Renal failure does not occur unless other disease

process present
 Highly responsive to corticosteroids (in children)
Minimum Change Nephrotic
85-90% of children respond to steroids
Syndrome tx
Adults may require longer courses of steroids

Persistent albuminuria (> 300 mg/24 hr), progressive

decline in GFR, elevated BP

Urinary albumin > 30 mg/24 h strongly predicts

development of diabetic nephropathy
Diabetic Nephropathy
Diabetic retinopathy found in > 90% of patients with
type I DM with diabetic nephropathy

Diabetic nephropathy single most important cause of

ESRD in U.S., 40% of all dialysis patients

Diabetic Nephropathy time Rare during first 5 years of DM

course Peak incidence after 15-20 years DM

Treatment: vigorous control BG; treat HBP; ACE

Diabetic neuropathy tx inhibitors have an antiproteinuric effect; may help in
microalbuminuria even with normal BP

Advanced diabetic nephropathy including nephrotic

Kimmelstiel-Wilson Disease
syndrome

5 stages;

Stage I: hyper filtration (increased GFR) and

microalbuminuria

Stage II: Silent Stage

Stages of Renal Disease in DM

Stage III. Incipient Nephropathy Stage: persistent
hyperfiltration early, but GFR starts to decrease;
early hypertension

Stage IV: fixed proteinuria, HTN, declining GFR

Stage V: ESRD

Type I vs. Type II Diabetes and
nephropathy
Factors that increase risk of
progression to ESRD among pts
with T2DM
Measures to Prevent Progression
Antihypertensives useful for
diabetics
Can Diabetic Nephropathy be
Prevented?
Acute Nephritic Syndrome
Most common cause of acute
nephritic syndrome
Approximately 40% of patients with type I & 20% of
patients with type II develop nephropathy.
Abundant evidence that risk of nephropathy with
progression to ESRD is similar in two groups.
HTN
Albuminuria or proteinuria
Smoking
Poor glycemic control (Insulin resistance)
Maintain BP in mid-normal range, 125/75, preferably
with use of ACE inhibitors
Reduce proteinuria to less than 1 g/day: ACE
inhibitors
Stop Smoking
ACEIs and ARBs
-try to use ACEIs because ARBs are expensive
Studies suggest that dietary modification & increase
physical activity can reduce risk of type 2 diabetes
Inhibition of renin-angiotensin system with ACE
inhibitor or angiotensin II-receptor antagonist
decrease both BP & albuminuria
Characterized by development over days of
azotemia, HTN, edema, hematuria, proteinuria &
sometimes oliguria (Non-nephrotic range)
RBC casts on UA
Proteinuria (1-2 g per 24 hr)
Most forms of acute GN are mediated by humoral
immune mechanisms
Post streptococcal glomerulonephritis
 Treatment supportive: diuretics, Rx. Hypertension

Antibiotics if Streptococcus cultured

Post Strep GN tx
Complete recovery occurs 90-95%

Proteinuria/hematuria may persist for 1-2 years

IgA Nephropathy is final diagnosis in 50% of patients

with asymptomatic hematuria submitted to renal
biopsy

Key finding on biopsy: mesangial IgA deposits

IgA Nephropathy (Berger's Most common form of glomerulonephritis worldwide

DIsease)
Typically presents as gross hematuria after a viral
(respiratory) illness

Men affected more than women 3:1

Renal biopsy required for diagnosis

Characterized by gradual onset of hematuria,

proteinuria, & renal failure which progresses over a
period of weeks to months
Rapidly Progressive
Glomerulonephritis (RPGN) Crescentic GN is usually found on renal Bx.
-labs
-bx Some 50 % require dialysis within 6 months of dx.
-prognosis
-tx Combination of glucocorticosteroids in pulsed
doses, cyclophosphamide & intensive plasma
exchange may be useful although few prospective
clinical trial are available
 Pulmonary hemorrhage (cough, hemoptysis,
dyspnea) 70% (Goodpasture's syndrome)

Renal failure: rapid, oliguric, hematuric with modest

proteinuria
Anti-Glomerular Basement
Antibody Disease
Treatment: aimed at reducing circulating preformed
anti-GBM antibodies by daily plasma exchange for 14
days
Cytotoxic therapy with cyclophosphamide and
immunosuppression with corticosteroids

May be idiopathic or associated with other diseases

Important association with Hepatitis C
Three types:
Membranoproliferative
Type I most common; immune complexes, C
Glomerulonephritis (MPGN)
Type II "dense-deposit disease", C3 nephritic factor
in serum; activation of alternate C pathway
Type III mixed features

Autoimmune disease affecting skin, kidneys, joints,

serous membranes & blood vessels

Systemic Lupus
More common in women aged 20-40 M:F 9:1
Erythematosus(SLE)

Common presenting symptoms: fever, arthralgia,

typical malar or butterfly rash; photosensitivity

High-dose I.V. corticosteroids (methylprednisolone)

followed by oral

Cytotoxic agents(Cyclophosphamide)
SLE Treatment Options

Dialysis and Transplantation: many patients

experience improvement of other SLE-related
symptoms after starting dialysis
 Small-vessel vasculitis associated with necrotizing
granulomatous inflammation affecting upper & lower
respiratory tracts and kidneys

Renal pathology not specific for WG

Clinical features: fever, malaise, purpura rash,

Wegener's Granulomatosis(WG) pulmonary hemorrhage, sinusitis (septal perforation,
saddle nose deformity)

Prognosis poor without treatment (90% mortality 2

years)
Steroids and cytotoxic agents can produce remission
in about 75%
11% progress to ESRD

An increasing cause of chronic renal disease

Associated with heavy proteinuria (nephrotic

HIV-associated nephropathy syndrome range) & progressive renal failure
(HIVAN)
Usually diagnosed when CD4 count < 200

95% in young black men, mean age 33, M:F 10:1

Hereditary form of Glomerulonephritis

Usually presents in childhood with recurrent gross

hematuria, mild proteinuria, nephrotic syndrome is
rare
Hereditary Nephritis (Alport's)

Dx suggested by family history of kidney disease,

kidney failure, deafness & ocular abnormalities

Renal failure usually develops by age 30

 Isolated proteinuria/ Postural proteinuria
-Generally < 2 g protein/day
-Bland urinary sediment
-Normal renal function (GFR normal)
-Absence of proteinuria while lying flat and return of
proteinuria on standing
Asymptomatic Urinary
-Long-term prognosis excellent
Abnormalities

Isolated Hematuria/Benign recurrent hematuria

-Defined as asymptomatic hematuria after other
possibilities are excluded
-Renal biopsy normal
-50% remission after 5 years, good prognosis

Crescent formation in the B. Rapidly progressive glomerulonephritis

glomeruli are commonly seen in
which glomerulonephritis

A. Post streptococcal
glomerulonephritis
B. Rapidly progressive
glomerulonephritis
C. Berger's (IgA nephropathy)
D. Minimal change disease
(Lipoid nephrosis)
E. None of the above

The most common form of D. IgA nephropathy

primary glomerular disease
worldwide is:

A. Alport's syndrome
B. HIV-associated nephropathy
C. Post-streptococcal
glomerulonephritis
D. IgA nephropathy
You are on hospital rounds and A. Nephrotic syndrome
you evaluate a 50 year old male
with known glomerulonephritis.
Today, the patient has worsening
generalized edema,
hyperlipidemia,proteinuria in
excess of 3.5 grams per day and
hypoalbuminemia.

All of these findings are

consistent with:

A. Nephrotic syndrome
B. Nephritic syndrome
C. Uremic syndrome
D. Goodpasture's syndrome

What glomerular structure is C. Mesangium

affected in virtually all diabetics,
irrespective of the presence of
proteinuria?

A. Bowman's space
B. Afferent Arterioles
C. Mesangium
D. Basement membrane
E. Podocytes

Which of the following therapies D. Beta Blockers

are not beneficial in treating
diabetic kidney disease:

A. ACE inhibitors
B. ARB receptor antagonists
C. Aggressive blood sugar
control
D. Beta Blockers
A 43-year-old man has had A. Membranous glomerulonephritis
increasing malaise for the past 3
weeks. PE he has a BP of 150/95
mmHg and 1+ pitting edema of
the lower extremities to the
knees.
Dipstick UA shows no glucose,
blood, ketones, nitrite, or
urobilinogen, & microscopic UA
reveals no RBC/hpf and only 1
WBC/hpf. Additional laboratory
studies show a 24 hour urine
protein of 4.1 gm.
His serum creatinine is 2.2 mg/dL
with BUN of 40 mg/dL. His
hepatitis B surface antigen is
positive.

Which of the following is the

most likely diagnosis?

A. Membranous
glomerulonephritis
B. Systemic lupus
erythematosus(SLE)
C. Acute tubular necrosis
D. Diabetic nephropathy
E. Post-streptococcal
glomerulonephritis

Nephrotic range proteinuria in C. 3.5 grams protein/24 hours

adults is defined as greater than:
A. 1 gram protein/24 hours
B. 2 grams protein/24 hours
C. 3.5 grams protein/24 hours
D. 5 grams protein/24 hours
A 50-year-old man was A. Kimmelstiel-Wilson disease
diagnosed at age 15 with type 1
diabetes mellitus. His disease has
been poorly controlled, as
evidenced by elevated
hemoglobic A1C levels.
He develops a non-healing ulcer
of his foot at age 35. At age 45
he has an increasing serum urea
nitrogen and a urinalysis shows
specific gravity 1.012, pH 6.5, 2+
protein, no blood, 1+ glucose,
netaive leukocyte esterase,
negative nitrite, and no ketones.

Which of the following renal

diseases is he most likely to
have?
A. Kimmelstiel-Wilson disease
B. Papillary necrosis
C. Crescentic glomerulonephritis
D. Acute pyelonephritis

The most common cause of E. Membranous

Nephrotic Syndrome in Adults is
A. HIVB. Hepatitis C
C. Focal Sclerosis (FSGS)
D. Minimal change
E. Membranous

60-year-old male has diabetic A. ACE inhibitors

retinopathy, proteinuria,
hypertension, a serum creatinine
of 1.5 mg/dL, and CHF. What is
the preferred antihypertensive?

A. ACE inhibitors
B. Calcium channel blockers
C. Beta blockers
D. Alpha blockers
A 12-year-old boy is a member C. Alport syndrome
of a family with a history of renal
disease, with males more
severely affected than females.
He is found to have auditory
nerve deafness, corneal
dystrophy, and ocular lens
dislocation. A urinalysis shows
microscopic hematuria.
A renal biopsy is performed.
Microscopically, the glomeruli
show glomerular capillaries with
irregular basement membrane
thickening and attenuation with
splitting of the lamina densa. The
mesangial matrix is increased
and epithelial cells may appear
foamy.

Which of the following is the

most likely diagnosis?
A. Goodpasture's syndrome
B. IgA Nephropathy
C. Alport syndrome
D. Dominant polycystic kidney
disease
E. DM type I

Clinical findings that would help C. Hematuria & red blood cell casts
differentiate nephritic syndrome
from nephrotic syndrome
include

A. Edema
B. Hypertension
C. Hematuria & red blood cell
casts
D. Heavy proteinuria
E. White blood cell casts
Which of the following is the C. urine albumin: creatinine ratio
preferred screening test for
microalbuminuria?

A. urine protein electrophoresis

B. urine dipstick for protein
C. urine albumin: creatinine ratio
D. 24-hour urine for protein
E. 24-hour creatinine clearance

The cells that form the main C. mesangial cells

supporting structure of the
glomerulus are called"

A. macula densa
B. endothelium
C. mesangial cells
D. podocytes
A 36 YO Asian man with a E. IgA nephropathy
history of asthma presents with a
complaint of red urine.
He describes 5 days of nasal
congestion and dry cough. He
notes no sore throat, fever, chills,
myalgias, arthralgias, or flank
pain.
There is no family history of
renal disease. Urinalysis shows 1+
protein with 30-50 RBC but no
WBC.
The same symptom complex
occurred 6 months and twelve
months earlier. CBC and
peripheral blood smear is
normal. His serum creatinine is
normal.

Which one of the following is the

most likely diagnosis?
A. Nephrolithiasis
B. Transitional cell carcinoma of
the bladder
C. Hemolytic uremic syndrome
D. Post-streptococcal
glomerulonephritis
E. IgA nephropathy
Patients with solid tumors(lung, E. Membranous glomerulopathy
stomach, breast, colon, &
prostate) who develop nephrotic
syndrome usually have which
form of glomerular disease?

A. Minimal change disease

B. Diffuse proliferative
glomerulonephritis
C. Membranoproliferative
glomerulonephritis
D. Focal and segmental
glomerulosclerosis
E. Membranous glomerulopathy

The components of the D. Oliguria

nephrotic syndrome include all
of the following EXCEPT:

A. Proteinuria > 3.5 grams/day

B. Hypoalbuminemia
C. Edema
D. Oliguria
E. Hyperlipidemia

Which of the following E. All of the above

conditions produce marked
proteinuria (Excretion of > 3.5
grams daily) ?

A. Neprhotic Syndrome
B. Systemic lupus erythematosus
C. Renal vein thrombosis
D. Amyloidosis
E. All of the above
A 50-year-old man was A. Nodular glomerulosclerosis
diagnosed at age 15 with type 1
diabetes mellitus. His disease has
been poorly controlled, as
evidenced by elevated
hemoglobin A1C levels. He
develops a non-healing ulcer of
his foot at age 35. At age 45, he
has an increasing serum urea
nitrogen and a urinalysis shows
sp gr 1.012, pH 6.5, 1+ protein, no
blood, 1+ glucose, negative
leukocyte esterase, negative
nitrite, and no ketones.

Which of the following renal

diseases is he most likely to
have?
A. Nodular glomerulosclerosis
B. Hyperplastic arteriolosclerosis
C. Papillary necrosis
D. Crescentic glomerulonephritis
E. Pyelonephritis

Double contours ("tram-tracks") C. Membranoproliferative glomerulonephritis

of the glomerular capillary wall
are a characteristic histologic
feature of which glomerular
disease?

A. Minimal change disease

B. Membranous glomerulopathy
C. Membranoproliferative
glomerulonephritis
D. Focal segmental
glomerulosclerosis
E. Acute post-infectious
glomerulonephritis
Which of the following B. It is usually resistant to steroid therapy.
statements about minimal
change disease is FALSE?

A. It is the most common cause

of nephrotic syndrome in young
children.
B. It is usually resistant to steroid
therapy.
C. By light microscopy, the
glomeruli display no identifiable
abnormalities.
D. By immunofluorescence, no
glomerular immune deposits are
identified.
E. The major finding by electron
microscopy is foot process
effacement (i.e. fusion).

Which of the following A. It is more common in adults than children.

statements about hemolytic
uremic syndrome is FALSE?

A. It is more common in adults

than children.
B. It may follow a gastrointestinal
infection with Shigella or certain
strains of E. Coli.
C. The verotoxin is toxic to
endothelial cells by inhibition of
protein synthesis.
D. Outbreaks have been
associated with consumption of
undercooked hamburger meat.
E. The major pathologic finding
in the kidney is fibrin thrombosis
of glomerular capillaries and
small vessels.
Which disease is responsible for A. Minimal change disease
the most frequent form of
nephrotic syndrome in children?

A. Minimal change disease

B. IgA nephropathy
C. Poststreptococcal
glomerulonephritis
D. Henoch-Schönlein purpura
E.Hemolytic-uremic syndrome

The presence of which of the D. Red blood cell casts

following urinalysis findings is
most indicative of
glomerulonephritis

A. Oval fat bodies

B. Proteinuria
C. Broad waxy casts
D. Red blood cell casts
E. White blood cell casts

The most common cause of end- D. Diabetic nephropathy

stage renal disease in the United
States is

A. Chronic glomerulonephritis
B. Polycystic kidney disease
C. Hypertensive nephrosclerosis
D. Diabetic nephropathy