Glomerular

Diseases
RIA D. ESTEVEZ-IMPERIAL, MD
PEDIATRIC NEPHROLOGY

Hematuria
Normal

range hematuria is defined

as:
a. RBC = 0-3/hpf
b. RBC = 0-5/hpf
c. RBC = >3/hpf
d. RBC = >5/hpf

Hematuria
Hematuria

at least 5 RBCs/uL of urine

False (+):
- child w/ fever or after exercise
- menstrual blood
- alkaline urine pH>9
- contamination w/ oxidizing agents (H2O2)

Hematuria
False

negative:
- formalin (used as urine
preservative)
- high urinary concentrations of
ascorbic acid

Hematuria
Red urine w/o RBCs
- heme (+) urine presence of
either hemoglobin or myoglobin
- heme (-) urine ingestion of drugs,
foods, food dyes or presence of
urinary metabolites

Causes of hematuria
Glomerular:

from within the nephron

Non

glomerular:

from the pelvocalyceal

system, ureter, bladder
or urethra.

Acute Nephritic
Syndromes

Acute Nephritic Syndrome

Hematuria
Edema
Hypertension
Renal

insufficiency

Acute Post Streptococcal

Glomerulonephritis
Most

common form of nephritis in

children
Male predominance
3-7 years old

Acute Post Streptococcal

Glomerulonephritis
Group A B-hemolytic streptococcus
1-2

weeks after streptococcal

pharyngitis
3-6 weeks after streptococcal
pyoderma

Pathophysiology
Antigen-antibody
complex deposition
in kidney
Neutrophilic
infiltration
Inflammation of
glomerular
capillaries

Increased ECF
volume

Activation of
RAAS

Sodium and water

retention

Edema
Hypertension

Renal blood
flow

Renal
Insufficiency

Diagnosis
Urinalysis
RBCs,

RBC casts, proteinuria

Complete
C3

blood count anemia

low
Evidence of streptococcal infection

Phases of Acute PSGN

Oliguric
phase

Diuretic
phase

Recovery
phase

Management
Fluid

restriction
Salt restriction
Diuretics
Antibiotics (Penicillin)
Anti-hypertensives

Complications
Secondary to hypertension and renal failure
Encephalopathy

(10%)
Pulmonary congestion
Seizures
Uremia
Heart failure

What to monitor?
Renal

chart is very important

including :
daily

weighing of child

blood

pressure 6 hourly

Input

and urine output monitoring

diet

Salt restriction in case of high

blood pressure and edema

Bed

rest

Regular

monitoring of vital signs

Other Infections associated

with GN
Bacterial

Endocarditis (Viridans

strep)
Shunt infections (S.epidermidis)
Syphilis
Hepatitis B and C viruses
Candidiasis
Parasitic infections (malaria,
schistosomiasis, filiaria,
trypanosoma and toxoplasmosis

Isolated Glomerular Diseases

w/ Recurrent Gross
Hematuria

IgA Nephropathy
(Berger Nephropathy)
gross

hematuria often occurs an

upper respiratory or GI infection
may be assoc w/ loin pain
normal C3

Alport Syndrome
single

or recurrent episodes of gross

hematuria
1-2 days after an URI
extrarenal symptoms: hearing deficits
ocular abnormalities
Family history of renal disease

Thin Glomerular Basement

Membrane Disease
isolated hematuria in multiple
family members w/o renal
dysfunction
episodic gross hematuria may also
be present, after a respiratory
illness

Membranoproliferative GN
- Most common cause of chronic
glomerulonephritis in older children &
young adults.
Diagnosis made by renal biopsy
Presents with proteinuria
50% progress to ESRD
Low C3

Systemic Dieseases with

Glomerulonephritis

Lupus Nephritis
Presents

with symptoms of SLE

Lupus Nephritis
May

be the only manifestation (20%)

Diagnosis:
detection

of circulating antinuclear
antibodies
confirmed by demonstrating Ab that react w/
double stranded DNA
C3

& C4 levels are reduced in active

disease

HSP Nephritis
Small

vessel vasculitis
criteria:
palpable purpuric rash arthritis
abdominal pain
glomerulonephritis
typically appear 1-3 wks after an URTI
Renal manifestations occur up to 12 wks
after the initial presentation of HSP
Prognosis: favorable w/ CKD risk at 2-5%

Hemolytic Uremic Syndrome

Triad:

1. microangiopathic hemolytic anemia

2. thrombocytopenia
3. uremia
Etiology: diarrhea caused by Shiga like toxin
prod E. coli 0157:H7 precedes 80% of HUS
Less commonly, may present after an URTI

Hemolytic Uremic Syndrome

Most

common in children < 4yo

Sudden onset of pallor, irritability,
weakness, lethargy & oliguria
occurring 5-10 days after the initial
GI or respiratory illness
PE: dehydration, edema, petechiae,
hepatosplenomegaly & marked
irritability

Hemolytic Uremic Syndrome

Management:

Supportive care
attention to fluid & electrolytes
control of hypertension
aggressive nutrition
early institution of dialysis

Rapidly Progressive GN
Rapid

progression to ESRD
Histopathology: crescents

Goodpasture Disease
Characteristics:

- pulmonary hemorrhage
- GN assoc w/ antibodies directed
against epitopes of type IV collagen
w/in the alveolar basement
membrane of the lungs & GBM

Non glomerular causes of

hematuria

Renal Vein Thrombosis

In

NB & infants:
asphyxia
dehydration
shock
sepsis
congenital hypercoagulable
states
infants born to mother w/ DM

Renal Vein Thrombosis

In

older children:
nephrotic syndrome
cyanotic heart disease
inherited hypercoagulable states
exposure to angiographic
contrast agents

Renal Vein Thrombosis

Sudden

onset of gross hematuria &

unilateral or bilateral flank masses

Ultrasound

shows marked enlargement,

& radionuclide studies reveal little or no
renal function in the affected kidney(s)

Doppler

flow studies of the inferior vena

cava & renal vein confirm the diagnosis

Renal Vein Thrombosis

Primary

treatment:
supportive care: correction of fluid &
electrolyte imbalance
treatment of renal insufficiency
Treatment w/ anticoagulation &
thrombotic agents is controversial

Whats wrong with this picture?

Hematologic Diseases causing

hematuria
Sickle

Cell Nephropathy
- results from microthrombosis 2 to
sickling in the relatively hypoxic,
acidic, hypertonic medulla where
vascular stasis is present
- addnl symptoms: polyuria, RTA
and proteinuria

Hematologic Diseases causing

hematuria
Inherited

and Acquired disorders of

coagulation*
- hemophilia
-DIC
-thrombocytopenia

*hematuria is not usually the presenting

complaint but develops after other
manifestations

Anatomic Abnormalities
associated with hematuria
ARPKD:

bilateral flank masses in infant w/:

pulmonary hypoplasia,
oligohydramnios
HTN
absence of renal cysts by
sonography of parents

Anatomic Abnormalities
Associated w/ Hematuria
ADPKD

4th to 5th decade of life

affecting many organ systems
mostly affecting first degree
relatives

Lower urinary tract causes of

hematuria
Hemorrhagic

cystitis

Urinary

tract infection
Drugs: Cyclophosphamide
Heavy

exercise benign condition

w/ hematuria resolving w/in 48 hrs
after cessation of exercise

Other causes of Hematuria

Tumors
Trauma

Proteinuria

Proteinuria: Screening
1. Urine dipstick test sensitive to
albumin
- negative
- trace (10-20 mg/dL)
- 1 + (30 mg/dL)
- 2+ (100 mg/dL)
- 3+ (300 mg/dL)
- 4+ (1000-2000 mg/dL)

Proteinuria
2. Quantification:
- 24-hr Urine CHON excretion
detects all kinds of protein including
globulin & low molecular wt protein
- Random Urine Chon/Crea ratio
fairly accurate measure of total daily CHON
excretion

Proteinuria
Normal:

<4mg/m2/hr
Abnormal excretion: 4-40 mg/m2/hr
Nephrotic range: >40 mg/m2/hr

Proteinuria
False

(-):
- dilute urine (SG < 1.005)
- or disease states in w/c dominant urinary protein is
not albumin

False

(+):
gross hematuria
contamination w/ antiseptic agents
urinary pH > 7
phenazopyridine therapy

Proteinuria: Causes
1.

Transient Proteinuria
- benign condition
- occurs in physiologic situations
w/o overt renal disease

Transient Proteinuria
Causes:

temperature >38.3C
dehydration
heart failure
stress

exercise
cold exposure
seizures

Transient Proteinuria
Urine

dipstick tests rarely exceed

2+
No evaluation or therapy needed

Proteinuria: Orthostatic
(Postural)
a.

Features:
- negative to trace morning sample
- abnormally elevated in the
afternoon or upright position
- benign
- rare in adult

Proteinuria: Causes
Orthostatic Proteinuria
Most

common cause of persistent

proteinuria in school aged children &
adolescents
Excrete normal or minimally increased
amts of protein in supine position
In upright position, protein excretion
increases 10-fold

Proteinuria: Causes
2. Overflow Proteinuria
- increased plasma concentration of
filterable proteins

Proteinuria:
Overflow(Prerenal)
b. Diagnosis:
Myoglobinuria
B2-microglobulinemia
Myelomonocytic leukemia
Bence Jones proteinuria

Proteinuria: Causes
3. Glomerular Proteinuria
1. Loss of (-) charges in the GBM
2. increase pore size
3. direct injury to GBM
4. disease related changes in
glomerular hemodynamics

Proteinuria: Glomerular
Nephrotic Syndrome
IgA Nephropathy
Alport syndrome
DM Nephropathy
Goodpasture
MPGN
Lupus Nephritis
RPGN
HSP Nephritis
Mesangial Proliferative GN

Proteinuria: Causes
4. Tubular Proteinuria
impaired tubular reabsorption of
normally filtered urine

Proteinuria: Tubular

Hereditary diseases (Wilsons)

Toxic injury (cadmium, lead, gentamicin, vit D)
Metabolic causes (hypokalemia)
Tubulopathies (Fanconi syndrome, Dent disease
Others: diuretic phase of ATN)

Nephrotic Syndrome
Proteinuria
Hypoalbuminemia
Hyperlipidemia
Edema

Congenital Nephrotic
Syndrome

- occurs within the 1st 3 months of life

- most common: Finnish type
(Scandinavian descent)
- massive proteinuria, marked edema and
large placenta
- progressive renal failure w/ death by
age 5y/o

Secondary Nephrotic
Syndrome

suspected in pts w/:

age >8yo
hypertension
hematuria
renal dysfunction
extrarenal symptomatology
depressed C3

Idiopathic Nephrotic
Syndrome
Primarily

a pediatric disorder (15

times more than in adult)
Males
2-6 years old

Pathophysiology

Increased
permeability of
the glomerular
capillary wall

Leakage of
protein

hypoalbuminemi
a

Edema

Clinical Manifestations
Edema

(periorbital, bipedal, genital,

pleural effusion)
Anorexia
Irritability
Abdominal pain
Diarrhea

Diagnosis
Urinalysis
Low

serum albumin (<2.5 g/dL)

Hypercholesterolemia
Anemia
Normal C3

Nephrotic Syndrome
3

histologic types:
- minimal change disease
- mesangial proliferation
- focal segmental glomerulosclerosis

When to admit?
Severe
Large

symptomatic edema:

pleural effusions
Ascites
Genital edema

Management
Supportive
Fluid and sodium restriction as necessary
Diuretics
Elevation of scrotum with pillows
Albumin
hypertension,

congestion and heart failure with

rapid infusion
Mandates close monitoring of volume status
and renal function

What to monitor?
Do

chart of renal disease

Intake:

The fluid intake of the child is recorded

following each meal. It is important to keep
proper fluid balance sheets (intake and output
records)

Urine:

The patients urine must be carefully

measured

Body

weight: The patient is weighed daily to

determine changes in the degree of edema

How to care for a nephrotic

patient?

Care of the skin : the skin is bathed daily and whenever

necessary. Special attention is given to the neck, under arms,
groin and other moist area of the body. The male genitalia
are bathed and dusted with a soothing powder. Never use
adhesive because it leads to scratching and infection.

Position : The patient is turned frequently to prevent

respiratory infection, the childs head is elevated from time
to time during day to reduce edema of eyelids, it may be
necessary to bathe the eyes to prevent the accumulation of
the exudates.

Always keep him away from patient with infection.

Management
Medical Treatment
Prednisone
Initial

Therapy: 60 mg/BSA x 6-8 weeks

Maintenance therapy: 40 mg/BSA EOD x
4 weeks then tapered over 3 months
Other

immunosuppressants:

Mycophenolate

mofetil, Cyclosporin A,
Cyclophosphamide, Azathioprine

Nephrotic syndrome
Steroid

dependent:
relapse while on alternate day therapy or w/in 28
days of stopping prednisone

Frequent

relapsers:
relapse >4x in a 12 month period

Steroid

resistant:
fail to respond to prednisone w/in 8 wks

Complications
Increased

susceptibility to bacterial
infections (spontaneous bacterial
peritonitis)
Thromboembolism
Myocardial infarction