Renal: Part I

Test Question
You like having 15 questions during
board review instead of 10.

A. True
B. False
Question #1
The mother of a 5-year-old female brings her daughter to
your clinic on Monday morning because when she went
potty this morning her urine was red. She is afebrile and
has no complaints of dysuria or musculoskeletal pain. Her
BP is 94/55 and her urinalysis is negative for blood,
protein, nitrites, and leukocyte esterase. Microscopy
reveals 1 RBC and no casts. You notice scratches on the
girls fingers, and her mother reports that they have just
returned from a friends farm and went berry pickin over
the weekend.
Of the following, the next MOST appropriate step is:
A. Reassurance
B. Renal U/S
C. Creatinine kinase
D. BMP
E. Urine culture
Hematuria
5 or more RBCs per high-power field in 3
consecutive fresh, centrifuged specimens
obtained over the span of several weeks
(+) dipstick for heme
Myoglobinuria
Hemoglobinuria
(-) dipstick for heme
Drugs (sulfa, nitrofurantoin, salicylates,
phenazopyridine, phenolphthalein)
Toxins (lead, benzene)
Food (food coloring, beets, blackberries, rhubarb,
paprika)
Glomerular Bleeding
Discolored urine
RBC casts
Distorted RBC morphology
Causes

Microscopic Macroscopic (Gross)

Symptomatic
Asymptomatic + proteinuria
Isolated asymptomatic
Gross Hematuria
Underlying cause is found in 56% of
cases
Common causes:
UTI
Trauma
Coagulopathy
Crystalluria
Nephrolithiasis
Question #2
The mother of a 3-year-old male comes to clinic for follow-up of
hematuria. The results of todays UA are:
pH 6.0
3 + blood
Negative for protein, nitrite, and leukocyte esterase
10 to 20 RBCs/HPF
0 WBCs
These results are similar to the UA you performed 2 weeks ago. The
patients BP is 105/58, but otherwise the physical exam is normal.
Being the astute clinician that you are, you ask mom about any family
history of renal disease. She mentions that both of her older brothers
are on dialysis.
Of the following, the MOST likely cause of this patients hematuria is:
A. Benign familial hematuria
B. Polycystic kidney disease
C. Alport syndrome
D. Sickle cell disease
E. Ureteropelvic junction obstruction
Family History is Important!
Alport syndrome
X-linked (85%), autosomal recessive, and
autosomal dominant
Mutation in Type IV collagen of GBM
Kidney failure by 2nd or 3rd decade in males
Sensorineural hearing loss
Anterior lenticonus
Females may only have microhematuria
Family History is Important!
Benign familial hematuria
Autosomal dominant
But many people are unaware
Also mutation in type IV collagen of GBM
Microscopic hematuria with occasional gross
episodic hematuria (<10%)
Proteinuria and HTN are unusual
Family History is Important!
Sickle cell disease and trait
Occlusion of the vasa recta capillaries result in
renal infarct
Hematuria more common in males
Unilateral, left more common
Recurrence in 40% of cases
Contributing factors
Hypoxia
Acidosis
High osmolality
Stasis
Symptomatic Microscopic
Hematuria
If accompanied by elevated proteinuria on
first morning urine higher likelihood of
underlying renal disease
Clinical manifestations
Nonspecific
Fever, malaise, weight change
Extrarenal
Malar rash, purpura, arthralgia/arthritis, headaches
Localized
Dysuria, suprapubic pain, flank pain, edema,
oliguria
Question #3
The results of a urinalysis for a 13-year-old male in your
practice reveal:
pH 6.0
3+ blood
Negative glucose, protein, nitrite, and leukocyte esterase
5 to 10 RBCs/HPF
He has never noticed any changes in his urine, has no
complaints, takes no medications, and has no family
history of kidney disease.
Of the following, the MOST likely associated urinary
finding is:
A. Bacteriuria
B. Hypercalciuria
C. Hemoglobinuria
D. Protein-to-creatinine ratio 1.0
E. Myoglobinuria
Isolated Asymptomatic
Hematuria
Rarely have significant renal disease
25% normalize within 5 years
Rarely have gross hematuria
Get good family history!
Monitor for HTN and proteinuria
Hypercalciuria
Risk for urolithiasis
Urinary Ca/Cr > 0.2 or 24 hour urinary calcium
excretion > 4 mg/kg/day
Mostly idiopathic
Consider immobilization, diuretics, vit D intoxication,
hyperparathyroidism, and sarcoidosis
Question #4
A 14-year-old female has 3+ blood, 2+
protein, and 10 to 20 RBCs/HPF on
urinalysis. She has no symptoms.
Of the following, the BEST next step is:
A. Refer to nephrology
B. Renal U/S
C. Urine culture
D. Urinary calcium-to-creatinine ratio
E. Repeat UA with first morning urine
Asymptomatic hematuria +
proteinuria
In most cases, resolution of one or both
features
Determine if proteinuria is orthostatic
First morning urine
Persistent proteinuria is more indicative
of a glomerular process
Refer to nephrology
Diagnostic Evaluation
Diagnostic Evaluation
First stage
BP, UA +/- urine culture
Second stage
Search for underlying disease especially if edema, HTN,
systemic symptoms, etc.
BMP
ASO
Complement
ANA
Hepatitis panel
HIV
CBC
Hgb electrophoresis
Renal U/S, biopsy, cystoscopy when indicated
Refer to nephrology unless the cause is clear (UTI,
postinfectious)
Question #5
An 8 yo M presents to the ED with c/o dark urine
for the past 24 hours. Per Mom, this has never
happened before. He is a very healthy boy, with the
exception of being treated with antibiotics for a sore
throat 2 weeks ago. On exam, his BP was found to
be 130/82, and there was some mild periorbital
edema bilaterally. Of the following, the most likely
set of laboratory findings in this patient is:
A. Normal complement levels; 3+ protein, no blood on UA
B. Elevated complement levels; 1+ protein, 1+ blood on UA
C. Low complement levels; trace protein, 3+ blood on UA
D. Low complement levels; 3+ protein, no blood on UA
E. Normal complement levels; no blood or protein on UA
Pathophysiology
Caused by a reaction to a nephritogenic
strain of group A beta-hemolytic
Streptococcus
Multiple pathogenic mechanisms
inflammation of the glomeruli
Deposition of Ag-Ab complexes in the glomeruli
In situ deposition of nephritogenic Ag with
formation of immune complexes
Direct activation of complement by the
nephritogenic Ag within the glomeruli
Presentation
Timeline
10-14 days after pharyngitis
3-6 weeks after pyoderma
Clinical features
Classic nephritic syndrome
Gross hematuria
Edema (fluid overload can pulmonary
edema)
HTN
Renal insufficiency
Laboratory Findings
Low C3
UA
Hematuria*
Proteinuria
RBC casts
BMP
Mild renal insufficiency
Evidence of past streptococcal infection
Streptozyme
Anti-DNAase B
Question #6
Of the following, which most accurately
describes the natural course of PSGN:
A. Renal function improves within 3 weeks,
complement values normalize within 8-12 weeks
B. Renal function improves within 6-24 months,
complement values normalize within 8-12 weeks
C. Renal function improves within 3 weeks,
complement values remain low indefinitely
D. Renal function continues to deteriorate,
complement levels remain low indefinitely
E. Renal function improves within 3 weeks,
complement values normalize within 2-4 weeks
Treatment and Prognosis
Supportive management
Antibiotics (Rx Strep infection)
For Fluid overload:
Fluid/ Na restriction
Diuretic therapy
Monitor electrolytes and renal function
Anti-hypertensives
Treatment and Prognosis
Prognosis is excellent!
Renal function improves within 3 weeks
Complement values normalize within 8-12
weeks
Microscopic hematuria may persist 6-24 months
Indications for renal biopsy:
Renal function or BP abnormal for >4wks
Proteinuria present for >6mos
Serum complement concentrations remain low
for >12wks
Definitions
Primary nocturnal enuresis = nighttime wetting
in a child who has never been dry on
consecutive nights for longer than 6 months
Dryness is expected to be achieved by 5 years of age
10 to 15% of 7-year-olds still have bedwetting
99% of children are dry by 15 years
Incontinence = uncontrollable leakage of urine
that may be intermittent or continuous and
occurs after continence should have been
achieved
Leakage that occurs during the day is daytime
incontinence
Dysfunctional voiding = inappropriate muscle
contraction during voiding
Question #7
A 7-year-old boy has nighttime bedwetting. No
one else in the family wet the bed, but his
mother his concerned about his weight and that
he is constantly tired during the day. Other than
being overweight, his physical exam and
screening UA are normal.
The MOST likely cause of his nocturnal
enuresis is:
A. Genetic predisposition
B. Bladder dysfunction
C. He is a deep sleeper
D. Occult spinal dysraphism
E. Obstructive sleep apnea
Causes of Nocturnal Enuresis
No data to support deep
sleep theory

Obstructive sleep apnea

atrial natriuretic factor leads to increased
diuresis
T & A has been shown to cure enuresis

Abnormal circadian release of ADH

Causes of Nocturnal Enuresis
Bladder dysfunction
Smaller-than-normal functional bladder
capacity at night

Higher bladder instability

Daytime + Nighttime = higher degree of

abnormalities and treatment failure
Causes of Nocturnal Enuresis
Genetics
1 parent with enuresis = 44% chance of child
affected
2 parents with enuresis = 77% chance of child
affected
Psychological factors
30% greater chance of enuresis in kids with
ADHD
Maturational delay
Fine and gross motor clumsiness, perceptual
dysfunction, speech defects co-exist
Secondary Enuresis
New-onset nighttime wetting on
consecutive nights after a 6-month or
greater period of dryness
Usually not related to an organic cause
Stressful events can be the source
Birth of a sibling, move, death in the family
Evaluation
History Physical Labs
Nights/week Distended bladder Urinalysis +/- Urine cx
Episodes/night Fecal impaction
Fluid intake Phallus and meatus
Caffiene Labial adhesions
Polyuria, polydipsia Muscle tone
Urgency, frequency, Reflexes and sensation
dysuria
Abnormal urine stream Skin over spine (tuft of
hair or sacral dimple)
History of UTIs
Constant wetness
Bowel complaints
Sleep apnea
Neuro/dev history
Question #8
An 8-year-old female is diagnosed with
primary nocturnal enuresis. The parents
are interested in therapy.
The MOST effective treatment for
ending the enuresis is:
A. Desmopressin
B. Alarm therapy
C. Imipramine
D. Anticholinergics
E. Limiting dairy products before bed
Treatment of Nocturnal Enuresis
Behavioral Medical
Limit nighttime fluid intake Desmopressin
Limiting dairy products 4 hours Anticholinergics
before bed
Voiding before bed Imipramine
Alarm therapy Combination therapy
Alarm Therapy
Most effective
Success rates as high
as 66 to 70%
Most difficult to
employ
Must be used every
night
Requires 3 to 4 months
for results
Parents may need to
wake up child if the
child does not wake to
alarm
Offers a real cure
No adverse effects
Daytime Wetting
Can be caused by stressful events
Divorce, death in the family, abuse

Children with daytime wetting may have

a difficult temperament
Increased risk for constipation and
encopresis
Classification of Daytime Wetting
Storage problem
Neurologically normal who cannot fill and store
Neurologically abnormal who have high
pressure bladder
Hypersensitive bladder
Inadequate sphincter tone
Emptying problem
Failure to empty completely with little residual
urine
May be neurologic, anatomic, muscular, or
fucntional
Question #9
A 7-year-old female patient has nighttime
and daytime wetting. You order a UA and
urine culture. Her physical exam is normal.
Which of the following should also be
included in your initial evaluation?
A. Post-void residual
B. VCUG
C. Urodynamics
D. MRI of the spine
E. Cystoscopy
Evaluation
History Physical Labs
Age of toilet training Meatal stenosis UA
Pattern of wetting Hypospadias Urine culture
Volume of wetting Tight phimosis Postvoid residual
Times/day Female epispadias
Time of day (during Labial adhesions
play)
History of UTIs Intralabial masses
Nighttime wetting Back and sacrum
Bowel function (skid Rectal exam
marks)
Social history
Ectopic Ureter
Females
No history of day- or
nighttime dryness
Constant dribbling
Evaluate with MR
urography, CT, or
IVP
Refer to pediatric
urology
Manifestations of Storage
Problems
Urge incontinence
Frequent attacks of a
strong desire to urinate
countered by hold
maneuvers such as
squatting, dancing, and
curtseying
Uninhibited bladder
contractions
Dampness rather than
soaking
Functional bladder
capacity is usually small
Storage Problems
Overflow incontinence
Infrequent and incomplete voiding
Overtime decreased sensation of the need to void
Usually large wetness
Daytime incontinence
Infrequent or delayed voiding, especially
associated with distraction or play
Small to large urine loss
Associated with behavior problems
Development after continence should prompt
referral
Storage Problems
Urinary frequency
Sudden need to urinate very frequently,
sometime up to 30 times per day
Ages 3 to 8
Self-limited
Related to psychological stressors
Manifestations of Emptying
Problems
Lazy bladder syndrome
Void 3 or fewer times a day
Must strain abdominal muscles to void
Intermittent stream and cannot empty bladder completely
Recurrent UTIs
Constipation
Detrusor sphincter dyssynergia (DSD)
Inappropriate contraction of the
external urethral sphincter during bladder
contraction
Staccato type of voiding
Post-void residual
spinning-top urethra
Emptying Problems
Hinman syndrome
Nonneurogenic neurogenic bladder
Longstanding DSD leads to detruser
decompensation
Can lead to renal insufficiency and failure
Other Types of Daytime Wetting
Giggle incontinence
Complete bladder emptying with extreme
laughter
Females age 10 to 20
No associated voiding abnormalities
Cataplectic phenomenon that exists in
patients with narcolepsy
Question #10
The mother of a 5-year-old female complains
that her daughters underwear is always
damp, even just after urinating. The girl states
that she feels dribbling soon after she goes
pee-pee. The patient is overweight, and
sometimes has trouble balancing on the toilet.
The MOST likely cause of her symptoms is:
A. Constipation
B. Vaginal reflux
C. Urinary tract infection
D. Lazy bladder syndrome
E. Daytime incontinence
Other Types of Daytime Wetting
Vaginal reflux
Dribbling associated with urine being trapped in
the vaginal introitus after voiding and leaking out
when the child walks away
Often seen in overweight and young girls
Also seen with vaginal adhesions
Underwear is always damp
Diagnose by postvoid vaginal exam with Valsalva
eliciting urine from the introitus
Treat by having patient sit backward on toilet and
keep thighs separated
Therapy
Behavioral therapy
Encourage voiding q 2 hours
Avoid bladder irritants (caffiene, carbonated
drinks, citrus-content beverages, red dyes)
Sit on the toilet 30 minutes after a large meal
with feet supported for 10 min (pelvic floor
relaxation)
Bowel program
Most patients have some form of constipation
High-fiber diet
Medications (polyethylene glycol)
Therapy
Anticholinergic agents for urinary
frequency
Biofeedback for emptying problems
(DSD, etc)
Alpha-blocking drugs for emptying
problems
Nephrotic Syndrome
Heavy proteinuria and hypoalbuminemia
Edema
Hyperlipidemia
Pathophysiology of Proteinuria
Edema
Pathophysiology of Edema
Classic theory:
Decrease in plasma oncotic pressure secondary
to hypoalbuminemia water extravasation into
the interstitial space decrease in intravascular
volume activation of the RAA system
aldosterone increases reabsorption of Na
edema
Not fully supported by clinical evidence
Plasma volume decreased only in some children
Studies have failed to demonstrate elevations in
the RAA hormones
Pathophysiology of
Hyperlipidemia
Increased VLDL, IDL, and LDL
secondary to:
Overproduction in the liver due to low
plasma albumin concentration
Low oncotic pressure and impaired
catabolism of apolipoprotein B and VLDL
chylomicrons
Epidemiology
Incidence: 2.7 new cases/ 100,000 children
per year
Sex predilection: 2:1 (males:females) in
childhood; sex difference wanes by
adolescence
Increased familial incidence (siblings)
Mean age of onset 3.4 yrs (Asians) and 4.2 yrs
(Europeans)
African American and Hispanic children have
greater incidence of nephrotic syndrome, a
more severe form and poorer prognosis
Differential Diagnosis
Classification
Primary Secondary
Minimal change
nephrotic syndrome
(MCNS)
85% of cases
Focal segmental
glomerulosclerosis
(FSGS)
10-15% of cases
Membranous
nephropathy (MN)
4% of cases
Question #11
Which of the following is the best
prognostic indicator in children with
nephrotic syndrome?
A. Age< 10 yo at time of diagnosis
B. UPr/Ucr <4.0
C. Steroid responsiveness
D. Serum creatinine <1.1
E. Serum albumin>2.0
Further Classification
Steriod-sensitive nephrotic syndrome
MCNS
Steriod-resistant nephrotic syndrome
Congenital nephrotic syndrome
FSGS
MN
Histopathology
Light microscopy glomeruli normal
Electron microscopy fusion of the
epithelial foot processes
Clinical Features
Additional symptoms:
Anorexia
Irritability
Fatigue
Abdominal discomfort
Diarrhea
Respiratory tract infection preceding onset
common (not likely pathogenic)
History of allergy is reported in 50% of
children with MCNS
Question #12
A 4 yo M presents to your office with a 3 day h/o
diarrhea, irritability, and poor PO intake. His eyelids
have also been swollen for 2 days, which Mom
attributed to pink eye. This morning, she noticed
that his scrotum appeared very swollen and
became concerned. You suspect nephrotic
syndrome. A urine protein to creatinine ratio greater
than what value would confirm your suspicion?
A. 0.2
B. 0.5
C. 1.0
D. 2.0
E. 3.0
Laboratory Features
Plasma protein markedly reduced
Albumin <2.5
Proteinuria
Estimation by dipstick
Confirmation by quantitative measurement
12 or 24 hour timed urine collection
>50mg/kg/d or 40mg/m2 indicative of nephrotic
syndrome
UPr/Ucr
Normal: Age >2 yo= <0.2, Age 6mos-2 yrs= <0.5
Nephrotic syndrome: >3.0
Laboratory Features
Elevated cholesterol, TG, and
lipoproteins
Low Na
Hyperlipidemia
Retention of water (increased ADH)
Low Ca
Hypoalbuminemia
Question #13
A 4 yo F presents with a 2 day h/o worsening
periorbital and labial swelling. Her BP is normal and
PE unremarkable except for the above noted edema.
Her UA shows 3+ protein and trace blood with 0-2
RBC/hpf. BUN and Cr are normal along with C3.
Albumin is 2.1 and LDL 165. Of the following, which
is the next best step in her management?
A. Renal biopsy
B. Prednisone therapy
C. Dialysis
D. Bilateral nephrectomy
E. Cyclosporine therapy
Question #14
What anticipatory guidance should you give the
patients family regarding the course and prognosis
of MCNS?
A. Your daughter will likely go on to develop ESRD
B. After one course of steroids, your daughter will likely not
need anymore treatment for this illness
C. Your daughter will likely respond to the steroids;
however, there is a strong probability that she will
eventually relapse
D. Your daughter will not likely to respond to the steroids
and will need a renal biopsy
E. Your daughter will likely be admitted to the hospital
several times in the next month from complications of this
illness
Treatment and Course
Indications for Renal Biopsy
Presentation
Massive proteinuria that starts during fetal
life
Elevated AFP with normal US findings
Most affected children born preterm
(~2500g)
Edema and abdominal distension evident
soon after birth
Albumin usually <1.0
Also losing many other proteins metabolic
disturbances (lipid abnormalities)
atherosclerotic changes as early as the first
postnatal year
Treatment
Initial
Sustaining a good nutritional state
Controlling edema
Preventing complications
Uni-or bilateral nephrectomy
To control massive loss of protein
Eventual kidney transplant
CNS can recur in transplanted kidneys
Histopathology
Initially, is sclerosis of some of the
glomeruli (focal) that involves only part
of the glomerular tuft (segmental)
Progresses to
global, extensive
glomerulosclerosis
and tubular atrophy
Causes
Heterogeneous
Genetic
Small percentage
Idiopathic
Heroin-induced
nephropathy
AIDS
Multiple myeloma
Alport syndrome
Reflux nephropathy
Diabetic nephropathy
Obesity
Clinical Features
Major signs edema and albuminuria, but
HEMATURIA more frequent in FSGS
than in MSNS
FSGS cannot be diagnosed at
presentation
Most children are started on prednisone
therapy and lack of response at 4 weeks
prompts renal biopsy diagnosis of FSGS
20% are responsive to prednisone
Clinical Features (cont)
Disease progression variable
ESRD reached b/t 2-10 yrs
In patients who rapidly progress to ESRD,
there is a high likelihood of recurrence in the
transplanted kidney
Treatment
NO DEFINITIVE EVIDENCE THAT ANY
DRUG IS EFFECTIVE!!
Pulse methylprednisolone: minimal benefit
Alkylating agents (cyclophosphamide): little
therapeutic effect
Cyclosporine
Induces remission in 25-50% in those with steroid-
resistance
Patients relapse promptly when the drug is
discontinued
Serious adverse effects if the drug is continued for
long periods
Treatment (cont)
Recurrence in transplanted kidney is a
major problem
Reported in up to 50% of transplanted
children with FSGS
Risk factors:
Older than age 6 at onset
Progression to ESRD in less than 3 years
Treated with cyclosporine +/or
plasmapheresis
Partial or total remission in a minority of cases
Histopathology
Diffuse, irregular thickening of the GBM
in the absence of any signs of
inflammation
Electron microscopy: electron-dense
deposits distorting the GBM
Cause
Infections
Hepatitis B
Malaria
Syphilis
AI disease
SLE
Crohn disease
Tumors
Wilms tumor
Neuroblastoma
Idiopathic
Drugs
Clinical Features
Very rare in children but can present at any
age
Presentation
Proteinuria or nephrotic syndrome
(Hematuria and HTN rare)
Treatment
Steroids and immunosuppressive drugs (not
good results)
Clinical course
Spontaneous remission in 25-50%
25-30% develop renal insufficiency
Question #15
A 5 yo F with h/o MCNS presents to the
ED with a one day h/o fever to 102,
chills and mild abdominal pain. What
illness must you consider in this patient?
A. Pneumonia
B. Adenovirus gastroenteritis
C. Shigella gastroenteritis
D. Peritonitis
E. Pancreatitis
Complications of Nephrotic
Syndrome
ARF
Thromboembolic events
Due to loss of antithrombin III and protein S in
the urine
Antiphospholipid syndrome
Infections
Due to loss of factor B, a decrease in IgG and
impaired T-cell function
Most common infection= peritonitis
Streptococcus pneumoniae (decreasing with
vaccination)
Complications of Nephrotic
Syndrome
Anasarca and pulmonary edema
Stunting of growth
Side effect of prolonged steroid use
Reduced bone mineral density
Steroids
Vit D deficiency
Ancillary Therapies
Diuretics +/- salt-poor albumin
Edema only requires treatment when associated
with severe ascites, peritonitis, respiratory
distress or heart failure
Albumin usually given when serum albumin <1.5
ACE inhibitors/ ARBs
Statins
Vaccination
Conjugated pneumococcal vaccine
Low Na diet
Vitamin D and Ca supplementation