Transcript December Board Review - LSU School of Medicine

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
Symptomatic
Asymptomatic + proteinuria
Isolated asymptomatic
Macroscopic (Gross)
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 today’s 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 patient’s 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,
dysuria
Reflexes and sensation
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
before bed
Anticholinergics
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
play)
Labial adhesions
History of UTIs
Intralabial masses
Nighttime wetting
Back and sacrum
Bowel function (“skid
marks”)
Rectal exam
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 daughter’s 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

Minimal change
nephrotic syndrome
(MCNS)
 85% of cases

Focal segmental
glomerulosclerosis
(FSGS)
 10-15% of cases

Membranous
nephropathy (MN)
 4% of cases
Secondary
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
patient’s 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 (con’t)

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 (con’t)

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