Transcript Finance Subcommittee Update March 17, 2005

Metro New York / New Jersey
Pediatric Board Review Course
Pediatric Nephrology
June, 2009
Leonard G. Feld MD PhD
Levine Children’s Hospital
Charlotte, NC
March 17, 2005
For the Exam
Fluid and Electrolyte Metabolism
A.
Composition of body fluids -Intracellular,
extracellular, Electrolytes (sodium,
potassium, chloride), Protein
B.
Acid-base physiology -Normal mechanisms
and regulation, Acidosis, alkalosis
C.
Electrolyte abnormalities - Sodium –
Hypernatremia; Hyponatremia; Potassium
Hyperkalemia; Hypokalemia; Chloride
imbalance
D.
Disease states, specific therapy - Pyloric
stenosis, gastroenteritis, acute renal failure,
shock, SIADH, Cystic fibrosis, Dehydration,
Hyperosmolar non-ketotic coma
March 17, 2005
For the Exam
Renal Disorders
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
Normal function, proteinuria, hematuria, persistent microscopic hematuria, causes of
gross and microscopic hematuria, nonhematogenous etiology of red urine,dysuria,
Incontinence - Nocturnal, functional, daytime incontinence,
Congenital - Renal dysplasia, unilateral multicystic dysplastic kidney, autosomal
dominant polycystic kidney disease, autosomal recessive polycystic kidney disease,
Juvenile nephronophthisis, Renal agenesis
Abnormalities of the collecting system, kidney, and bladder – Hydronephrosis,
Hydroureter and megaureter, Ureterocele, Vesicoureteral reflux,
Abnormalities of the urethra - Posterior urethral valves, Urethral stricture
Hereditary nephropathy - Familial nephritis, Congenital nephrotic syndrome
Acquired - Infection of the urinary tract (Pyelonephritis, Cystitis), acute
glomerulonephritis, Nephrotic syndrome, Hemolytic-uremic syndrome, HenochSchoenlein purpura,IgA nephropathy
Renal failure - Prerenal failure, Intrinsic renal failure , chronic renal failure,
Other - Trauma, renal injuries, Urethral injury, Toxins, Renal stones, Renal tubular
acidosis, Hereditary conditions with renal manifestations, Nephrogenic diabetes,
insipidus, Cystinosis
Hypertension – General, Renal, Vascular, Adrenal, Pheochromocytoma, Cushing
syndrome, Miscellaneous causes, Essential hypertension, Administration of drugs,
Traction on legs
March 17, 2005
Outline
• Fluid and Electrolyte abnormalities
– Dehydration
• Renal
– Hematuria
– Proteinuria
– Hypertension
– Urinary tract infections
– Glomerulonephritis
March 17, 2005
Case 1: Dehydration
A 4 mo old infant presents with a four to five day history of low grade
fever (38-38.5oC), numerous watery diarrhea and decreased activity. Since
the child refused to take her usual breast milk volume or solid foods, the
mother and grandmother substituted non-carbonated soda (Coca-cola, ginger
ale, apple juice or orange juice will have ~550-700 mOsm/kg H2O) with less
than 5 mEq/L of sodium), and “sweet” (sugar added) iced tea. Over the last 12
hours there were a few episodes of emesis and there were less wet diapers.
On examination the child was lethargic, dry mucous membranes, no
tears, sunken eyeballs, and reduced skin turgor. Vitals signs were the
following: Blood pressure 74/43 mmHg; Temperature of 38oC, respiratory rate
of 36 per minute and pulse of 175 beats per minute. The weight was 6 kg.
Weight at the time of her immunization 7 days ago was 6.6 kg. There were no
other significant findings.
March 17, 2005
Electrolyte Composition of Body
Fluid Compartments
March 17, 2005
BODY WATER DISTRIBUTION
TOTAL BODY WATER (TBW)
0.6 x Body Weight (BW)
EXTRACELLULAR FLUID
(ECF)
0.2 x BW
Interstitial Fluid
¾ of ECF
March 17, 2005
Plasma
¼ of ECF
INTRACELLULAR FLUID (ICF)
0.4 x BW
Clinical Assessment
Fluid
Deficit
Clinical
Status
Clinical
Assessment
Mild
( 5%)
50 cc/kg
Compensated
Moderate
(10%)
100 cc/kg
Decompensated Very dry mucosa, < skin
turgor, sunken eyes, deep
resp, weak pulses, cool
extremities, oliguria
Severe
(15%)
150 cc/kg
Shock
March 17, 2005
Thirsty, HR, Normal BP
tears, slightly dry mucosa,
alert/restless, [urine]
Intense thirst,  BP, cap
refill > 3 sec, weak pulses,
apnea/rapid breathing,
coma, anuria
Maintenance Requirements
Body wt
0-10 kg
10-20 kg
20 kg
TBW
100 ml/kg
1000 ml +
50 ml/kg for
each kg >
10kg
1500 +
20 ml/kg for
each kg >
20kg
Na+
3 mEq/kg
3 mEq/kg
3 mEq/kg
K+
2 mEq/kg
2 mEq/kg
2 mEq/kg
Cl-
5 mEq/kg
5 mEq/kg
5 mEq/kg
March 17, 2005
Deficit
Type of Dehydration
based on serum [Na] in
mEq/L
Water
Sodium
(mL/kg)
(mEq/kg)
Potassium
(mEq/kg)
Isonatremic [Na] 130-150
100-120
8-10
8-10
Hyponatremic [Na] < 130
100-120
10-12
8-10
Hypernatremic [Na] > 150
100-120
2-4
0-4
March 17, 2005
Laboratory
Sodium 124 mEq/L, chloride 94 mEq/L normal 98 -118
mEq/L), potassium 4 mEq/L (normal 4.1-5.3 mEq/L),
bicarbonate (or total CO2) was 12 mEq/L (normal 2028 mEq/L or mmol/L), serum creatinine 0.8 mg/dL
(normal ~0.3-0.5 mg/dL), blood urea nitrogen 40
mg/dL, blood glucose 70 mg/dL; complete blood count
was normal except for a hemocrit of 38% (normal ~
36%);
March 17, 2005
Hyponatremia
•
•
•
•
•
Serum [Na+] < 130 mEq/L
Water shifts into cells – lower ECF volume
<125 mEq/L – nausea and malaise
< 120 mEq/L – headache, lethargy,
<115 mEq/L – seizure and coma
March 17, 2005
Loss of hypertonic Fluid and Sodium from the ECF secondary to Dehydration
NORMAL
0.25 Liters
0.40 Liters
280
280
mOsm/L
35 Na
64 K
0
0
Loss
0.10 LIters
AFTER LOSS
400
0.15 Liters
10 K
10 Na
280
200
55 K
10 Na
15 Na
0
0.40 Liters
0
0
AFTER OSMOTIC ADJUSTMENT
0.116 Liters
0.434 Liters
258
258
15 Na
54 K
10 Na
0
March 17, 2005
NORMAL ECF
0
NORMAL ICF
Question 1: What is the appropriate
parenteral solution
A. 5% dextrose + 0.45% isotonic saline +
40 mEq KCl /L
B. 0.45% isotonic saline + 40 mEq KCl /L
C. 0.9% isotonic saline + 40 mEq KCl /L
D. 5% dextrose + 40 mEq KCl /L
E. 5% dextrose + 0.2% isotonic saline
March 17, 2005
Approach
For this 6.6 kg infant
Maintenance requirements for 24 hours
Water
100 mL / kg x 6.6 kg = 660 mL
Sodium
3 mEq / 100 mL x 660 mL = 20 mEq
Potassium
2 mEq / 100 mL x 660 mL = 13 mEq
For this 6 kg infant with hyponatremic dehydration at 10%
Deficits for 24 hours
Water Pre-illness weight – Illness weight =
6.6 – 6 kg = 0.6 kg = 600 mL
Sodium
10 mEq x 6.6 kg = 66 mEq
Potassium
8 mEq x 6.6 kg = 53 mEq
March 17, 2005
Points on Hypernatremic Dehydration
NORMAL
0.25 Liters
0.40 Liters
280
280
mOsm/L
35 Na
64 K
0
0
413
0.15 Liters
AFTER LOSS
0.40 Liters
280
Loss
0.10 LIters
31 Na
62 K
2 Na
80
2K
2 Na
0
0
0
AFTER OSMOTIC ADJUSTMENT
0.195 Liters
0.355 Liters
318
318
37 Na
62 K
2 Na
0
NORMAL ECF
March 17, 2005
0
NORMAL ICF
Hypernatremia – SLOW and CLOSE
Key points: look quiet then irritable on stimulation; may look
better than % of dehydration based on weightd
Fluid selection: 5% dextrose + ¼ isotonic saline (~30-40 mEq/L of
Na) + 20 mEq KCl /L
• 1st 24 hrs: 24 hrs of Maintenance + ½ deficit
• 2nd 24 hrs: 24 hrs of Maintenance + ½ deficit
• Close monitoring of serum sodium every 2-3 hours.
Some have suggested using a higher [sodium] – 0.45% isotonic
saline or even isotonic saline to restore ECF volume then
moving to a lower
• sodium containing solution to restore the water deficit. This
approach may also reduce the possibility of dropping the
serum sodium too quickly and preventing neurological
problems.
March 17, 2005
Hematuria
Case: Susan is an 8 year old noted on
routine exam to have moderate hematuria
on dipstick. She has an unremarkable
past medical history. Family history is
negative in the parents and siblings for
any renal disease. History of hematuria is
unknown. A repeat urine in one week is
still positive and a urine culture showed
no growth.
March 17, 2005
Question 2: Which of the following test is the next
step in the evaluation?
A. VCUG and urine culture
B. Renal sonogram and urine calcium to
creatinine ratio
C. Urology referral
D. CBC and Direct Coombs
E. Recheck in two years
March 17, 2005
More on Hematuria
• Repeat a first AM void following restricted
activity , perform a microscopic on a fresh urine
• Check the family members
• If there is still blood without protein, casts,
crystals, normal BP with or without a strong
family history, no further work-up is generally
required. However a renal sonogram and
urine calcium to creatinine ratio
• Caveat - Family anxiety because of the
connotation of blood and cancer in adults.
March 17, 2005
Glomerular v. Non-glomerular bleeding
• Glomerular
– oliguria, edema, hypertension, proteinuria, anemia
• Non-glomerular
–
dysuria, frequency, polyuria, pain or colic, hx
exercise
–
crystals on microscopic
–
mass on exam
–
medication history - sulfas, aspirin, diuretics
March 17, 2005
Initial evaluation of the patient with hematuria
•
•
All patients: BUN, creatinine, kidney and bladder ultrasound, urine
calcium to creatinine ratio
Who should be worked up
– Presence of proteinuria and/or hypertension ,
– History consistent with infectious history, HSP, systemic symptoms, medication
use or abuse, strong family history of stones or renal disease/failure.
– Persistent gross hematuria
– Family anxiety - limit evaluation
•
Probable glomerular hematuria
– C3, ASO titer
– possible: hepatitis, HIV, SLE serology , SSD
– renal biopsy – not for persistent microscopic without proteinuria, decreased renal
function, and/or hypertension
•
Probable non-glomeurlar hematuria
–
–
–
–
urine culture, urine Ca/creatinine ratio
possible: hemoglobin electrophoresis,
coagulation studies, isotope scans,
Flat plate, CT, ??IVP, cystoscopy
March 17, 2005
Pearls for Hematuria
• Hematuria may be an important sign of renal or
bladder disease
• Proteinuria (as we will discuss) is the more
important diagnostic and prognostic finding.
• Hematuria almost never is a cause of anemia
• The vast majority of children with isolated
microscopic hematuria do not have a treatable
or serious cause for the hematuria, and do not
require an extensive evaluation. So a VCUG,
cysto and biopsy are not indicated.
March 17, 2005
More Pearls
• Urethrorrhagia – boys with bloody spots in the
underwear
– Presentation – prepuberal ~ 10 yrs
– It is painless
– Almost 50% will resolve in 6 months and > 90% at 1
year; it may persist for 2 yrs
– Treatment – watchful waiting in most cases
• Painful gross hematuria – usually infection,
calculi, or urological problems; glomerular
causes of hematuria are painless.
March 17, 2005
More Pearls – gross hematuria
• Gross hematuria is often a presentation of
Wilms’ tumor
• All patients with gross hematuria require
an imaging study.
• If a cause of gross hematuria is not
evident by history, PE or preliminary
studies, the differential includes
hypercalciuria or SS trait
• Cysto is rarely helpful
March 17, 2005
Case 3
• 7 year old boy developed gross tea colored hematuria
after a sore throat and upper respiratory infection. No
urinary symptoms but urine output was decreased. He
complained of mild diffuse lower abdominal pain. There
is no fever, rash or joint complaints. Past med history
was unremarkable but had intermittent headaches for
two years.
•
On exam he was well (afebrile) with a BP of 95/65
mHg, no edema, some suprapubic tenderness and red
tympanic membranes. The mother thinks that a similar
episode occur on vacation a few months ago.
•
Urinalysis shows 20 RBCs/hpf, 5-10 WBCs, 100
mg/dL of protein, rare cellular and hyaline casts. Serum
creatinine is 0.8 mg/dL, C3 100 (normal).
March 17, 2005
Question 3: The most likely cause
of the gross hematuria is:
A.
B.
C.
D.
E.
Myoglobinuria
Urinary tract infection
Obstructive uropathy
IgA nephropathy
Benign familial hematuria
March 17, 2005
IgA
• IGA nephropathy
– Boys > girls
– Mostly normotensive, with persistent
microscopic hematuria
– Chronic glomerulonephrits – up to 40% of
primary glomerulonephritis
– Complement studies are nl, some inc IgA
– Prognosis – not so good if > 10 yrs of age,
proteinuria, reduced GFR, hypertension and
no macrohematuria
March 17, 2005
Acute
Glomerulonephritis
Low Complement
Normal Complement
Systemic diseases
Systemic diseases
SLE
Subacute Bact Endocarditis
Shunt nephritis
Essential mixed cryoglobulinemia
Visceral abscess
Polyarteritis nodsa
Hypersensitivity vasculitis
Wegener’s
HSP
Goodpasture’s
Renal diseases
Acute proliferative GN
Membranoproliferative GN
Renal diseases
IGA
RPGN Anti-GBM, immune complex GN
Serologic evidence of antecedent strep infection
(ASO, anti-Dnase B, streptozyme
Positive
Negative
Lupus
Essential mixed cryoglobulinemia
Shunt nephritis
Visceral abscess
MPGN
Non-strep infection
PSAGN
Strep endocarditis
YE
S
Clinical evidence to
support endocarditis
Blood cultures
Echocardiogram
March 17, 2005
NO
Treat PSAGN
Glomerular
Non-glomerular
Urinalysis
Dysmorphic RBC
Cellular casts
Brown/tea color
Bright red
Clots
Crystals
Protein
+
+
++
+
+
+
++
+
+
-
History
Family Hx of ESRD
Systemic disease
Nephrolithiasis
Trauma
Symptomatic vomiting
+
+
-
+
+
+
Physical
Hypertension
Systemic signs
Edema
Abdominal mass
Genital bruising
++
+
+
-
+
+
+
March 17, 2005
Red or Tea colored/ Brown Urine
Fresh Centrifuged Urine Sample
Sediment Red with
Red Cells
Hematuria
Supernatant Red without
Red Cells
Hemoglobinuria*
Myoglobinuria
* Hemoglobinuria will have
a red or pink hue to the
serum
NOTE: If there is no red sediment, no RBCs
and a clear supernatant, consider other
causes such as urates, bile pigments,
beets,
porphyria, some medications, etc.
March
17, 2005
Question 4
On routine physical examination, an 8-yearold boy is found to have microscopic
hematuria. The first step in your
evaluation should be.
A. Examine the urine sediment
B. Order an renal ultrasound
C. Obtain a voiding cystourethrogram
D. Perform a CBC in the office
E. Order an ASO titer and C3
March 17, 2005
Question 5
An 8-year-old boy presents with tea colored
urine. He has very mild edema. History of
strep infection about 2 weeks ago. The
work-up should include all the following
except.
A. Complement studies
B. Serum creatinine
C. Urinalysis for protein
D. Monitor blood pressure and urine output
E. Obtain a renal ultrasound
March 17, 2005
Acute glomerulonephritis: clinical
• May be clinically asymptomatic (? 90%)
with low C3 and hematuria
• Usually within 3 weeks after strep infection
– mean about 10 days
• Periorbital, peripheral edema
• Hematuria - coke-colored, tea-colored,
reddish/brown
• Nonspecific findings such as abdominal
pain, malaise, anorexia, headaches, pallor
March 17, 2005
Acute glomerulonephritis: DD
• Acute Poststreptococcal glomerulonephritis
(PSAGN) – most common
• Acute Postinfectious or nonstreptococcal
postinfectious glomlerulonephritis 9AIAGN)
– Bacterial: endocarditis (low C3), shunt nephritis (low
C3), pneumococcal pneumonia, etc.
– Viral: hepatitis B, infectious mononucleosis, varicella,
etc,
– Parasites:
• Other: SLE (low C3), membranoproliferative GN
(low C3), hyperthyroidism, HSP (nl C3)
March 17, 2005
Acute glomerulonephritis:
evaluation/ treatment
• Evaluation
–
–
–
–
ASO, C3, C4
Renal function
Evaluation for hypertension and oliguria
Magnitude of proteinuria
• RX – supportive
– Admission for hypertension, oliguria, impaired renal
function, nephrotic syndrome
• Prognosis: C3 normalizes by 12 weeks,
hypertension and other abnormalities resolve by
2-3 months, hematuria may persist for 6-24 mo
March 17, 2005
Proteinuria
Case 6: John is an 12 year old noted on a
basketball team physical to have 2+
protein on dipstick. There are no recent
illnesses. He has an unremarkable past
medical history and he is not taking any
medications. Family history is negative in
the parents and siblings for any renal
disease.
March 17, 2005
Question 6: Which of the following
is the best approach?
A.
B.
C.
D.
E.
Obtain a 1st AM urine for protein
Perform a complete biochemical profile
Obtain a C3, ASO and ANA
Refer for a renal biopsy
Schedule a renal sonogram and VCUG
March 17, 2005
What does Orthostatic Proteinuria
mean?
Protein
Excretion
Threshold of Detection
Normal
March 17, 2005
Orthostatic
Recumbant
Erect
More on Proteinuria
• Repeat a first AM void following restricted
activity, perform a microscopic on a fresh
urine; also an alkaline pH may give a false
positive result
• If there is still protein perform a more
formal orthostatic test. If orthostatic, no
further work-up is generally required,
although no indemnification from
subsequent renal disease.
March 17, 2005
Causes of Proteinuria
• Transient
–
fever, emotional stress, exercise, extreme cold,
abdominal surgery, CHF, infusion of epinephrine
• Orthostatic
–
Transient or fixed / reproducible
• Persistent
–
–
–
Glomerular disease: MCNS, FSGS, MPGN, MN
Systemic:
SLE, HSP, SBE, Shunt infections
Interstitial:
reflux nephropathy, AIN, hypoplasia,
hydronephrosis, PKD
March 17, 2005
Question 7
A four-year boy presents with a 5-day history of
swollen eyes and “larger ankles”. On exam he
has periorbital and pretibial edema. The most
appropriate tests include all the following
except.
A. Urinalysis
B. Blood tests for total protein and albumin
C. Serum creatinine
D. Sedimentation rate
E. Serum complement (C3)
March 17, 2005
Definitions (Pearl)
• Urine protein to creatinine ratio
–
–
–
Normal:
Mild to moderate:
Heavy or severe:
< 0.2 (< 0.15 adolescents)
0.2 to 1.0
> 1.0
• Persistent proteinuria: present both in the
recumbent and the upright posture; even in this
situation, proteinuira is less during recumbency
March 17, 2005
Nephrotic Syndrome
•
Primary Nephrotic Syndrome:
– Minimal change disease (~75%) – mean age 4 yrs
• No hematuria, nl C3, no hypertension, nl creatinine
–
–
–
–
Membranoproliferative GN (~ 5-10%)
FSGS (5-10%)
Proliferative GN, Mesangial proliferation
Membranous nephropathy
• Secondary Nephrotic Syndrome:
– SLE, HSP, diabetes mellitus, HIV, vasculitis, malignancy (lymphoma,
leukemia), drugs (heroin, inteferon, lithium), infections (toxo, CMV,
syphilis, hepatitis B and C)etc.
• Congenital/Infantile Nephrotic Syndrome:
– Finnish-type congenital nephrotic syndrome,Denys-Drash syndrome
– Diffuse mesangial sclerosis, Nail-patella syndrome
March 17, 2005
Nephrotic Syndrome - RX
Corticosteroid treatment
• Induction therapy:
–
–
•
Maintenance therapy (following above induction therapy)
–
–
•
Exclude active infection or other contraindications prior to steroid therapy.
Oral prednisone or prednisolone at 60 mg/m2/d (~2 mg/kg/d) daily for 4 weeks.
Oral prednisone or prednisolone at 40 mg/m2 (or ~1.5 mg/kg) given as a single dose
on alternate days for 4 weeks.
NOTE: Some nephrologists recommend daily induction steroid treatment for 6 weeks,
followed by alternate day maintenance therapy for another 6 weeks.
Relapse therapy
–
–
For infrequent relapses, Prednisone 60 mg/m2/d (~2 mg/kg/d) given as a single
morning dose until proteinuria has resolved for at least 3days.
Following remission of proteinuria, prednisone is reduced to 40 mg/m2 (or ~1.5 mg/kg)
given as a single dose on alternate days for 4 weeks. Prednisone may then be
discontinued or a tapering regimen.
Frequently relapsing nephrotic syndrome is defined as steroid-sensitive nephrotic
syndrome with 2 or more relapses within 6 months or more than 3 relapses
within a 12-month period.
March 17, 2005
Hypertension
March 17, 2005
Hypertension
Question 8: David is a 10 year old boy first noted
to have an elevated blood pressure of 123/85
during a annual physical examination. Pt has a
long history of learning and behavioral issues.
He has a previous history of headaches that
were evaluated with a CT scan of the brain and
sinuses. On following evaluation in one week,
his BP is126/86 mmHg with a weight > 99%ile
for age and a height at ~50th %ile.
March 17, 2005
Question 8: What is the most appropriate initial
testing for this child?
A. Renal mag-3 flow scan
B. Electrolytes, BUN, Creatinine,
Bicarbonate
C. Renal Sonogram with doppler
D. Urinary screening for drugs
E. 24 hour urine for catecholamines
March 17, 2005
BP Classification
Grade of hypertension
Definition
Appropriate next step
“White-coat” hypertension
BP levels >95th percentile in a
physician's office or clinic, but
normotensive outside a clinical
setting
Readings may be obtained at
home with appropriate family
training or with the assistance of
a school nurse, or with the use of
ambulatory BP monitoring
(ABPM)
Normal
< 90th %ile
Pre-hypertension
>120/80 mm Hg should be
considered pre-hypertensive or
90-95%ile
Additional readings may be
obtained at home with
appropriate family training or
with the assistance of a school
nurse
Stage I hypertension
95th -99th %ile + 5 mmHg
Organize a diagnostic evaluation
in a non-urgent, phased approach
Stage II hypertension
Average SBP or DBP that is >5
mm Hg higher than the 99th
percentile
Organize a diagnostic evaluation
over a short period of time in
conjunction with
pharmacological treatment
Hypertensive urgency and
emergency
Average SBP or DBP that is >5
mm Hg higher than the 95th
percentile, along with clinical
signs or symptoms
Hospitalization and treatment to
lower the blood pressure
March 17, 2005
Estimate of Hypertension
Estimate without height adjustment
1. If systolic BP equals or exceeds
100 + 2 times pt age in yrs
2. If diastolic BP equals or exceeds
70 + pt age in yrs
Estimate with height adjustment
1. If systolic BP at 95th %tile for age and sex
Add 4 mmHg to the value at the 50th %tile
2. If diastolic BP at 95th %tile for height
Add 2 mmHg to the value at the 50th %tile
March 17, 2005
Evaluation of Hypertension
Historical
Information
Physical
Examination
Neonatal history
Family history
Dietary history
Risk Factors (smoking, alcohol use,
drug use)
Non-specific / specific symtomatology
Review of Systems - sleep and exercise
patterns, etc.
Vital signs
(including extremities)
Height/Weight
Specific attention to organ systems cardiac, eye, abdominal or other
bruits, etc.
Consider ambulatory blood pressure
monitor
Evaluation Phase 1
CBC, urinalysis, urine culture, electrolytes, BUN, creatinine,
thyroid studies, uric acid
plasma renin, lipid profile, echocardiogram, renal ultrasound
with duplex doppler
Evaluation Phase 2
Selected studies based on magnitude of the hypertension and/
or other clinical /laboratory findings
Renal flow scan (MAG 3)
CT Angiography (CTA)
MRA (may not provide adequate evaluation for
peripheral renal vascular lesions)
Renal arteriography with renal vein sampling
Plasma / urine catecholamines and/or steroid concentrations
March 17, 2005
Indications for Treatment
•
•
•
•
•
Symptomatic hypertension
Secondary hypertension
Hypertensive target-organ damage
Diabetes (types 1 and 2)
Persistent hypertension despite
nonpharmacologic measures
March 17, 2005
Pharmacologic Therapy
for Childhood Hypertension
• The goal for antihypertensive treatment in
children should be reduction of BP to
<95th percentile, unless concurrent
conditions are present. In that case, BP
should be lowered to <90th percentile.
• Severe, symptomatic hypertension should
be treated with intravenous
antihypertensive drugs.
March 17, 2005
Urinary Tract
Infections
March 17, 2005
Case 9
• A 4 mo old girl presents with low grade
fever, mid-lower abdominal pain and
nighttime-incontinence. She is not
eating well. Prior visits she had normal
blood pressure, urinalysis and excellent
growth. dUrinalysis shows hematuria,
30 mg/dL of protein, leukocyte esterase
and positive nitrite. Urine culture is
obtained.
Feld - 10/98
55
Question 9: What is the most likely bacterial cause
of her urinary tract infection?
A.
B.
C.
D.
E.
Proteus mirabilis
E. coli
Coagulase positive Staphlococus
Alpha hemolytic Streptococcus
Klebsiella pneumoniae
March 17, 2005
Bacteriology /Pathogenesis UTI - 1
• Most Common - E. Coli, coliforms
• Virulence Factors
• adherence to uroepithelium by P-fimbriae
• endotoxin release
• Pyelo vs cystitis - 80 to 20%
Feld - 10/98
57
Bacteriology /Pathogenesis UTI 2
• Perineal / urethral factors
– uncircumcised - 10-20x risk
– ? Urethral caliber (infant girls)
– other myths such as bubble bath, wiping
techniques
• Low Urinary factors
– dysfunctional voiding ; constipation
• Other - indwelling catheters, congenital
anomalies, Vesicoureteral reflux, sexual
activity
Feld - 10/98
58
Diagnosis
• Leukocyte test and nitrite test
• Urine culture > 40-50,000 CFU/mL
• Pyuria - not on recurrent UTIs
Feld - 10/98
59
Clinical Issues
• Lower tract - frequency, urgency,
enuresis, dysuria
• Upper tract - fever - nearly all in boys
under 1 year of age; females peak in
first year but still significant through the
first decade
• Asymptomatic bacteriuria - low risk
Feld - 10/98
60
Radiological Evaluation
• Renal ultrasound - anatomy, size, location,
echogenicity
• DMSA (2nd choice glucoheptanate SGH) - cortical integrity, photopenic regions,
differential function, abscess
• CT scan - abscess
• VCUG - standard for first UTI; radionuclide
for follow-up or siblings
• IVP - NO WAY
Feld - 10/98
61
Grades of Reflux
Feld - 10/98
62
Reflux Recommendations
“the simple way”
• GRADES
I - III
Antibiotics
• GRADES
IV - V
Surgery
Feld - 10/98
63
Treatment
• Oral
– SMX-TMP, Amoxicillin/Clavulanate
– Cefuroxime, cefprozil, cefixime, cefprodoxime
• Parenteral
– Neoates: Ampicillin / Gentamicin
– Older Children:
• Advanced level cephalosporin
• Beta lactam + beta lactamase inhibitor
• Aminoglycoside (+ ampicillin)
Feld - 10/98
64
Case10: Case History
• A 12 mo old girl is diagnosed with the
first febrile UTI. She is not eating well.
UA shows pyuria and bacteria. Urine
culture is obtained and shows >
100,000 colonies of E. Coli. Antibiotics
are given.
Feld - 10/98
65
Question 10: What is the most
appropriate next step?
A.
B.
C.
D.
E.
Perform a DMSA renal scan
Refer to urology for cystoscopy
Perform a renal sonogram and VCUG
Perform urodynamics and flow studies
Repeat urine culture in 3 months
March 17, 2005
Glomerulonephritis / Acute
renal failure
March 17, 2005
Case 11
• A 3 year old boy was attending summer
camp. Five days later he presents with
diarrhea, abdominal pain and appear pale.
His mother finds out that there was cook out
at camp. On examination the child is pale
and is unable to void. His laboratory testing in
your office shows a WBC of 26,000,
hemoglobin of 8 g/dL, platelets 98,000,
Serum creatinine of 1 mg/dL, BUN 54 mg/dL,
urinalysis with large blood, 100 mg/dL of
protein.
Feld - 10/98
68
Question 11: What is the most likely
diagnosis?
A.
B.
C.
D.
E.
Henoch Schoenlein Purpura
Post streptococcal glomerulonephritis
IgA nephropathy
Acute pyelonephritis
Hemolytic uremic syndrome
March 17, 2005
Clinical prodrome
• Diarrhea prodrome 1-15 days
• Abdominal pain – may be confused with
ulcerative colitis, appendicitis, rectal
prolapse, intussusception
• Pallor
• Irritability, restlessnes
• Edema – after rehydration
• Oliguria/anuria
HUS: Clinical manifestations
•
•
•
•
•
•
Thrombocytopenia
Hemolytic anemia
Renal failure
Neurologic (irritability, seizure, CVA)
Pancreatitis (IDDM) and colitis
Hypertension
HUS: Pathogenesis
• Endothelial cell damage occurs secondary
to toxin injury via binding to glycolipid
receptor or lipopolysaccharide absorption.
HUS: Differential diagnosis
• Other forms of acute Glomerulonephritis /
renal failure
• Vasculitis
• Urosepsis
• Renal vein thrombosis
• Coagulopathy (DIC)
Conservative management
• Fluid restriction to <insensible losses plus
urine output
• Foley catheter – limit to 24-48 hrs
• Blood transfusion / platelets
• Routine use of antibiotics controversial
• Diuretics
• Nutrition
Surgical Complications
•
•
•
•
•
•
•
Toxic megacolon
Rectal prolapse
Colonic gangrene
Intussusceptions
Perforation
Strictures
Mimic appendicitis, IBD
Outline – Part 2
• Acute renal failure
• Chronic renal failure
• More Fluids & Electrolytes
• Tubular disorders
• Cystic kidney disease
March 17, 2005
SCENARIO
A 6 year boy is diagnosed as having ALL. He is started on
chemotherapy and his white blood cell count drops
precipitously. The child is discharged and the family is
encouraged. However, after two days at home he spikes a
temperature to 39 C. The parents contact the heme/ onc
fellow who tells them to come to the hospital immediately.
On arrival to the ER, the child is a bit lethargic. His BP is
60/40.
What is the most important first step in the management of
this child?
What are the most useful diagnostic tests?
What are the possible causes of his condition?
How should his condition be treated?
March 17, 2005
Acute Renal Failure (ARF) vs
Pre-renal Azotemia
• Key maneuver is restore RBF to
distinguish reversible pre-renal state from
short-term irreversible
• Options
– Bolus infusion of crystalloid solutions
– Infusion of albumin
– Administration of pressors
– Administration of antagonists of clinical
condition as in anaphylaxis
March 17, 2005
ARF: Diagnosis
Pre-renal
AGN
UA
Marginal
value
Key
RTEC
RBC casts
Marginal value
SG
>1.020
>1.020
1.0081.012
1.008-1.012
UNa
<20
<20
>40
>40
FENA
<1%
<1%
>1%
>1%
Uosm
>400
>400
200-400
200-400
March 17, 2005
ATN
Obstruction
ARF: Diagnosis
• AGN
– PSAGN
– HSP
– SLE
– MPGN
– Wegener’s
March 17, 2005
ARF: Diagnosis
• ATN
– Unreversed pre-renal azotemia
– Nephrotoxic meds
– Contrast agents
– High calcium, uric acid, phosphate
– Rhabdomyolysis (myoglobin)
– Intravascular hemolysis (hemoglobin)
March 17, 2005
ARF: Diagnosis
• Obstructive uropathy
– PUV
– Prune belly
– Vesicoureteric reflux
– Neurogenic bladder (myelomeningocele)
– Megacystis/megaureter
– Secondary: stones, fibrosis
• Effect of age and gender
March 17, 2005
ARF: Testing
•
•
•
•
•
Key labs: BUN, creatinine, K
EKG
CXRay
Renal ultrasound
Specific blood tests based on underlying
condition
March 17, 2005
ARF: Management
• Urgent issues
– Potassium
• Calcium
• Glucose/insulin
• NOT bicarbonate
– Blood pressure: parenteral therapy
• Labetalol
• Nitroprusside
– ECF volume
March 17, 2005
ARF: Conservative
Management
• Potassium
– Diet restriction
– Kayexalate
• Blood pressure
– IV/PO meds
• ECF volume
– Na restriction
– Diuretic use – need for furosemide
March 17, 2005
ARF: Indications for Dialysis
•
•
•
•
Refractory hyperkalemia
Refractory hypertension
Symptomatic ECF volume overload
Symptomatic azotemia
– Infection
– Bleeding
– CNS changes
March 17, 2005
ARF: Pearls
• Pre-renal azotemia and AGN are similar
• ATN and post-renal failure are similar
• Potassium kills first in ARF
March 17, 2005
SCENARIO
A 6 year boy is seen at a routine physical examination.
Although he has no specific complaints, his mother says he
has been very listless and his appetite is very poor. He has
not been playing well with his friends in play group. Although
he is toilet trained he seems to be having more accidents
during the night.
On examination, he looks a bit pale and tired. His height has
fallen from the 50% at his last visit 18 months ago to 10%. His
BP is 106/62 mm Hg.
What is the most important first step in the diagnosing this
child’s problems?
What are the likely causes his condition?
How should his condition be treated?
March 17, 2005
CKD: Diagnosis
• Stages
– CKD I: renal injury GFR >90
– CKD II: GFR 60-90
– CKD III: GFR 30-60
– CKD IV:GFR 15-30
– CKD V: ESRD
March 17, 2005
CKD: Common features
•
•
•
•
Impact on growth
Impact on bone: osteodystrophy
Impact on puberty
Impact on development – social and
cognitive
March 17, 2005
CKD: Causes
• Non-glomerular
– Hypoplasia/dysplasia
– Reflux nephropathy
– Obstructive uropathy
• PUV
• Prune Belly
• Neurogenic bladder
March 17, 2005
CKD: Clinical manifestations
• Growth failure
– Dependent on age of onset
– Dependent on level of GFR
• UTIs
– Pyelonephritis
• Electrolyte abnormalities
– Pseudohypoaldosteronism
– Nephrogenic DI
•MarchNeurocognitive
disability
17, 2005
CKD: Diagnosis
• Structural assessment
• Imaging studies
– US
– VCUG: dye vs radioisotope
– DMSA scan
– Retrograde studies, etc
March 17, 2005
CKD: Diagnosis
ARF
Younger child, abd mass, UTI
UA
WBC, impaired concentration
US, VCUG, DMSA
Retrograde studies
Cystoscopy, urodynamics
March 17, 2005
SCENARIO
A 15 year old girl comes to the clinic because she has not had
her period for the last 8 months. She feels tired all the time at
home school and is having a hard time concentrating in
school.
She is not taking any medications except for occasional
NSAIDs for headaches and some vitamins. Her parents are in
good health.
On examination, her height and weight are normal. Her BP is
162/98 mm Hg. She is pale and has a mild amount of edema
in both legs. She has no rash or arthritis.
What is the most important first step in diagnosing this
adolescent’s problem?
What are the most likely causes?
How should her condition be treated?
March 17, 2005
CKD: Causes
• Glomerular
– FSGS
– HUS
– SLE
– Membranoproliferative MPGN)
– Alport
– IgA Nephropathy
– Membranous nephropathy
– NOT diabetic or hypertensive nephropathy
March 17, 2005
CKD: Clinical manifestations
• Growth failure
– Dependent on age of onset
• Hypertension
– Role of ECF volume and PRA
• Electrolyte abnormalities
– Acute
– Hyperkalemia
• Edema
•MarchSigns
17, 2005 of underlying disease
CKD: Diagnosis
• Low value of radiology tests
• Blood tests
– C3, C4, CH50
– ASLO
– ANA, dsDNA, Ro, La, Sm
– ANCA
– Anti-GBM
– Renal biopsy
March 17, 2005
CRF: Management
• Nutritional supplementations
– CHO deficiency
• Protein restriction
– Impact on growth
– Effect in more advanced CKD
• BP control
– Disease progression
– ACEI/ARB
March 17, 2005
CRF: Management
• Interference with renin-angiotensin
aldosterone axis
– Safety of ACEI even with advanced CKD
– Role of combined ACEI/ARB
– Effect of aldosterone antagonists
• Safety issues
– Hyperkalemia
– Reduction in GFR
March 17, 2005
CRF: Management
• Endocrine treatments
– rhGH
• Doubles growth velocity
• Minimal risk of progression
– Erythropoietin
• Nearly always effective
• Antibody induced pure red cell aplasia
– Calcitriol
• IV route
• More selective agents
March 17, 2005
CRF: Pearls
• Chronic glomerular diseases have oliguria
vs chronic tubular diseases which can
have polyuria and sodium loss
– Nocturia and enuresis may indicate CRF
• Severity of growth failure and
neurocognitive deficits are inversely
related to age of onset of CRF
March 17, 2005
CRF: More pearls
• Most important feature of nutritional
support is to correct low caloric intake
• Medication doses need to be adjusted as
GFR declines
• Almost no form of CRF is a
contraindication to transplant
March 17, 2005
SCENARIO
A 10-day male infant presents with a history of irritability,
low grade fever, emesis and diarrhea. Prenatal and family
history is non-contributory. On examination the infant is
irritable, temp is 38°C, has mottled skin and a capillary
refill of 4 sec. The systolic blood pressure is barely
palpable and the pulse is 195 beats/min. The anterior
fontanelle is flat.
Hemoglobin
18 g/dl
White cell count
30,000
Platelets
280,000
What are key features in the history and examination?
What studies would you perform?
What is your initial therapy?
What is your initial diagnosis (es)?
March 17, 2005
Electrolyte Disorders: Sodium
• KEY function of Na+
– ECF cation
– Maintenance of intravascular compartment
• Disturbances in ECF volume are
secondary to disturbances in Na+ balance
• ECF volume assessment is clinical
– Reduced – see dehydration above
– Increased – pulmonary and/or peripheral
edema
March 17, 2005
Electrolyte disorders: Sodium
Assess ECF
Measure serum Na
High ECF
March 17, 2005
Normal ECF
Low ECF
Electrolyte Disorders: Sodium
•
•
•
•
History
Source of Na loss
Change in body weight
Renal response to low ECGF volume
– Oliguria
– Reduced urine Na+
– Reduced FENA
March 17, 2005
Electrolyte disorders: Sodium
120
100
80
ICF
ECF
60
40
20
0
Normal
March 17, 2005
Hypo
Hyper
Electrolyte disorders: Sodium
• Hypernatremia
– Risk factors
•
•
•
•
Breast feeding
Feeding errors
Impaired thirst
Impaired access to water
– Presentation
• Irritability, seizures
– Treatment
• SLOW
• HYPOTONIC FLUIDS – 1/5 NS
March 17, 2005
Electrolyte disorders: Sodium
• Hyponatremia
– Risk factors
•
•
•
•
•
Feeding errors (Keating)
Salmonella diarrhea
Increased extra-renal salt loss
Pain, anesthesia, post-operative picture
Female gender
– Presentation
• Lethargy, seizures
– Treatment
• ?SLOW
• Correction 25 mmol/L OR 130 mmol/L over initial 48 hr
March 17, 2005
Electrolyte disorders: Sodium
• Bad outcomes
• Brain
– Hemorrhage and cerebral edema in
hypernatremia
– Osmotic demyelinating syndrome and acute CNS
deterioration in Hyponatremia
• DKA
– ?Hyponatremia (100 glucose mg/dl  1.6 Na meq/l)
– Comparison to hypernatremia
March 17, 2005
SCENARIO
A 4-week old infant presents with a history of irritability, low
grade fever and poor feeding. Prenatal and family history is
non-contributory. On examination the infant is irritable,
temp is 37°C, has dark skin and a capillary refill of 4 sec.
The systolic blood pressure is barely palpable and the
pulse is 195 beats/min. The anterior fontanelle is sunken.
Hemoglobin
18 g/dl
White cell count
30,000
Platelets
280,000
What are key features in the history and examination?
What studies would you perform?
What is your initial therapy?
What is your initial diagnosis (es)?
March 17, 2005
Electrolyte Disorders: Potassium
• KEY function of K+
– ICF cation
– Transmembrane potential, secretion,
neuromechanical coupling
• Disturbances in K+ reflect sudden
changes in serum concentration and
transmembrane ratio
• Assessment is linked to cardiac impact of
abnormal K+ concentration
March 17, 2005
Electrolyte disorders: Potassium
• Regulatory organs
– Kidney secretion
• Na+
• Urine flow rate
– Adrenal
• Aldosterone
– GI tract
• Transmembrane
–
–
–
–
pH
Osmolality
Beta adrenergics
Insulin
• Diet
March 17, 2005
Potassium
• Key tests
– BUN, Cr, Na, K, bicarbonate
– Urine K useless
– Urine Na/K ratio
– Hormones
• PRA
• Aldosterone
March 17, 2005
Electrolyte disorders: Potassium
• Hyperkalemia
– EKG
• Peaked T waves
– Treatment
•
•
•
•
•
March 17, 2005
Calcium infusion
Glucose/insulin
NOT Bicarbonate
Kayexalate
DIALYSIS
Hyperkalemia: differential diagnosis
• No real disease
– Increase cells: WBC, polycythemia, thrombocytosis,
crush injury
– Transmembrane
• Renal
– ARF
– CRF
– Liddle’s
• Adrenal
– Adrenal failure
– Congenital adrenal hyperplasia – ambiguous genitalia
– Isolated renin abnormalities
March 17, 2005
Hyperkalemia: Work-up
•
•
•
•
BUN, creatinine, Na, K, Bicarbonate
PRA
Aldosterone
Urinary Na/K ratio
March 17, 2005
Electrolyte disorders: Potassium
• Hypokalemia
– EKG
• U waves
– Treatment
• Restore ECF volume to 2hyperaldosteronism
• PO potassium
– Limitations: tolerance
• IV potassium
– Limitation: 0.3 meq/kg/hr
– Central vs peripheral IV
March 17, 2005
Hyperkalemia: differential diagnosis
• Systemic
– Malnutrition
• Adrenal
– Adrenal overactivity
– Congenital adrenal hyperplasia
– Primary renin abnormalities
• Renal
– DKA
– Osmotic diuresis
March 17, 2005
SCENARIO
A 15 month child presents with a history of poor feeding
and impaired growth. Prenatal and family history is noncontributory. On examination the infant’s height and
weight are below the 5th percentile. The systolic blood
pressure is 102 and the pulse is 110. The rest of the
examination is normal.
Na
138
Cl
114
Bicarbonate
16
What are key features in the history and examination?
What studies would you perform?
What is your initial therapy?
What is your initial diagnosis (es)?
March 17, 2005
Electrolyte disorders: acid-base
Acid load
Acute
Chronic-Kidney
Proximal
Chronic-Kidney
Distal
Lung
Reclaim filtered
bicarbonate
Regenerate
Titrated bicarbonate
Large frequent
doses
March 17, 2005
1-3 mmol/kg/day
Electrolyte disorders
• Anion gap
• [Na] – {[Cl] + [HCO3]}
• Normal value: 4-12
• Impact of serum albumin
March 17, 2005
Electrolyte disturbances: RTA
• Metabolic acidosis
– Normal anion gap -- hyperchloremic
• Diarrhea
• RTA
– High anion gap -- normochloremic
• MUDPIES or KUSSMAUL
• Key entities:
–
–
–
–
–
March 17, 2005
DKA
Lactic acidosis
Uremia
Metabolic disease
Toxins
Electrolyte disturbances: RTA
• Proximal
– Low K
– Primary
– Secondary
•
•
•
•
March 17, 2005
Glycogen storage
Wilson’s, fructose intolerance, tyrosinemia
PTH, Vitamin D
Cystinosis
Electrolyte disturbances: RTA
• Distal
– Primary
– Secondary
• Transplant rejection
• Drugs: amphotericin, cisplatinum
• Collagen vascular disease
March 17, 2005
Electrolyte disorders: RTA
• Assessment
– SMAC: Cl– VBG: Bicarbonate
– Urine: calcium, citrate
– Urine anion gap: unmeasured cation (NH4+)
– Xrays
March 17, 2005
Electrolyte disturbances: RTA
• Treatment
• Proximal
– Higher doses of bicarbonate
– More frequent dosing
– Exacerbation of hypokalemia with Rx
• Distal
– 1-3 mmol/kg varying with age and diet
– 3 doses
–
Stabilization
of
K
with
Rx
March 17, 2005
Electrolyte disorders: Fanconi’s
Fanconi’s
Syndrome
Complete proximal
tubule dysfunction
RTA
March 17, 2005
Glycosuria
Phosphaturia
TRP
Amino
Aciduria
Electrolyte disorders: metabolic
alkalosis
• Extrarenal/GI loss of K
– CF
• Vomiting
– NG suction
– Pyloric stenosis
• Distal GI loss of bicarbonate
– Chloride diarrhea
• Renal
– Bartter’s
– Gitelman’s
– Apparent mineralocorticoid excess (AME)/licorice
March 17, 2005
Electrolyte disorders: DI
• Central
• Nephrogenic
• Risk of CNS disease
– 1/12 (1/3 X ¼) of loss from ECF
– Limited access to water
– Altered thirst
March 17, 2005
Electrolyte disorders: DI
• Central
– AVP replacement
• Nephrogenic
– Adequate water intake
– Low solute diet
– Hydrochlorothiazide
March 17, 2005
Electrolytes: Pearls
There are three pure renal causes of FTT –
azotemia, DI, and RTA
RTA causes hyperchloremic acidosis
Bartter’s and Gitelman’s differ in calcium
excretion – high in former low in latter
March 17, 2005
Thank you
GOOD LUCK
March 17, 2005