Transcript Slide 1

Metropolitan New York / New
Jersey Pediatric Board Review
Course
Pediatric Nephrology
May, 2008
Leonard G. Feld MD PhD
Levine Children’s Hospital
Charlotte, NC
Howard Trachtman MD
Schneider Children’s Hospital
New Hyde Park, NY
Materials
• Consider all other material to help you
achieve a passing score
– American Academy of Pediatrics – Pediatrics
Review and Education Program (PREP),
Pediatrics in Review.
Renal / Urology
• General
– Normal function
– Proteinuria
– Hematuria
• Persistent microscopic hematuria
• Causes of gross and microscopic hematuria
– Dysuria / Incontinence
• Congenital
– Renal dysplasia
– Abnormalities of the collecting system, kidney,
bladder
Renal / Urology
• Acquired
– Infection of the urinary tract
– Acute glomerulonephritis
– Nephrotic syndrome
– Hemolytic uremic syndrome
– Henoch-Schoenlein purpura
– IgA nephropathy
• Other
– Renal Failure,Trauma, renal stones, RTA
Renal / Urology
• Hypertension
• Nephrogenic diabetes insipidus
• Cystinosis
Outline – Part 1
• Hematuria
• Proteinuria
• Hypertension
• Urinary tract infections
• Glomerulonephritis
A 3-week-old 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 of of 39.0°C, has mottled skin and a capillary
refill of 4 sec. The systolic blood pressure is normal and the
pulse is 185 beats/min. The anterior fontanelle is full.
Hemoglobin
White cell count
Platelets
14 g/dl
30,000
110,000
What studies would you like to perform.
What is your initial therapy?
What is your initial diagnosis (es)?
Answers
• Blood culture, urine, CXR, and LP
• Fluid resuscitation + broad spectrum
antibiotics
• Late onset neonatal sepsis / meningitis
Suggested
Evaluation and Management of the Febrile Infant <60 Days of Age
GLOBAL ASSESSMENT
Appears Toxic
Appears Moderately Ill
or Your Are Not Sure
Appears Generally Well
Treat Expectantly
Hospitalize
See Table 1
Evaluate for Possible
Sepsis, Hospitalize and
Treat
Skin, Soft Tissue, Bone or
Joint Infection?
NO
YES
Evaluate as Indicated
Hospitalize and Treat
See Table 1
WBC with Differential
Urinalysis
WBC = 5,000 - 15,000 /mm3, AND Band Count < 1,500 /mm3 AND
Urinalysis < 10 WBC/HPF in Unspun Sediment and Negative Gram Stain (OR
< 10 WBC/HPF in Spun Sediment)
YES
History of Prematurity, Perinatal Problems,
Underlying Condition, Previous Antimicrobial
agents
NO
LP = CSF Analysis; Cultures of Blood, CSF,
Urine (Suprapubic or catheter specimen only)
Hospitalize and Give Parenteral Antimicrobial
Therapy
YES
NO
Culture Blood and Urine
(Suprapubic or catheter
specimen only)
Observe without
Antimicrobial Therapy
Physician Identified to Assume Full
Responsibility for Outpatient Management
Hospitalize
NO
YES
NO
Option 1
No Antimicrobial
Therapy
Caregiver with Good Observation Skills,
Telephone in Home, Can Meet Responsible
Physicians within 30 Minutes
Manage as Outpatient, Instruct Parents to
Watch For SEE BELOW ….*
Phone Follow-up Within 12 Hours, Re-Examine
Within 24 Hours
Option 2
Empiric
Antimicrobial
Therapy
LP - CSF Analysis; Culture Blood, CSF,
Urine (Suprapubic or catheter specimen
only)
* 1.) skin changes like a new rash or a change in a rash that is already present
2.)
3.)
4.)
5.)
6.)
7.)
8.)
discoloration like duskiness, cyanosis, mottling
the extremities feel cool
the infant feeds poorly, or vomits
the infant is difficult to comfort
the infant is difficult to arouse or is less interactive with the parent than usual
any evidence of a seizure, like eye rolling or quick jerky movements
bulging of the soft spot (anterior fontanelle)
From Consensus in Pediatrics Fever In Infants and Children, Feld LG, Hyams J eds. Mead Johnson Nutritionals, 2007.
PEARL – No question on the
< 28 day old febrile infant
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.
What is the next step? What would be a major
consideration for a referral to a pediatric
nephrologist?
• 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.
• Caveat - Family anxiety because of the
connotation of blood and cancer in adults.
Classification of Hematuria
• Microscopic (vast majority of the cases)
–
–
Transient
Persistent
• Macroscopic (urologic / renal disorders)
–
–
Transient
Persistent (> 2 weeks)
• Persistent microscopic/ Transient
macroscopic
–
IgA or Berger’s; benign recurrent hematuria
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
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
Initial evaluation of the patient with hematuria
• All patients: BUN, creatinine, CBC, kidney
and bladder ultrasound
• Probable glomerular hematuria
– C3, ASO titer
– possible: hepatitis, HIV, SLE serology
– renal biopsy
• Probable non-glomeurlar hematuria
–
–
–
–
urine culture, urine Ca/creatinine ratio
possible: hemoglobin electrophoresis,
coagulation studies, isotope scans,
Flat plate, CT, ??IVP, cystoscopy
Pearls for Hematuria
• Hematuria is 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.
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.
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
is hypercalciuria, SS trait, or thin basement
membrane disease.
• Cysto is rarely helpful
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 with a BP of 95/65, no edema,
some suprapubic tenderness and red tympanic
membranes.
The mother thinks that a similar episode occur on
vacation a few months ago.
WHAT WOULD YOU LIKE TO DO?
Tests
•
•
•
•
Normal electrolytes
Creatinine 0.5 mg/dl
Urinalysis – large blood, no protein
Urine culture – no growth
More to the story
• She calls with a recurrent episode of gross
hematuria with a URI three months later
• So what do you do ?
Other tests
• ANA, ANCA, ASO, Family screening
• Complement – C3NF
Now what
• 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
Acute
Glomerulonephritis
Normal
Complement
Low 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
Renal diseases
IGA
RPGN Anti-GBM, immune complex GN
Acute proliferative GN
Membranoproliferative 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
Clinical evidence
to support
endocarditis
YES
Blood cultures
Echocardiogram
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
++
+
+
-
+
+
+
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)
On routine physical examination, an 8-yearold boy is found to have microscopic
hematuria. The first step in your evaluation
should be.
• Examine the urine sediment
• Order an intravenous pyelogram
• Obtain a voiding cystourethrogram
• Perform a CBC in the office
• Order an ASO titer
An 8-year-old boy presents with tea colored
urine. He has very mild edema. The workup should include all the following except.
• Complement studies
• Serum creatinine
• Urinalysis for protein
• Monitor blood pressure and urine output
• Obtain an intravenous pyelogram and
VCUG
Proteinuria
John is an 12 year old noted on a basketball
team physical to have 2+ protein on
dipstick. He has an unremarkable past
medical history. Family history is negative
in the parents and siblings for any renal
disease. A repeat urine in one week in his
PMD’s office is still positive.
What is the next step? Should you refer?
• 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 workup is generally required, although no
indemnification from subsequent renal disease.
• Caveat - Family anxiety because of the
connotation of protein and friends told them
about kidney failure.
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
What does Orthostatic Proteinuria
mean?
Protein
Excretion
Threshold of Detection
Normal
Orthostatic
Recumbant
Erect
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
Hypertension
Hypertension
Case: David is a 10 year old boy first noted to
have an elevated blood pressure of 140/85
during a PE for headaches. Pt has a long history
of learning and behavioral issues. Headache
evaluation was normal (CT, sinus,etc.). Referred
for evaluation. Initial evaluation noted a Ht / Wt >
99%tile, BP of 128/86 mmHg, normal ultrasound
and renal scan, although a plasma renin of 8
ng/ml/min (nl < 2).
Do you perform an angiogram?
Definition of Hypertension
The 4th Report on High Blood Pressure in Children and
Adolescents
• Hypertension—average SBP and/or DBP that is
greater than or equal to the 95th percentile for
sex, age, and height on 3 or more occasions.
• Prehypertension—average SBP or DBP levels
that are greater than or equal to the 90th
percentile, but less than the 95th percentile.
– Adolescents with BP levels greater than or equal to 120/80
mmHg should be considered prehypertensive.
Evaluation of Hypertension
Historical
Information
Physical
Examination
Vital signs
(including extremities)
Height/Weight
Specific attention to organ
systems - cardiac, eye,
abdominal or other bruits,
etc.
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.
Consider ambulatory blood
pressure monitor
Evaluation Phase 1
CBC, urinalysis, urine culture, electrolytes, BUN,
creatinine, 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
Therapeutic Lifestyle Changes
• Normal
Encourage healthy diet, sleep, and physical
activity.
• Prehypertension Recommend weight management
counseling if overweight; introduce physical activity and
diet management.
• Stage 1 hypertension Recommend weight
management counseling if overweight; introduce
physical activity and diet management.
• Stage 2 hypertension Recommend weight
management counseling if overweight; introduce
physical activity and diet management.
Indications for Treatment
•
•
•
•
•
Symptomatic hypertension
Secondary hypertension
Hypertensive target-organ damage
Diabetes (types 1 and 2)
Persistent hypertension despite
nonpharmacologic measures
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.
Urinary Tract
Infections
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. Antibiotics are given
(SMX-TMP).
• How to proceed?
– What are some of your concerns?
– Radiographic follow-up
– Long-term monitoring
Feld - 10/98
43
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
44
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
45
Diagnosis
• Leukocyte test and nitrate test
• Urine culture > 40-50,000 CFU/mL
• Pyuria - not on recurrent UTIs
Feld - 10/98
46
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
47
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
48
Grades of Reflux
Feld - 10/98
49
Reflux Recommendations
“the simple way”
• GRADES
I - III
Antibiotics
• GRADES
IV - V
Surgery
Feld - 10/98
50
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
51
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. Antibiotics are given
(SMX-TMP).
• How to proceed?
– What are some of your concerns?
– Radiographic follow-up
– Long-term monitoring
Feld - 10/98
52
The Suggested Answers
• What are your concerns?
– Voiding history
• Radiographic studies
– ultrasound and VCUG
• Follow-up (no reflux)
– cultures every month for three months,
then every other month for six months
( every 4 months)
• Follow-up (reflux) - antibiotics
Feld - 10/98
53
Glomerulonephritis / Acute
renal failure
Case History
• 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 How to proceed?
– What are some of your concerns?
Feld - 10/98
55
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
Case
• A four year old boy presents with a three day
history of periorbital swelling and sox
indentations around his ankles. He has been
healthy without any intercurrent illnesses. The
family and past medical history are
unremarkable. On examination he has pretibial
edema and has gained 2.5 kg since his
examination 2 months ago for an otitis media.
• What are your thinking?
Nephrotic Syndrome
Definition
• Nephrotic syndrome is a clinical state
characterized by heavy proteinuria and
hypoalbuminemia, often associated with
edema, hypercholesterolemia, and
generalized hyperlipidemia.
PRIMARY NEPHROTIC
SYNDROME
• 90% childhood cases
• unassociated with systemic
disease
CLINICAL PRESENTATION (1)
• EDEMA is the major symptom - first
periorbital, then generalized. Happy
parents: “finally my child is gaining
weight”.
• Soft and pitting in nature.
• May cause anasarca with ascites, pleural
effusions, labial and scrotal swelling.
CLINICAL PRESENTATION (2)
•
•
•
•
Poor appetite
Diarrhea during massive edema
Hepatomegaly
Abdominal pain (need to r/o peritonitis or
surgical abdomen)
• Respiratory difficulty
• Hypertension (15%-20% of MCNS)
LABORATORY FEATURES
•
•
•
•
•
PROTEINURIA is the primary abnormality.
“Selective”- almost entirely albuminuria
> 40 mg/m2/hr or
U protein/creatinine ratio > 1 (mg/mg)
due to loss of charge selectivity of
glomerular basement membrane
COMPLICATIONS OF
NEPHROTIC SYNDROME
INFECTION
• Impaired resistance to infection
– -low immunoglobulin levels
– -generalized protein deficiency
– -defective opsonization
– -splenic hypofunction
– immunosuppressive therapy
• Peritonitis
• Pneumococcal infection
TREATMENT
• Diuretics ?
• Albumin & Lasix infusion
• Prednisone 60 mg/m2/d x 4 weeks,
then 40 mg/m2 every other day x 4
wk
• Alternatives
– Cyclophosphamide 2-3 mg/kg/d x 8
weeks, not to exceed 200 mg/kg
– Chlorambucil
– Cyclosporine
Requirements at a glance
Nephrolithiasis
Presentation
• Most patients present with abdominal, flank or pelvic
pain depending upon the location of the calculus.
Referred pain may be localized to the scrotum, penis or
female genitalia.
• Patients may have associated nausea and vomiting,
gross hematuria, or symptoms of a urinary tract infection
(urinary frequency, dysuria, etc.)
• Not all patient with urinary calculi have gross or
microscopic hematuria
• 20% of patients with microscopic hematuria and
hypercalciuria will develop a urinary calculus within five
years.
Requirements at a glance
Nephrolithiasis
Medical Evaluation
• Family history is paramount as pediatric stones may be associated
with inherited disorders such as cystinuria, primary hyperoxaluria or
renal tubular acidosis.
• Patient’s past medical history including low fluid intake, dietary
exess or deficiencies may predispose to calcium oxalate stone
formation.
• Patients with a history of hyperthyroidism, myeloproliferative
disorders, gastrointestinal disorders, chronic urinary tract infections
or immobilization may be at increased risk for stone formation.
• Infants with a history of furosamide (Lasix) use are at an increased
risk for stones and nephrocalcinosis.
• Pediatric patients with a history of stones are at an increased risk for
recurrent stone formation
Requirements at a glance
Nephrolithiasis
Radiographic evaluation
• CT scan without contrast is the most sensitive study for the
detection of urinary calculi.
• KUB and renal ultrasound may be useful in specific situations.
Laboratory Evaluation
• Urinalysis of a first morning void including pH, specific gravity and
present of bacteria are useful in the evaluation.
• Measurement of serum electrolytes including sodium, potassium,
bicarbonate, chloride, uric acid, calcium, phosphorus and creatinine
may provide useful information.
• A 24 hour urine analysis for volume, calcium, oxalate, citrate, uric
acid, cystine, sodium, phosphate and creatinine. Measurements
must be corrected to patient body mass.
Outline – Part 2
• Dehydration
• Acute renal failure
• Chronic renal failure
• Fluids & Electrolytes
• Tubular disorders
• Cystic kidney disease
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)?
Dehydration: Clinical
• Importance of clinical history
– Feeding history (BF, formula error)
– Other conditions (CF, CV disease)
• Features to assess: change in weight,
altered VS, orthostatic changes.
turgor/refill, fontanelle, tears
• No specific diagnostic laboratory test –
only supportive
• Key feature is reversibility
Dehydration: Laboratory
• Urine
– S.G.
– UNa, FENA, Uosm
– Microscopic examination
• Blood
– BUN, creatinine
– Bicarbonate
Dehydration: Therapy
• Emergent therapy
– 10-20 ml/kg boluses
– Isotonic solution
– Repeat until any evidence of improvement
• Correction therapy
– Isotonic over 24 hours
– Ongoing losses: diarrhea, vomiting
• Maintenance therapy
Dehydration: Pearls
• Dehydration is reversible
• Dehydration is a misnomer and reflects
loss of sodium not water
• Isotonic solutions are fluid of choice
• FENA is best test to assess severity of
dehydration
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?
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
ARF: Diagnosis
Pre-renal
AGN
ATN
Obstruction
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
ARF: Diagnosis
• AGN
– PSAGN
– HSP
– SLE
– MPGN
– Wegener’s
ARF: Diagnosis
• ATN
– Unreversed pre-renal azotemia
– Nephrotoxic meds
– Contrast agents
– High calcium, uric acid, phosphate
– Rhabdomyolysis (myoglobin)
– Intravascular hemolysis (hemoglobin)
ARF: Diagnosis
• Obstructive uropathy
– PUV
– Prune belly
– Vesicoureteric reflux
– Neurogenic bladder (myelomeningocele)
– Megacystis/megaureter
– Secondary: stones, fibrosis
• Effect of age and gender
ARF: Testing
•
•
•
•
•
Key labs: BUN, creatinine, K
EKG
CXRay
Renal ultrasound
Specific blood tests based on underlying
condition
ARF: Management
• Urgent issues
– Potassium
• Calcium
• Glucose/insulin
• NOT bicarbonate
– Blood pressure: parenteral therapy
• Labetalol
• Nitroprusside
– ECF volume
ARF: Conservative
Management
• Potassium
– Diet restriction
– Kayexalate
• Blood pressure
– IV/PO meds
• ECF volume
– Na restriction
– Diuretic use – need for furosemide
ARF: Indications for Dialysis
•
•
•
•
Refractory hyperkalemia
Refractory hypertension
Symptomatic ECF volume overload
Symptomatic azotemia
– Infection
– Bleeding
– CNS changes
ARF: Pearls
• Pre-renal azotemia and AGN are similar
• ATN and post-renal failure are similar
• Potassium kills first in ARF
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?
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
CKD: Common features
•
•
•
•
Impact on growth
Impact on bone: osteodystrophy
Impact on puberty
Impact on development – social and
cognitive
CKD: Causes
• Non-glomerular
– Hypoplasia/dysplasia
– Reflux nephropathy
– Obstructive uropathy
• PUV
• Prune Belly
• Neurogenic bladder
CKD: Clinical manifestations
• Growth failure
– Dependent on age of onset
– Dependent on level of GFR
• UTIs
– Pyelonephritis
• Electrolyte abnormalities
– Pseudohypoaldosteronism
– Nephrogenic DI
• Neurocognitive disability
CKD: Diagnosis
• Structural assessment
• Imaging studies
– US
– VCUG: dye vs radioisotope
– DMSA scan
– Retrograde studies, etc
CKD: Diagnosis
ARF
Younger child, abd mass, UTI
UA
WBC, impaired concentration
US, VCUG, DMSA
Retrograde studies
Cystoscopy, urodynamics
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?
CKD: Causes
• Glomerular
– FSGS
– HUS
– SLE
– Membranoproliferative MPGN)
– Alport
– IgA Nephropathy
– Membranous nephropathy
– NOT diabetic or hypertensive nephropathy
CKD: Clinical manifestations
• Growth failure
– Dependent on age of onset
• Hypertension
– Role of ECF volume and PRA
• Electrolyte abnormalities
– Acute
– Hyperkalemia
• Edema
• Signs 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
CRF: Management
• Nutritional supplementations
– CHO deficiency
• Protein restriction
– Impact on growth
– Effect in more advanced CKD
• BP control
– Disease progression
– ACEI/ARB
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
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
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
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
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)?
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
Electrolyte disorders: Sodium
Assess ECF
Measure serum Na
High ECF
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
Electrolyte disorders: Sodium
120
100
80
ICF
ECF
60
40
20
0
Normal
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
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
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
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)?
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
Electrolyte disorders: Potassium
• Regulatory organs
– Kidney secretion
• Na+
• Urine flow rate
– Adrenal
• Aldosterone
– GI tract
• Transmembrane
–
–
–
–
pH
Osmolality
Beta adrenergics
Insulin
• Diet
Potassium
• Key tests
– BUN, Cr, Na, K, bicarbonate
– Urine K useless
– Urine Na/K ratio
– Hormones
• PRA
• Aldosterone
Electrolyte disorders: Potassium
• Hyperkalemia
– EKG
• Peaked T waves
– Treatment
•
•
•
•
•
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
Hyperkalemia: Work-up
•
•
•
•
BUN, creatinine, Na, K, Bicarbonate
PRA
Aldosterone
Urinary Na/K ratio
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
Hyperkalemia: differential diagnosis
• Systemic
– Malnutrition
• Adrenal
– Adrenal overactivity
– Congenital adrenal hyperplasia
– Primary renin abnormalities
• Renal
– DKA
– Osmotic diuresis
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)?
Electrolyte disorders: acid-base
Acid load
Acute
Chronic-Kidney
Proximal
Chronic-Kidney
Distal
Lung
Reclaim filtered
bicarbonate
Regenerate
Titrated bicarbonate
Large frequent
doses
1-3 mmol/kg/day
Electrolyte disorders
• Anion gap
• [Na] – {[Cl] + [HCO3]}
• Normal value: 4-12
• Impact of serum albumin
Electrolyte disturbances: RTA
• Metabolic acidosis
– Normal anion gap -- hyperchloremic
• Diarrhea
• RTA
– High anion gap -- normochloremic
• MUDPIES or KUSSMAUL
• Key entities:
–
–
–
–
–
DKA
Lactic acidosis
Uremia
Metabolic disease
Toxins
Electrolyte disturbances: RTA
• Proximal
– Low K
– Primary
– Secondary
•
•
•
•
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
Electrolyte disorders: RTA
• Assessment
– SMAC: Cl– VBG: Bicarbonate
– Urine: calcium, citrate
– Urine anion gap: unmeasured cation (NH4+)
– Xrays
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
Electrolyte disorders: Fanconi’s
Fanconi’s
Syndrome
Complete proximal
tubule dysfunction
RTA
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
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
Electrolyte disorders: DI
• Central
– AVP replacement
• Nephrogenic
– Adequate water intake
– Low solute diet
– Hydrochlorothiazide
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
Thank you
GOOD LUCK