Leonard G. Feld MD PhD
Levine Children’s Hospital
Charlotte, NC
Howard Trachtman MD
Schneider Children’s Hospital
New Hyde Park, NY

• Consider all other material to help you achieve a passing score
– American Academy of Pediatrics – Pediatrics
Review and Education Program (PREP),
Pediatrics in Review.

• 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

• 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

• Hypertension
• Nephrogenic diabetes insipidus
• Cystinosis

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)?

• 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
Treat Expectantly
Hospitalize
See Table 1
Appears Moderately Ill or Your Are Not Sure
Evaluate for Possible
Sepsis, Hospitalize and
Treat
NO
WBC with Differential
Urinalysis
Appears Generally Well
Skin, Soft Tissue, Bone or
Joint Infection?
YES
Evaluate as Indicated
Hospitalize and Treat
See Table 1
WBC = 5,000 - 15,000 /mm3, AND Band Count < 1,500 /mm
3
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
YES
NO
LP = CSF Analysis; Cultures of Blood, CSF,
Urine (Suprapubic or catheter specimen only)
Hospitalize and Give Parenteral Antimicrobial
Therapy
NO
Culture Blood and Urine
(Suprapubic or catheter specimen only)
Observe without
Antimicrobial Therapy
Physician Identified to Assume Full
Responsibility for Outpatient Management
NO
Hospitalize
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.) discoloration like duskiness, cyanosis, mottling
3.) the extremities feel cool
4.) the infant feeds poorly, or vomits
5.) the infant is difficult to comfort
6.) the infant is difficult to arouse or is less interactive with the parent than usual
7.) any evidence of a seizure, like eye rolling or quick jerky movements
8.) 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.

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.

• 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
– 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

• 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

• 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.

• 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 .

• 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?

• Normal electrolytes
• Creatinine 0.5 mg/dl
• Urinalysis – large blood, no protein
• Urine culture – no growth

• She calls with a recurrent episode of gross hematuria with a URI three months later
• So what do you do ?

• ANA, ANCA, ASO, Family screening
• Complement – C3NF

• 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
Low Complement
Normal
Complement
Systemic diseases
SLE
Subacute Bact Endocarditis
Shunt nephritis
Essential mixed cryoglobulinemia
Visceral abscess
Renal diseases
Acute proliferative GN
Membranoproliferative GN
Systemic diseases
Polyarteritis nodsa
Hypersensitivity vasculitis
Wegener’s
HSP
Goodpasture’s
Renal diseases
IGA
RPGN -
Anti-GBM, immune complex GN
PSAGN
Strep endocarditis
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
Blood cultures
Echocardiogram
Clinical evidence to support endocarditis
YE
S NO
Treat PSAGN

Urinalysis
History
Physical
Dysmorphic RBC
Cellular casts
Brown/tea color
Bright red
Clots
Crystals
Protein
Family Hx of ESRD
Systemic disease
Nephrolithiasis
Trauma
Symptomatic vomiting
Hypertension
Systemic signs
Edema
Abdominal mass
Genital bruising
Glomerular
+
-
-
+
-
+
+
++
+
-
-
+
++
+
+
-
-
Non-glomerular
-
+
+
-
+
-
-
+
++
+
+
-
+
-
-
+
+

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

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.

• Urine protein to creatinine ratio
–
–
–
Normal: < 0.2 (< 0.15 adolescents)
Mild to moderate: 0.2 to 1.0
Heavy or severe: > 1.0
• Persistent proteinuria: present both in the recumbent and the upright posture; even in this situation, proteinuira is less during recumbency

Protein
Excretion
Threshold of Detection
Normal Orthostatic
Recumbant
Erect

• 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

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?

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.

Historical
Information
Evaluation of Hypertension
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, 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

• 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.

• Symptomatic hypertension
• Secondary hypertension
• Hypertensive target-organ damage
• Diabetes (types 1 and 2)
• Persistent hypertension despite nonpharmacologic measures

• 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.

• 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

• 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

• 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

• Leukocyte test and nitrate test
• Urine culture > 40-50,000 CFU/mL
• Pyuria - not on recurrent UTIs
Feld - 10/98 46

• 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

• 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

Feld - 10/98
49

• GRADES I - III Antibiotics
• GRADES IV - V Surgery
Feld - 10/98 50

• 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

• 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

• 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
• Follow-up (reflux) - antibiotics
Feld - 10/98
( every 4 months)
53

• 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

• 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

• Thrombocytopenia
• Hemolytic anemia
• Renal failure
• Neurologic (irritability, seizure, CVA)
• Pancreatitis (IDDM) and colitis
• Hypertension

• Endothelial cell damage occurs secondary to toxin injury via binding to glycolipid receptor or lipopolysaccharide absorption.

• Other forms of acute Glomerulonephritis / renal failure
• Vasculitis
• Urosepsis
• Renal vein thrombosis
• Coagulopathy (DIC)

• 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

• Toxic megacolon
• Rectal prolapse
• Colonic gangrene
• Intussusceptions
• Perforation
• Strictures
• Mimic appendicitis, IBD

• 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 is a clinical state characterized by heavy proteinuria and hypoalbuminemia, often associated with edema, hypercholesterolemia, and generalized hyperlipidemia.

• 90% childhood cases
• unassociated with systemic disease

• 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.

• Poor appetite
• Diarrhea during massive edema
• Hepatomegaly
• Abdominal pain (need to r/o peritonitis or surgical abdomen)
• Respiratory difficulty
• Hypertension (15%-20% of MCNS)

• PROTEINURIA is the primary abnormality.
• “Selective”- almost entirely albuminuria
• > 40 mg/m 2 /hr or
• U protein/creatinine ratio > 1 (mg/mg)
• due to loss of charge selectivity of glomerular basement membrane

• Impaired resistance to infection
– -low immunoglobulin levels
– -generalized protein deficiency
– -defective opsonization
– -splenic hypofunction
– immunosuppressive therapy
• Peritonitis
• Pneumococcal infection

• Diuretics ?
• Albumin & Lasix infusion
• Prednisone 60 mg/m 2 /d x 4 weeks, then 40 mg/m 2 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.

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
White cell count
Platelets
18 g/dl
30,000
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)?

• 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

• Urine
– S.G.
– UNa, FENA, Uosm
– Microscopic examination
• Blood
– BUN, creatinine
– Bicarbonate

• 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 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?

• 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

UA
SG
UNa
FENA
Uosm
Pre-renal
Marginal value
>1.020
<20
AGN ATN
Key
RBC casts
RTEC
>1.020
1.008-
1.012
<20 >40
Obstruction
Marginal value
1.008-1.012
>40
<1%
>400
<1%
>400
>1% >1%
200-400 200-400

• AGN
– PSAGN
– HSP
– SLE
– MPGN
– Wegener’s

• ATN
– Unreversed pre-renal azotemia
– Nephrotoxic meds
– Contrast agents
– High calcium, uric acid, phosphate
– Rhabdomyolysis (myoglobin)
– Intravascular hemolysis (hemoglobin)

• Obstructive uropathy
– PUV
– Prune belly
– Vesicoureteric reflux
– Neurogenic bladder (myelomeningocele)
– Megacystis/megaureter
– Secondary: stones, fibrosis
• Effect of age and gender

• Key labs: BUN, creatinine, K
• EKG
• CXRay
• Renal ultrasound
• Specific blood tests based on underlying condition

• Urgent issues
– Potassium
• Calcium
• Glucose/insulin
• NOT bicarbonate
– Blood pressure: parenteral therapy
• Labetalol
• Nitroprusside
– ECF volume

• Potassium
– Diet restriction
– Kayexalate
• Blood pressure
– IV/PO meds
• ECF volume
– Na restriction
– Diuretic use – need for furosemide

• Refractory hyperkalemia
• Refractory hypertension
• Symptomatic ECF volume overload
• Symptomatic azotemia
– Infection
– Bleeding
– CNS changes

• 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?

• 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

• Impact on growth
• Impact on bone: osteodystrophy
• Impact on puberty
• Impact on development – social and cognitive

• Non-glomerular
– Hypoplasia/dysplasia
– Reflux nephropathy
– Obstructive uropathy
• PUV
• Prune Belly
• Neurogenic bladder

• Growth failure
– Dependent on age of onset
– Dependent on level of GFR
• UTIs
– Pyelonephritis
• Electrolyte abnormalities
– Pseudohypoaldosteronism
– Nephrogenic DI
• Neurocognitive disability

• Structural assessment
• Imaging studies
– US
– VCUG: dye vs radioisotope
– DMSA scan
– Retrograde studies, etc

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?

• Glomerular
– FSGS
– HUS
– SLE
– Membranoproliferative MPGN)
– Alport
– IgA Nephropathy
– Membranous nephropathy
– NOT diabetic or hypertensive nephropathy

• Growth failure
– Dependent on age of onset
• Hypertension
– Role of 
ECF volume and

PRA
• Electrolyte abnormalities
– Acute
– Hyperkalemia
• Edema
• Signs of underlying disease

• Low value of radiology tests
• Blood tests
– C3, C4, CH50
– ASLO
– ANA, dsDNA, Ro, La, Sm
– ANCA
– Anti-GBM
– Renal biopsy

• Nutritional supplementations
– CHO deficiency
• Protein restriction
– Impact on growth
– Effect in more advanced CKD
• BP control
– Disease progression
– ACEI/ARB

• 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

• 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

• 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

• 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
White cell count
Platelets
18 g/dl
30,000
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)?

• 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

Assess ECF
Measure serum Na
High ECF Normal ECF Low ECF

• History
• Source of Na loss
• Change in body weight
• Renal response to low ECGF volume
– Oliguria
– Reduced urine Na+
– Reduced FENA

120
100
80
60
40
20
0
ICF
ECF
Normal Hypo Hyper

• Hypernatremia
– Risk factors
• Breast feeding
• Feeding errors
• Impaired thirst
• Impaired access to water
– Presentation
• Irritability, seizures
– Treatment
• SLOW
• HYPOTONIC FLUIDS – 1/5 NS

• 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

• 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
White cell count
Platelets
18 g/dl
30,000
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)?

• 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

• Regulatory organs
– Kidney secretion
• Na+
• Urine flow rate
– Adrenal
• Aldosterone
– GI tract
• Transmembrane
– pH
– Osmolality
– Beta adrenergics
– Insulin
• Diet

• Key tests
– BUN, Cr, Na, K, bicarbonate
– Urine K useless
– Urine Na/K ratio
– Hormones
• PRA
• Aldosterone

• Hyperkalemia
– EKG
• Peaked T waves
– Treatment
• Calcium infusion
• Glucose/insulin
• NOT Bicarbonate
• Kayexalate
• DIALYSIS

• 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

• BUN, creatinine, Na, K, Bicarbonate
• PRA
• Aldosterone
• Urinary Na/K ratio

• 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

• 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 5 th percentile. The systolic blood pressure is 102 and the pulse is 110. The rest of the examination is normal.
Na
Cl
138
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)?

Acid load
Acute
Lung
Chronic-Kidney
Proximal
Chronic-Kidney
Distal
Reclaim filtered bicarbonate
Regenerate
Titrated bicarbonate
Large frequent doses
1-3 mmol/kg/day

• Anion gap
• [Na] – {[Cl] + [HCO3]}
• Normal value: 4-12
• Impact of serum albumin

• Metabolic acidosis
– Normal anion gap -- hyperchloremic
• Diarrhea
• RTA
– High anion gap -- normochloremic
• MUDPIES or KUSSMAUL
• Key entities:
– DKA
– Lactic acidosis
– Uremia
– Metabolic disease
– Toxins

• Proximal
– Low K
– Primary
– Secondary
• Glycogen storage
• Wilson’s, fructose intolerance, tyrosinemia
• 
PTH,

Vitamin D
• Cystinosis

• Distal
– Primary
– Secondary
• Transplant rejection
• Drugs: amphotericin, cisplatinum
• Collagen vascular disease

• Assessment
– SMAC: Cl-
– VBG: Bicarbonate
– Urine: calcium, citrate
– Urine anion gap: unmeasured cation (NH4+)
– Xrays

• 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

Fanconi’s
Syndrome
Complete proximal tubule dysfunction
RTA Glycosuria
Phosphaturia

TRP
Amino
Aciduria

• 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

• Central
• Nephrogenic
• Risk of CNS disease
– 1/12 (1/3 X ¼) of loss from ECF
– Limited access to water
– Altered thirst

• Central
– AVP replacement
• Nephrogenic
– Adequate water intake
– Low solute diet
– Hydrochlorothiazide

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

GOOD LUCK