metropolitan new york / new jersey pediatric board review course pediatric nephrology may, 2008

Metropolitan New York / New Jersey Pediatric Board Review

Course

Pediatric NephrologyMay, 2008

Leonard G. Feld MD PhDLevine Children’s Hospital

Charlotte, NCHoward Trachtman MD

Schneider Children’s HospitalNew 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 14 g/dlWhite cell count 30,000Platelets 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

* 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)

GLOBAL ASSESSMENT

Appears ToxicAppears Moderately Illor Your Are Not Sure

Appears Generally Well

Treat ExpectantlyHospitalizeSee Table 1

Evaluate for PossibleSepsis, Hospitalize and

Treat

Skin, Soft Tissue, Bone or Joint Infection?

WBC with DifferentialUrinalysis

WBC = 5,000 - 15,000 /mm3, AND Band Count < 1,500 /mm3 ANDUrinalysis < 10 WBC/HPF in Unspun Sediment and Negative Gram Stain (OR

< 10 WBC/HPF in Spun Sediment)

Evaluate as IndicatedHospitalize and Treat

See Table 1

History of Prematurity, Perinatal Problems, Underlying Condition, Previous Antimicrobial

agents

LP = CSF Analysis; Cultures of Blood, CSF, Urine (Suprapubic or catheter specimen only)Hospitalize and Give Parenteral Antimicrobial

Therapy

Culture Blood and Urine (Suprapubic or catheter

specimen only)Observe without

Antimicrobial Therapy

Physician Identified to Assume Full Responsibility for Outpatient Management

Hospitalize

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

LP - CSF Analysis; Culture Blood, CSF, Urine (Suprapubic or catheter specimen

only)

NO

NO YES

YES NO

YES

NO

NO

Option 2Option 1

YES

No Antimicrobial Therapy

Empiric Antimicrobial

Therapy

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

Low ComplementNormal

Complement

Systemic diseasesSLE

Subacute Bact EndocarditisShunt nephritis

Essential mixed cryoglobulinemiaVisceral abscess

Systemic diseasesPolyarteritis nodsa

Hypersensitivity vasculitisWegener’s

HSPGoodpasture’s

Renal diseasesAcute proliferative GN

Membranoproliferative GN

Renal diseasesIGA

RPGN -Anti-GBM, immune complex GN

Serologic evidence of antecedent strep infection(ASO, anti-Dnase B, streptozyme

PSAGNStrep endocarditis

LupusEssential mixed cryoglobulinemia

Shunt nephritisVisceral abscess

MPGNNon-strep infection

Clinical evidence to support

endocarditis

Blood culturesEchocardiogram Treat PSAGN

Positive Negative

Glomerular Non-glomerular

Urinalysis Dysmorphic RBCCellular castsBrown/tea colorBright redClotsCrystalsProtein

++

+++--+

--+

++++-

History Family Hx of ESRDSystemic diseaseNephrolithiasisTraumaSymptomatic vomiting

++---

--+++

Physical HypertensionSystemic signsEdemaAbdominal massGenital 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-year-old 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 work-up 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 work-up 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: < 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

What does Orthostatic Proteinuria mean?

Normal Orthostatic Recumbant

Erect

Threshold of Detection

ProteinExcretion

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.

HistoricalInformation

PhysicalExamination

Neonatal historyFamily historyDietary history

Risk Factors (smoking,alcohol use, drug use)Non-specific / specific

symtomatologyReview of Systems - sleepand exercise patterns, etc.

Vital signs(including extremities)

Height/WeightSpecific attention to organ

systems - cardiac, eye,abdominal or other bruits,

etc.

Consider ambulatory bloodpressure monitor

Evaluation Phase 1

CBC, urinalysis, urine culture, electrolytes, BUN,creatinine, plasma renin, lipid profile,

echocardiogram, renal ultrasound with duplexdoppler

Evaluation Phase 2Selected studies based on magnitude of the

hypertension and/ or other clinical /laboratoryfindings

Renal flow scan (MAG 3)CT Angiography (CTA)

MRA (may not provide adequate evaluation forperipheral renal vascular lesions)

Renal arteriography with renal vein samplingPlasma / urine catecholamines and/or steroid

concentrations

Evaluation of Hypertension

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

Feld - 10/98 43

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 44

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 45

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 46

Diagnosis

• Leukocyte test and nitrate test

• Urine culture > 40-50,000 CFU/mL

• Pyuria - not on recurrent UTIs

Feld - 10/98 47

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 48

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 49

Grades of Reflux

Feld - 10/98 50

Reflux Recommendations“the simple way”

• GRADES I - III Antibiotics

• GRADES IV - V Surgery

Feld - 10/98 51

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 52

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 53

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

Glomerulonephritis / Acute renal failure

Feld - 10/98 55

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?

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 glanceNephrolithiasis

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.


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


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

SCENARIOA 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/dlWhite cell count 30,000Platelets 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

SCENARIOA 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

RBC casts

RTEC Marginal value

SG >1.020 >1.020 1.008-1.012

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

SCENARIOA 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

ARFYounger child, abd mass, UTI

UAWBC, impaired concentration

US, VCUG, DMSA

Retrograde studiesCystoscopy, urodynamics

SCENARIOA 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

SCENARIOA 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/dlWhite cell count 30,000Platelets 280,000


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

High ECF Normal ECF Low ECF

Measure serum Na

Electrolyte Disorders: Sodium

• History

• Source of Na loss

• Change in body weight

• Renal response to low ECGF volume– Oliguria– Reduced urine Na+– Reduced FENA


0

20

40

60

80

100

120

Normal Hypo Hyper

ICF

ECF


• 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

SCENARIOA 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/dlWhite cell count 30,000Platelets 280,000


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


• 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


• Hypokalemia– EKG

• U waves

– Treatment• Restore ECF volume to 2hyperaldosteronism• 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

SCENARIOA 15 month child presents with a history of poor feeding and impaired growth. Prenatal and family history is non-contributory. 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 138Cl 114Bicarbonate 16


Electrolyte disorders: acid-base

Acid load

AcuteChronic-Kidney

ProximalChronic-Kidney

Distal

RegenerateTitrated bicarbonate

Reclaim filtered bicarbonate

Lung

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


• Proximal– Low K – Primary– Secondary

• Glycogen storage• Wilson’s, fructose intolerance, tyrosinemiaPTH, Vitamin D• Cystinosis


• 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


• 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’sSyndrome

Complete proximal tubule dysfunction

RTA GlycosuriaPhosphaturia

TRPAmino 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

metropolitan new york / new jersey pediatric board review course pediatric nephrology may, 2008

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