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Pediatric nephrology

Eva Pazkov
Department of Pediatrics, University
Hospital Hradec Krlov
Charles University in Prague,
Medical Faculty Hradec Krlov

Lecture topics
Hemolytic-uremic syndrome
Akute and chronic glomerulonephritis
Nephrotic syndrome
Overview of glomerular diseases classification
Urinary tract infections
Congenital abnormalities
Vesico-ureteral reflux
Urinary tract obstructions

Hemolytic-uremic syndrome
Most frequent etiology of pediatric ARF
Etiology: multifactorial, preceded by infections with GIT
strains of E-coli

0 157 H7, binding to endothelial cells, verotoxin production,

important hereditary and constitutional factors
Infection source most frequently diary products

Characteristics: hemolytic anemia + thrombocytopenia +

Clinical signs: in infants and toddlers, fever, vomiting and
diarrhea precedes by 7-10 days, prominent paleness,
petechiae, nephropaty with renal insufficiency: oliguria,
weakness, edema, CNS signs: sleepiness, agitation,
convulsions; hepatosplenomegaly, subicterus

Hemolytic-uremic syndrome
Lab signs: low hemoglobin, slightly elevated
bilirubin, schistocytes in blood smear,
thrombocytopenia, negative direct Coombs test,
proteinuria, hematuria, casts, hyperazotemia
Therapy: renal failure treatment, peritonal
dialysis in children 3 months to 3 years (60 80
%), hemodialysis in preschool children,
transfusion in extreme anemia, antiaggregation ?
(dipyridamole), antihypertensive drugs
Prognosis: better in infants, worse in older

after ARF sometimes progression to CRF

used to have 25% mortality

Differential diagnosis: discolored urine with
blood or other compounds
Urine colors:
Dark yellow:

concentrated urine
bile pigments


beetroot, blueberries

Dark brown or black:

hemogentis acid

Etiology of hematuria in children

Glomerular disease
Infection (bacterial, viral, tbc)
Hematologic disorder: coagulopathy, thrombocytopenia,
sickle cell anemia, renal vein thrombosis
Stones, hypercalciuria
Anatomic abnormality: congenital anomalies,
polycystic kidneys, tumors, vascular anomalies
Excersise (overexcersising)
Medications: heparin, aspirin, sulfonamids, penicilin,
Asymptomatic mikroskopic hematuria: 0,5 2% school

Glomerulonephritis (GN)
Immunologicly mediated inflammation of
GN immunokomplex IK noted in
glomerular membrane induction of
pathologic changes
GN based on antibodies against basal

Primary (isolated kidney disease)

Secondary (in rheumatic, vascular, metabolic

Glomerulonephritis (GN)
Rapidly progressive
Classification according to renal biopsy

histologic finding, electronmicroskopic picture,

immunofluorescence, (immunocomplex types with
IgG, IgA, IgM)

Lab picture of glomerulonephritides

Glomeral damage: hematuria + proteinuria
Quantitative protenuria: selective (albumin)
nonselective (albumin+globulins)
Tubular proteinuria low molecular weight proteins: 2microglobulin
Fibrin degradation products fibrin in urine
Dynamics of GF rate or plasmatic creatinine level
ASLO, C3, C4, CIK, anti-basal membrane Ab
Serum IgA elevated in 50% of glomerulopathies
Arterial hypertension

Acute glomerulonephritis (AGN)

Immunocomplex disease with abrupt onset, 10% of all
Age peak 5. 12. years
Male:female ratio 2:1
Streptococci group A (nephritogenic types 1,2,4,12),
plus other microbes and viruses
1-2 weeks after respiratory infection or pyoderma
Prominent clinical sign: macroskopic hematuria
Other signs: edema in 3/4 of children and hypertension
in 1/2 of children, oliguria, proteinuria, decreased
glomerular filtration, fluid retention
Low C3 complement, usually normalizes in several
weeks (hypocomplementemia lasting over 6-8 weeks
leads to suspicion of mesangiocapillary GN)

Acute glomerulonephritis (AGN)

Clinical signs: weakness, fatigue, back pain, headache,
Regression within 3 weeks, proteinuria a edema quickly
faint within 5-10 days
Prognosis: 95% get well, 5% RPGN or CGN
Therapy: bed res, PNC, diet with salt and protein
reduction in edemas, diuretics in oliguria,
antihypertensive drugs in HT, hemodialysis in ARI, fluid
balance measurement, BP monitoring
Cave! Hypertensive crisis (consciousness)
Residual microskopic hematuria sometimes more than
year, neednt have significant negative influence on

Rapidly progressive GN
RPGN fast, irrevesible glomerular damage
Oliguria or anuria, ARI lasting weeks, months, rarely in children
1. RPGN with anti-basal membrane antibodies (Goodpasture syndrome)
2. RPGN with granular deposits (IK type)
3. RPGN with ANCA antibodies
Clinical picture:

acute nephrotic syndrome

proteinuria over 5g/24 h
erythrocyturia over 50x106/24 h
renal function decrease


early corticosteroids + immunosupressive drugs

pulse therapy with methylpredisolone + cyclophosphamide
plasmapheresis (CIK elevated)

Prognosis: grim

Chronic glomerulonephritis
Lasting years, progressive
Histologic finding classification
Urinary syndromes hematuria and proteinuria
Inflammatory changes: diffuse, focal, segmental
Proliferative endocapillary
extracapillary (worse)
Morphologic division

Mesangioproliferative GN
1. No clinical manifestation + mild
hematuria + mild proteinuria
Therapy: symptomatic
2. With nephrotic syndrome: (edema +
proteinuria + hypertension)

Therapy: corticoids + cyclophosphamide

Membranoprolipherative GN
Mesangial enlargement + thickening of basal
Localisation of deposites:
1. subendothelial
2. intramembranous
3. subepithelial

Urinanalysis: higher proteinuria + hematuria

with nephrotic syndrome
Therapy: glucocorticoids
Prognosis: uncertain

IgA nephropathy Bergers

Predominance of IgA deposites in mesangium
Absence of systemic inflammatory disease (SLE, anaphylactoid
1. primary (Bergers GN)
2. secondary (in H-S purpura)
mesangial prolipheration
20 25% of all CGN
IK nephropaty (after transplantation recurrs)
Clinical signs:

male : female = 2 : 1
episodes of gross hematuria and microscopic HU in relation to infections
renal functions normal, proteinuria small (< 1g / 24 h)
C3 in serum normal

Therapy: supportive care

Progression in 30 % (BP - elevation, RI, proteinuria)
immunosupression: glucocorticoids + cyclophosphamide , pulsed

Alport syndrome
X - linked
Most frequent hereditary nephritis, progressive
Variability in clinical manifestation, histologic character
Histology: mesangial proliferation, thickening of capillary
wall, progression of glomerular sclerosis, interstitial
inflammation, fibrosis
Clinical signs: asymptomatic microscopic hematurie (or
episodes of macroscopic hematuria)
+ proteinuria biopsy
+ vision, hearing impairment
Therapy: specific doesnt exist (RI in 2./3. decenium)

Membranous GN
Rare in children as a reason for hematuria x most frequent reason of
nephrotic syndrome in adults

secondary (conjoined with hepatitis B)
Histology: diffuse thickening of GBM, deposits of IgG + C3 on the
epithelial side of the membrane
Immunocomplex disease
Clinical signs:

major nonselective proteinuria + mld hematuria

2nd decade of life
nephrotic syndrome (proteinuria + microscopic hematuria)
BP normal, C3 normal

Renal biopsy
Prognosis: mostly spont. regression, sometimes persistant proteinuria
Therapy: restriction on salt + diuretics, or intermittent prednisone

Other GN
Focal segmental glomerulosclerosis

nonselective proteinuria
severe course
in 10 years only 50% non-dialysed

Acute interstitial nephritis

interstit. infiltrates (LY, EO, PMN, PB)

edema, tubule necrosis
etiology: meds, hypersensitivity ?, Ab anti-basal
membrane of tubules
renal biopsy
high dose corticoids

Nephrotic syndrome
Incidence 2:100 000
Functional a structural disorder of glomerular filter
Types of NS:

Primary idiopathic

Congenital NS finnish type, AR

First days of weeks, or months after birth:

edema, low birth weight, large placenta

proteinuria, hematuria
death within 2 years of age

Primary idiopathic nephrotic syndrome

= minimal change disease
Most frequent in toddlers and pre-schoolers
Etiopathogenesis unclear
Higher leak of glomerular membrane, histologically normal
Insufficient tubular resorption tubular damage
Proteinuria albumin, gammaglobuline, IgG
Hypoproteinemia low albumin, high alfa2 and beta globulins
Hyperlipidemia hypercholesterolemia
Hypoproteinemic edemas, tubular reabsorption of Na and H20 and elevation
of aldosterone clearence
Clinical signs:

from full health hypoproteinemic edemas (eyelids, scrotum, hypogastrium,

paleness, anorexia, diarrhea, eryhtema, decrease in infectious resistance

Laboratory findings:

Urine: protein 3 15 g/d, rarely ery

FW: high, GF and urea normal
Hypercholesterolemia high

Reversible changes, remission and relapse after 10 years

Secondary nephrotic syndrome


systemic inflammation (SLE, HS purpura, diabetes mellitus,
vascular disorders (thrombosis of renal vein, constrictive
infections malaria, syphilis
toxins and alergens
tumor (hemoblastosis)

Ortostatic proteinuria

13 15 years
Vertically proteinuri
Horisontally no proteinuria
Etiology ?
High children with prominent lumbar scoliosis

Nephrotic syndrome investigations

and therapy
Investigations necessary in this diagnosis in a hospitalized

blood: FW, KO and diff., biochemistry urea, kreatinin, uric acid, Na,
K,Cl, CaP, cholesterole, ALT, AST, total protein, albumin,
electroforesis of proteins
indicated (suspicion of CGN): ASLO, CIK, C3,C4, quant. Ig, ANF,
ANCA, anti ds DNA, HBsAg
Hamburger sediment 1-2x per week
Quantitative proteinuria in 24 h and selectivity 2x week
KBU 3x
creatinine clearence
concentration test with Adiuretin after stable state reached
Abdominal US (ascites !) and urinary tract

Necessary measures: weight 1x d, belly circumference 1x d,

edema, fluid balance, BP 2-3x daily
1. attack treatment: Prednison 2 mg/kg/d (max. 80 mg/d)
div. in 3 doses till 6 weeks and followed 2 mg/kg/once in two
days in 1 morning dose q 6 weeks

Nephrotic syndrome investigations

and therapy
Supportive care and regime modification
Bed rest the long the disease lasts

Albumin 1g/kg/dose in 3h infusion followed by

furosemide 1 2 mg/kg/dose, possible to repeat 2
4x day during 1 2 days
Indication: hypalbuminemia < 20 g/l, oliguria, massive edema
incl. ascites and hydrothorax

Furosemide 1-2 mg/kg/dose p.o. 2x 4x day in

oliguria, elevated edemas
In corticotherapy necessary Kalium chloratum tbl. and
Calcium tbl., vitamins B,C substitution
Mantoux II to rule out TBC recommended before the

Nephrotic syndrome


Relapse treatment:
Prednison 2 mg/kg/d (max. 80 mg/d) in 3 daily doses till negative
proteinuria, = 6x consecutive negative urinanalysis and then 2
mg/kg/every 2nd day 6 weeks
regimen modalities and supportive care the same
Indications for renal biopsy in nephrotic syndrome:
newborns and infants high probability of congenital NS
children older than 8 y in first attack of NS probability of CGN
corticoresistant NS (= no response to treatment with CS in 8 weeks)
NS with frequent relapses (2 and more relapses in 6 months and
relapsing within 2 months after corticotherapy finished)
corticodependent NS (relapse during alternate CS dosing or within 2
weeks after corticotherapy finished)
patients with significant signs of chronic nephritis hypertension,
azotemia, hypocomplementemia, macroscopic hematuria

Glomerular diseases classification

Prominent glomerular impairment
Primary glomerular disease (glomerulonephritis

Mild glomerular abnormalities

Focal/segmental impairment (only mild glomerular abnormalities)
Diffuse glomerulonephritis
Membranous glomerulonephritis (membranous nephropathy)
Proliferative glomerulonephritis
Mesangial proliferative glomerulonephritis
Mesangiocapillary glomerulonephritis (membranoprolifer. GN type I
and III)
Opaque deposits disease (membranoprolif. GN type II)
Gromerular sclerosis

Non-classified forms of glomerulonephritides

Glomerular diseases classification

Glomerulonephritis in systemic inflammaotry disease

Lupus nephritis
Nephritis in Henoch-Schnlein purpura (anafylactoid purpura)
Berger nephritis (IgA nephropathy)
Goodpasture syndrome
Glomerular impairment in systemic infections
Infectious endocarditis
Shunt nephritis (in arteriovenous shunt)
Parasite nephropathy
Nephropathy in malaria

Glomerular diseases classification

Glomerular impairment in vascular disease

Periarteritis nodosa
Wegener granulomatosis
Thrombotic microangiopathy (hemolytic-uremic
syndrome and thrombotic thrombocytopenic purpura)
Glomerular thrombosis (intravascular coagulation)
Benign nephrosclerosis
Malignant nephrosclerosis
Scleroderma (systemic sclerosis)

Glomerular diseases classification

Glomerular impairment in metabolic diseases

Diabetic glomerulosclerosis
Nephropathy in dysproteinemia
Nephropathy in liver disease
Nephropathy in sickle cell anemia
Nephropathy in congenital cyanotic heart disease and pulmonary hypertension

Hereditary nephropathy

Alport syndrome
Benign recurrent hematuria
Thin basal membrane syndrome
Nail-patella syndrome (osteonychodysplasia)
Congenital nephrotic syndrome (finnish type)
Infantile nephrotic syndrome (french type)
Diffuse mesangial sclerosis)
Fabry disease etc.

Mixed glomerular disease

Nephropathy from toxemia in pregnancy (pre-eclamptic nephropathy)

Terminal renal impairment

Glomerular impairment after kidney transplantation

Urinary tract infections (UTI)

UTI classification:

with renal parenchyma impairment pyelonephritis
infections of lower urinary tract cystitis, urethritis
approx. 10-20% UTI not possible to specify from
history, clinical signs and basic lab investigation

Asymptomatic bacteriuria
bacteriuria not connected with clinical signs

Chronic or recurrent

Urinary tract infections

Ethiology of UTI:

Escherichia coli causes 80 90 % of UTI

Proteus causes up to 30 % cystitis in boys

Diagnosis of UTI:

clinical signs
lab findings

Urinary tract infections diagnosis

Clinical signs depend on age and infection localisation

acute pyelonephritis
newborns: sepsis, lethargy, irritability, convulsions, failure to thrive,
fever, protracted icterus
infants: fever (neednt be), vomiting, diarrhea, failure to thrive
toddlers: fever, abdominal pain, vomiting, diarrhea
children: fever > 38,5C, side or back pain

acute infection of lower urinary tract

frequent voiding, dysuria neednt be in children below 2 years of
age, body temperature to 38 C

chronic pyelonephritis
may have latent course
fatigue, subfebrilia of unknown origin, intermittent back and side
late sign polyuria, headache (hypertension)

chronic infekction of lower urinary tract

intermittent abdominal pain, dysuria, enuresis, constipation

Urinary tract infections diagnosis

Lab signs:

significant bacteriuria dg. criterium for UTI

significance of bacteriuria: middle flow urine
105 + /ml of urine
catheterised urine
104 + /ml of urine
suprapubic puncture every finding is positive
low count bacteriuria 102 - 104/ml of middle flow urine with concomittant pyuria finding
and clinical symptoms means UTI (Kunin, 1994)
pyuria > 10 leuko per field, up to 50% of children with UTI do not have pyuria (infants),
may occur in febrile state of different etiology
hematuria non-specific finding for UTI
macroskopic in 20 25% of children with cystitis

Acute pyelonephritis is characterised by other laboratory findings:

FW > 35 mm/h, CRP > 25 mg/l

decreased concentration capability in concetration test with Adiuretin < 900 mOsm/kg

Long term sequelae of UTI:

in 10% of children with acute PN scars in renal parenchyma, may lead to hypertension or
Risk factors for renal scarring:
urinary tract obstruction
VUR of higher grade
low age
delayed treatment
number of pyelonefritis attacks
unusual bacteriuria

Urinary tract infections studies

Acute pyelonephritis

Kidney and UT US within 2-3 days after treatment initiation

DMSA scan localisation of infection in acute phase, detection of
parenchyma scars in 3 6 months after end of treatment
MCG in 6 weeks after end of treatment, acute phase also
IVP exceptionally, in clinical indication, completion of cong.
abnormality investigation
urethra calibration in girls in 6 weeks after end of treatment
scheme is the same for every age in first attack of PN

Acute infections of lower urinary tract

urethra calibration in girl with relapses
in boy any age and in girls below 1 year of age after 1st UTI
in girls older than 1 year after 3rd UTI
Relapsing UTI urodynamic investigation

Urinary tract infections treatment

Leading factors:

localisation of UTI
anomaly of urinary tract

Acute pyelonephritis

treatment is initiated with parenteral atb

recommended first line atb :
aminoglykosides (gentamycin, amikacin, netromycin)
aminoglykoside + ampicil
amoxycilin clavulan
ate (Augmentin), or in combina
combinattion with aminoglykoside

ATB i.v. 5-10 days, followed with ATB p.o. till total 10-14 days (normalisation of lab. parameters)
ATB p.o. according to sensitivity of agens cotrimoxazol, cephalosporine, amoxycilin
in older children without major alteration treatment can be initiated p.o. :
es of 2. or
or 3. generation
generation (cefuroxime
(cefuroxime-axetil Zinnat)

amoxycillin clavulanate
adequate treatment = urine sterile within 24 h
fever lowered within 48 72 h
pyuria vanishes within 3 4 days
CRP < 20 mg/l in 4-5 days
normalisation of FW within 2-3 weeks
if no treatment effect within 2-3 days:
istance of etiol. agens
obstruction of urinary tract

supportive care: ibuprophen lowers the inflammation size ; hydration, catheterisation in cong.
kidney and urinary tract anomalies

Urinary tract infections treatment

Infections of lower urinary tract

ATB p.o. 5 days, infants 7 days with subsequent chemoprophylaxis until

exclusion of urinary tract abnormalities (Watson, 1994)
Recommended ATB: cotrimoxazol, cefalosporins, amoxilicin clavulanate,
One-dose or chort schedule (3 day) therapy of UTI not recommended in

Chemoprophylaxis aim: lower the risk of infection and renal scarring

Short-term: after urologic instrumentary investigation (catheterization of

urinary bladder, urethra calibration)
cotrimoxazol, trimethoprim full dose 48 h

Long-term: VUR, other conf. anomalies, prophylaxis in conservative

approach, 6 months after operation, obstruction of utrinary tract, frequently
relapsing UTI: 4 6 months, ev. longer
cotrimoxazol, trimethoprim, nitrofurantoin
infants under 4 months - ampicillin
cephalosporins I. generation (cefalexin, cefadroxil)
one daily dose in the evening (in infants recmmendation is BID)
medication does not have to be changed

Urinary tract infections treatment

Asymptomatic bacteriuria

infants and toddlers really asymptomatic?

necessary to rule out cotamination (e.g. physiologic
colonisation of preputium in boys with Pseudomonas
in first 6 months !)
ATB treatment p.o. 5 7 days
exclude urinary tract anomaly
girls of school age treat first attack
exclude anomaly of kidneys or urinary tract
functional kidney studies
gynekologic investigation
relapsing findings treat ?

Urinary tract infections

Prevention of UTI possibilities

GIT colonization with nonpathogenic E. coli strains

breast feeding (oligosaccharides in maternal milk blockP fimbriae)
hygiene, miction regimen, urine pH management, obstipation control
crainberry juice (vanilmandelic acid)
experimentally competitiv receptor analogues
rational ATB therapy
in relapsing UTI w/o anomaly vaccines - UroVaxom, autovaccines


do not underestimate UTI

do not delay the treatment
search for urinary tract anomalies especially in infants
PN + UT anomaly reason of 24% CRI in children ! (EDTA
statistics, 1994)

Congenital abnormalities
of urinary tract
1. Bilateral renal agenesis 1 : 4000 births

Potter syndrome (flat facies, pulmonary hypoplasia), oligohydramnion,

compression of the fetus by uterus, respiratory insufficiency, death in the 1.
week of life

2. Unilateral renal agenesis 1 : 1000 births

connected with compensatory hypertrophy of contralateral kidney

normal or minimally reduced kidney function
sometimes with skeletal, cardiovascular or genital abnormalities
VATER syndrome, Turner syndrome, Poland syndrome

3. Renal hypoplasia small kidneys

predisposes to progressive renal insufficiency over time

renal scarring
short stature especially in II. decade

4. Renal dysplasia usually unilateral

developmental abnormalities of organisation and differentiation of ducts

frequent obstructive anomalies (early fetal age)

Congenital abnormalities
of urinary tract

Cystic kidney dysplasia


polycystic kidneys impairment of both kidneys

infantile type AR inheritance
enlargement of both kidneys, multiple cysts in cortex and medulla
dilated collecting tubules, interstitial fibrosis and tubular atrophy
can occur in time lead to RI
liver fibrosis portal hypertension, bile duct ectasies and billiary
diagnosis US in newborn age
80% of children palpable renal enlargement, hepatomegaly,
PNO, proteinuria or hematuria
supportive care (hypertension and RI)


adult type polycystic kidneys AD inheritance

signs after 30 years of life, exceptionally in childhood
in children similar picture as a)
renal biopsy predominantly glomerular cysts

Vesicoureteral reflux - VUR

Usually inborn insufficiency of ureteral ostium into urinary
Less frequently secondary in infravesical obstruction or
Sometimes familiar
VUR potential threat increase of hydrodynamic pressure,
predisposing to UTI bacteria easily into renal pelvis
Reflux nephropathy = development and progression of renal
scars renal hypertension and RI
Normal vesicoureteral junction: ureteral tunnel leading through
the wall of the bladder, ratio 4-5:1 /length to diam./, primary
VUR ratio 1,5:1, lateral position of the opening
Less frequently duplicated ureters, ureterocoele
VUR conjoined with ureter diverticles
VUR in neurogenic bladder in meningomyelocoele

Vesicoureteral reflux - VUR

Clinical signs:

UTI, in girls under 1 year in 57%, over 1 year in 36%, in boys under 1 year and
between 2-16 years in 30%
DMSA scan proof of renal scarring

Classification: VUR grade 1-5:

in grade 1 scars in 15%

in grade 2 scars in 18%
in grade 3 scars in 27%
in grade 4. or 5. in 64%

MCG after 3-4 weeks after IMC (transient reflux)

Treatment: long-term prophylaxis with atb, trimetoprim-sulfamethoxazol,
sulfisoxazol, nitrofurantoin, frequent urine cultures (1 mo), if culture negative
for 3 months, then 3 mo apart
VUR grade 1 to 3 diminishes or vanishes over time
VUR grade 4 and 5 needs surgical interventiion and prophylactic atb
Complications of VUR hypertension and RI (proteinuria >1 g/d),
development of focal and segmental sclerosis and interstitial scarring

Obstruction of urinary tract

In any part of urinary tract: pelvis uretero-pelvic junction
ureter urinary bladder urethra
Ethiology: congenital stenosis, stones, infections, trauma,
tumors, ureterocoele, valves, neurogenic dysfunction,
diverticles, retroperitoneal fibrosis, foreign body, phimosis
Clinical signs:

obstruction can be asymptomatic until UTI

palpable resistance
Colic pain in stones


IVP VUG, MCG, ascendent pyelography, US, isotope

nephrography with diuretics
DMSA scan
Obstruction on several anatomic places


Surgical + infection treatment

Obstruction of urinary tract

Urinary tract valves

Common cause for infravesical obstruction in boys (1:50 000)

Dilation of prostatic urethra
Can be joined with VUR or hydronephrosis
IMC, narrow urine strain, high voiding pressure, low urine output
Dg.: US and MCG
Treatment: epicystostomy, valve ablation

Prune Belly sydrome

Absence or gross hypoplasia of abdominal wall musculature

Nondescended testes
Abnormalities of urinary tract: dilation of ureters, urinary bladder,
prostatic urethra, persisting urachus, pulmonary hypoplasia, GIT
anomalies, CV anomalies