Dr. B.Anjaiah, MD., DCh.,
Director, RIMS, Ongole
COMMON SYMPTOMS OF RENAL DISORDERS
IN CHILDREN
o Edema, Hematuria, Oligo-anuria, Dysuria
abnormalities of micturition, flank pain & ureteric colic
o Abdominal mass by observant mother
o Mild or subtle symptoms such as Failure to thrive,
anaemia, rickets
Differences in patterns of renal diseases in different ages
Neonates period
1) Congenital anomalies
or Kidney & U. Tract.
Detected byantenatal U/S
2) Abdominal MassMulticystic renal
dysplasia
Infancy to 3 yrs
1) Unexplained fever UTI
Non specific like F.T.T.
Diarrhoea, Vomiting
2) Urinary tract anomalies &
V.U. reflux
3) Abdominal Mass – Wilm’s
Tumor or Multicystic renal
dysplasia
4) H.U.S.: Severe dysentry
increased Oliguria anaemia
browsiness
5) Minimal change disease
6) R.T.A. and Fanconi’s
syndrome
3–6
Yrs
6-12 Yrs
1) Most
Common:
Minimal
Change
Disease,
Acute
PSGN
2) Rickets
1) Acute PSGN
2) Non –
Minimal
Change Disease
3) Acute on
CRF
4) Symptomatic
HTN
5) Collagen
Vascular
diseases
CLINICAL MANIFESTATIONS OF RENAL DISEASE
Hematuria:
Urine colour vary from frank red to shades of
Brown described as tea or cola coloured
Red coloured urine – Hemoglobinuria,
Methehemoglobinuria, Drugs like
Rifampicin
Brown coloured urine – Myoglobinuria, porphyria,
Alkaptonuria
Gross hematuria –
1) Older children – AC.GN
2) Hyper calciuria
3) Clotting disorders
4) Renal trauma
5) Haemorrhagic cystitis
6) Surgical – Papilloma of bladder(uncommon)
CLINICAL MANIFESTATIONS OF RENAL DISEASE
1) Cola / Red colour Urine
2) Proteinuria >30mg / dL
3) Red cell casts
4) Acute nephrotic syndrome –
If Yes to all the above features considered possibility of Glomerular
haematuria
Work Up:
CBC differential, Electrolytes, BUN/Cr ratio
S. Protein / albumin, Cholesterol,
C3C4
Aso titre / Anti DNase B, ANA, ANCA,
Throat/Stain culture
24 Urine – total protein, Creatinine Clearance
CLINICAL MANIFESTATIONS OF RENAL DISEASE
EDEMA:
Acute G.N – M.C. manifests as Facial puffiness. Gross
hematuria usually associated. If unrestricted
may involves hands, feet, legs. Edema is turgid
and does not readily pit - on pressure.
Nephrotic syndrome –
Edema develops insidiously starts as puffiness around
eyes most noticeable in the morning. Edema is soft & easily
pits on pressure.
In a child with edema Urine protein must be promptly
tested.
CLINICAL MANIFESTATIONS OF RENAL DISEASE
Abnormalities of micturition:
In a male infant – A poor urinary stream with full bladder,
suggesting
of obstruction in the urinary tract. Most
commonly posterior urethral valve.
Persistant dribbling of urine – Suggesting of abnormal
ureteric insertion distal to bladder neck.
Excessive crying during micturition & Straining – Suggestive
obstruction.
Retention of urine – Needs evaluation for a neurogenic
bladder or obstruction by a stone or tumour. Urgent imaging
& urological studies should be done.
CLINICAL MANIFESTATIONS OF RENAL DISEASE
OLIGURIA: A decreased urine output <0.5 – 0.8 ml/kg/hr is
important feature of renal disease.
Ex:
1) Infant with H/o. Vomiting & Diarrhoea, Physical
examination
showing
Tachycardia,
Drymucous
membranes & poor peripheral perfusion suspect prerenal
type of ARF.
2) A 6 year old child with recent pharyngitis presenting with
periorbital edema, HTN, Gross hematuria, Oliguria,
suggestive of AGN with ARF (Intrinsic ARF)
LAB INDICES FOR PRERENAL & INTRINSIC RENAL
FAILURE
Index
Pre renal
Renal
Sp. Gravity
>1.020
<1.010
Urine Osmolality >500 mmol/L <350 mmol/L
Urine Na+
<20
>40
FE Na+%
BUN/Cr. Ratio
<1
(<2.5 in
Neonates)
>20
>2
(>10 in
Neonates)
<20
CLINICAL MANIFESTATIONS OF RENAL DISEASE
POLYURIA:
Def: Urine out put >3-4 ml / kg/hr
-Early feature of obstructive uropathy.
- Tubulo intestitial lesions
- Persistent hypokalemia (Distal RTA)
Foul smelling urine: A cloudy foul – smelling urine suggests
UTI.
Cloudiness also attributed to precipitation of phosphates.
Dysuria, Flank pain: Suggestive of UTI. When associated
with Tenderness in Renal angle indicates pyelonephritis.
Ureteric colic, passage of stone or Gravel indicates calculus
formation in urinary tract.
CLINICAL MANIFESTATIONS OF RENAL DISEASE
Hypertension: Detected incidentally or presented with
symptoms such as headache & visual disturbances, seen in
Acute GN, Chronic renal failure.
Growth retardation: Physical retardation is an important
feature of chronic renal insufficiency. Also noted in renal
tubular acidosis, familial hypophosphatemic rickets, fanconi
syndrome.
Anaemia: Striking feature in chronic renal failure. Suspect
renal disease in any unexpained anaemia.
Abdominal mass:Possibility of multicystic renal dysphasia,
PCKD, hydronephrosis, wilm’s tumour are considered.
LABORATORY EXAMINATION
Urine Examination:
Importance: Essential for diagnosis of renal diseases.
Collection of specimen:
1) First morning specimen is preferred.
2) Collected in a clean container & enough quantity sent to
the laboratory.
3) For urine culture the specimen should be colelcted ina
sterile container and sent to the laboratory, where it is
plated within 15 mts or stored in refrigeratory at 40C.
LABORATORY EXAMINATION
Various methods of collection of Specimen
Mild stream urine:
1)
Widely used method
2)
Periurethral and prepucial organisms may contaminate the specimen.
3)
In older children who can cooperate specimen is obtained after proper local
cleaning.
4)
The initial part of urine is discarded & sample is collected in a sterile plastic
or glass bottle.
Bag Collection:
1)
This method is used in neonates & infants.
2)
A sterile bag is applied after careful cleaning & allowing the skin to dry and
removed immediately once baby has voided.
3)
Though convenient infants but given unacceptably high false positive
results.
4)
A negative culture helps to exclude UTI to a reasonable extent.
5)
A positive result better confirmed by examinations of a specimen obtained
by bladder aspiration.
LABORATORY EXAMINATION
Suprapubic bladder aspiration:
o Only reliable way to obtain urine specimen in neonates & infants and
children <2 years.
oThis method also used whenever the results of mid stream urine exam
not clear.
o Procedure: A 5-10 ml syringe with a thin needle is vertically inserted, 1-2
cm above the pubic & symphysis to a depth of 2-3cm.
o Precautions: Bladder should be full (can be confirmed by percussion or
U/S)
There are no significant complication.
Bladder Catheterisation: A urine specimen can also be safely
obtained in infants by bladder catheterization. When carried out, strict
aseptic precautions should be taken.
LABORATORY EXAMINATION
Specific Gravity: Normally urinary specific gravity is in
between 1.002 to 1.028.
Increased urinary specific gravity is seen in
dehydration, diarrhoea, excessive sweating, Glucosuria,
heart failure, Renal artery stenosis, SIADH.
Decreased urinary specific gravity is seen in
excessive fluids administration, diabetes insipidus, renal
failure, pyelonephritis.
LABORATORY EXAMINATION
Protein:
1)
Urine specimen should be clear & may be centrifuged if necessary.
2)
2 types of tests available: 1. Boiling test 2. Dip Stick test
Boiling test:
1)
10-15 ml of urine is taken in test tube and upper portion is boiled.
2)
If turbidity appears 3 drops of conc. Acetic acid are added and specimen is
boiled again.
3)
A zero to 4 + grading is used to record the concentration of protein.
4)
1+ - signifies 30-100 mg of protein/dl
5)
2+ - signifies 100-300 mg/dl
6)
3+ - signifies 300-1000 mg/dl
7)
4+ - signifies >1000 mg/dl
A false positive reaction may be seen with X-ray contrast media administration,
high doses of pencillin
A false negative reaction seen with alkaline or dilute urine, globulin or B.J.
Protein.
LABORATORY EXAMINATION
Dipstick methods (e.g., Uristix) are now widely used to test for
proteinuria, and are more convenient and equally reliable.
The reagent strips are impregnated with tetrabomophenol blue
buffered with citrate. Protein binds with the dye and causes a color change
from yellow to green.
Trace reaction on the dipstick corresponds to 5 to 20 mg/dl urinary
protein, + to 30 mg/dl, 2+to100mg/dl, 3+ to 300mg / dl and 4+ to 1000
mg/dl.
Light chain proteins, globulin and low molecular weight tubular
proteins are not detected by this method. Dilute urine may give a false
negative result. False positive results occur with very alkaline urine,
concentrated specimens and those contaminated with chlorhexidine.
A quantitative protein measurement may be done on 6 to 12 hr
urine specimens. Presence of protein in an amount greater than 4
mg/m2/hour is considered significant. Children with nephrotic syndrome
show a much greater amount of proteinuria that exceeds 40 mg/m2/hour.
LABORATORY EXAMINATION
Reducing Substances: Benedict’s test or Clinitest tablet
tests detect reducing substances. The glucose oxidase
method (Dextrostix) is specific for glucose.
Clinitest: Screening for chemically reactive indicator like
metallic dye cupric sulphate for glucose & galactose.
screened for diabetes & galactosemia.
Increased urinary glucose may give false +ve results in
case of excessive in take of acetyl salicylic acid, ascorbic acid,
amino salicylic acid.
False negative results are seen in intake of Levodopa,
Phenothiagenes.
LABORATORY EXAMINATION
Microscopic Examination:
A fresh, well-mixed specimen should
be examined. Presence of cellular
elements and casts should be noted.
Red cell casts indicate glomerular
inflammation. Clumping of neutrophils
(“white cell casts”) suggests acute
pyelonephritis. Red blood cells and
leukocytes can be counted under the
high power field and more accurately
ina counting chamber. With a Fuchs
Rosenthal counting chamber, 8000
RBC/ml and 2000 to 8000 WBC/ml
may normally be seen. More than 5
leukocytes
/HPF
along
with
bacteriuria suggests urinary tract
infection.
Dysmorphic RBC
RBC in Urine
Red Cell Cast
LABORATORY EXAMINATION
Microscopic Examination:
Leukocytes may occasionally be
absent despite significant bacteriuria.
Isolated presence of white cells is
also not confirmatory of UTI. More
than 5 RBC/HPF in a centrifuged
specimen is abnormal. The RBC
morphology
is
useful
in
distinguishing between glomerular
and
non-glomerular
causes
of
hematuria.
Presence
of
any
bacteria/HPF in fresh, uncentrifuged
urine correlates well with a colony
count of over 105 organisms/ml
indicating significant bacteriuria.
Fatty casts may be seen in patients
with nephrotic syndrome.
WBC Cast
Fatty Cast
Fine granular cast
LABORATORY EXAMINATION
Blood Tests:
Blood urea level: The normal level is 20-40 mg/dl. The upper limit may not
be exceeded until over 75 percent of kidney function is lost. Various factors
that renal perfusion and GFR (prerenal factors) cause a reversible
increase in blood urea levels, which are also increased when more urea is
produced as in excessive tissue breakdown, trauma, gastrointestinal
bleeding, use of drugs such as corticosteroids and tetracycline, and
hyperacatabolic states. The blood urea levels are low on a low protein
intake and in the presence of severe impairment of liver function (urea is
formed in liver by hepatic metabolism of aminoacids).
Serum Creatinine: The normal levels of serum creatinine range from 0.2 to
0.5 mg/dl during infancy to 0.4 to 0.8 mg/dl in older children. The level of
serum creatinine varies inversely with the GFR, of which it is a better
indicator than blood urea level. Serum creatinine is not readily affected by
prerenal factors. The rate of creatinine production depends upon the body
muscle mass and is relatively constant. Serum creatinine values are low
when the muscle is decreased, as in malnutrition. Bilirubin interferes with
creatinine measurements.
LABORATORY EXAMINATION
Blood Tests:
Serum Proteins: The levels of serum albumin are reduced in
patients with heavy proteinuria, occasionally to below 1.5 g/dl.
Serum Cholesterol: In children with nephrotic syndrome
hypercholesterolemia is typically present. It is related to the
severity and the duration of proteinuria.
Anti-Streptococcal antibody titer: The measurement of
antibody tier against ß-hemolytic streptococci is important for
the diagnosis of poststreptococcal GN. Latex agglutination
slide test kits are available, containing polystyrene latex
particles coated with stabilized streptolysis O and Dnase B as
the antigen that react with antibodies in the patient’s serum. A
titer of over 200 IU/ml is considered positive. ASLO titers are
elevated in children with streptococcal pharyngitis in over 80
percent of cases.
LABORATORY EXAMINATION
Blood Tests:
Serum Complement: The measurement of the levels of C3 and C4 in blood is
important in the diagnosis of postinfectious GN, membranoproliferative GN and
lupus nephritis, where decreased levels of C3 are typically present. The levels of
C3 may increase in acute inflammatory conditions such as rheumatoid arthritis with
an acute onset. In SLE serum C3 levels reflect disease activity. The normal range
of serum C3 is 70 to 120 mg/dl and that of serum C4 20 to 50 mg/dl.
Serum immunoglobulins: The The levels of serum IgA are increased in about 30 to
40 percent patients with IgA nephropathy and Henoch Schonlein vasculitis.
Antinuclear antibodies (ANA) and anti-ds DNA antibodies: Antinuclear antibodies
are directed against chromatin-associated or ribonucleoprotein particles. They are
increased in SLE, juvenile rheumatoid arthritis, polyarteritis nodosa and certain
liver diseases. An increase in anti-ds DNA antibody titer is diagnostic of SLE.
Antineutrophilic Cytoplasmic antibodies (ANCA): These antibodies are typically
detected in Wegener’s granulomatosis and in pauci-immune crescentic GN.
Renal Biopsy:
Crucial for the diagnosis of renal diseases involving
glomeruli, tubulointestitium and blood vessels.
Vim Silverman needle with Franklin modification or the
Tru-Cur needle are comonly used. A semi-automatic device
Biopty gun, a spring loaded fine biopsy needle with an
automatic firing is also satisfactory.
INDICATIONS FOR RENAL BIOPSY
Significant value
Less value
Steroid resistant nephrotic syndrome
Chronic renal failure
Acute renal failure of unknown cause
Non-nephrotic proteinuria
Rapidly progressive renal failure
Microscopic hematuria
Systemic renal disease
Inherited nephropathies
Renal allograft dysfunction
Biopsy Procedure:
Usually performed percutaneously.
An open biopsy may be considered in patients with shrunken
kidneys, a solitary kidney or with abnormalities of kidney fusion
or position.
PT, BT, coagulation time, platelet count are measured.
The renal size and location are confirmed with a plain
radiograph of the abdomen or an ultrasonogram before the
biopsy.
IV ketamine or diazepam are used for sedation.
The patient put in prone position with a folded towel or
bedsheet placed under his lower ribs and epigastrium to push
the kidneys posteriorly.
After infiltration of 1% Lignocaine into the skin and subcutaneous tissue
kidney is localized with a probing 23 gauge needle. As it enters the capsule
a distinct resistance is felt. Once in the kidney it moves with respiratory
excursions.
The entry of Tru-Cut biopsy needle into the kidney, when it pierces the renal
capsule, is indicated by slight resistance.
The outer sheath is rapidly advanced over the cutting needle and thereafter
the entire device withdrawn.
The tissue of biopsy is immediately fixed in buffered formalin, and the other
in saline for immunofluorescence study.
Bed rest advised for some hours after the biopsy.
Complications:
The risk of complications is increased in patients with bleeding diathesis,
uncontrolled hypertension and renal failure. Gross hematuria may occur in
about 10 percent cases.
Embolization of the bleeding vessel rarely may be considered, if gross
hematuria continues for several days. Formation of renal arteriovenous
fistula may occasionally occur, and is indicated by a bruit in the renal area.
Interpretation of Renal Biopsy:
The biopsy tissue should be preserved and processed with
utmost care. Thin sections and staining of excellent quality are
prerequisites for expert interpretation. The histology should be
examined by light microscopy using hematoxylin-cosin (H and
E), periodic Schiff( PAS) and silver methenamine staining in
all cases, and special stains as necessary.
Examination by immunofluorescence methods is also
necessary. Electronmicroscopic examination is very useful in
several
disorders
e.g.,
Alport
syndrome,
membranoproliferative GN and thin basement membrane
disease.