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Introduction
• The kidneys are two bean shaped organs
  lying retroperitoneally on each side of
  the vertebral column slightly above the
  level of umblicus.
• The range in length & weight,
  respectively, from approximately 6cm &
  24gms in a full term infant to more than
  equal to 12cm & 150gms in an adult
                                             2
NEPHRON
• Each kidney contains approx.
  1 million nephrons.
• In humans,formation of nephron is
  complete at 36-40 wks of gestation.,
  but functional maturation with
  tubular growth & elongation
  continues during the 1st decade of life
• B’coz new nephrons can’t be formed
  after birth,so any disease that results
  in progressive loss of nephrons can
  lead to renal insufficiency.

                                            3
Cont..

• A decreased number of nephrons
  secondary to LBW,prematurity &/or
  unknown genetic or environmental factor
  is hypothesised to be a risk factor for the
  development of primary HT &
  Progressive Renal Dysfunction in
  adulthood.


                                            4
Cont…
• A Nephron consist :-
• OUTER LAYER
   (the cortex)
  -glomeruli
  -PCT & DCT
  -CD
• INNER LAYER
   (the medulla)
   -Straight portion of tubules
   -LOH
   -vasa recta
   -terminal CD
                                  5
JUXTAGLOMERULAR APPARATUS
• The cells of the distal tubule in
  the part that comes in contact
  with the afferent arterioles of
  the glomerulus are more dense
  than the cells in the rest of
  tubule are called MACULA
  DENSA
• The smooth muscle cells of
  afferent arterioles that
  approximate macula densa
  contain prominent secretory
  cytoplasmic granules which are
  the site of renin activity.
                                         6
Cont…

• JGA is composed of the afferent
  & efferent arterioles,the macula
  densa & lacis cells located in the
  triangular space in between
  these structure.
• It is involved in systemic blood
  pressure regulation,electrolyte
  hemeostasis &
  tubuloglomerular
  feedback mechanism.


                                       7
RENAL VASCULATURE

• The renal artery arising from aorta
  divides into fine Segmental Arteries.
• The latter divides into the Interlobar
   Arteries,which branch into Arcuate
   Arteries near the junction of the Cortex
   & medulla.
• Interlobar arteries provide the afferent
  arterioles for the glomeruli.
• The glomerular capillaries join to form
  the efferent arteries that leaves the glomerulus & form an
  extensive network of peritubular capillaries that surround the
  tubules,mostly in the cortex,forming Vasa Recta.The VR along
  with LOH are responsible for the urine concenteration
                                                                   8
RENAL FUNCTIONS




                  9
DIAGNOSTIC EVALUATION

• Urine Examination
   -routine &
   -microscopic
• Evaluation of Renal Function
• Renal Biopsy
• Imaging

                                 10
URINE EXAMINATION

• It is the most important step for the diagnosis of renal
  disease.
• COLLECTION OF SAMPLE :
  -the 1st morning specimen is preferred
  -collected in a clean container
  -for culture, the specimen should be collected in a sterile
    container & sent to the lab. Immedietly, where it should be
     plated within 15minutes or stored in a refrigerator at 4
     degree celsius.Bacteria multiply rapidly at room
     tempt., which may give false positive results.


                                                                  11
Method of urine collection
• Midstream urine : a clean-catch midstream specimen is
                      widely used. In older children who can
  cooperate, midstream specimen is obtained after proper local
  cleaning .The initial part of urine is discarded.
• Bag collection : in neonates & infants, urine can be collected
                   in sterile bags. Not used for microscopic
  exam.
• Bladder catheterisation : a urine specimen can also be safely
                               obtained, in infants, by strict
  bladder catheterisation but requires some skills & experience.
• Suprapubic bladder aspiration : the only reliable way to
                                      obtain reliable urine
  specimen in neonates & young infants. In children <2 yrs of
  age it is most suitable method for a definitive diagnosis of UTI.
                                                                 12
URINE ROUTINE EXAMINATION

• SPECIFIC GRAVITY : full term infants have a
  limited concentrating ability with a maximum
  sp.gravity of 1.021 – 1.025.It is measured
  with clinical Hydrometer. Increase in sp.gravity
  may be ass. with dehydration, diarrhea, emesis,
  excessive sweating etc. while decrease in sp.gravity may be
  ass. with renal failure, DI, ATN, interstitial nephritis &
  excessive fluid intake.
• pH : tested with pH meter. Routine lab reports of pH are of
  no importnace.UTI with urea splitting organisms make urine
  highly Alkaline. Normal pH ranges from 4.6 -8.0. In fasting, the
  concentrated urine sample is highly Acidic .
                                                                 13
Cont…
 -A high urine may be due to RTA(type I),UTI,Vomitng & a low
  urinary pH may be due to DKA,diarrhea & starvation.


• PROTEIN :
   Boiling test : satisfactory but cumbersome.10-15 ml of urine
  is taken in a test tube & upper portion is boiled. If turbidity
  appears 3 drops of concentrated acetic acid are added &
  specimen is boiled again. A zero to +4 grading is used.




                                                                    14
Cont…
+1      Presence of slight   30-100mg of
        turbidity,through    protein/dl
        which print can be
        read
+2      Turbidity with slight 100-300mg of
        precipitates          protein/dl
+3      White cloudiness    300-1000mg
        with fine           protein/dl
        precipitate,through
        which black lines
        are not visible

+4      Large clumps of      >1mg of protein/dl
        white precipitates
                                                  15
Cont…
Dipstick methods(e.g uristix) : widely used
test for Proteinuria, more convenient &
equally reliable.
-Colour changes from yellow to green.
-light chain proteins & LMW tubular
 proteins are not detected by this method.
-Trace react.  5 to 20 mg/dl urinary prtn
           +1  30 mg/dl
           +2  100 mg/dl
           +3  300 mg/dl
           +4  > 1000 mg/dl

                                              16
Cont…
• Proteinuria in patients with Nephrotic Syndrome is massive
  (+3 or +4 by dipstick) & selective,constituted predominantly
  of Albumin,without loss of proteins of higher molecular wt.
• In the presence of tubular damage or physical injury to the
  glomerular barrier, the proteinuria is non selective.
• In renal parenchymal diseases,proteinuria is often quantified
  to assess degree of glomerular injury.
• Selective Proteinuria : intermediate sized(<1000kDa)
  proteins(albumin,transferrin) leaks through glomerulus.
• Nonselective proteinuria : range of different sized proteins
  leak through,including larger proteins(immunoglobulin)



                                                              17
Cont…
• Quantitative Measurement of Urine Protein
  -Accurate collection of urine over 24hr period is required to
  quantitate protein excretion.
  -A value of >4mg/m2/hr is considered abnormal, & >40/m2/hr
  indicates heavy proteinuria.

  -The range proteinuria in nephrotic so is massive
   proteinuria(>3.5gm/24hrs)
   while the range in nephritic s o is mild to moderate
   proteinuria(<3gm/24hrs)




                                                              18
Cont…
• Urine Protein/Creatinine Ratio : an approx. estimate of the
  severity of proteinuria also can be made by measurement of
  urine protein & urine creatinine on random urine sample.
   -Values >2 indicate Heavy Proteinuria
           <0.2 are insignificant.
   -Such measurements are of use in following response to
    therapy in various disorders, but seldom necessary in
    children with nephrotic syndrome.




                                                                19
Cont…

• GLUCOSE :the older methods(e.g benedict
  test) that detected reducing substance have
  mostly been replaced by Dipstick test,which is
  based on Glucose Oxidase Peroxidase linked
  reaction.
• BLOOD :detection of Hb by dipstick is based on an reaction,
  with a spotted +ve reaction indicating intact red blood cells &
  uniform +vity suggesting presence of free Hb.However the
  use of dipstick to detect hematuria is discouraged,b’coz
  reactions may often be false +ve(e.g myoglobinuria,oxidising
  substances,bacterial colonisation) or false –ve (e.g ascorbic
  acid,other reducing substances)

                                                                20
MICROSCOPIC EXAMINATION

• A fresh,well mixed specimen should be examined.
• Presence of cellular elements & casts should be noted.
• Red cell casts : indicate glomerular inflammation.




             Red cell casts & red cells in a pateint with glomerulonephritis

                                                                               21
Cont…
White cell casts :clumping of
       neutrophils suggests
       acute pyelonephritis



Epithelial cell cast :are noted in patients recovering from Acute
  tubular necrosis




                                                                    22
Cont…

Hyaline or Fatty casts : may be +nt
 in proteinuric states or in normal
 in normal individuals with
 concenterated urine.



• Red blood cells & leukocytes can be counted under the high
  power field & more accurately in a counting chamber.
• >5 leukocytes/HPF along with bacteruria suggests urinary
  tract infection.
• Neutrophils may also be detected in proliferative
  glomerulonephritis & interstitial nephritis,while the presence
  of Eosinophils in urine is specific of acute interstitial nephritis23
Cont…
• Hematuria is defined as presence of >5RBS/HPF in a
  centrifuged specimen.
• RBC morphology is useful in distinguishing bet. Glomerular &
  non glomerular causes of hematuria.
• The site of injury is likely to be the lower urinary tract if <25%
  urine correlates well with a colony count of over 105
  organisms/ml indicating significant bacteriuria.




                                                                   24
URINE CULTURE

• Definitions of +ve or –ve urine culture are dependent on the
  method of collection & the patients clinical status.
                  Diagnosis of Urinary Tract Infection
      Method of collection    Colony count(per ml)   Probability of infectn
      Suprapubic Aspiration Any number               99%
      Urethral catheterisatn >105                    95%
                              104 to 10 5            Very likely
                              103 To 104             Suspicious:repeat
                              <103                   unlikely
      Midstream void
      Boys                    >104                   Very likely
      Girls                   >105                   90-95%
                              104 to 105             Suspicious:repeat
                              <104                   unlikely                 25
EVAULUATION OF RENAL FUNCTION

• Various aspects of renal function are
  -GFR(Glomerular Filtration Rate)
  -RPF(Renal Plasma Flow)
  -Reabsorption & Excretion of various substances like Na+, K+,
  Ca+2, inorganic phosphate, glucose, urea, a.a, H2O & osmoles.
• In clinical practice
   -determination of Creatinine Clearance is a measure of GFR
   -water deprivation & vasopressin administration tests to
    determine urinary concentrating ability, &
  -bicarbonate & ammonium chloride loading test to examine
    urinary acidification are usually sufficient for diagnostic
    evaluation & measurement of kidney function.
                                                              26
Cont…
• The results of these tests are important in assessing the
  excretory function of the kidneys. For example, grading of
  chronic renal insufficiency and dosage of drugs that are
  excreted primarily via urine are based on GFR (or creatinine
  clearance).




                                                                 27
GLOMERULAR FUNCTION TEST
• The concept of clearance is based upon the fact that the rate
   of removal of a substance from the plasma must equal its
   simultaneous rate of excretion in urine.
• Thus if the urinary excretion rate & plasma concentration of a
   substance are known, we can calculate the volume of plasma
   from which that substance would have been completely
   removed. INULIN has been taken as a reference substance.
• The standard formula for clearance is : C = U x V
                                               P
C = clearence/min(ml/min)
U = urinary concenteration(mg/dl)
P = plasma concenteration(mg/dl)
V = urine volume/min(ml/min)
                                                               28
Cont…
• If a given substance is freely filtered & neither reabsorbed nor
  excreted, its clearance rate would accurately reflect GFR.
• The GFR can be estimated by measuring s.creatinine level &
  height.The formula proposed by SCHWARTZ is useful for
  children :
•            GFR(ml/min/1.73m2) = K x Height(cm)
                                       S.Creatinine(mg/dl)
  K = 0.34 (in preterm infant)
     = 0.45 (in term infants)
     = 0.55 (in children & adoloscent girls) &
     = 0.7 (in adoloscent males)


                                                                 29
Cont…


• Serum Creatinine & Creatinine Clearance :
• Creatinine is derived from the metabolism of creatine &
  phosphocreatine,the bulk of which is in muscle.
• Since creatinine is chiefly excreted by glomerular
  filteration,S.creatinine levels reflects changes in GFR.
• S.creatinine values are low when the muscle mass is
  decreased, as in malnutrition.
• Bilirubin interferes with creatinine measurements.




                                                             30
Cont…
• The normal values of S.creatinine are :
                  AGE                RANGE(mg/dl)
                  Cord                       0.6-1.2
                Newborn                      0.3-1.0
                <3 years                    0.17-0.35
                3-5 years                   0.26-0.42
                5-7 years                   0.29-0.48
                7-9 years                   0.34-0.55
                9-11 years                  0.35-0.64
               11-13 years                  0.42-0.71
               13-15 years                  0.46-0.81
               Adult Male                    0.7-1.3
              Adult Female                   0.6-1.1

                                                        31
Cont…
• CYSTATIN C : It is a LMW nonglycosylated protein produced at
  a constant rate by all nucleated cells in the body, freely
  filtered by the glomeruli, not secreted, but totally reabsorbed
  by the renal tubules.
• Little or no cystatin is excreted in urine.
• Normal adults have circulating level of approx. 1mg/l.
• This is better indicator of renal function as compared to
  creatinine in early stages of GFR impairment as it is
  independent of age,gender,body composition & muscle mass.
• Cystatin C can be estimated in blood by enzyme
  immunoassays or immunoturbidometry.Both techniques are
  currently kit based & expensive.

                                                                32
Cont…
• SINGLE INJECTION TECHNIQUE : in clinical practice,
  radionuclides are often used to estimate total GFR or to
  measure difference in clearance bet. one kidney compared to
  other in the same patient.
• The technique is based on use of a single injection, plasma
  disappearance curves to estimate the true GFR.
• Briefly, the radionuclide dye is injected & the signal from
  radiolabelled form is used to obtain measurment.
• The most commonly used Radionuclides for GFR are
  -DTPA (Diethyl triamine Penta-acetic acid)
  -EDTA (ethylene diamine tetra acetic acid) &
  -Iothalamate
• Iohexol,a non ionic non radioactive LMW radiocontrast
  agent,as an alternative to inulin,measured easily by HPLC(high
  performance liquid chromatography)
                                                              33
Cont…
• BLOOD UREA : A normal level of blood urea is often
  mistakenly regarded to indicate normal kidney function.
• In a steady state the blood urea may not rise beyond the
  upper range of normal(40mg/dl) even when 75% of the renal
  function is lost.
• On the other hand, prerenal factors that decreases renal
  perfusion & GFR,such as dehydration,causes an increase in
  blood urea levels.
• There may be transient rise in blood urea level due to :
  -high protein intake & excessive protein catabolism( e.g with
  severe infections,tissue break down,trauma,use of large doses
  of corticosteroids or tetracyclines)
  -gastrointestinal bleeding & inhibition of anabolism.
                                                              34
RENAL BLOOD FLOW
• Renal blood flow measurements are performed using the
  clearance of PAH(para aminohippurate)
• >90% PAH is extracted from the plasma during the 1st pass
  through the kidneys.Therefore, renal clearance of PAH is
  commonly used as an estimate of renal plasma flow(RPF).
• Plasma clearance following single injection of 131I-hippuran or
  99mTc-mercaptoacetyltriglycine(MAG-3)is an alternative

  method.
• Renal Blood Flow is calculated by dividing RPF by [1-
  hematocrit].
• Normal value ranges from 500 to 600 ml/min(abt.
  1200ml/min/1.73m2).
• Other methods-Color Doppler US,Contrast Enhanced US &
  MRI.                                                           35
URINARY CONCENTERATION
• Osmolality dependes upon the number of particles in a
  solution & not on their size or density.
• The maximal urinary concentration capacity varies with age
   - in neonates its abt. 700 mOsm/kg
   - in older children & adults it an rise up to 1200mosm/kg.
• Hyposthenuria(inability to increase urine osmolality > than
  that of plasma) is characteristic of Diabetes Insipidus as well
  as Diseases of Renal Medulla such as obstructive uropathy.
• Polyuria & polydipsia are stricking features.
• In chronic Renal Failure urine osmolality does not rise much
  above 400mOsm/kg & polyuria & polydipsia are not
  prominent.
• Osmolality = 2[Na+] + [Glucose]/18 + [ BUN ]/2.8
                                                                    36
Cont…
• URINARY CONCENTERATION TEST : Urinary concentrating
  ability needs to be tested in a setting of polyuria.If the 1st
  morning void after 12hrs of overnight fasting has osmolality
  exceeding 700 mOsm/kg,no further testing is required.In
  others, Water Deprivation Testing is done.
• Response to Vasopressin : subsequently,to confirm the lack of
  renal concentrating ability & distinguish Nephrogenic
  Diabetes Insipidus(NDI) from Central Diabetes
  Insipidus(CDI),a vasopressin test is performed.
  -Desamino-8-D-arginine Vasopressin(dDAVP,desmopressin) is
  administered nassly(5-10 ug in neonates & infants,20 ug in
  children) or by an I.M injection(0.4-1.0 ug in infants & young
  children,2 ug in older children).
• The changes in urine osmolality seen are :
                                                               37
Cont…


CONDITION             URINE OSMOLALITY ON CHANGES IN
                      WATER               OSMOLALITY WITH
                      DEPRIVATION(mOsm/kg dDAVP(mOsm/kg)
NORMAL                >800-900            MINIMAL OR NO
                                          INCREASE

COMPLETE CENTRAL DI   <300                SUBSTANTIAL INCREASE

PARTIAL CENTRAL DI    300-800             INCREASE OF >10%

NEPHROGENIC DI        <200-300            MINIMAL OR NO
                                          INCREASE
PRIMARY POLYDIPSIA    >500                MINIMAL OR NO
                                          INCREASE



                                                                 38
Tests Of Urinary Acidification

• Renal acidification mechanism are usually examined in
  children with suspected renal tubular acidosis.
• Urine pH : The pH of a fresh specimen of urine is tested with
  pH meter. A concentrated, fasting, morning sample of urine is
  acidic.A pH of <5.5 virtually excludes distal renal tubular
  acidosis.
• Urine Anion Gap : Urine anion gap is the difference between
  concentration of principal urinary cations(Na + k) &
  anion(cl)This difference is expected to estimate the
  unmeasured anions & cation,which normally include
  ammonium & bicarbonate.Since the latter is mostly
  reabsorbed ,urine anion gap is chiefly measure of ammonium
  excretion.
                                                              39
Cont…
• In presence of systemic metabolic acidosis,ammonium
  excretion is expected to be stimulated while the bicarbonate
  excretion is minimal,hence,the urine anion gap should be –ve
  due to obligatory chloride excretion with ammonium.
• In patients with renal tubular acidosis the gap remains +ve
  due to impaired ammonium production.
• Sodium Bicarbonate Loading Test : The Bicarbonate threshold
  is the plasma bicarbonate level at which bicarbonate appears
  in urine.
  -The bicarbonate threshold is determined by infusion of
  bicarbonate & increasing the plasma bicarbonate in a
  stepwise manner to elevate he serum bicarbonate level to 23-
  26mEq/l.
                                                             40
Cont…
  -3-5ml/kg sodium bicarbonate is administered orally or
   Intravenously,which increase the urine pH to more than 7.4.
  -Levels of bicarbonate & creatinine are measured in blood &
   random urine specimens.
  -Normally there is no bicaorbonaturia unless the plasma
   bicarbonate level exceeds 23-24mEq/l.
 -the urinary bicarbonate threshold is reduced is proximal renal
   tubular acidosis.The Fractional Excretion of bicarbonate
   (FEHCO3) is calculated by the formula :
          FEHCO3 = urine HCO3 X plasma creatinine X 100
                    plasma HCO3 X urine creatinine
 -The normal level of FEHCO3 are <5%.In proximal RTA,the
   FEHCO3 usually exceed 15%.
                                                               41
Cont…

• Other tests for urine acidification are
  -Urine PCO2
  -Ammonium Chloride Loading test




                                            42
Cont…
                       OTHER INVESTIGATIONS
•   S.proteins : S.albumin level
•   S.cholesterol: in Nephrotic So—hypercholesterolemia.
•   Anti Streptococcal Antibody Titer : antibody titer against
    hemolytic streptococcs is important for the diagnosis of
    Poststreptococcal GN(PSGN).A titer of >200 IU/ml is +ve.
•   S.complement : measurement of C3 & C4 levels in bld. is
    important for diagnosis of Postinfectious GN,
    Membranoproliferative GN & Lupus Nephritis, where
    decrease in C3 levels are +nt. The levels of C3 are increased in
    active Rheumatoid arthritis. The normal range of S.C3 is 70 to
    120 mg/dl & C4 20-50 mg/dl.
•   S.immunoglobulins : S.IgA levels are increased in abt 30-
    40%patients with IgA nephropathy & HSP.
                                                                   43
Cont…
• Antineutrophil cystoplasmic antibodies : are typically
  detected in Wegner’s granulomatosis & In Pauci-Immune
  Cresentric GN.




                                                           44
RENAL BIOPSY
• Expert evaluation of renal histology is important in the
   diagnosis of various renal parenchymal disease involving
   glomeruli, tubulo-interstitium & small blood vessels.
• The procedure has become has become
    much simpler with the use of automatic
    (biopsy gun,tru cut) devices & ultrasono
     -graphic visualization of kidney.
• INDICATIONS : Renal biopsy has a limited role in children.
Significant Value
-Streoid resistant nephrotic So
-Acute Renal Failure of Unknow Cause
-Rapidly Progressive Renal Failure
                                                               45
Cont…
-Systemic disease(Henoch-schonlein Purpura,Lupus Hemolytic
   Uremic So ,IgA nephropathy)
-Inherited Nephropathies e.g Alport So
-Renal allograft dysfunction
-Detection Of Calcineurin toxicity
Less Value
-Chronic renal Failure to ascertain etiology
-Non Nephrotic Range Proteinuria
-Microscopic Hematuria
-Steroid Sensitive Nephrotic So
A Renal Biopsy Is not required in uncomplicated cases of
   Postinfectious GN & corticosteroid responsive nephrotic So

                                                                46
Cont…
• BIOPSY PROCEDURE
-A renal biopsy is usually made percutaneously
-A history of bleeding & clotting disorders should be obtained.
-PT, BT, Coagulation time & Platelet count is measured.
-BP should be in normal range
-In Patients with acute renal failure,dialysis should be done to
   reduce azotemia & correct biochemical abnormalities before
   the biopsy.
-Renal size & location are confirmed with an US before biopsy.
-The Patient should be kept fasting for abt 3-4 hrs.
-Local anaesthesia can be used


                                                                   47
Cont…
-The child lies in prone position with a
  folded towel or bed sheet placed
  under his lower ribs & epigastrium to
  push the kidneys posteriorly &
  stabilize their position.
-The entry of biopsy needle into the kidney,when it pierces the
  renal capsule,is indicated by slight resistancce & once in kidney
  it moves wit respiratory excrusions
-2 core of tissue(abt. 8-10 mm long)
 are needed for adequate histological
 examination.

                                                                  48
Cont…
-One core is fixed in buffered formaline & other in saline(for
   immunofluorescencs study)
Interpretation of Renal Biopsy
• The histology should be examined by light microscopy using
   Hematoxylin & eosin(H & E),Periodic Schiff (PAS) & Silver
   Methanamine staining In all cases, & special stains as
   necessary.
• Electron microscopy is very useful in several disorders e.g
   Alport So, Membranoproliferative GN & thin Basement
   Membrane Disease.




                                                                 49
IMAGING
• DIAGNOSTIC PROCEDURES
• RADIONUCLIDE STUDIES




                          50
DIAGNOSTIC PROCEDURES
• Plain X-Ray Film Of The Abdomen : The utility of a plain X-ray
  film of abdomen has decreased with the introduction of US &
  later CT scanning.Most UT disorders can be imaged using
  these methods,which gives more information
  than the Plain X-ray.The later still has a role in
  detecting small renal calculi,ureteric calculi
  with minimal or no proximal dilatation,
  spinal evaluation in neurogenic states,
  evaluation of metastatic bone disease from
  a neuroblastoma & screneing for renal
  osteodystrophy.


                                                               51
Cont…
• Excretory Urography : Newer techniques especially US in
    combination with radionuclide studies have largely replaced
    excretory urography & IVP(Intravenous Pyelography).
-After careful preparatn
 on the previous evening
 (a liquid diet,laxative)
 2.5 -3 ml/kg of a
 nonionic contrast agent
 is administered intravenously.
-Intial film is taken at 5 mins. After contrast agent followed by
    another at 10-15 mins. & a late pelvic film to visualize the UB.
-Excretory urography should be avoided in neonates b’coz of
    their poor ability to concneterate contrast medium.            52
Cont…
• Ultrasonography : it provides
    an excellent information
    about the anatomy of the
    urinary tract.
   -High resolution images in
    multiple planes may be
    obtained.
  -The procedure is ideally suited
    for children since,it is painless & requires no sedation or
    administration of any contrast reagent,& be carried out even
    bedside.
  -US guidance can be used in invasive procedures e.g. fine
    needle aspiration & biopsy.
 -                                                               53
Cont…
• Quantitative measurements of renal growth is possible on 2D
  US Doppler technique when used in conjunction with 2D
  imaging is particularly informative.




• The major drawback of US is that it is operator dependent.


                                                               54
Cont…
• Antenatal Ultrasonography : US during pregnancy can detect
  fetal anomalies.Presence of dilation of urinary
  system,echotexture of renal parenchyma,appearance of
  urinary bladder & the amniotic fluid are carefully examined.
• Vesicoureteric reflux is the commonest cause of dilated
  urinary tract & pelviureteric junction obstruction that is
  isolated hydronephrosis.
• Oligohydramnios on US
  indicates poor renal
  function.




                                                             55
Cont…
• Computed Tomography (CT SCAN) : CT,besides providing
  anatomical information,also gives functional status of the
  kidneys if an IV contrast agent is used.
• The main role of CT urinary tract imaging is for examining
  mass lesions of the kidney,bladder or retroperitoneum that
  secondarily affect the urinary
  system.
• These masses may be congenital
  (teratoma), inflammatory(abscess),
  traumatic(hematoma) or
  neoplastic(wilm’s tumor).


                                                  WILMS TUMOR   56
Cont…
• CT scan can detect a non functioning or a
  poorly functioning kidney.
• With the advent of Multidetector Row CT
  (MDCT),it is possible to acquire high
  resolution images with faster speed &
  hence,less motion blur in small children.
• With MDCT it has become possible
  to get high resolution reformatted
  images in coronal & sagittal planes;
  which is crucial for extent
  assessment of renal or
  retroperitoneal masses (e.g. extent
  of IVC thrombus in wilms tumor)
                                              57
Cont…
• Magnetic Resonance Imaging(MRI) :Though there are several
  advantages of this imaging modality like nonionizing
  nature,multiplaner
  imaging capability &
  superior soft tissue
  contrast resolution,
  its use is limited in
  pediatric practice b’coz
  of motion related
  problem & requirement
  of sedation & general
  anaesthesia.
                                                          58
Cont…
• Important uses of MRI in pediatric
  renal pathologies include MR
  Urography in cases of hydronephrosis,
  duplex moeity, ectopic ureter : MR
  angiography in cases of suspected renal
  artery stenosis.

                         The added advantage of MRI in
                         evaluation of renal masses is that IVC
                         thrombus can be detected without any
                         contrast.

                                                              59
Cont…
• Micturating Cystourethrogram : MCU is an important
  procedure necessary for the diagnosis & evaluation of severity
  of Vesicoureteric reflux, & detection of the abnormalities of
  bladder & urethra.
• The contrast agent
  is introduced into
  the bladder through
  a catheter.
• Films are taken while
  child is voiding.
• The catheter should be introduced with strict aseptic
  precautions.

                                                              60
Cont…
• Patients at high-risk of systemic sepsis(infants,children with
  dilated urinary tract,congenital heart disease0 should receive
  prophylactic treatment with oral amoxicillin or parentral
  gentamycin 30-60 mins. prior to procedure.




                                                               61
Cont…
• Special Imaging Procedures :
  -Several other imaging procedures are employed to visualize
   the urinary system.
  -these include nephrostogram, ureterostogram, retrograde
   pyelogram & angiography.
CHOICE OF IMAGING PROCEDURES
• US evaluation is usually the 1st procedure in patient with
   suspected urinary tract disease.
• It is often diagnostic ( e.g. hydronephrosis,cystic disease of
   kidney ) or provides enough information to suggest the next
   appropriate investigation.


                                                                   62
RADIONUCLIDE STUDIES

• Radionuclide studies are complementary to structural imaging
  methods of the pediatric urinary tract.
• Nuclear medicine procedures are relatively noninvasive,
  requring only an i.v injection.
• They require neither fasting nor bowel preparation.
• They can be performed on an outpatient basis without the
  need for anaesthesia.
• They have neither systemic toxic effects(e.g. osmotic
  effect,hemodynamic overload) nor allergic reactions,with
  minimal absorbed radiation dose.
• Radionuclide studies & US evaluation of genitourinary
  morphology have significantly reduced the need for i.v
  urography.                                                 63
Cont…
• Radiopharmaceuticals : radiopharmaceuticals used for
  evaluation of the kidneys may be classified into three
  principle groups.

A) Radiopharmaceuticals that are rapidly eliminated by the
    kidneys & thus enable evaluation of filteration & drainage
    function(Renal Dynamic Scintigraphy) namely 99mTc-
    DTPA,99mTc-MAG & 99mTc-LL-EC.

B) Radiopharmaceuticals that concentrate in the renal
    parenchyma for a sufficiently long time to enable detailed
    scintigraphic mapping of regional functioning renal
    parenchyma(Renal Cortical scintigraphy) namely 99mTc-
    DMSA.
                                                                 64
Cont…


C) Radiopharmaceuticals are either used exclusively for
  non-imaging clearance studies namely GFR (51Cr-
  EDTA) or ERPF(131I-OIH) measurements or used for
  both (99mTc-DTPA, 99mTc-MAG3 & 99mTc-LL-EC)




                                                          65
Cont…

                   Static Renal Scan
• The Radiopharmaceutical is 99mTc- DMSA.
• It is given intravenously. Image is obtained in 2 hours.
• It binds sufficiently to the renal tubules and lasts for several
  hours. This will permit good renal cortical imaging.
• The main clinical application
  of DMSA scan is in acute
   pyelonephritis in children.




                                                                     66
Cont…
• Acute Pyelonephritis in Children
  -The diagnosis of AP in children is difficult based on clinical
   and laboratory findings.
  -Intravenous urography and renal sonography have a low
   sensitivity and underestimate the degree of parenchymal
   involvement.
 -DMSA scan is highly sensitive for the diagnosis of acute
   pyelonephritis in children.
  -In acute stage of AP, segmental renal infection causes
   inflammatory process which results in edema. Edema causes
   focal vasculature pressure. This will result in ischemia.
 -This stage manifests on the scan as focal reduced uptake.
 -Later on, ischemia resolves completely in most cases or may
   progress and scar develops in few cases
                                                                    67
Cont…
• On DMSA scan, the scar manifests as focal cortical defect.
• The presence of renal scarring usually mandates prolonged
  prophylactic antibiotics to prevent further attacks of AP and
  further scarring.




                                                                  68
Cont…

           Renal Dynamic Imaging
• Renogram is graphical representation of the arrival, uptake
  & elimination of radiopharmaceutical by the kidneys.
• Usually a tracer is injected as a bolus & data collection
  starts immediately.
• The flow of activity through kidneys is recorded for 35-45
  mins. & computer reconstructs the renogram when user
  marks the region of interest over the kidneys.
• Renogram has a characteristic shape,& may be considered
  as having three distinct phases.
• Radiopharmaceuticals :Filtered agents (DTPA)
                            Tubular agents (MAG3)            69
Cont…




        70
Cont…
• Vascular Phase : The 1st phase consist of a rapid rise & sharp
  fall in count rates during the 1st passage of the bolus after i.v
  injection of 99mTc-DTPA.This is b’coz of low 1st pass extraction
  of tracer by the kidney.This phase normally lasts for 30 secs in
  99mTc-DTPA renogram.

  But this phase merges
  with subsequent phase
  in 99mTc-MAG3
  renogram b’coz of
  high extraction
  fraction.

                                                                  71
Perfusion/Vascular phase : 30-60 images are taken over 1
minute immediately post injection.This phase givens an idea
                 about renal vasculature




                                                              72
Cont…
• Cortical Transit Phase : This phase corresponds to the renal
   handling of the radionuclide as it is taken up by the kidneys &
   passes through the nephrons.In a well hydrated subject,the
   second phase,the time to reach the peak lasts approximately
   180-300 secs after the injection.The time to reach the peak
   may be delayed by a variety of conditions,such as :
a) An obstructive process preventing or delaying excretion of
    the tracer.
b) Renal artery stenosis causing a decrease in supply of tracer to
    the kidney,
c) Dehydrated states producing low urine flow rate, or
d) Renal parenchymal disease.


                                                                73
Uptake Phase : Image is taken every 15 seconds.
This phase represents radiopharmaceutical extraction from
                      blood stream.
   Peak uptake is expected in 4-6 minutes post injection




                                                            74
Cont…
• Excretory Phase : The period of declining amplitude after the
  peak is the 3rd phase of renogram.The beginning of this phase
  of the renogram corresponds to the time at which activity
  starts moving away from the region-of-interest & appears in
  the bladder.The 3rd phase of the renogram curve reflects
  predominantly the excretory function function of the kidney
  & measured in terms of its half time(t1/2), i.e the time taken
  for the counts to decline to one half of the maximum count
  rate.The excretory phase normally begins 5 mins after
  injection & usually approaches the baseline about 20 mins
  after the injection




                                                               75
Renal perfusion phase




                        76
Renal uptake phase




                     77
Excretory Phase




                  78
Cont…
• Intraventions During Renogram
-Diuretic Renogram :Frusemide is used to produce a rapid
   diuresis & helps to differentiate obstructive dilatation from
   nonobstructive dilatation of upper urinary tract. In the, latter
   there is prompt clearing of the radionuclide.
-Captopril Renogram : ACE I temporarily dilates the efferent
   arteries, which are normally vasoconstricted,& thus reduces
   net filtration pressure & GFR, which is reflected in the
   renogram.This is the basis of its use in patients with suspected
   renal artery stenosis.




                                                                 79
Cont…
• Clinical Applications of Dynamic Imaging Studies
  -Dilated collecting system (hydronephrosis)
  -Residual function in atrophic kidney

   -Dynamic renal scan is recommended as the initial screening
   study in patients found on IVU or US to have hydronephrosis
   without obvious cause ..
  -It is used to follow patients
   with managed (treated)
   obstructive hydronephrosis



                                                                 80
Cont…
             GLOMERULAR FILTERATION RATE
• The most useful measure of kidney function is the glomerular
  filtration rate(GFR).
• The total kidney GFR is equal to the sum of the filtration rates
  in each of the functioning nephrons
• GFR is measured indirectly through the concept of clearance.
                   Clearance = Ux X V
                                  Px
  Where Ux & Px are urine & plasma concenteration of the
  substance X & V is urine flow rate(ml/min).
• When a substance is freely filtered & not protein bound,& is
  not reabsorbed,secreated or metabolised by the kidney,then
  its clearance is similar to GFR.
                                                                 81
Cont…
• Renal Clearance of INULIN is the Gold Standard for
  determination of GFR.
• 51Cr-EDTA clearance closely resembles Inulin clearance & it is
  the radionuclide of choice for GFR estimation in Europe.
• However, 99m Tc-DPTA is often the preferred agent, because
  99m Tc-DPTA is inexpensive,easily available & renal imaging can

  be simultaneously performed.
• GFR can be estimated based upon either plasma clearance or
  upon the tracer uptake by the kidneys.
• The kidney of the newborn & young infant has several
  functional limitations including a relatively low GFR
• The increases from13-15ml/min/1.73m2 in the premature
  infant to 15-60ml/min/1.73m2 in the full term infant,to 63-
  80ml/min/1.73m2 at 8 wks of life.                              82
Cont…
• Along with increase in GFR, tubular function of the kidney
  gradually mature & reach adult level by 1-2 yrs of life.
• Renal uptake of dynamic tracers may be lower in newborns
  than older children & adults.
• A normal dynamic radionuclide study in newborns during the
  1st or 2nd week of life may demonstrate faint,delayed renal
  uptake of the tracer with or without appearance in the
  bladder at the expected time.




                                                                83
Cont…




        84

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Renal Function Tests by Dr.Ankur Puri

  • 1. 1
  • 2. Introduction • The kidneys are two bean shaped organs lying retroperitoneally on each side of the vertebral column slightly above the level of umblicus. • The range in length & weight, respectively, from approximately 6cm & 24gms in a full term infant to more than equal to 12cm & 150gms in an adult 2
  • 3. NEPHRON • Each kidney contains approx. 1 million nephrons. • In humans,formation of nephron is complete at 36-40 wks of gestation., but functional maturation with tubular growth & elongation continues during the 1st decade of life • B’coz new nephrons can’t be formed after birth,so any disease that results in progressive loss of nephrons can lead to renal insufficiency. 3
  • 4. Cont.. • A decreased number of nephrons secondary to LBW,prematurity &/or unknown genetic or environmental factor is hypothesised to be a risk factor for the development of primary HT & Progressive Renal Dysfunction in adulthood. 4
  • 5. Cont… • A Nephron consist :- • OUTER LAYER (the cortex) -glomeruli -PCT & DCT -CD • INNER LAYER (the medulla) -Straight portion of tubules -LOH -vasa recta -terminal CD 5
  • 6. JUXTAGLOMERULAR APPARATUS • The cells of the distal tubule in the part that comes in contact with the afferent arterioles of the glomerulus are more dense than the cells in the rest of tubule are called MACULA DENSA • The smooth muscle cells of afferent arterioles that approximate macula densa contain prominent secretory cytoplasmic granules which are the site of renin activity. 6
  • 7. Cont… • JGA is composed of the afferent & efferent arterioles,the macula densa & lacis cells located in the triangular space in between these structure. • It is involved in systemic blood pressure regulation,electrolyte hemeostasis & tubuloglomerular feedback mechanism. 7
  • 8. RENAL VASCULATURE • The renal artery arising from aorta divides into fine Segmental Arteries. • The latter divides into the Interlobar Arteries,which branch into Arcuate Arteries near the junction of the Cortex & medulla. • Interlobar arteries provide the afferent arterioles for the glomeruli. • The glomerular capillaries join to form the efferent arteries that leaves the glomerulus & form an extensive network of peritubular capillaries that surround the tubules,mostly in the cortex,forming Vasa Recta.The VR along with LOH are responsible for the urine concenteration 8
  • 10. DIAGNOSTIC EVALUATION • Urine Examination -routine & -microscopic • Evaluation of Renal Function • Renal Biopsy • Imaging 10
  • 11. URINE EXAMINATION • It is the most important step for the diagnosis of renal disease. • COLLECTION OF SAMPLE : -the 1st morning specimen is preferred -collected in a clean container -for culture, the specimen should be collected in a sterile container & sent to the lab. Immedietly, where it should be plated within 15minutes or stored in a refrigerator at 4 degree celsius.Bacteria multiply rapidly at room tempt., which may give false positive results. 11
  • 12. Method of urine collection • Midstream urine : a clean-catch midstream specimen is widely used. In older children who can cooperate, midstream specimen is obtained after proper local cleaning .The initial part of urine is discarded. • Bag collection : in neonates & infants, urine can be collected in sterile bags. Not used for microscopic exam. • Bladder catheterisation : a urine specimen can also be safely obtained, in infants, by strict bladder catheterisation but requires some skills & experience. • Suprapubic bladder aspiration : the only reliable way to obtain reliable urine specimen in neonates & young infants. In children <2 yrs of age it is most suitable method for a definitive diagnosis of UTI. 12
  • 13. URINE ROUTINE EXAMINATION • SPECIFIC GRAVITY : full term infants have a limited concentrating ability with a maximum sp.gravity of 1.021 – 1.025.It is measured with clinical Hydrometer. Increase in sp.gravity may be ass. with dehydration, diarrhea, emesis, excessive sweating etc. while decrease in sp.gravity may be ass. with renal failure, DI, ATN, interstitial nephritis & excessive fluid intake. • pH : tested with pH meter. Routine lab reports of pH are of no importnace.UTI with urea splitting organisms make urine highly Alkaline. Normal pH ranges from 4.6 -8.0. In fasting, the concentrated urine sample is highly Acidic . 13
  • 14. Cont… -A high urine may be due to RTA(type I),UTI,Vomitng & a low urinary pH may be due to DKA,diarrhea & starvation. • PROTEIN : Boiling test : satisfactory but cumbersome.10-15 ml of urine is taken in a test tube & upper portion is boiled. If turbidity appears 3 drops of concentrated acetic acid are added & specimen is boiled again. A zero to +4 grading is used. 14
  • 15. Cont… +1 Presence of slight 30-100mg of turbidity,through protein/dl which print can be read +2 Turbidity with slight 100-300mg of precipitates protein/dl +3 White cloudiness 300-1000mg with fine protein/dl precipitate,through which black lines are not visible +4 Large clumps of >1mg of protein/dl white precipitates 15
  • 16. Cont… Dipstick methods(e.g uristix) : widely used test for Proteinuria, more convenient & equally reliable. -Colour changes from yellow to green. -light chain proteins & LMW tubular proteins are not detected by this method. -Trace react.  5 to 20 mg/dl urinary prtn +1  30 mg/dl +2  100 mg/dl +3  300 mg/dl +4  > 1000 mg/dl 16
  • 17. Cont… • Proteinuria in patients with Nephrotic Syndrome is massive (+3 or +4 by dipstick) & selective,constituted predominantly of Albumin,without loss of proteins of higher molecular wt. • In the presence of tubular damage or physical injury to the glomerular barrier, the proteinuria is non selective. • In renal parenchymal diseases,proteinuria is often quantified to assess degree of glomerular injury. • Selective Proteinuria : intermediate sized(<1000kDa) proteins(albumin,transferrin) leaks through glomerulus. • Nonselective proteinuria : range of different sized proteins leak through,including larger proteins(immunoglobulin) 17
  • 18. Cont… • Quantitative Measurement of Urine Protein -Accurate collection of urine over 24hr period is required to quantitate protein excretion. -A value of >4mg/m2/hr is considered abnormal, & >40/m2/hr indicates heavy proteinuria. -The range proteinuria in nephrotic so is massive proteinuria(>3.5gm/24hrs) while the range in nephritic s o is mild to moderate proteinuria(<3gm/24hrs) 18
  • 19. Cont… • Urine Protein/Creatinine Ratio : an approx. estimate of the severity of proteinuria also can be made by measurement of urine protein & urine creatinine on random urine sample. -Values >2 indicate Heavy Proteinuria <0.2 are insignificant. -Such measurements are of use in following response to therapy in various disorders, but seldom necessary in children with nephrotic syndrome. 19
  • 20. Cont… • GLUCOSE :the older methods(e.g benedict test) that detected reducing substance have mostly been replaced by Dipstick test,which is based on Glucose Oxidase Peroxidase linked reaction. • BLOOD :detection of Hb by dipstick is based on an reaction, with a spotted +ve reaction indicating intact red blood cells & uniform +vity suggesting presence of free Hb.However the use of dipstick to detect hematuria is discouraged,b’coz reactions may often be false +ve(e.g myoglobinuria,oxidising substances,bacterial colonisation) or false –ve (e.g ascorbic acid,other reducing substances) 20
  • 21. MICROSCOPIC EXAMINATION • A fresh,well mixed specimen should be examined. • Presence of cellular elements & casts should be noted. • Red cell casts : indicate glomerular inflammation. Red cell casts & red cells in a pateint with glomerulonephritis 21
  • 22. Cont… White cell casts :clumping of neutrophils suggests acute pyelonephritis Epithelial cell cast :are noted in patients recovering from Acute tubular necrosis 22
  • 23. Cont… Hyaline or Fatty casts : may be +nt in proteinuric states or in normal in normal individuals with concenterated urine. • Red blood cells & leukocytes can be counted under the high power field & more accurately in a counting chamber. • >5 leukocytes/HPF along with bacteruria suggests urinary tract infection. • Neutrophils may also be detected in proliferative glomerulonephritis & interstitial nephritis,while the presence of Eosinophils in urine is specific of acute interstitial nephritis23
  • 24. Cont… • Hematuria is defined as presence of >5RBS/HPF in a centrifuged specimen. • RBC morphology is useful in distinguishing bet. Glomerular & non glomerular causes of hematuria. • The site of injury is likely to be the lower urinary tract if <25% urine correlates well with a colony count of over 105 organisms/ml indicating significant bacteriuria. 24
  • 25. URINE CULTURE • Definitions of +ve or –ve urine culture are dependent on the method of collection & the patients clinical status. Diagnosis of Urinary Tract Infection Method of collection Colony count(per ml) Probability of infectn Suprapubic Aspiration Any number 99% Urethral catheterisatn >105 95% 104 to 10 5 Very likely 103 To 104 Suspicious:repeat <103 unlikely Midstream void Boys >104 Very likely Girls >105 90-95% 104 to 105 Suspicious:repeat <104 unlikely 25
  • 26. EVAULUATION OF RENAL FUNCTION • Various aspects of renal function are -GFR(Glomerular Filtration Rate) -RPF(Renal Plasma Flow) -Reabsorption & Excretion of various substances like Na+, K+, Ca+2, inorganic phosphate, glucose, urea, a.a, H2O & osmoles. • In clinical practice -determination of Creatinine Clearance is a measure of GFR -water deprivation & vasopressin administration tests to determine urinary concentrating ability, & -bicarbonate & ammonium chloride loading test to examine urinary acidification are usually sufficient for diagnostic evaluation & measurement of kidney function. 26
  • 27. Cont… • The results of these tests are important in assessing the excretory function of the kidneys. For example, grading of chronic renal insufficiency and dosage of drugs that are excreted primarily via urine are based on GFR (or creatinine clearance). 27
  • 28. GLOMERULAR FUNCTION TEST • The concept of clearance is based upon the fact that the rate of removal of a substance from the plasma must equal its simultaneous rate of excretion in urine. • Thus if the urinary excretion rate & plasma concentration of a substance are known, we can calculate the volume of plasma from which that substance would have been completely removed. INULIN has been taken as a reference substance. • The standard formula for clearance is : C = U x V P C = clearence/min(ml/min) U = urinary concenteration(mg/dl) P = plasma concenteration(mg/dl) V = urine volume/min(ml/min) 28
  • 29. Cont… • If a given substance is freely filtered & neither reabsorbed nor excreted, its clearance rate would accurately reflect GFR. • The GFR can be estimated by measuring s.creatinine level & height.The formula proposed by SCHWARTZ is useful for children : • GFR(ml/min/1.73m2) = K x Height(cm) S.Creatinine(mg/dl) K = 0.34 (in preterm infant) = 0.45 (in term infants) = 0.55 (in children & adoloscent girls) & = 0.7 (in adoloscent males) 29
  • 30. Cont… • Serum Creatinine & Creatinine Clearance : • Creatinine is derived from the metabolism of creatine & phosphocreatine,the bulk of which is in muscle. • Since creatinine is chiefly excreted by glomerular filteration,S.creatinine levels reflects changes in GFR. • S.creatinine values are low when the muscle mass is decreased, as in malnutrition. • Bilirubin interferes with creatinine measurements. 30
  • 31. Cont… • The normal values of S.creatinine are : AGE RANGE(mg/dl) Cord 0.6-1.2 Newborn 0.3-1.0 <3 years 0.17-0.35 3-5 years 0.26-0.42 5-7 years 0.29-0.48 7-9 years 0.34-0.55 9-11 years 0.35-0.64 11-13 years 0.42-0.71 13-15 years 0.46-0.81 Adult Male 0.7-1.3 Adult Female 0.6-1.1 31
  • 32. Cont… • CYSTATIN C : It is a LMW nonglycosylated protein produced at a constant rate by all nucleated cells in the body, freely filtered by the glomeruli, not secreted, but totally reabsorbed by the renal tubules. • Little or no cystatin is excreted in urine. • Normal adults have circulating level of approx. 1mg/l. • This is better indicator of renal function as compared to creatinine in early stages of GFR impairment as it is independent of age,gender,body composition & muscle mass. • Cystatin C can be estimated in blood by enzyme immunoassays or immunoturbidometry.Both techniques are currently kit based & expensive. 32
  • 33. Cont… • SINGLE INJECTION TECHNIQUE : in clinical practice, radionuclides are often used to estimate total GFR or to measure difference in clearance bet. one kidney compared to other in the same patient. • The technique is based on use of a single injection, plasma disappearance curves to estimate the true GFR. • Briefly, the radionuclide dye is injected & the signal from radiolabelled form is used to obtain measurment. • The most commonly used Radionuclides for GFR are -DTPA (Diethyl triamine Penta-acetic acid) -EDTA (ethylene diamine tetra acetic acid) & -Iothalamate • Iohexol,a non ionic non radioactive LMW radiocontrast agent,as an alternative to inulin,measured easily by HPLC(high performance liquid chromatography) 33
  • 34. Cont… • BLOOD UREA : A normal level of blood urea is often mistakenly regarded to indicate normal kidney function. • In a steady state the blood urea may not rise beyond the upper range of normal(40mg/dl) even when 75% of the renal function is lost. • On the other hand, prerenal factors that decreases renal perfusion & GFR,such as dehydration,causes an increase in blood urea levels. • There may be transient rise in blood urea level due to : -high protein intake & excessive protein catabolism( e.g with severe infections,tissue break down,trauma,use of large doses of corticosteroids or tetracyclines) -gastrointestinal bleeding & inhibition of anabolism. 34
  • 35. RENAL BLOOD FLOW • Renal blood flow measurements are performed using the clearance of PAH(para aminohippurate) • >90% PAH is extracted from the plasma during the 1st pass through the kidneys.Therefore, renal clearance of PAH is commonly used as an estimate of renal plasma flow(RPF). • Plasma clearance following single injection of 131I-hippuran or 99mTc-mercaptoacetyltriglycine(MAG-3)is an alternative method. • Renal Blood Flow is calculated by dividing RPF by [1- hematocrit]. • Normal value ranges from 500 to 600 ml/min(abt. 1200ml/min/1.73m2). • Other methods-Color Doppler US,Contrast Enhanced US & MRI. 35
  • 36. URINARY CONCENTERATION • Osmolality dependes upon the number of particles in a solution & not on their size or density. • The maximal urinary concentration capacity varies with age - in neonates its abt. 700 mOsm/kg - in older children & adults it an rise up to 1200mosm/kg. • Hyposthenuria(inability to increase urine osmolality > than that of plasma) is characteristic of Diabetes Insipidus as well as Diseases of Renal Medulla such as obstructive uropathy. • Polyuria & polydipsia are stricking features. • In chronic Renal Failure urine osmolality does not rise much above 400mOsm/kg & polyuria & polydipsia are not prominent. • Osmolality = 2[Na+] + [Glucose]/18 + [ BUN ]/2.8 36
  • 37. Cont… • URINARY CONCENTERATION TEST : Urinary concentrating ability needs to be tested in a setting of polyuria.If the 1st morning void after 12hrs of overnight fasting has osmolality exceeding 700 mOsm/kg,no further testing is required.In others, Water Deprivation Testing is done. • Response to Vasopressin : subsequently,to confirm the lack of renal concentrating ability & distinguish Nephrogenic Diabetes Insipidus(NDI) from Central Diabetes Insipidus(CDI),a vasopressin test is performed. -Desamino-8-D-arginine Vasopressin(dDAVP,desmopressin) is administered nassly(5-10 ug in neonates & infants,20 ug in children) or by an I.M injection(0.4-1.0 ug in infants & young children,2 ug in older children). • The changes in urine osmolality seen are : 37
  • 38. Cont… CONDITION URINE OSMOLALITY ON CHANGES IN WATER OSMOLALITY WITH DEPRIVATION(mOsm/kg dDAVP(mOsm/kg) NORMAL >800-900 MINIMAL OR NO INCREASE COMPLETE CENTRAL DI <300 SUBSTANTIAL INCREASE PARTIAL CENTRAL DI 300-800 INCREASE OF >10% NEPHROGENIC DI <200-300 MINIMAL OR NO INCREASE PRIMARY POLYDIPSIA >500 MINIMAL OR NO INCREASE 38
  • 39. Tests Of Urinary Acidification • Renal acidification mechanism are usually examined in children with suspected renal tubular acidosis. • Urine pH : The pH of a fresh specimen of urine is tested with pH meter. A concentrated, fasting, morning sample of urine is acidic.A pH of <5.5 virtually excludes distal renal tubular acidosis. • Urine Anion Gap : Urine anion gap is the difference between concentration of principal urinary cations(Na + k) & anion(cl)This difference is expected to estimate the unmeasured anions & cation,which normally include ammonium & bicarbonate.Since the latter is mostly reabsorbed ,urine anion gap is chiefly measure of ammonium excretion. 39
  • 40. Cont… • In presence of systemic metabolic acidosis,ammonium excretion is expected to be stimulated while the bicarbonate excretion is minimal,hence,the urine anion gap should be –ve due to obligatory chloride excretion with ammonium. • In patients with renal tubular acidosis the gap remains +ve due to impaired ammonium production. • Sodium Bicarbonate Loading Test : The Bicarbonate threshold is the plasma bicarbonate level at which bicarbonate appears in urine. -The bicarbonate threshold is determined by infusion of bicarbonate & increasing the plasma bicarbonate in a stepwise manner to elevate he serum bicarbonate level to 23- 26mEq/l. 40
  • 41. Cont… -3-5ml/kg sodium bicarbonate is administered orally or Intravenously,which increase the urine pH to more than 7.4. -Levels of bicarbonate & creatinine are measured in blood & random urine specimens. -Normally there is no bicaorbonaturia unless the plasma bicarbonate level exceeds 23-24mEq/l. -the urinary bicarbonate threshold is reduced is proximal renal tubular acidosis.The Fractional Excretion of bicarbonate (FEHCO3) is calculated by the formula : FEHCO3 = urine HCO3 X plasma creatinine X 100 plasma HCO3 X urine creatinine -The normal level of FEHCO3 are <5%.In proximal RTA,the FEHCO3 usually exceed 15%. 41
  • 42. Cont… • Other tests for urine acidification are -Urine PCO2 -Ammonium Chloride Loading test 42
  • 43. Cont… OTHER INVESTIGATIONS • S.proteins : S.albumin level • S.cholesterol: in Nephrotic So—hypercholesterolemia. • Anti Streptococcal Antibody Titer : antibody titer against hemolytic streptococcs is important for the diagnosis of Poststreptococcal GN(PSGN).A titer of >200 IU/ml is +ve. • S.complement : measurement of C3 & C4 levels in bld. is important for diagnosis of Postinfectious GN, Membranoproliferative GN & Lupus Nephritis, where decrease in C3 levels are +nt. The levels of C3 are increased in active Rheumatoid arthritis. The normal range of S.C3 is 70 to 120 mg/dl & C4 20-50 mg/dl. • S.immunoglobulins : S.IgA levels are increased in abt 30- 40%patients with IgA nephropathy & HSP. 43
  • 44. Cont… • Antineutrophil cystoplasmic antibodies : are typically detected in Wegner’s granulomatosis & In Pauci-Immune Cresentric GN. 44
  • 45. RENAL BIOPSY • Expert evaluation of renal histology is important in the diagnosis of various renal parenchymal disease involving glomeruli, tubulo-interstitium & small blood vessels. • The procedure has become has become much simpler with the use of automatic (biopsy gun,tru cut) devices & ultrasono -graphic visualization of kidney. • INDICATIONS : Renal biopsy has a limited role in children. Significant Value -Streoid resistant nephrotic So -Acute Renal Failure of Unknow Cause -Rapidly Progressive Renal Failure 45
  • 46. Cont… -Systemic disease(Henoch-schonlein Purpura,Lupus Hemolytic Uremic So ,IgA nephropathy) -Inherited Nephropathies e.g Alport So -Renal allograft dysfunction -Detection Of Calcineurin toxicity Less Value -Chronic renal Failure to ascertain etiology -Non Nephrotic Range Proteinuria -Microscopic Hematuria -Steroid Sensitive Nephrotic So A Renal Biopsy Is not required in uncomplicated cases of Postinfectious GN & corticosteroid responsive nephrotic So 46
  • 47. Cont… • BIOPSY PROCEDURE -A renal biopsy is usually made percutaneously -A history of bleeding & clotting disorders should be obtained. -PT, BT, Coagulation time & Platelet count is measured. -BP should be in normal range -In Patients with acute renal failure,dialysis should be done to reduce azotemia & correct biochemical abnormalities before the biopsy. -Renal size & location are confirmed with an US before biopsy. -The Patient should be kept fasting for abt 3-4 hrs. -Local anaesthesia can be used 47
  • 48. Cont… -The child lies in prone position with a folded towel or bed sheet placed under his lower ribs & epigastrium to push the kidneys posteriorly & stabilize their position. -The entry of biopsy needle into the kidney,when it pierces the renal capsule,is indicated by slight resistancce & once in kidney it moves wit respiratory excrusions -2 core of tissue(abt. 8-10 mm long) are needed for adequate histological examination. 48
  • 49. Cont… -One core is fixed in buffered formaline & other in saline(for immunofluorescencs study) Interpretation of Renal Biopsy • The histology should be examined by light microscopy using Hematoxylin & eosin(H & E),Periodic Schiff (PAS) & Silver Methanamine staining In all cases, & special stains as necessary. • Electron microscopy is very useful in several disorders e.g Alport So, Membranoproliferative GN & thin Basement Membrane Disease. 49
  • 50. IMAGING • DIAGNOSTIC PROCEDURES • RADIONUCLIDE STUDIES 50
  • 51. DIAGNOSTIC PROCEDURES • Plain X-Ray Film Of The Abdomen : The utility of a plain X-ray film of abdomen has decreased with the introduction of US & later CT scanning.Most UT disorders can be imaged using these methods,which gives more information than the Plain X-ray.The later still has a role in detecting small renal calculi,ureteric calculi with minimal or no proximal dilatation, spinal evaluation in neurogenic states, evaluation of metastatic bone disease from a neuroblastoma & screneing for renal osteodystrophy. 51
  • 52. Cont… • Excretory Urography : Newer techniques especially US in combination with radionuclide studies have largely replaced excretory urography & IVP(Intravenous Pyelography). -After careful preparatn on the previous evening (a liquid diet,laxative) 2.5 -3 ml/kg of a nonionic contrast agent is administered intravenously. -Intial film is taken at 5 mins. After contrast agent followed by another at 10-15 mins. & a late pelvic film to visualize the UB. -Excretory urography should be avoided in neonates b’coz of their poor ability to concneterate contrast medium. 52
  • 53. Cont… • Ultrasonography : it provides an excellent information about the anatomy of the urinary tract. -High resolution images in multiple planes may be obtained. -The procedure is ideally suited for children since,it is painless & requires no sedation or administration of any contrast reagent,& be carried out even bedside. -US guidance can be used in invasive procedures e.g. fine needle aspiration & biopsy. - 53
  • 54. Cont… • Quantitative measurements of renal growth is possible on 2D US Doppler technique when used in conjunction with 2D imaging is particularly informative. • The major drawback of US is that it is operator dependent. 54
  • 55. Cont… • Antenatal Ultrasonography : US during pregnancy can detect fetal anomalies.Presence of dilation of urinary system,echotexture of renal parenchyma,appearance of urinary bladder & the amniotic fluid are carefully examined. • Vesicoureteric reflux is the commonest cause of dilated urinary tract & pelviureteric junction obstruction that is isolated hydronephrosis. • Oligohydramnios on US indicates poor renal function. 55
  • 56. Cont… • Computed Tomography (CT SCAN) : CT,besides providing anatomical information,also gives functional status of the kidneys if an IV contrast agent is used. • The main role of CT urinary tract imaging is for examining mass lesions of the kidney,bladder or retroperitoneum that secondarily affect the urinary system. • These masses may be congenital (teratoma), inflammatory(abscess), traumatic(hematoma) or neoplastic(wilm’s tumor). WILMS TUMOR 56
  • 57. Cont… • CT scan can detect a non functioning or a poorly functioning kidney. • With the advent of Multidetector Row CT (MDCT),it is possible to acquire high resolution images with faster speed & hence,less motion blur in small children. • With MDCT it has become possible to get high resolution reformatted images in coronal & sagittal planes; which is crucial for extent assessment of renal or retroperitoneal masses (e.g. extent of IVC thrombus in wilms tumor) 57
  • 58. Cont… • Magnetic Resonance Imaging(MRI) :Though there are several advantages of this imaging modality like nonionizing nature,multiplaner imaging capability & superior soft tissue contrast resolution, its use is limited in pediatric practice b’coz of motion related problem & requirement of sedation & general anaesthesia. 58
  • 59. Cont… • Important uses of MRI in pediatric renal pathologies include MR Urography in cases of hydronephrosis, duplex moeity, ectopic ureter : MR angiography in cases of suspected renal artery stenosis. The added advantage of MRI in evaluation of renal masses is that IVC thrombus can be detected without any contrast. 59
  • 60. Cont… • Micturating Cystourethrogram : MCU is an important procedure necessary for the diagnosis & evaluation of severity of Vesicoureteric reflux, & detection of the abnormalities of bladder & urethra. • The contrast agent is introduced into the bladder through a catheter. • Films are taken while child is voiding. • The catheter should be introduced with strict aseptic precautions. 60
  • 61. Cont… • Patients at high-risk of systemic sepsis(infants,children with dilated urinary tract,congenital heart disease0 should receive prophylactic treatment with oral amoxicillin or parentral gentamycin 30-60 mins. prior to procedure. 61
  • 62. Cont… • Special Imaging Procedures : -Several other imaging procedures are employed to visualize the urinary system. -these include nephrostogram, ureterostogram, retrograde pyelogram & angiography. CHOICE OF IMAGING PROCEDURES • US evaluation is usually the 1st procedure in patient with suspected urinary tract disease. • It is often diagnostic ( e.g. hydronephrosis,cystic disease of kidney ) or provides enough information to suggest the next appropriate investigation. 62
  • 63. RADIONUCLIDE STUDIES • Radionuclide studies are complementary to structural imaging methods of the pediatric urinary tract. • Nuclear medicine procedures are relatively noninvasive, requring only an i.v injection. • They require neither fasting nor bowel preparation. • They can be performed on an outpatient basis without the need for anaesthesia. • They have neither systemic toxic effects(e.g. osmotic effect,hemodynamic overload) nor allergic reactions,with minimal absorbed radiation dose. • Radionuclide studies & US evaluation of genitourinary morphology have significantly reduced the need for i.v urography. 63
  • 64. Cont… • Radiopharmaceuticals : radiopharmaceuticals used for evaluation of the kidneys may be classified into three principle groups. A) Radiopharmaceuticals that are rapidly eliminated by the kidneys & thus enable evaluation of filteration & drainage function(Renal Dynamic Scintigraphy) namely 99mTc- DTPA,99mTc-MAG & 99mTc-LL-EC. B) Radiopharmaceuticals that concentrate in the renal parenchyma for a sufficiently long time to enable detailed scintigraphic mapping of regional functioning renal parenchyma(Renal Cortical scintigraphy) namely 99mTc- DMSA. 64
  • 65. Cont… C) Radiopharmaceuticals are either used exclusively for non-imaging clearance studies namely GFR (51Cr- EDTA) or ERPF(131I-OIH) measurements or used for both (99mTc-DTPA, 99mTc-MAG3 & 99mTc-LL-EC) 65
  • 66. Cont… Static Renal Scan • The Radiopharmaceutical is 99mTc- DMSA. • It is given intravenously. Image is obtained in 2 hours. • It binds sufficiently to the renal tubules and lasts for several hours. This will permit good renal cortical imaging. • The main clinical application of DMSA scan is in acute pyelonephritis in children. 66
  • 67. Cont… • Acute Pyelonephritis in Children -The diagnosis of AP in children is difficult based on clinical and laboratory findings. -Intravenous urography and renal sonography have a low sensitivity and underestimate the degree of parenchymal involvement. -DMSA scan is highly sensitive for the diagnosis of acute pyelonephritis in children. -In acute stage of AP, segmental renal infection causes inflammatory process which results in edema. Edema causes focal vasculature pressure. This will result in ischemia. -This stage manifests on the scan as focal reduced uptake. -Later on, ischemia resolves completely in most cases or may progress and scar develops in few cases 67
  • 68. Cont… • On DMSA scan, the scar manifests as focal cortical defect. • The presence of renal scarring usually mandates prolonged prophylactic antibiotics to prevent further attacks of AP and further scarring. 68
  • 69. Cont… Renal Dynamic Imaging • Renogram is graphical representation of the arrival, uptake & elimination of radiopharmaceutical by the kidneys. • Usually a tracer is injected as a bolus & data collection starts immediately. • The flow of activity through kidneys is recorded for 35-45 mins. & computer reconstructs the renogram when user marks the region of interest over the kidneys. • Renogram has a characteristic shape,& may be considered as having three distinct phases. • Radiopharmaceuticals :Filtered agents (DTPA) Tubular agents (MAG3) 69
  • 70. Cont… 70
  • 71. Cont… • Vascular Phase : The 1st phase consist of a rapid rise & sharp fall in count rates during the 1st passage of the bolus after i.v injection of 99mTc-DTPA.This is b’coz of low 1st pass extraction of tracer by the kidney.This phase normally lasts for 30 secs in 99mTc-DTPA renogram. But this phase merges with subsequent phase in 99mTc-MAG3 renogram b’coz of high extraction fraction. 71
  • 72. Perfusion/Vascular phase : 30-60 images are taken over 1 minute immediately post injection.This phase givens an idea about renal vasculature 72
  • 73. Cont… • Cortical Transit Phase : This phase corresponds to the renal handling of the radionuclide as it is taken up by the kidneys & passes through the nephrons.In a well hydrated subject,the second phase,the time to reach the peak lasts approximately 180-300 secs after the injection.The time to reach the peak may be delayed by a variety of conditions,such as : a) An obstructive process preventing or delaying excretion of the tracer. b) Renal artery stenosis causing a decrease in supply of tracer to the kidney, c) Dehydrated states producing low urine flow rate, or d) Renal parenchymal disease. 73
  • 74. Uptake Phase : Image is taken every 15 seconds. This phase represents radiopharmaceutical extraction from blood stream. Peak uptake is expected in 4-6 minutes post injection 74
  • 75. Cont… • Excretory Phase : The period of declining amplitude after the peak is the 3rd phase of renogram.The beginning of this phase of the renogram corresponds to the time at which activity starts moving away from the region-of-interest & appears in the bladder.The 3rd phase of the renogram curve reflects predominantly the excretory function function of the kidney & measured in terms of its half time(t1/2), i.e the time taken for the counts to decline to one half of the maximum count rate.The excretory phase normally begins 5 mins after injection & usually approaches the baseline about 20 mins after the injection 75
  • 79. Cont… • Intraventions During Renogram -Diuretic Renogram :Frusemide is used to produce a rapid diuresis & helps to differentiate obstructive dilatation from nonobstructive dilatation of upper urinary tract. In the, latter there is prompt clearing of the radionuclide. -Captopril Renogram : ACE I temporarily dilates the efferent arteries, which are normally vasoconstricted,& thus reduces net filtration pressure & GFR, which is reflected in the renogram.This is the basis of its use in patients with suspected renal artery stenosis. 79
  • 80. Cont… • Clinical Applications of Dynamic Imaging Studies -Dilated collecting system (hydronephrosis) -Residual function in atrophic kidney -Dynamic renal scan is recommended as the initial screening study in patients found on IVU or US to have hydronephrosis without obvious cause .. -It is used to follow patients with managed (treated) obstructive hydronephrosis 80
  • 81. Cont… GLOMERULAR FILTERATION RATE • The most useful measure of kidney function is the glomerular filtration rate(GFR). • The total kidney GFR is equal to the sum of the filtration rates in each of the functioning nephrons • GFR is measured indirectly through the concept of clearance. Clearance = Ux X V Px Where Ux & Px are urine & plasma concenteration of the substance X & V is urine flow rate(ml/min). • When a substance is freely filtered & not protein bound,& is not reabsorbed,secreated or metabolised by the kidney,then its clearance is similar to GFR. 81
  • 82. Cont… • Renal Clearance of INULIN is the Gold Standard for determination of GFR. • 51Cr-EDTA clearance closely resembles Inulin clearance & it is the radionuclide of choice for GFR estimation in Europe. • However, 99m Tc-DPTA is often the preferred agent, because 99m Tc-DPTA is inexpensive,easily available & renal imaging can be simultaneously performed. • GFR can be estimated based upon either plasma clearance or upon the tracer uptake by the kidneys. • The kidney of the newborn & young infant has several functional limitations including a relatively low GFR • The increases from13-15ml/min/1.73m2 in the premature infant to 15-60ml/min/1.73m2 in the full term infant,to 63- 80ml/min/1.73m2 at 8 wks of life. 82
  • 83. Cont… • Along with increase in GFR, tubular function of the kidney gradually mature & reach adult level by 1-2 yrs of life. • Renal uptake of dynamic tracers may be lower in newborns than older children & adults. • A normal dynamic radionuclide study in newborns during the 1st or 2nd week of life may demonstrate faint,delayed renal uptake of the tracer with or without appearance in the bladder at the expected time. 83
  • 84. Cont… 84