1. Scope and limitations of
renal function assessment

2. • The function of kidney is maintains the normal volume and composition of body fluids.
• Regulate homeostasis of water and acid – base in the body as well as to excrete the
metabolic waste products such as urea and creatinine.
• Other than this kidney also perform some endocrine function such as secretion of renin and
erythropoietin. Conversion of 1, 25 dihydroxy- cholecalceferol is also done by kidney.
• Many primary processes like 1) Glomerular filtration
2) Tubular secretion
3) Tubular re absorption that perform the renal funcation.

3. • Primitive nephrons begin to excrete urine at around the 9th week of gestation.
• At the 3rd trimester the hourly fetal urine production is as high as 30 to 40 ml/h and it
constitutes around 90% of amniotic fluid.
• At 36 weeks of gestation fetal GFR only 5% of surface corrected adult value.
• But at the time of delivery, renal physiology rapidly switches to a fluid restrictive mode
because increase level of aldosterone, vasopressin, catecholamines and parenchymal
perfusion and GFR increase dramatically in response to fall in PVR, but not adaptive change
it only 30ml/1.73m2 and is not until 2 years of age that GFR reach normal adult like
125ml/1.73m2.

5. Renal Function Tests-
The tests aim at
1)Monitor function by:- - Glomerular Filtration Rate
- Biochemistry (Non Protein Nitrogens ,Plasma renin etc.)
- Urinalysis
- Combined biochemical analyses
- Nuclear Scans
2)Detect renal damage:- -Renal Cortical Scan
3)Help determine etiology :- -Renal Dynamic Scan
- Renal Cortical Scan

6. Renal Function Evaluation
The evaluation of renal function begin with,
1) Patient`s history
2) Physical examination of urine
3) Laboratory studies
4) Nuclear scan
5) Antenatal assessment of renal function

7. 1) Patient`s history:
-Persistent low urine output(oliguria) or significant impairment in renal
concentration capacity(polyuria) should be evident from the history
2) Physical examination of urine:
-examination of the urinary sediment may provide evidence of renal
disease if proteinuria and /or cellular elements and cast are present.

8. 3)Laboratory studies
A. GLOMERULAR FILTRATION RATE-
Glomerular filtration rate (GFR) is the most commonly used measure of kidney function.
GFR can be quantified by measuring the clearance rate of a substance from the plasma.
The substance often referred to as the marker, can be
endogenous :1) creatinine
2) cystatin C
exogenous :1) Inulin
2) Iohexol
Nuclear GFR

9. It must have a stable plasma concentration and should be filtered, not
reabsorbed, secreted, synthesized, or metabolized, by the kidney so that the
filtered only.
The renal clearance of the substance x (Cx) can be obtained by multiplying
the urinary concentration of substance x (Ux) times the urinary flow rate in
ml/min (V) divided by the plasma concentration of substance x (Px)
Cx=(Ux X V)/Px

11. Inulin
• Urinary inulin clearance is considered the gold standard for measuring GFR
because inulin has all the properties of an ideal marker. It is freely filtered by
the glomerulus, is not secreted or reabsorbed in the tubules, and is not
synthesized or metabolized by the kidney
• Plasma Inulin Clearance:
• Continuous Infusion Method- more accurate,
• Single Bolus Injection Method – easy to perform
• The single bolus injection method tends to overestimate GFR. Measurement of
inulin clearance remains the gold standard for assessing GFR; however, most
laboratories cannot routinely measure inulin, which makes this test
impractical because more time consuming and high cost.

12. Creatinine Clearance
• Creatinine clearance (Ccr) measurement has been widely used and
correlates well with inulin clearance within the normal range of GFR.
• Creatinine is an amino acid derivative produced in muscle cells.
• It is freely filtered, and about 10% of the creatinine found in urine is
secreted by the proximal tubules.
• Tubular secretion varies among and within individuals.
• As GFR declines, the percentage of secreted creatinine increases;
therefore Ccr at low GFR significantly overestimates true GFR.

13. Iohexol
• Iohexol is a safe, nonionic, low osmolar contrast agent (MW 821 Da). It is
eliminated exclusively by the kidneys, where it is filtered but not secreted,
metabolized, or reabsorbed.
• It has less than 2% binding to protein. Therefore it makes an ideal marker
of GFR and a good alternative to radiotracers clearance of Iohexol correlates
well with measured inulin clearance. But it is high cost nd exogenous.

14. Cystatin C
• Cystatin C is a low molecular weight protein (13.36 KD) member of the cystatin
super family. It is produced by all nucleated cells and exhibits a stable production
rate. Cystatin C is freely filtered by the glomerulus and metabolized after tubular re-
absorption.
• Cystatin C is influenced less by age, gender, and muscle mass than creatinine.
Levels decline from birth to age 1, and then remain stable until about 50 years of
age.
• However it has been found by some to be influenced by cigarette smoking, high
C reactive protein, steroid use and thyroid disorders.

15. Nuclear GFR
Serum Cr and BUN determination are not so accurate in acute change of renal
function ,in different metabolic states , when there are differences in muscle mass
and some medication.
Evaluation of GFR with the nuclear medicine method is accurate and precise.
GFR can be accurately measured using a radioactive tracer such as 125I-
iothalamate, 51Cr EDTA or technetium 99m (99mTc) DTPA. The most accurate
method is based on the plasma disappearance curve after a single bolus injection.
The clearance of the radiotracer is given by the injected dose divided by the area
under the curve.

16. There are numerous methods for evaluation of GFR after injection Tc-DTPA which
are usually categorized into:
1)Camera based methods: in this no need to do blood sampling and the time of
study is shorter , but not accurate.
The test requires serial blood sampling to obtain an accurate plasma disappearance
curve. In general, the more blood samples acquired over time, the more accurate
the calculated GFR value will be. However, to avoid obtaining too many blood
samplings, two simplified methods have been proposed for routine clinical use in
children.

17. A. The Slope Intercept Method-
• The slope intercept method requires two blood samples acquired 2 and 4 hours post
injection
B. The Distribution Volume Method-
• The distribution volume method requires only one blood sample at 2 hours post-injection. It
appears to be valid for children of any age except those with very poor renal function (GFR 30
ml/min/1.73 m2).
A major limitation of these methods is the presence of significant edema. In this situation, the
disappearance of the tracer will be influenced by its diffusion into an expanded extra cellular
volume and erroneously elevating the calculated GFR. Infiltration of the radiotracer at the injection
site can also cause erroneous elevation of GFR.

18. B. BIOCHEMISTRY-
NPN (Non - Protein Nitrogen)
NPN (Non - Protein Nitrogen) is a term that can be used for a bunch of different substances that have
the element nitrogen in them, but are not proteins. There are many different (more than 15) unrelated
NPNs, but we will discuss only 2 of them:
1. Blood Urea Nitrogen (BUN),
2. Creatinine
In general, plasma NPNs are increased in renal failure and are commonly ordered as blood tests to
check renal function
BUN (Blood Urea Nitrogen)
BUN is an old term, but still in common use
To convert BUN to Urea : BUN x 2.14 = Urea (mg / dl)

19. Urea is a product of protein catabolism which produces ammonia. Ammonia is
very toxic – converted to urea by the liver, liver convert’s ammonia and CO2 into
urea which ultimately is filtered by the glomerulus but also reabsorbed by renal
tubules ( 40 % ) Some of this is lost through the skin and the GI tract ( < 10 % )
• Plasma BUN is affected by
• 1. Renal function
• 2. Dietary proteins
• 3. Protein catabolism

20. Plasma Creatinine-
• Plasma creatinine is often used to assess the level of renal function. During
the early neonatal period, plasma creatinine reflects the maternal creatinine.
• It then decreases to 0.4 mg/dl (35 mol/L) by the middle of the second
postnatal week in full-term infants.
• After this initial decline, plasma creatinine remains relatively stable for the
first 2 years, reflecting proportional increases in GFR and muscle mass.
• Plasma creatinine then increases progressively to attain levels of about 0.9 ±
0.2 mg/dl in males and 0.7 ± 0.2 mg/dl in females.

21. • Creatinine is formed at a constant rate by the muscles as a function of muscle
mass it is removed from the plasma by glomerular filtration and is not absorbed
by the renal tubules and is also minimally secreted. The secretion is saturable.
• Therefore: Plasma creatinine is a function of glomerular filtration practically
Unaffected by other factors. It’s a very good test to evaluate renal function.
• Increased plasma creatinine is associated with decreased glomerular filtration
(renal function). Glomerular filtration may be 50 % of normal before plasma
creatinine is elevated. Its concentrations are very stable from day to day - If there
is a delta check, it’s very suspicious and must be investigated.

23. Predicting GFR from creatinine levels-
• In the classical clearance formula, the numerator Uvol X Ucr is the excretion
rate of creatinine; in steady state this must equal the rate of production.
• Since the rate of production is a function of muscle mass, Schwartz tested
different parameters of body size to provide the best correlation with GFR
measured by Creatinine clearance.
• The body length appeared to have the best correlation.
Schwartz formula: GFR (ml/min/1.73 m2) =K X Ht / Pcr
• Where K is constant determined by regression analysis provided in Table for
different ages, Ht = height in cm, and Pcr =plasma creatinine.

24. Table Mean K Value For Schwartz Formula
Cr mg/dl Cr
mol/L
Low birth weight infants 1year 0.33 29.2
Full term Infants 1year 0.45 39.8
Children 2-12 years 0.55 48.6
Females 13-21 years 0.55 48.6
Males 13-21 years 0.70 61.9
µmol/L

25. C. Urinalysis
1. Routine Examination-
It is best if the urine specimen is evaluated within 1 hour after voiding, and ideally after
the first morning void.
A. Turbidity-
Cloudy urine can be normal and is most often the result of crystal formation at room
temperature. Uric acid crystals form in acidic urine, and phosphate crystals form in
alkaline urine. Cellular material and bacteria can also cause turbidity.
Most common cause of cloudy urine is phosphaturia
B. Specific gravity-
Specific gravity is measured in a refractometer, Glucose, abundant protein, and iodine-
containing contrast materials can give falsely high readings. Normal specific gravity is
between 1.003 and 1.030.
To detect Nocturnal Enuresis in this specific gravity is low, correlating to dilute urine,it
suggests the possibility of diabetes insipidus(DI).

26. C. pH
pH levels are estimated using pH meter, indicator paper or dipstick. Levels can be inappropriately
high with hypokalemia, and they can also be used to assess various types of renal tubular acidosis
D. Protein 8
Protein can be found in the urine of healthy children, with a reasonable upper limit being 150 mg/24
hr (4 mg/m2/hr). Persistent proteinuria should be precisely quantified by a timed 24-hr urine
collection. Normal: <4 mg of protein/m2/hr; significant: 4–40 mg/m2/hr; nephrotic range: >40
mg/m2/hr.2
If unable to obtain a timed urine sample, excretion can be estimated by the ratio of urine protein to
creatinine concentrations spot urine sample. Ratios (mg/mg) <0.5 in children who are <2 years old
and <0.2 in older children are normal. A ratio >2 suggests nephrotic range proteinuria.
E. Other-
Like sugars, ketones, myoglobins, bilirubin etc are usually the reflection of some systemic illness
rather than renal.

27. 2. Microscopy-
A. RBCs-
Centrifuged urine usually contains fewer than 5 RBCs/hpf. Significant hematuria is
5 to 10 RBCs/hpf. Dysmorphic, small RBCs suggest a glomerular origin, whereas
normal RBCs suggest lower tract bleeding.
B. Sediment
Using light microscopy, unstained, centrifuged urine can be examined for formed
elements, including casts, cells, and crystals.
For instance, hematuria with muddy brown casts, granular casts, waxy casts, and
epithelial casts is indicative of tubular damage and suggests acute tubular
necrosis.
RBC casts imply the presence of glomerular disease and WBC casts indicate
pyelonephritis. Normal urine contains hyaline casts (< 100/ml of urine).

28. C. Epithelial cells
Squamous epithelial cells (>10 per low-power field) are useful as an index of
possible contamination by vaginal secretions in females or by foreskin in
uncircumcised males.
D. White blood cells (WBCs)
Greater than 5 WBCs/hpf is suggestive of a urinary tract infection (UTI). Sterile
pyuria is rare in the pediatric population. If present, it is usually transient and
accompanies systemic infection, for example, with Kawasaki disease. May also be
a sign of urolithiasis.
E. Bacteria
Gram stain is used to screen for UTIs. One organism per high-power field in un-
centrifuged urine represents at least 105 colonies/mL.

29. COMBINED BIOCHEMICAL ANALYSES-
FeNa-
• Fractional excretion of sodium (FeNa) is one of the most commonly used tests for
tubular integrity. There is no “normal” for fractional excretion of sodium. It must be
interpreted in the context of each patient’s sodium and volume status.
• In the face of extra cellular volume contraction, the appropriate response will be
conservation of sodium and water. Therefore the fractional excretion of sodium will be
low, usually with a FeNa of less than 1% in children and less than 2.5% in neonates.
• If tubular damage such as in acute tubular necrosis has occurred, the fractional
excretion of sodium will be inappropriately elevated. FeNa will be more than 2% in
children and more than 2.5% in neonates. Urinary sodium will generally be more than 30
mEq/L.

30. FeNa can be calculated as follows:
Where UNa = urinary concentration of sodium, Pcr = plasma
Creatinine, PNa = plasma sodium, and Ucr = urinary creatinine.

31. Urea/creatinine ratio-
• Normal BUN / Creatinine ratio is 10 – 20:
• 1. In pre-renal renal failure because of acute rise in BUN there is increase in BUN /
Creatinine ratio.
• In post-renal or causes both BUN and Creatinine are elevated so the ratio doesn’t
changes much while in the renal causes there is decrement in the ratio.
• The ratio is also decreased in intrinsic renal damage, low dietary protein or severe liver
disease.