rft is described in detail . function of kidney, objectives of doing the test. the various test available for assessing the renal function with clinical interpretation is available.
2. Formation of
urine as the waste
product
Excretion of NPN
substances
Metabolic –
Gluconeogenesis,
Urea cycle
Regulation of salt
& water balance
Regulation of
acid-base balance
Production of Hormones –
Renin , Calcitriol,
Erythropoietin.
Functions of KIDNEY
3. Early detection,
Assessment of the
extent of renal
damage
Measure the
progression of renal
damage
Monitoring and
adjusting the dose
of renal toxic drugs
Renal Function Tests –required for……
4. Early detection of possible renal damage &
assessment of its severity
Measure progression of the renal impairment
& efficacy of corrective therapy
Predict when renal replacement therapy may
be necessary
Monitor safe & effective use of drugs, which
are principally eliminated through urine.
OBJECTIVES OF RFT :
6. Segment of nephron Reabsorption of Secretion of
Proximal convoluted
tubule (PCT)
Na+, Cl–, HCO3 (85%),
Glucose (100%),
Amino acids (100%),
Uric acid,
Water (obligatory).
H+,
acid and bases,
NH4
+ ,
Loop of Henle Na+, Cl–, Ca++, Mg++
Distal convoluted
tubule (DCT)
Na+, Cl–,
Water (facultative)
H+, K+, NH4
+, uric
acid
Glomerular function – filter the incoming blood – formation of
ultra filtrate of blood – cells , large proteins are retained,
metabolic waste products are filtered.
Tubular function – about 170 L ultra filtered is formed , only
1.5 L excreted as Urine.
Selective reabsorption and secretion of molecules.
7. Renal Threshold
is the plasma level above which the compound is
excreted in urine.
maximum reabsorptive capacity of the substances - Tubular
maximum or Tm.
Ex – Glucose - 180 mg/dl , Tm - 375 mg/min
Lactate - 60 mg/dl
Bicarbonate - 28 mEq/L
• Lowered renal threshold - at lower blood levels compounds
are excreted in urine .
Renal glycosuria , Renal tubular acidosis
8. I. To screen for kidney disease
• Complete urine analysis
• Plasma urea and creatinine
• Plasma electrolytes
II. To assess renal function
a. To assess glomerular function
• Glomerular filtration rate - Clearance tests
• Glomerular permeability - Proteinuria
b. To assess tubular function
• Specific gravity
• Reabsorption & Secretion tests
• Concentration and dilution tests
• Renal acidification
11. CLASSIFICATION OF RENAL FUNCTION TESTS
On the basis of functions
1.Test measuring GFR
2.Test measuring tubular
function
On the basis of clinical applications
1.Routine clinical tests
a. Complete urine analysis
b. Measurement of NPN in blood
c. Measurement of serum electrolytes
2. Markers of GFR - Clearance tests
3.Markers of glomerular permeability
- Proteinuria
4. Markers of tubular function
a. Urinary &plasma osmolality
b. Concentration & dilution test
c. Test to assess renal acidification
12. Tests for assessment of glomerular function
Renal clearance test -
Markers of GFR
Blood urea and serum
creatinine
Proteinuria- Marker of
glomerular
permeability
Hematuria
RFT
13. It is the volume of fluid filtered from the glomerular
capillaries into the Bowman's capsule per unit time
Normal – 120 to 125 ml/min/1.73 m2
Affected by -
Age, sex, BSA, protein intake and pregnancy.
Loss of functional nephrons (>75%) - ↓ GFR
General index to assess severity of renal damage.
GFR
14. • Measurement of the clearance is predominantly a
test of glomerular filtration rate (GFR).
• Renal plasma flow is 700ml/min and GFR is 125
ml/min –so only 1/5th of the plasma brought to
glomeruli becomes the glomerular filtrate -
FILTRATION FRACTION
GFR decreases
• Age
• BP is below 80 mmHg
• Obstruction to the renal flow (calculi and enlarged
prostate)
15. Clearance tests -
the volume of plasma, completely cleared of a
substance , per unit time ( ml /min) .
C = UV / P
mg of cr./100ml urine
Cr.Cl.= ------------------ X ml. of urine exr/ min
(ml/min) mg of cr. /100 ml plasma
16. The amount of substance excreted in urine is the result of–
• Glomerular Filtration
• Tubular Reabsorption / secretion.
Urinary excretion rate = Filtration rate - Reabsorption
rate + Secretion rate
19. • Endogenous - Creatinine and Urea
• Exogenous - Inulin (gold standard)
,51Cr-labelled EDTA, 99Tec-labelled
EDTA - not used in clinical practice.
Substances used for clearance test
Renal clearance test used to assess the rate
of glomerular filtration and renal blood flow
24. Creatinine Clearance - ideal marker to measure
GFR
• Procedure - 500 ml of water
– After 30 min. – Discard that sample.
– After 60 min. – Collect the sample.
– Note the Volume of urine= V
– collect Blood Sample .
– Estimate Sr. , Urine Creatinine by Jaffe`s
method
– Early marker for Renal impairment rather
than Plasma Creatinine level.
25. • Males 85-125ml/min
• Females 80-115ml/min
When corrected for surface area, the cr cl value will
become comparable b/w males, females and children,
which is about 100 ml/min/1.73 sq meter.
Creatinine co-efficient
• Urinary creatinine expressed in mg /kg body wt
• Value raised in muscular dystrophy
Males 20-28mg/kg
Females 15-21mg /kg
Creatinine
Creati
nine
26. INTERPRETATION OF CREATININE CLEARANCE
• Dec. cr cl - very sensitive indicator of reduced GFR
• Because of the steady rate of creatinine excretion,
substances in the urine are conveniently measured "per
gram of creatinine".
• Urine creatinine is used to check whether the 24 hr
urine sample does actually contain total urine volume or
not.
• However still creatinine is generally considered a somewhat
more sensitive and specific test of renal function than BUN
27. Urea clearance
• Normal -75 ml/min
• It is not as sensitive as creatinine clearance –
• 40-60% of urea is reabsorbed by renal tubule
• Influenced by number of extra renal factors – dietary
proteins, fluid intake, Hemorrhage, infection etc.
28. Plasma cystatin C –
• Small MW protease inhibitor syn by nucleated cells
• Cleared by glomerulus
• Plasma conc is measure of GFR.
Plasma ß2-Microglobulin estimation
• Plasma concentration increases as the GFR declines
• Estimation involves expensive immunoassay- not
useful in clinical practice
GFR estimation- new endogenous markers
29. serum urea , creatinine – used as convenient but
insensitive measure of GFR.
• Serum creatinine concentration is an insensitive
index of renal function, as it may not appear to be
elevated until the GFR has fallen below 50% of
normal.
• So serum cr increases late in renal failure.
• eGFR is an improvement on serum creatinine to
estimate GFR and should be interpreted cautiously.
30. • Estimated GFR (eGFR)
• The relatively poor inverse correlation between
serum creatinine and GFR can be improved by
taking into account some of the confounding
variables, such as age, sex, ethnic origin and body
weight.
31. Blood urea nitrogen (BUN)
• Estimates the nitrogen content of urea.
• Urea – MW 60, of which 28 comes from the two nitrogen
atoms.
Urea = BUN x (60/28), Urea= BUN x 2.14.
• Normal BUN is 10-18 mg/dL.
• Increased BUN or urea - ‘Azotemia’.
• Azotemia- retention of nitrogenous waste products
excreted by the kidney. It is either due to increased
protein catabolism or impaired kidney function.
32. Normal urinary protein excretion - less than 150 mg/24 hours,
made up of mostly - albumin (5 mg/L), Tamm Horsfall
glycoprotein and alpha-1 microglobulin (5 mg/L)
• Albuminuria is always pathological
• Proteinuria in urine is an indicator of leaky glomeruli
Endothelial cell – impermeable to RBC
Glomerular BM – impermeable to Albumin
33. • The glomerulus act as a selective filter of the
blood passing through capillaries.
• Urea, glucose ,creatinine and electrolytes are
freely filtered
• Urinary concentration of proteins depend on the
permeability of glomerular membrane and the
reabsorptive capacity of PCT
• 99% of the filtered proteins are reabsorbed by
healthy kidney
34. Proteinuria-
First sign of Glomerular injury, before ↓ in GFR.
↑ Glomerular permeability - smaller molecules of albumin
pass through damaged glomeruli more readily than
the heavier globulins. NEPHROTIC SYNDROME
↓Tubular reabsorption - Retinol binding protein (RBP) and
alpha-1 microglobulin in urine increased.
Overflow proteinuria - SMW proteins are increased in
blood, they overflow into urine.
Bence-jones proteins – Multiple myeloma
Monoclonal light chains of Ig,
35.
36.
37. Urogenic protienuria - due to
inflammation of lower urinary tract,
when proteins are secreted into the
tract.
Nephron loss proteinuria -occurs when
functional Nephrons are reduced
GFR is decreased
Remaining Nephrons are over working
38. • Microalbuminuria / minimal albuminuria /
paucialbuminuria
– small quantity of Albumin is excreted 30-300mg/day
• Early indicator of nephropathy in HTN , D.M.
• is an indicator of future renal failure
• The test should be done at least once in an year.
• It is expressed as albumin-creatinine ratio;
• normal ratio Males < 23 mg/gm of creatinine
Females < 32 mg/gm of creatinine
39. Test to assess Tubular function
• SPECIFIC GRAVITY :
• simplest test
• index of concentrating ability of tubules
• 1/α volume
• Increase in sp.gravity - dehydration, DM.
• Decrease in sp.gravity - renal failure, DI, ATN &
excessive fluid intake.
• Fixed sp.gr – 1.010 – ISOSTHENURIA - CRF
39
40. Measurement of Osmolality
• depends on the number of osmotically active particles
• Urine samples vary widely from (60 milliosmol/ kg to
1200 milliosmol/kg).
• Plasma osmolality is 285-300 mosm/kg
• ratio of osmolality of urine/plasma - 3-4.5
• Osmolality is measured by osmometer and based on the
depression of freezing point
40
41. Urine Conc. Test / Fluid deprivation test
earliest manifestation of tubular damage may be difficulty in
concentrating the urine.
Early dinner no food/fluid after 6 PMbladder emptied @
7AM discarded specimens collected @ 8 AM &
9AMatleast one should have SG >1.022 or Osm >850
mOsm/kg
Dehydration – ADH – Reabsorption
If S.G < 1.022 – D.I ( ↓ADH ) - {ADH stimulation test}
measurement of the volume of urine excreted during the day
and the night is another simple index of tubular function
Night vol is ½ of day vol.
Nocturia – early indicator of tubular dysfunction.
42. Urine Dilution Test
more sensitive and less harmful than concentration test.
Pt. completely empties bladder (at 7 am) after overnight fast
drinks 1L /1.2L water hourly urine specimens collected
for next 4 hrs
A normal person will excrete almost all the water load within
4 hours and the specific gravity of at least one
sample should fall to 1.003 and osmolality to 50 mosmol/kg.
43. Urine Acidification test / NH4Cl Loading test –
To ∆ Hyperchloremic Met. Acidosis .
0.1 g/kg body wt. of enteric coated NH4Cl –
Collect urine sample every hr. , from 2 hrs – 8hrs.
Normally – pH of atleast 1 U. sample - <5.3.
NH4 excretion – 30 – 90 m.mole /hr.
CRF – pH -low , ↓NH4.
RTA – pH – not < 5.3.
Liver disease is a contraindication to perform this test
44. Dye Excretion Test or PSP Test Phenolsulphonphthalein(Phenol red)
It is dye of choice for excretory function of kidney.
PSP dye – non-toxic and 94% excreted by tubular secretion.
i.v inj. -6mg of PSP in 1ml .of saline .
Collect urine – 15, 30, 60, 120 min.
Normal – 15 min sample - > 25 % of dye
1st hr- 40 – 60 % dye
Impaired excretion - < 23% dye in 15 min.
- 2hr. Can be Normal
45. Renal Imaging studies
Plain radiograph of abdomen
IVP / Intravenous pyelography
USG, CT Scan, MRI Scan
Renal biopsy
Strictly speaking, these are not considered to be
RFTs, but very useful in present day clinical
practice for structural & functional assessment of
kidneys.
46. Forms of renal failure
Two forms: acute (acute kidney injury) and
chronic (chronic kidney disease)
Acute kidney injury (AKI)
• Previously called acute renal failure (ARF), is a
rapid loss of kidney function.
• The causes categorised into prerenal, renal, and
postrenal.
• Diagnosed on the basis of clinical history and
laboratory data.
• A diagnosis is made when there is rapid reduction
in kidney function, as measured by serum urea,
creatinine, or based on a rapid reduction in urine
output, termed oliguria.
47.
48.
49.
50. Chronic kidney disease (CKD)
• Previously called chronic renal disease, is a progressive loss
of renal function over a period of months or years.
• Most common causes - diabetic nephropathy, hypertension,
and glomerulonephritis.
• ARF can be reversible but CKD is not.
End stage kidney disease
51.
52.
53.
54.
55. • A 17 yr old man was involved in a road traffic accident.
Both femur were fractured and his spleen was ruptured.
Two days after surgery and transfusion of 16 units of
blood, the following results were found:
Plasma
• Sodium - 136 mmol/L (135-145)
• Potassium - 6.1 mmol/L (3.5-5)
• Urea - 20.9 mmol/L (2.5-7)
• Creatinine - 190 μmol/L (70-110)
• Phosphate - 2.8 mmol/L (0.80-1.35)
• Bicarbonate - 17 mmol/L (24-32)
Pt was producing only 10 ml of urine /hr, spot urinary Na
8mmol/L.
57. • A 56 yr old man attended the renal out pt clinic because of
polycystic kidney, which had been diagnosed 20 yr
previously. He was Hypertensive and following blood results
Plasma
• Sodium - 132 mmol/L (135-145)
• Potassium - 6.2 mmol/L (3.5-5)
• Urea - 23.7 mmol/L (2.5-7)
• Creatinine - 360 mol/L (70-110)
• eGFR - 14ml/min per 1.73 m2
• Phosphate - 2.6 mmol/L (0.80-1.35)
• Bicarbonate - 13 mmol/L (24-32)