Renal Function Tests

CLINICAL PATHOLOGY DEPARTMENT

• Objectives
• Enumerate the functions of kidney
• Discuss the biochemical test which are done to assess the function of
kidney
• Discuss the abnormalities in biochemical tests associated with renal
impairment
Renal Function Tests
• Kidney Functions
• Excretory
• Homeostatic
• Endocrine
• Metabolic
Renal Function Tests
• Renal Function
• Excretory Functions
• Formation and excretion of urine \
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
• Excreting toxic substances in synergy with liver
• Homeostatic function
• Regulation of blood volume
• Regulation of blood pH
• Regulation of serum electrolytes; Na, K, Cl and Ca
• Reabsorption of essential nutrients
Renal Function Test

• Endocrine function
• Erythropoietin
• Renin Angiotensin system
• Vitamin D activation
• Degradation of hormones like insulin and aldosterone
• Metabolic function
• Along with liver site for gluconeogenesis
Renal Function Tests
• The following parameters are commonly included in assessing renal function
(the normal values/reference range is mentioned)
• • Serum Urea ( 15-45 mg/dl)
• Serum Creatinine (0.6 – 1.2 mg/dl)
• Serum Uric acid (males 3.5-7.2 mg/dl, females 2.6-6 mg/dl)
• • Total protein (6.4-8.1 g/dl)
• Serum albumin (3.2-4.6 g/dl)
• • Serum electrolytes
• Na (136-146 mEq/L)
• K (3.5-5.1 mEq/L)
• Cl (101-109 mEq/L)
• Phosphate (2.8-4 mg/dl) • Calcium (8.8-10.2 mg/dl)
Renal Function Tests
• Renal function tests; Why needed?
• To assess functional capacity of kidneys
• To diagnose renal impairment
• To assess the severity and progression of renal impairment
• To assess the effectiveness of treatment
Renal Function Tests
• Causes of renal disease
• Pre-renal
• Any condition that results in reduced blood flow to kidneys
• Severe blood loss
• Hemolysis
• Renal
• Damage to renal tissue, glomerular basement membrane or tubules
Glomerulonephritis
Diabetic or hypertensive nephropathy
Tubular damage due to toxic substances
• Post Renal
• Obstruction to urine outflow
Ureteric or urethral stone
Prostatic cancer
This list not exhaustive, these are only few common causes of renal disease
Renal Function Tests
• Renal function test
• Can be divided into two categories
• Test for glomerular function
• Serum Urea
• Serum Creatinine
• Clearance tests
• Tests for tubular function
• Urine concentration test
• Dilution test
• Para amino hippuric acid clearance test
• Acidification test
• Urine examination
• Important for assessing both glomerular and tubular function
Renal Function Tests
• The following parameters are commonly included in assessing renal function
(the normal values/reference range is mentioned)
• Serum Urea ( 15-45 mg/dl)
• Serum Creatinine (0.6 – 1.2 mg/dl)
• Serum Uric acid (males 3.5-7.2 mg/dl, females 2.6-6 mg/dl)
• Total protein (6.4-8.1 g/dl)
• Serum albumin (3.2-4.6 g/dl)
• Serum electrolytes
• Na (136-146 mEq/L)
• K (3.5-5.1 mEq/L)
• Cl (101-109 mEq/L)
• Phosphate (2.8-4 mg/dl) • Calcium (8.8-10.2 mg/dl)
Renal Function Tests
• Complete hemogram • Hemoglobin
• total RBC
• RBC indices
• MCH (Mean corpuscular hemoglobin)
• MCV (Mean corpuscular volume
• PCV (Packed cell volume)
• MCHC (Mean corpuscular Hemoglobin concentration)
• RDW (Red cell distribution width)
• ESR
Renal Function Tests
• Routine urine examination
• Physical appearance
• Colour
• pH
• Specific gravity
• Analytes
• Protein
• Glucose
• Ketones
• Bilirubin
• Urobilinogen
• Leucocyte
• Nitrite
• Microscopy
• RBC
• Pus Cells
• Epithelial cells • Casts
• Crystals
• • 24 hour urine protein
• Albumin/creatinine ration (ACR)
Renal Function Tests
Clearance test
• Clearance of substance is defined as the volume of plasma that is
cleared of that substance in unit time
• Inulin clearance accurately measures GFR as it is neither secreted or
absorbed by the renal tubules
• However it is not routinely done in patients.
• In clinical setting estimated GFR (eGFR) is more commonly used; it is
calculated from serum creatinine value
Renal Function Tests
Estimated GFR
• The Cockcroft-Gault formula for estimating creatinine clearance (CrCl)
is routinely as a simple means to provide a reliable approximation of
residual renal function in all patients with CKD. The formulas are as
follows:
• CrCl (male) = ([140-age] × weight in kg)/(serum creatinine × 72)
• However this has been extensively modified and there are online
calculators of eGFR from serum creatinine and body weight of
patients
• The eGFR is used to determine the stage of chronic kidney disease
Renal Function Tests
• Changes in serum analytes in kidney disease
• Serum Urea and creatinine
They both are increased in renal disease
Urea increases more in glomerular disease as compared to creatinine
Urea is a less reliable indicator than creatinine as it is affected by many factors such as;
• Protein intake
• Dehydration
• Muscle breakdown
• Serum Uric acid
It may increase in chronic kidney disease but not sufficient to cause gout
However raised uric acid is a bad prognostic indicator for chronic renal disease
Renal Function Tests
Changes in serum analytes in kidney disease
• Total protein and albumin
- Both serum total protein and albumin is decreased in chronic kidney disease
(CKD) due to increased proteinuria
- Even though proteinuria may also be seen in acute kidney disease but it usually
does not alter the total protein and albumin
• Serum electrolytes
-Sodium is decreased (hyponatremia) and potassium is increased (hyperkalemia)
in chronic kidney disease (CKD) as kidney reabsorb sodium in exchange of potassium
-Chloride and phosphate is increased in CKD
-Calcium is decreased as vitamin D is deficient
Renal Function Tests
Changes in hemogram and urine analysis in kidney disease
• RBC count and hemoglobin is decreased in advanced stages of kidney disease due to
deficiency of erythropoietin
• Urine examination reveals
- Proteinuria is seen in both acute and chronic kidney disease as well as kidney infection
-Proteinuria can be of two types
• In the initial stages very less amount of albumin escapes into urine; microalbuminuria (30 to 300
mg/day)
• Frank proteinuria ( when it is greater than 300 mg/day)
• Best evaluated in 24 hour urine sample
• In spot urine albumin/creatinine ratio is used to evaluate proteinuria
-Presence of RBC may indicate glomerulonephritis , acute nephritis, kidney infection
-Presence of pus cells, esterase positivity, nitrites may indicate bacterial infection
Renal Function Tests
Tests for tubular function
• Urine concentration test
• In CKD kidneys loses the ability to concentrate urine
• Specific gravity is measured in urine
• Low fixed specific gravity is indicative of chronic kidney disease
• Dilution test
• After overnight water deprivation patient is asked to take 1200ml of
water in half hour, urine specific gravity is measured in samples
collected over next 4 hours. At least one sample should show sp gr of
1.003 or below
Renal Function Tests
Tests for tubular function
• Para amino hippuric acid clearance test
• PAH is unique in that it is completely excreted in one passage
through kidney as it is both filtered and secreted.
• Therefore clearance of PAH is a measure of renal plasma flow
• Acidification test
• In this the ability to acidify urine is tested after administering
0.1g/kg ammonium chloride gelatin coated samples
URNE ANALYSIS
• Reference Range
• Normal values are as follows:
• Color – Yellow (light/pale to dark/deep amber)
• Clarity/turbidity – Clear or cloudy
• pH – 4.5-8
• Specific gravity – 1.005-1.025
• Glucose - ≤130 mg/d
• Ketones – None
• Nitrites – Negative
• Leukocyte esterase – Negative
• Bilirubin – Negative
• Urobilirubin – Small amount (0.5-1 mg/dL)
URINE ANALYSIS
• Blood - ≤3 RBCs
• Protein - ≤150 mg/d
• RBCs - ≤2 RBCs/hpf
• WBCs - ≤2-5 WBCs/hpf
• Squamous epithelial cells - ≤15-20 squamous epithelial cells/hpf
• Casts – 0-5 hyaline casts/lpf
• Crystals – Occasionally
• Bacteria – None
• Yeast - None
Kidney Function Test Normal
Rangr
• The normal range of Blood Urea Nitrogen is between 7 - 20 mg/dL
• The normal range of Blood Urea is between 10 - 50 mg/dL
• The normal range of Creatinine is between for Males: 0.6-1.2, and Female is
between 0.5-1.1 mg/dL
• The normal range of Calcium is between 8.5-10.5 mg/dL
• The normal range of Phosphorus is between 2.40–4.40 mg/dL
• The normal range of Uric Acid is between 3.4-7.0 mg/dL
• The normal range of Sodium is between 135-148 mmol/L
• The normal range of Potassium is between 3.5-5.0 mmol/L
• The normal range of Chloride is between 98-106 mmol/L
Renal Function Tests
• Creatinine Clearance (CrCl)
• Creatinine clearance (CrCl) is the volume of blood plasma cleared of creatinine
per unit time. It is a rapid and cost-effective method for the measurement of
renal function. Both CrCl and GFR can be measured using the comparative
values of creatinine in blood and urine. The CrCl rate approximates the
calculation of GFR since the glomerulus freely filters creatinine. However, it is
also secreted by the peritubular capillaries, causing CrCl to overestimate the
GFR by approximately 10% to 20%. However, because a small amount of
creatinine is released by the filtering tubes in the kidneys, creatinine clearance
is not exactly the same as the GFR. In fact, creatinine clearance usually
overestimates the GFR, particularly in patients with advanced kidney failure.
Furthermore, CrCl was calculated by the Cockcroft-Gault equation:
Renal Function Tests
• CrCl (mL/min) = (140 – age) × Weight (Kg) × 0.85 (if subject is
woman) / (72 × Serum Creatinine mg/dL)
• From the other hand, obstruction within the kidney or dysfunction
from another disease such as congestive heart failure may play a
pivotal role in decreasing CrCl level. Moreover, CrCl overestimates
GFR due to the secretion of creatinine from the tubules in normal
individuals. In patients with CKD, there is increased extrarenal and
decreased urinary elimination of creatinine leading to overestimation
of GFR from serum creatinine.
Renal Function Tests
• Measurements of Microalbuminuria
• The glomeruli of kidney are not permeable to substances with high molecular weight so plasma proteins are
absent in normal urine. When glomeruli are damaged or diseased, they become more permeable and
plasma proteins may appear in urine. The smaller molecules of albumin pass through damaged glomeruli
more readily than the heavier globulins. Albuminuria is always pathological. Large quantities (a few grams
per day) of albumin are lost in urine in nephrosis. Small quantities are seen in urine in acute nephritis,
strenuous exercise and pregnancy.
• Microalbuminuria (MAU) is also called minimal albuminuria or paucialbuminuria. It is identified, when small
quantity of albumin (30–300 mg/day) is seen in urine. The test is not indicated in patients with overt
proteinuria (+ve dipstick). Early morning midstream sample is preferred. MAU is an early indication of
nephropathy in patients with diabetes mellitus and hypertension. Hence, all patients who are known
diabetics and hypertensive should be screened for MAU. It is an early indicator of onset of nephropathy. The
test should be done at least once in an year. It is expressed as albumin-creatinine ratio; normal ratio being:
Males < 23 mg/g of creatinine & Females < 32 mg/g of creatinine
• Patients showing higher values on more than one occasion are considered to have MAU. Confirmed by
overnight urine collection and calculation of albumin excretion rate. A value more than 20 mg/min confirms
MAU. The selectivity of the membrane provides an assessment of glomerular damage
Renal Function Tests
• Chronic Kidney Disease (CKD)
• GFR < 60 mL/min/1.73m² for 3 months or more with or without kidney
damage indicates CKD. CKD is a silent killer, incidence is increasing worldwide
and is the progressive loss of renal function which is a growing problem that
affects approximately 12 % of the adult population. Kidney disease is very
common, but silent, and progresses very slowly. Major risk factors of CKD are
diabetes mellitus, hypertension, glomerular nephritis, urinary tract infection,
autoimmune diseases, kidney stones and toxic effects of some drugs. The
early symptoms of kidney failure are Polyuria (passing more urine), Nocturia
(passing more urine during night), Pedal edema (puffiness of face), High blood
pressure, Unexplained anemia, Fatigue (lassitude and tiredness),
Microalbuminuria and Mild elevation of serum creatinine
Renal Function Tests
• Acute Kidney Injury (AKI)
• AKI is the abrupt kidney dysfunction, usually due to renal tubular cell injury. It is
characterized by rapid rise of serum creatinine and low urine output. Onset of AKI can
be swift and often deadly. In AKI, serum creatinine, the current standard for assessing
kidney function, can take hours or days to respond to acute kidney damage. Novel
biomarkers of tubular injury, such as neutrophil gelatinaseassociated lipocalin (NAGL),
kidney injury molecule-1 (KIM-1), liver fatty acid binding protein (LFABP), and
interleukin18 (IL-18) may enable the early detection of acute kidney injury before or in
the absence of a change in GFR. Out of these, urinary neutrophil gelatinase-associated
lipocalin (uNGAL) is found to be the best to predict acute kidney injury. The uNGAL
could be most useful when sCr is in the middle range. NAGL is a small molecule
(molecular weight 25 kDa). It is found in neutrophils as well as in renal tubular
epithelium, where its expression is dramatically increased in ischemic or nephrotoxic
injury
Kidney Function Test Normal Range
• The normal range of Blood Urea Nitrogen is between 7 - 20 mg/dL
• The normal range of Blood Urea is between 10 - 50 mg/dL
• The normal range of Creatinine is between for Males: 0.6-1.2, and Female is
between 0.5-1.1 mg/dL
• The normal range of Calcium is between 8.5-10.5 mg/dL
• The normal range of Phosphorus is between 2.40–4.40 mg/dL
• The normal range of Uric Acid is between 3.4-7.0 mg/dL
• The normal range of Sodium is between 135-148 mmol/L
• The normal range of Potassium is between 3.5-5.0 mmol/L
• The normal range of Chloride is between 98-106 mmol/L