Renal Function Tests

Neim Bedewi (MSc. in Clinical Pharmacy)

Lecturer, Haramaya University, Ethiopia

1
 Introduction
• Through the excretion of water and solutes, the kidneys are
responsible in large part for maintaining homeostasis within the body.
• They also function in the activation and synthesis of many substances
that affect
➢ Blood pressure (BP)
➢ Mineral metabolism, and
➢ Red blood cell (RBC) production.
2
 Kidney Physiology
• The functional unit of the kidneys is the nephron, and each of the two
kidneys contains about 1 million nephrons.
• The major components of the nephron include the glomerulus,
proximal tubule, loop of Henle, distal tubule, and collecting duct.
• Blood is delivered to the glomerulus, the filtering portion of the
nephron, via the afferent arteriole.

3
 Cont.…
• Acting as microfilters, the pores of glomerular capillaries allow
substances with a molecular weight of up to 40,000 daltons to pass.
• Plasma proteins (albumin) and RBCs do not normally pass through.
• Most drugs are small enough to be freely filtered, with the exception
of large proteins & drugs bound to plasma proteins.
• The proximal tubule reabsorbs large quantities of H2O and solute.
• Na+ passively follows the reabsorption of H2O back into the blood.
4
 Cont.…
• Glucose, uric acid, Cl-, HCO3-, amino acids, urea, H+, PO43-, Ca2+, and
Mg2+ also are primarily reabsorbed in PCT.
• Na+, Cl-, Mg2+, and H2O are further reabsorbed in the loop of Henle.
• The distal tubule controls the amounts of Na+, K+, HCO3-, PO43-, & H+
that are excreted.
• The collecting duct regulates the amount of water in the urine.

5
 Cont.…
• Substances can enter the nephron from the peritubular blood or
interstitial space via secretion.
• In addition, substances can be reabsorbed from primarily the distal
tubule back into the systemic circulation via the peritubular
vasculature.
• Creatinine enters the tubule primarily by filtration through the
glomerulus.
6
 Cont.…
• Blood flow to the kidneys is determined, in large part, by cardiac
output with about 20% or 1.2 L/min directed to the kidneys.
• Renal plasma flow (RPF) is directly related to renal blood flow (RBF)
by taking the patient’s hematocrit (Hct) into consideration as follows:
RPF = RBF X (1–Hct)
• The normal value for RPF is about 625 mL/min.

7
 Cont.…
• Of the plasma that reaches the glomerulus, about 20% is filtered and
enters the PCT, resulting in a GFR of about 125 mL/min.
• GFR: used as a measure of the degree of kidney excretory function.
• The kidneys filter about 180 L of fluid each day; of this amount, they
excrete only 1.5 L as urine.
➢ Many solutes, such as creatinine and many renally eliminated
drugs, are concentrated in the urine.
8
 ASSESSMENT OF
KIDNEY
9
FUNCTION
 Serum Creatinine
• Normal range: Adults, 0.6–1.2 mg/dL (53–106 mmol/L); Young children,
0.2–0.7 mg/dL (18–62 mmol/L)
• Creatinine, which is produced in the muscle, is a spontaneous
decomposition product of creatine and creatine phosphate.
• Muscle mass, sex, age, race, medications, method of laboratory analysis,
and low-protein diets….. Can affect SCr concentration.

10
 SCr….
• Once creatinine is released from muscle into plasma, it is excreted
renally almost exclusively by glomerular filtration and is not
reabsorbed or metabolized by the kidney.
• A decrease in the GFR results in an increase in the SCr conc.
• Rule of thumb
➢ A doubling of the SCr level roughly corresponds to a 50%
reduction in the GFR.
11
 Blood Urea Nitrogen
• Normal range: 8–23 mg/dL (2.9–8.2 mmol/L)
• Urea nitrogen is a waste product that comes from protein breakdown.
• Produced by the liver, transported in the blood, & excreted by the
kidneys.
• The serum concentration of urea nitrogen (i.e., BUN) is reflective of
renal function because the urea nitrogen in the blood is filtered
completely at the glomerulus of the kidney and then reabsorbed and
tubularly secreted within nephrons. 12
 BUN….
• Acute or chronic renal failure is the most common cause of an
elevated BUN.
• In addition, several nonrenal factors such as unusually high protein
intake, disease states that increase protein catabolism (or upper GI
bleeding), and glucocorticoid therapy can increase the BUN conc.
• Liver disease and a low protein diet can lead to a lower BUN
concentration.
• A patient’s hydration status will also influence BUN. 13
 BUN to SCr Ratio
• A normal ratio is roughly 15:1
• Ratios >20:1 are observed in patients with decreased blood flow to
the kidney (e.g., prerenal disease such as dehydration or conditions
involving reduced cardiac output) or conditions involving increased
protein in the blood (e.g., dietary intake or an upper GI bleed).
• whereas ratios from 10:1 to 20:1 suggest intrinsic kidney damage.

14
 BUN to SCr….
• Situations in which the BUN:SCr ratio is <15:1 are seen in patients
with renal failure, significant malnourishment (decreased intake of
protein), or severe liver disease in which the liver is no longer able to
form urea.
• It is important to note that BUN can change independent of the renal
function, and, therefore, SCr is more useful in estimating renal function.

15
 Creatinine Clearance
• Reference Range: 90–130 mL/minute
• Because creatinine is cleared almost exclusively through the
glomerulus in the kidney, CrCl can be used as a clinically useful
measure of a patient’s GFR.
• CrCl: a valuable clinical parameter because many renally eliminated
drugs are dose adjusted based on the patient’s renal function.

16
 Creatinine Clearance….
• To determine actual CrCl, the patient’s urine is collected for a 24-hour
period, and the concentration of urine creatinine (mg/dL), total volume
of urine collected during the 24-hour period (mL/minute), and SCr
(mg/dL) are determined.

• Time-consuming and expensive, and incomplete collections can

substantially underestimate renal function. 17
 Creatinine Clearance….
• Estimating CrCl can be done using equations that consider a patient's
height, weight, sex, age, & Scr.... Cockcroft–Gault formula
• Utilized to estimate renal function when SCr is stable
• Typically, clinicians use ideal body weight (IBW) in the calculation of
estimated CrCl; however, actual body weight (ABW) may be used
when ABW is less than IBW

18
 Creatinine Clearance….
• Cockcroft–Gault formula

➢ Has the highest correlation and the greatest accuracy in

patients with SCr concentrations <1.5 mg/dL
• The Cockcroft–Gault formula must be multiplied by 85% to calculate
CrCl for females…….Why????

19
 Creatinine Clearance….
• Another approach to estimating CrCl is the Jelliffe method.

• Must be multiplied by 90% to calculate the CrCl for females.

➢ Underestimates CrCl for patients with SCr values <1.5 mg/dL.
• For patients with liver dysfunction....
➢ Under/Over predictions of CrCl???
• These equations should not be utilized in patients with rapidly
changing GFR (e.g.AKI). 20
 Estimated GFR
• eGFR is a calculated value that estimates the kidneys' GFR based on
SCr, age, gender, and race.
• There are several formulas used to calculate eGFR, including:
✓ Modification of Diet in Renal Disease (MDRD) equation &
✓ Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
➢ To identify those patients at risk for complications arising
from CKD
21
 eGFR….
Chronic Kidney Disease Stages
Stages GFR (mL/min/1.73 m2) Interpretation
1 > 90 Normal or high GFR
2 60-89 Mildly decreased
A 45-59 Mildly to moderately decreased
3
B 30-44 Moderately to severely decreased
4 15-29 Significantly decreased
5 < 15 Kidney failure
22
 eGFR….
• The MDRD equation provides an estimated GFR.

• Patients at age extremes may be particularly vulnerable to errors.

• In patients with low muscle mass (e.g., cachectic patients) or those with
unstable renal function.
➢ Cautious interpretation
• Underestimation of renal function: patients with eGFR >60 mL/min/1.73m2
23
 eGFR….
• CKD-EPI equation: based on standardized SCr, age, sex, and race.

• Where S c = standardized serum creatinine, κ = 0.7 for females and 0.9

for males, α = –0.329 for females and –0.411 for males, min indicates the
minimum of S c/κ or 1, and max indicates the maximum of S c/κ or 1.
• The same degree of accuracy as the MDRD equation for patients with
eGFR <60 mL/min/1.73 m2.
24
 eGFR….
• The usefulness of the CKD-EPI equation may be particularly evident in
➢ Younger patients without kidney disease
➢ Younger type 1 diabetics without microalbuminuria, or
➢ Those considering kidney donation with GFR ~ing normal values
• Use in patients with unstable renal function.

25
 Medication Safety
1. Antihypertensives/cardiac medications
➢ ACE-Is,ARBs, aldosterone antagonists, direct renin inhibitors
• Avoid in people with suspected functional renal artery stenosis
• Start at lower dose in people with GFR <45 mL/min/1.73 m2
• Assess GFR & serum K+ within 1 wk. of starting or following any dose
escalation
• Do not routinely discontinue in people with GFR <30 mL/min/1.73 m2
➢ Why??? 26
 Medication Safety….
2. Analgesics
➢ NSAIDS
• Avoid in people with GFR <30 mL/min/1.73 m2
• Prolonged therapy is not recommended in people with GFR <60
• Should not be used in people taking lithium
• Avoid in people taking RAAS blocking agents
➢ Opioids
• Reduce dose when GFR <60 mL/min/1.73 m2
• Use with caution in people with GFR <15 mL/min/1.73 m2
27
 Medication Safety….
3. Antimicrobials
➢ Penicillin
• Risk of crystalluria when GFR <15 mL/min/1.73 m2 with high doses
• Neurotoxicity with benzylpenicillin when GFR <15 with high doses
➢ Aminoglycosides
• Reduce dose and increase dosage interval when GFR <60 mL/min/1.73 m2
• Monitor serum levels (trough and peak)
• Avoid concomitant ototoxic agents such as furosemide 28
 Medication Safety….
4. Hypoglycemics
➢ Sulfonylureas
• Avoid agents that are mainly renally excreted (e.g., glyburide/glibenclamide)
• Agents metabolized by liver may need reduced dose when GFR <30
➢ Metformin
• Suggest avoiding when GFR <30, but consider risk-benefit if GFR is stable
• Review use when GFR <45 mL/min/1.73 m2
• Probably safe when GFR ≥45 mL/min/1.73 m2
• Suspend in people who become acutely unwell
29
 Medication Safety….
5. Anticoagulants
➢ LMWHs
• Halve the dose when GFR <30 mL/min/1.73 m2
• Consider switch to conventional heparin or alternatively monitor
plasma anti-factor Xa in those at high risk for bleeding
➢ Warfarin
• Increased risk of bleeding when GFR <30 mL/min/1.73 m2
• Use lower doses and monitor closely when GFR <30 30
 Role of the Pharmacist in Kidney Disease
Care
• A significant role in the care of patients with acute or CKD.
• Contribute to medication management, providing dosing
adjustments, monitoring for drug-related adverse effects, &
ensuring drug safety.
• Play a vital role in patient education, promoting medication
adherence, & providing lifestyle recommendations to optimize
kidney health.
31
Liver Function Tests

32
 Introduction
• The liver is the largest solid organ in the human body. It plays a
central role in all of the body’s biochemistry.
• Thus, liver function tests can give a clearer picture of any of the
functions of the liver:
➢ Synthesis,
➢ Excretion, or
➢ Detoxification
• These tests can also help indicate liver injury. 33
 Liver Function
• Metabolic Functions
• Excretory Functions
• Metabolism and Detoxification
• Hematological Functions
• Storage Functions

34
 Liver tests & the LFT panel
• This panel generally includes:
➢ Aminotransferases
➢ Aspartate aminotransferase (AST)
➢ Alanine aminotransferase (ALT)
➢ Bilirubin
➢ Alkaline phosphatase (ALP), & Albumin.
• LFT is a misnomer because not all of these tests actually
measure liver function (aminotransferases reflect liver injury).
35
 LFT panel….
• Liver has several functions, and different tests reflect these
different functions.
➢ Cholestatic and Hepatocellular.
• In cholestatic disease, there is an abnormality in the excretory
function of the liver.
• In hepatocellular disease, there is primary inflammation and
damage to the hepatocytes themselves
36
 Categories of Liver Tests
Process Most closely related tests
• Albumin
Protein synthesis • Prealbumin
• PT/INR (clotting factors)
• Bilirubin
• ALP
Excretion
• 5'-nucleotidase
• GGT
• AST
Hepatocellular injury
• ALT
Detoxification • Ammonia (NH3+) 37
Tests of synthetic liver function
• Albumin and clotting proteins
➢ One of the functions of the liver is to synthesize proteins
that circulate in the blood
• Measurement of the levels of these proteins in the blood
provides a reflection of the ability of the liver to synthesize them
• The liver has an enormous reserve function, so that it may
synthesize normal amounts of proteins despite significant liver
damage. 38
 Albumin
• Normal range: 4–5 g/dL (40–50 g/L)
➢ Maintaining plasma oncotic pressure
➢ Binding and transport
• Reduced in patients with cirrhosis (chronic synthetic dysfunction)
➢ Levels are often normal in acute viral hepatitis or drug-
related hepatotoxicity…… Why???

39
 Albumin….
• Albumin levels may be low due to
➢ Malnutrition/malabsorption, protein loss from the gut,
kidney, or skin, or increased blood volume
• Negative acute phase reactant… Low in systemic inflammation
• At very low concentrations (<2–2.5 g/dL)
➢ Peripheral edema, Ascites, or Pulmonary edema.
• Low albumin can affect concentration of highly protein bind
drugs; phenytoin, salicylates, warfarin and calcium 40
 Prothrombin Time
• Normal range: 12.7–15.4 sec
➢ Rate of conversion of prothrombin to thrombin.
• Prothrombin time requires factors II, V, VII, and X, and, as these
are made in the liver.
• An abnormal PT is often caused by
➢ Liver injury
➢ Vitamin K deficiency
➢ Warfarin therapy 41
 International normalized ratio
• INR & PT measure the same reactions, but INR is more accurate
due to adjustments for lab variations…. Preferred Vs. PT
➢ Initiation & maintenance of anticoagulant therapy (warfarin)

• INR= [PT(patient)/PT(control)]ISI

➢ ISI is the international sensitivity index rating assigned to a

particular thromboplastin reagent (1.0 -1.4)
• For normal pts. who are not on anticoagulation, the INR 1.0
42
 INR….
• INR therapeutic range varies depending on the indication (warfarin)
➢ For DVT, PE, VTE Px….. INR: 2.0-3.0
➢ For mechanical heart valve replacement… INR: 2.5-3.5
• What if INR is outside of the therapeutic range???
➢ High INR
➢ Low INR
• Medications, vitamin K intake, alcohol use, & medical conditions
(HF, cancer, & thyroid disorders) can influence the INR. 43
 Tests of Excretory Liver Function &
Cholestasis
• Bile, Bile pigments, Cholesterol
• Laboratory tests do not distinguish between intrahepatic and
extrahepatic cholestasis.
• Laboratory abnormalities primarily associated with cholestasis
➢ Elevation of ALP, 5'-nucleotidase, γ-glutamyl
transpeptidase (GGT), and bilirubin

44
 Alkaline Phosphatase
• Reference range: 30-120 U/L
• Mainly in bone & liver (the cells lining the bile canaliculi)
• Excreted by liver into bile.... Sensitive indicator of biliary obstruction
• ALP elevation suggests cholestatic disorders but doesn't
differentiate intrahepatic from extrahepatic issues.
• Levels > 4X normal indicate cholestatic disorders (75% of pts.).
• Elevated GGT along with ALP strongly indicates a liver origin.
45
Gamma-Glutamyl Transpeptidase
• Reference Range: Male, 9–50 IU/L; Female, 8–40 IU/L
• Found in kidney, liver, intestine, prostate, & pancreas
➢ Important in the evaluation of hepatobiliary disease
➢ Sensitive in biliary obstruction & cholecystitis
• A sensitive indicator of recent or chronic alcohol exposure.
• GGT/ALP ratio >2.5 being highly indicative of alcohol abuse
• Anticonvulsants (phenytoin & phenobarbital)….. GGT & ALP
46
 Bilirubin
• Total bilirubin: 0.1–1.0 mg/dL; Indirect: 0.2–0.6 mg/dL; Direct: 0.2–
0.4 mg/dL
• A breakdown product of Hgb and is formed in the RES
• It is initially a large lipophilic molecule bound to albumin.
• The liver plays a central role in bilirubin excretion.
➢ Must be converted into a water-soluble form before excretion
➢ Liver links bilirubin to glucuronic acid, making it water soluble
➢ Conjugated form is then excreted into bile & eliminated in feces
47
 Indirect Vs. Direct Bilirubin
• Direct bilirubin reacts quickly in the van der Bergh reaction.
• Indirect bilirubin requires dissolving agents for detection.
• Urine dipsticks measure direct bilirubin.
• Elevated bilirubin causes jaundice (yellow skin and eyes).
• Icterus becomes visible when total bilirubin exceeds 2–4 mg/dL.
• Extremely high bilirubin levels may be neurotoxic in infants.

48
 Indirect Hyperbilirubinemia
• Hemolysis or reduced hepatic conversion to direct bilirubin
• Patients with primarily unconjugated hyperbilirubinemia (>70%
indirect) generally do not have serious liver disease
• Hemolysis, Gilbert syndrome, Crigler-Najjar syndrome, or
various drugs, including probenecid and rifampin

49
 Direct Hyperbilirubinemia
• Bilirubinemia with >50% in the direct fraction
• Elevated D. bilirubin implies hepatic or biliary tract disease
➢ Secretion of bilirubin or clearance of bile from the liver
• Cholestatic: elevated bilirubin is primarily conjugated
• Hepatocellular: significant in both direct & indirect bilirubin
• In normal functioning kidney
➢ D. bilirubin rarely rise very high even in severe cholestatic
50
 Evaluation of Elevated Bilirubin Concentrations
in Context of Other Test Results
Total D. I. ALT, AST, Differential
bilirubin Bilirubin Bilirubin GGT Diagnosis
Hemolysis
Gilbert synd.
Moderately Normal or Moderately Crigler-Najjar
Normal
elevated low elevated synd.
Neonatal jaundice

Moderately Moderately Congenital

Normal Normal syndromes
elevated elevated
Mildly Mildly Moderately Moderately Hepatobiliary
elevated elevated elevated elevated disease
 Aspartate Aminotransferase
• Reference Range: 0–35 IU/L
• AST abundance in heart and liver tissue.
➢ Moderate presence in skeletal muscle, kidney, & pancreas.
• Release into blood during acute cellular injury.
• Used to evaluate myocardial injury & liver disease prognosis.
• MI: AST elevation >95% after MI; Peak levels after 24 to 36 hrs,
returning to normal in 4-5 days.
52
 AST….
• Acute Hepatic Necrosis: Viral hepatitis or Hepatotoxin (CCl4)
➢ Significant AST elevation in acute hepatic necrosis
➢ Increased AST & ALT levels before clinical symptoms
• Parenchymal liver disease
➢ 100X increase in ULN of both AST & ALT
• Intrahepatic cholestasis, post-hepatic jaundice, or cirrhosis
• Moderate elevations of AST, depends on extent of necrosis
• Cirrhosis: AST >>> ALT and AST increase ~4-5X than ULN
53
 AST….
• Alcoholic liver disease: AST:ALT is usually greater than 2:1.
• Elevated AST: with hepatitis, alcoholic liver disease, cholestasis,
pericarditis, AMI, trauma, CHF, mononucleosis, severe burns,
renal infarction, pulmonary infarction, & acute pancreatitis.
• Medications:
➢ Acetaminophen, NSAIDs, ACEIs, nicotinic acid, INH,
sulfonamides, erythromycin, griseofulvin & fluconazole.
54
 Alanine Aminotransferase
• Reference Range: 0–40 IU/L
• ALT is an intracellular enzyme present in liver tissue. It is also
located in myocardial, muscle, and renal tissue.
• Elevations in serum ALT are more specific for liver injury.
• Both AST & ALT elevated…. Liver cell structure affected.
• ALT:AST <1.0
➢ Viral hepatitis or acute hepatitis
55
ENDOCRINE TESTS

56
THYROID FUNCTION
DIABETES MELLITUS
Thyroid-Stimulating Hormone
• Reference range: 0.3-5 μU/mL
➢ Hypothyroidism or Hyperthyroidism…. Screening & Tx
• Elevated TSH
➢ Indicative of hypothyroidism
➢ In pts. taking thyroid replacement therapy
➢ Increase the dose of thyroid medication
➢ Metoclopramide & other DA antagonists may increase
57
 TSH….
• Low TSH
➢ Abnormally low TSH (< 0.10)…. Hyperthyroidism
➢ In pts. taking thyroid replacement therapy
➢ Dose reduction
➢ Dopamine, levodopa & glucocorticoids can decrease TSH
levels
• TSH should be monitored 6 to 8 weeks after initiation or a
change in therapy. 58
 Total Thyroxine
• Normal Range: 4-12 μg/dL
• Thyroxine (T4) is the predominant circulating thyroid hormone
➢ Measure functional status of thyroid gland
➢ Monitor thyroid therapy
• Total serum thyroxine measures both free thyroxine & thyroxine
bound to thyroxine-binding proteins.
• T4 levels may be affected by conditions that increase or
decrease the thyroxine-binding proteins. 59
 Total thyroxine….
• Increased T4
➢ Hyperthyroidism, pregnancy, hepatitis….
➢ Estrogen replacement therapy, OCs, tamoxifen, & raloxifene.
• Decreased T4
➢ Mainly hypothyroidism, also in renal failure, malnutrition, liver
disease
➢ Salicylates, phenytoin, phenobarbital, and carbamazepine
60
 Free Thyroxine
• Normal Range: 0.8-2.7 ng/dL
• Free T4 is a more accurate reflection of clinical thyroid status
➢ Confirm the Dx of hypothyroidism or hyperthyroidism
• Free T4 levels may be increased or decreased by amiodarone
and iodides and decreased with lithium

61
 Total Triiodothyronine
• Normal Range: 80-200 ng/dL
• T3 is three to four times more potent than T4
• Used in the diagnosis of hyperthyroidism or T3 toxicosis
Increased T 3
• Hyperthyroidism, T3 thyrotoxicosis, & high dose of levothyroxine
Decreased T3
• Hypothyroidism, malnutrition, & anorexia.
• Corticosteroids and propranolol 62
Glycosylated Hemoglobin
• Normal Range (Hemoglobin A1c): between 4% and 6%
• % of hemoglobin A molecules that are glycosylated
• As the serum glucose becomes more elevated, more glucose
binds to the hemoglobin
• HbA1c reflects average BG for the previous 2-3 months.
➢ For DM pts. target HbA1c < 7%
• Estimated Average BG…… eAG(mg/dL) = 28.7 × A1c − 46.7
63