Measurement of renal function

Question 1

Why measure renal function

Answer 1

Identification of renal impairment in your patient

Modification of dosage of drugs which are cleared by the kidneys

Question 2

Patients at risk of developing renal failure

Answer 2

Extremes of age: neonates and the elderly

Polypharmacy

Specific disease states: hypertension, chronic heart failure, diabetes, arthritis, renal disease, recurrent urinary tract infections

Patients receiving long term analgesics

Transplant patients

Drug therapy

Patients undergoing imaging procedures

Question 3

Monitoring a patient’s renal function

Answer 3

Patients clinical condition

Modern imaging techniques

Biochemical data

Question 4

Fluid balance affected

Answer 4

Clinical sign: oedema

Symptoms: breathlessness

Question 5

Electrolyte refulation especially K+, Na+, PO42- and Ca2+ affected

Answer 5

Clinical signs: abnormal ECG, absent P waves, broad QRS complex, peaked T waves

No symptoms

Question 6

EPO production affected

Answer 6

Clinical signs: pallor

Symptoms: fatigue

Question 7

Vitamin D3 affected

Answer 7

Clinical signs: osteomalacia

Symptoms: bone pain

Question 8

Excretion affected

Answer 8

Clinical signs: raised blood urea and creatinine concentrations

Symptoms: pruritis, nausea and vomiting

Question 9

Acid base balance affected

Answer 9

Clinical signs: low blood pH and bicarbonate levels

Symptoms: deep and rapid respiration

Question 10

Use of bedside clinical data

Answer 10

Weight charts

Fluid balance chart

Degree of oedema

Results of urine dipstick testing (urinalysis for protein, blood, glucose)

Question 11

Modern imaging techniques

Answer 11

Macroscopic views of renal blood flow, filtration and excretory function

Some used clinically, some only currently used experimentally in the lab

Question 12

Renography

Answer 12

Gamma camera planar scintigraphy

Positron emission tomography

Single photon emission computerised tomography

Question 13

Biochemical data

Answer 13

Useful for identifying renal impairment

Blood markers of renal function

• plasma or serum creatinine
• plasma or serum urea or blood urea nitrogen

Question 14

Creatinine

Answer 14

Breakdown product of creatine phosphate in muscle

Generally produced at a constant rate

Filtered at the glomerulus with some secretion into the proximal tubule

Normal range in plasma: 40-120umol/L

Question 15

Plasma creatine increased by

Answer 15

Large muscle mass, dietary intake

Drugs which interfere with analysis

Drugs which inhibit tubular secretion

Ketoacidosis

Ethnicity (higher creatine kinase in black population)

Question 16

Plasma creatinine decreased by

Answer 16

Reduced muscle mass

Cachexia/ starvation

Immobility

Pregnancy (increased plasma volume in mother)

Severe in liver disease

Question 17

Plasma creatinine as an indicator of renal function

Answer 17

Normal adult adult range: 100 (40-120)

Normal kidney function: 120- 150

Mildly reduced kidney function: 150-300

Moderately reduced kidney function: 300-500

Severely reduced kidney function: 500-700

Very severely reduced kidney function: >700

Question 18

Urea

Answer 18

Liver produces urea in urea cycle as waste product of protein digestion

Filtered at the glomerulus, secreted and reabsorbed in the tubule

Plasma urea BUN

Normal range: 2.5-7.5mmol/L

Question 19

Blood urea nitrogen increased by

Answer 19

High protein diet

Hypercatabolic conditions

Gastrointestinal bleeding

Muscle injury

Drugs

Hypovolaemia

Question 20

Blood urea nitrogen decreased by

Answer 20

Malnutrition

Liver disease

Sickle cell anaemia

SIADH

Question 21

Examples of renal clearance

Answer 21

Filtered by the glomerulus and not reabsorbed e.g. inulin

Filtered and some of the filtered portion is reabsorbed e.g. Na+

Filtered and completely reabsorbed e.g. glucose and amino acids

Primarily secreted into the tubule e.g. PAH

Question 22

Clearance

Answer 22

The volume of plasma completely cleared of a given substance in unit time

Provides information about functions of the kidney

• glomerular filtration
• tubular reabsorption
• tubular secretion

Question 23

Renal clearance drawbacks

Answer 23

Measuring clearance means measurement of overall nephron function- 2 million nephrons in both kidneys

Gives sum of all transport processes occurring

No information about precise tubular sites of mechanisms of transport

Question 24

Glomerular filtration rate

Answer 24

Rate at which filtrate is produced in the kidneys

Can be measured clinically and used as an indicator of renal function

Can be estimated by measurement of clearance of cretinine

More accurate estimation is measurement of inulin clearance as it is not secreted into tubule

Question 25

Inulin clearance for measurement of GFR

Answer 25

Plant polysaccharide Freely filtered but not secreted and not reabsorbed Rate of excretion in urine equals rate of filtration by the kidneys

Question 26

Drawbacks of inulin clearance to measure GFR

Answer 26

Not clinically useful - must be administered by IV to get relatively constant plasma or serum levels - chemical analysis of inulin in serum and urine is technically demanding - could use radiolabelled compounds instead - may also bind to proteins and distort results - problems of IV infusion of GFR markers are avoided by using an endogenous substance with inulin like properties e.g. creatinine

Question 27

Creatinine clearance

Answer 27

Filtered at the glomerulus but some also secreted into the proximal tubule Using the equation would over estimate GFR by about 20% in humans Colorimetry methods used to measure creatinine under estimates creatinine concentrations by about 20% 2 errors cancel each other out

Question 28

Adjustments due to body surface area

Answer 28

Creatinine clearance can also be adjusted to take account of body surface area Corrected creatinine clearance= meausre CrCl x1.71/BSA

Question 29

Estimation of GFR using serum creatinine only

Answer 29

Allows estimation of GFR without having to collect urine samples Cockcroft- Gault Formula Modification of diet in renal disease formula

Question 30

Using PAH clearance to measure renal blood flow

Answer 30

If a substance is completely cleared from the plasma its clearance rate will be equal to renal plasma flow Clearance of PAH can be used to estimate this Not normally present in blood