7 Renal Function Flashcards
Why is urinalysis done?
- East to collect.
- Readily available.
- Avg. daily output is 1200mL.
What are the renal functions?
- Excretion of waste, drugs, and toxins.
- Fluid and electrolyte balance.
- Regulation of acid-base balance.
- Secretion of hormones.
How much blood is received by the kidneys?
~1200 to 1500 mL of blood per minute is received by the kidneys to filter.
What mechanisms facilitate filtration through the kidneys?
Facilitated by pressure difference and semipermeability of the glomerular basement membrane
What substances can pass through the kidneys and what is filtered out?
Water, electrolytes, glucose, amino acids, urea, creatinine, etc. can pass through, but large molecules like albumin and cells can NOT.
Glomerulus filters out 125 to 130 mL of a protein and cell free fluid called glomerular filtrate
What is the Glomerular Filtration Rate (GFR)?
GFR = Volume of blood filtered per minute by the kidneys.
Why does the nephron reabsorb substances and how?
Reabsorption:
Need water, sodium, potassium, chloride, glucose, amino acids, etc.
Active transportation to get back to the blood
If substance exceeds capacity then it will be excreted in urine
Think glucose renal threshold
What is secreted by the nephron and by what methods?
- If substance exceeds capacity then it will be excreted in urine
Think glucose renal threshold. Excess substances: Na, K, Cl, HCO3-, Ca, Mg, Phos, etc. - Secretes products of cellular metabolism.
- Excretion of waste, drugs, and toxins: Urea, creatinine, uric acid
Active and passive transport.
What is ADH and what does it do? What stimulates its release?
- Peptide hormone released by posterior pituitary
- Released in response to ↑ plasma osmolality or ↓ blood volume
- Stimulates water reabsorption: ↑ plasma water levels, Plasma osmolality returns to normal
What is Aldosterone, what regulates it and what does it do?
- Corticosteroid produced by the adrenal cortex
- Influenced by renin-angiotensin mechanism. Released in response to ↓ blood volume or ↓ blood pressure
- Stimulates sodium reabsorption:
↑ plasma sodium levels
↑ water reabsorption
Blood volume returns to normal
What role does the kidneys play in acid-base balance?
Conserves bicarbonates and removes metabolic acids.
What hormones does the kidney secrete?
- Renin
- Erythropoietin.
- 1,25-dihydroxy vitamin D3
- Prostaglandins.
What does the hormone renin do?
Renin:
↓ blood volume or ↓ blood pressure causes ↑ in renin
Results in ↑ angiotensin I > ↑ angiotensin II (vasoconstrictor) > ↑ blood pressure > ↑ aldosterone = sodium reabsorption and water conservation
What does erythropoietin do?
Erythropoietin
Hypoxia (anemia) causes ↑ in erythropoietin
Acts on erythroid progenitor cells in the bone marrow to ↑ RBCs
What does 1,25-dihydroxy vitamin D3 do?
1,25-dihydroxy vitamin D3:
Kidneys form active vitamin D which ↑ calcium in the body and modulates the skeleton by:
↑ intestinal absorption of calcium and phosphate
↓ renal excretion of calcium and phosphate
↓ PTH production
Regulates osteoblast function and bone resorption
What does Prostaglandins do?
Prostaglandins
Cyclic fatty acids that increase renal blood flow, sodium and water excretion, and renin release
Oppose function of renal vasoconstriction from angiotensin
What is in a renal panel?
Renal Panel:
- Urea and Creatinine
- Total Protein and albumin
- Osmolality
- Electrolytes: Na, K, Cl, Calcium and Phosphate
- Calculations: Urea/Creatinine Ratio, Creatinine Clearance, and eGFR
Is 24 hr urine collected with preservative or not?
Collect 24 hr urine without preservative.
What are the adult reference values for sodium, potassium, chloride, calcium, phosphate, and osmolality?
Sodium 40-200 mmol/d
Potassium 40 - 80 mmol/d
Chloride 110-250 mmol/d
Calcium
Male <= 6.9 mmol/d
Female: <= 6.2 mmol/d
Phosphate 13 -42 mmol/d
Osmolality 50 - 1200 mOsm/kg
Review the purpose of each of these on slide 13.
What is increased protein in urine called? What can it indicate?
Proteinuria
Urine protein testing can be used to evaluate renal disease.
What are some case where proteins are seen in the urine?
Proteins that have been filtered by the glomeruli and not retained are excreted:
- Glomerular or tubular defects
- Can also be seen in cases of: hypertension, diabetes mellitus, vascular disease, neoplasia, and some infectious diseases
What is the preferred specimen for assessing total protein in urine?
24 hr specimen
What is the reference range for total protein in urine?
Total protein reference range: < 0..14 g/d
Why is albumin in urine used?
Albumin in urine can be an indication of kidney disease
Note: Trace or small amounts of albumin can be present normally with strenuous exercise
Further investigation required to determine cause
What is microalbuminuria?
Microalbuminuria –> Small excretion of albumin in urine
What is Overtnephropathy?
Overtnephropathy –> Persistent high levels of albumin in urine
What is the general process for evaluating monoclonal protein from 24 hr urine?
- 24 hour urine –> Needs to be aliquoted and centrifuged (concentrated) prior to running
- Urine proteins are separated in an electric field according to their size, shape, and electric charge
- Monoclonal band (M-spike) in the urine of patients with monoclonal gammopathies
- Followed with immunofixation to identify immunoglobulin heavy and/or light chain
In what patients are monoclonal band (M-spike) evaluated for?
Monoclonal band (M-spike) in the urine of patients with monoclonal gammopathies:
a) Multiple Myeloma,
b) Primary amyloidosis and
c) Light chain deposition disease
What are Bence-Jones Proteins? And what patients are seen with these?
Bence-Jones Proteins
- Free light chain in serum and can pass through glomerulus into urine
- Seen in patients with Multiple Myeloma or Waldenstrom’s
What is the reference range for monoclonal protein?
Negative for monoclonal proteins
What can replace the 24 hr urine electrophoresis process and for what purpose?
- Serum Free Light Chain analysis can replace 24 hour urine electrophoresis process
- Used in the monitoring of treatment and assessment of disease progression
What are NPN compounds and list them?
Nonprotein nitrogen (NPN) compounds are waste products formed in the body as a result of degradative metabolism of amino acids, proteins, and nucleic acids.
- Creatinine
- Urea
- Ammonia
- Uric Acid
What is creatinine?
Creatinine: Muscle creatine and creatine phosphate spontaneously dehydrates and forms the waste product creatinine at a constant rate related to muscle mass
Changes greatly from person to person (age, gender, ethnicity, muscle mass, diet, medications, etc.)
What is urea?
Urea:
Proteins are broken down into amino acids > deaminated to form ammonia (toxic!)> ammonia is converted to urea in the liver
What is the measurement of ammonia used for?
Ammonia
Used to assess liver function
If conversion to urea cannot occur, toxic amounts of ammonia may spill into urine or blood
What is uric acid?
Uric Acid –> Uric acid is formed as a waste product of purine metabolism
What is the clinical significance of creatinine measurement?
Increase of creatinine could indicate:
- Chronic Kidney Disease (CKD) - Defined as abnormalities of kidney structure and/or function that have long-term health implications.
a) Abnormalities must be present for greater than 3 months
b) Main causes are diabetes and hypertension - Can be asymptomatic so laboratory monitoring is key!
- Most common cause of death for people with CKD is associated cardiovascular disease
What are the adult reference ranges for creatinine measurement in plasma and urine?
Creatinine Adult Reference Ranges
Plasma:
Female is 35-97µmol/L
Male is 44-106µmol/L
Urine:
8.0-16.0mmol/dWhat is the Jaffe method of creatinine measurement?
In an alkaline solution, creatinine + picrate → creatinine picrate (red-orange complex)
Rate of change measured 2 times at 520nm using a spec
Proportional to the creatinine concentration
What is the pro/con of the Jaffe measurement of Creatinine?
Pro: Simple and inexpensive
Con: Ingredients contain picric acid so there is a safety risk
What substances may interference in the measurement of creatinine in the Jaffe method?
Creatinine Jaffe Method interferences:
Bilirubin, ketones, ascorbate, and glucose may interfere.
What is the enzymatic method of creatinine method?
- Creatinine is hydrolyzed to creatine by creatininase
- Creatine is converted to sarcosine by creatine amidinohydrolase
- Sarcosine is oxidized to glycine, formaldehyde, and hydrogen peroxide by sarcosine oxidase (SOD)
- The hydrogen peroxide, catalyzed by peroxidase, reacts with 4-aminophenazone and HTIBa to form a quinone imine chromogen quantified at 550nm
- Color intensity of the chromogen is directly proportional to the creatinine concentration in the specimen
What substances may interfere with the measurement of creatinine by the enzymatic method?
Bilirubin or ascorbate may interfere
What creatinine clearance?
Creatinine clearance: Rate of clearance of creatinine is used as a measurement of glomerular function.
Creatinine is created at a relatively constant rate and not reabsorbed by the nephron.
Remember: waste product produced by muscles from creatine and creatine phosphate
What are the collection requirements for creatinine clearance?
Requirements:
- 24 hour urine collection –> No preservative. Refrigerated during collection.
- Plasma sample –> Collected ideally at the half-way point in the 24 hour urine collection.
What is the reference range for creatinine clearance?
Creatinine Clearance: 75-125mL/min/1.73m2
What is the equation for creatinine clearance, CrCl and units?
CrCL = [Ucr x Vur / (Pcr x t) ] x (1.73/A),
where
CrCl (mL/min/1.73m2) – Creatinine Clearance
Ucr – Urine creatinine value
Vur – volume of urine in mL/24 hours
1.73 – Average body surface in m2
PCr – Plasma creatinine value (may be SCr if serum is used for analysis)
t = usually 1440 (minutes in 24 hours)
A – Actual body surface area as determined from height and weight of patient
Refer to nomogram on next slide.
Note: must convert Ucr and/or PCr so they are in the same units
What is the glomerular filtration rate (GFR)?
Glomerular filtration rate (GFR) is defined as the rate at which the kidneys filter plasma constituents through the glomerulus.
What is the estimated glomerular filtration rate? What is the benefit of this method?
Estimated Glomerular Filtration Rate (eGFR):
- eGFR is automatically provided when plasma creatinine is requested. Formula developed to estimate glomerular filtration rate without a 24 hour urine collection.
- Earlier detection of chronic kidney disease
What is the relationship between GFR and plasma creatinine?
GFR and creatinine have an inverse relationship
↑ concentrations of plasma creatinine are present with ↓ GFR
What is the adult reference range for eGFR?
Reference Range for eGFR
≥ 60 mL/min/1.73m2
< 60 mL/min/1.73m2 indicative of chronic kidney disease
In acute kidney injury what substance levels rise more quickly than creatinine and what is its source?
- Levels of cystatin C rise more quickly than creatinine in acute kidney injury (AKI)
- Cystatin C - Low-molecular-weight protein produced by most body tissues. Produced at a constant rate and filtered by the glomerulus.
What is the benefit of using Cystatin C and when is it used? Who requests it?
- Unaffected by diet, race, age, and muscle mass
- Therefore, more useful to use cystatin C measurement in individuals with atypical muscle mass than to use creatinine measurement.
- Can only be requested by nephrologists
How are samples for cystatin C measurements obtained?
Serum sample collected, frozen, and sent to In-Common Laboratories
Measured using nephelometry
What is the reference range for Cystatin C?
Cystatin C Reference Range: 0.27 – 1.20 mg/L
Can GFR be estimated from Cystatin C measurement? Reference range?
Yes, GFR can be estimated from measured Cystatin C
CYSCeGFR > 90 mL/min
How much urea is reabsorbed?
Urea - 40% passively reabsorbed by tubules
What is azotemia and uremia?
Terms:
Elevated concentration of urea in blood is azotemia
High plasma urea + renal failure = uremia
What are the clinical significance of urea increases?
Urea Increases
Pre-renal – CHF, shock, hemorrhage, dehydration, increased protein catabolism, high protein diet
Renal – acute and chronic renal failure, renal disease including glomerular nephritis and tubular necrosis
Post-renal – urinary tract obstruction (calculi, tumour, or infection)
What are the clinical significance of urea decreases?
Urea Decreased
Low protein intake (“tea and toast” diet in elderly or malnutrition, severe vomiting, severe diarrhea, liver disease, and pregnancy
What is the method to measure urea?
Enzymatic Methods:
- NAD+ measured at 340nm
- Urea and water is broken down by urease into 2NH4 and CO3. NH4 is then broken down by GLDH (glutamate dehydrogenase) to become glutamate + water.
- Indicator dye: NH4+ + pH indicator → color change
- Ion selective electrode (ISE) –> use enzyme ISE as urea is non-ionic.
What is the urea / creatinine ratio useful for?
When assessed with plasma creatinine can be used to diagnosis pre-renal, renal, and post-renal hyperuremia
When is urea / creatinine ratio calculated? What is the reference range?
Automatically calculated and reported when urea is elevated and creatinine is requested
Urea/Creatinine Ratio = [Urea (mmol/L) x 1000]/Creatinine (μmol/L)
Reference Range = < 70
What leads to a high or low pre-renal changes in the urea / creatinine ratio, a normal renal ratio and postrenal increased ratio?
Pre-renal
High urea/normal Creatinine = ↑ ratio
Low urea/normal Creatinine = ↓ ratio
Low protein intake or severe liver disease
Renal –> High urea/high creatinine = N ratio
Postrenal –> High urea/high creatinine = ↑ ratio
Where is uric acid secreted and reabsorbed in the renal tubules?
Filtered by glomeruli and secreted by distal tubules into urine and reabsorbed in first part of proximal tubule for reuse
What is the clinical significance of increased uric acid in urine?
Increased Uric Acid Concentrations:
Gout –> Precipitation of monosodium urate or uric acid crystals in joints or tissues – painful!
Also increased in chemotherapy, renal failure, inherited disorders, purine rich diet, kidney stones
What are the two methods uric acid is measured by and the main enzymes or chemical condition involved?
Uric Acid Measurement:
- Chemical Method –> Phospho-tungstic acid in requires alkaline conditions
- Coupled Enzymatic Reaction –> Uses Uricase to make allantoin and H2O2 from uric acid. H2O2 and peroxidase makes a chromogenic product that is measured.
