Assessment of Renal Function Flashcards
What are the main functions of the kidney?
- Homeostasis: water, salt, acid-base status
- Excretion of waste products: non-proteinous nitrogen compounds; urea , creatinine, uric acid, and excess inorganic substances; sodium, Cl, Ca, K, Mg, sulfate, and excess water.
- Hormone production: erythropoietin, renin, prostaglandins, 1a-vitD3 hydroxylation.
What are symptoms of Kidney Disease?
- Often none
- Symptoms/signs of hypertension such as swollen ankles, high blood pressure, headaches, visual disturbances
- Changes in urinary frequency or volume
- In stages 4 and 5 of CKD: fatigue, nausea, vomiting, poor appetite, shortness of breath, fluid retention.
Reduction of 50-60% functional renal mass may occur before any signs or biochemical abnormalities manifest. Regular monitoring of those at risk therefore very important; CVD, HT, DM, genetically at risk individuals
What are some laboratory investigations for Kidney Disease?
- Imaging: Ultrasounds, CT/MRI
- Histology and microscopy (although renal biopsy rarely used)
- Immunology
- Biochemistry: Urinalysis and Quantitative biochemical markers
What are the advantages and disadvantages of imaging?
Advantages
- Size/ symmetry/ obstruction to urine flow anywhere
- Imaging of kidney, bladder, ureters, prostate gland
Disadvantages
- Expensive
- Difficult to assess extent of functional damage.
What is seen on histology of the kidney?
Acellular
- Hyaline
- Granular
- Waxy
- Fatty
- Pigment
- Crystal
Cellular
- RBC
- WBC
- Bacterial
- Epithelial
Which immunological tests are done in the kidney?
- Complement: low C4 seen in Systemic Lupus Erythematosus (SLE) & cryoglobulinaemia.
- Anti-glomerular basement membrane antibodies: associated with Goodpasture’s disease (kidney & lung disease).
- cANCA: associated with vasculitis esp. Wegener’s disease.
- pANCA: associated with vasculitis.
What are disadvantages of immunological testing and histology/microscopy?
Immunological: Only useful in specific diseases
Histology/Microscopy: Biopsy invasive, only a ‘snapshot’.
What is Anuria, Polyuria, and Oliguria?
- Anuria: <100mL/24h
- Oliguria: <400mL/24h
- Polyuria: >3L/24h OR >50mL/kg mass/24h
What are some limitations for Urinalysis?
- Potential for operator error.
- Inter-operator variability, even with automation.
- Requires fresh urine, in date, properly stored dipsticks
- Poor sensitivity and specificity - sensitivity depends on concentration of urine
What are some interferences for Urinalysis?
- Blood analysis: menstruation (+ve), vit. C (-ve)
- Protein analysis: infected urine (+ve), dilute urine (-ve)
What are Quantitative biochemical measurements?
Glomerular filtration/function
- Urea
- Creatinine
- Proteinuria
Tubular function
- Urine volume/osmolality
- pH
- Phosphate
- Aminoaciduria
- Glycosuria
- β2-microglobulin
What is the biochemical measurement used for Fanconi Syndrome?
Assessment of Tubular function using
- Phosphate
- Aminoaciduria
- Glycosuria
What are ideal markers of kidney function?
- Freely filtered
- Not reabsorbed
- Not secreted
- Not metabolized
- Not synthesized in the renal tubules/ kidney
What are some exogenous markers of kidney function?
- Inulin (‘gold standard’)
- 125I-Iothalamate
- 51Cr-EDTA
- 99mDTPA
- Iohexol
What are advantages and disadvantages of Inulin?
Inulin (‘gold standard’)
Advantages
- Metabolically inert sugar
- Provides good GFR estimation
Disadvantages
- Non-endogenous (intravenous administration)
- Assay not widely available
- Expensive
What are the endogenous markers of Kidney Function?
- Urea: end product of nitrogenous compound metabolism (esp. amino acids), freely filtered at glomerulus.
- Creatinine: product of muscle metabolism, fairly constant rate of production, removed by glomerular filtration.
- Cystatin C: small protein produced by all nucleated cells - not affected by muscle mass, age, gender or race. Affected by thyroid function and some drugs.
- NGAL (Neutrophil Gelatinase Associated Lipocalin):‘Up and coming’ marker of acute kidney injury
What are disadvantages of Urea as a endogenous markers?
- Some passive reabsorption in renal tubules
- Raised in GI bleeds/high protein diets, low in liver disease
What are advantages of Serum/plasma creatinine?
Advantages
- Quick
- Cheap & convenient
Disadvantages
- Interferences (e.g. Jaffe method – ketones, bilirubin). Many labs now use enzymatic assays
- GFR falls to <50ml/min before creatinine rises
What is the Glomerular Filtration Rate?
- Thought to be most reliable measurement of the functional capacity of the kidneys which indicates number of functioning nephrons.
- It is the most sensitive and specific marker of changes in overall renal function.
↓ GFR = ↑ plasma/serum creatinine
↓ GFR = ↓ urine creatinine (reduced creatinine clearance)
How is Creatine measured?
- Urine creatinine (in 24h period)
- Serum/plasma creatinine (single sample at same time)
What is the equation for clearance?
(CrCl ml min-1 ) = (Urine creatinine mmol/L x Urine vol (mL)) / (Plasma/serum creatinine mmol/L x time (min))
How is a 24h urine collected?
Day 1:
- 8am empty bladder (discard output)
- Commence 24h urine collection. All urine now passed until 8am next day must be collected into container.
Day 2:
- 8am collect final urine output into container
- Go to phlebotomy dept – hand in urine specimen and provide a blood sample to accompany urine collection to lab
What are the 4 variables used for eGFR calculation?
- Serum creatinine
- Age
- Sex
- Ethnicity
When should eGFR not be used?
- AKI
- Children
- Pregnancy
- Malnourished
- Oedematous states
- Muscle wasting diseases
- Amputees
What is the measure for Proteinuria?
- 24h protein excretion (<0.15g/24h)
- Protein:creatinine ratio (PCR)
- •Albumin:creatinine ratio (ACR)
- Microalbumin (ability to detect albumin at low levels in urine)
- Urinary sediment (RBC, hyaline, casts)
What is the numerical criteria for nephrotic syndrome?
Protein loss >3g/24h can result in ‘nephrotic syndrome’
What do RBC casts imply?
RBC casts imply haemoglobinuria because of glomerular disease
What are the classifications for Proteinuria?
- Normal
- Overflow (e.g. Bence-Jones proteinuria)
- Glomerular (e.g. albuminuria): increased permeability means that larger and larger proteins are excreted, e.g. albumin, IgG. NON-SELECTIVE
- Tubular (e.g. B2 or A1 microglobunuria): decreased reabsorption of the freely filtered small proteins (e.g. RBP). These then appear in relatively higher quantities than albumin in the urine
- Secreted (e.g. Tamm-Horsfall proteinuria)
Why does proteinuria occur in kidney disease?
- Increases in filtered load (increased glomerular vascular permeability) or
- Decrease in reabsorptive capacity (due to tubular damage).
What are assumptions for PCR and ACR?
- Urine output 1.5L
- Creatinine excretion 10mmol/day
- Binary gender: male/female (not transgender or other)
How are electrolytes used to measure kidney function?
- K: often high due to ↓GFR=inability of excretion. Can be low in some conditions.
- Na: can be low/high/normal. Often useful to assess fluid status.
- Ca: often low due to defective 1αhydroxylation of vitamin D which takes place in the kidney
- PO4 and Mg: often high due to ↓GFR=inability of excretion (however are sometimes low due to increased renal losses especially post-Tx)
What is the definiton of Chronic Kidney Disease?
- Abnormalities of kidney function or structure present for more than 3 months, with implications for health’
- Includes all people with markers of kidney damage and those with a GFR <60 ml/min/1.73 m2 on at least 2 occasions separated by a period of at least 90 days (with or without markers of kidney damage).
What are some NICE recommendations for testing in CKD?
- Advise people not to eat any meat in the 12 hours before having a blood test for eGFRcreatinine
- Interpret eGFRcreatinine with caution in extremes of muscle mass e.g. body builders, amputees, muscle wasting disorders. Reduced muscle mass will lead to overestimation and increased muscle mass to underestimation of the GFR
- Consider using eGFRcystatin C at initial diagnosis to confirm or rule out CKD in people with: –an eGFRcreatinine of 45–59 ml/min/1.73 m2, sustained for at least 90 days and no proteinuria (albumin:creatinineratio [ACR] less than 3 mg/mmol) or other marker of kidney disease
–
What are the stages of Acute Kidney Injury?
Stage 1:
- SCr criteria: Increase ≥ 26μmol/L within 48hrs or increase ≥1.5 to 1.9 x reference SCr
- Urine Output Criteria: <0.5 mL/kg/hr for > 6 consecutive hrs
Stage 2:
- SCr criteria: Increase ≥ 2 to 2.9 x reference SCr
- Urine Output Criteria: <0.5 mL/kg/ hr for > 12hrs
Stage 3:
- SCr criteria: Increase ≥354μmol/L or increase ≥3 x reference SCr or Commenced on renal replacement therapy (RRT)
- Urine Output Criteria: <0.3mL/kg/hr for > 24hrs or anuria for 12hrs
What are the considerations made when measuring the creatinine for AKI?
- The reference serum creatinine should be the lowest creatinine value recorded within 3 months of the event. If a reference serum creatinine value is not available within 3 months and AKI is suspected repeat serum creatinine within 24 hours
- Reference serum creatinine value can be estimated from the nadir serum creatinine value if patient recovers from AKI
What is the recommendations made after diagnosis for AKI?
Monitor people for the development or progression of CKD for at least 2–3 years after acute kidney injury, even if serum creatinine has returned to baseline
