Assessment Of Renal Function Flashcards
What are the major functions of the kidney?
Homeostasis – water balance, sodium and potassium (salts), acid/base balance (pH)
Excretion of waste products – creatinine and urea (nitrogen compounds), excess inorganic substances
Hormone production: renin, erythropoietin (RBC synth, leads to anaemia if not produced), 1a-VitD3 hydroxylation (absence leads to bone weakening)
What are the symptoms of kidney disease?
Symptoms/signs of hypertension (swollen ankles, high blood pressure, headaches, visual disturbances)
Changes in urinary frequency or volume (many will not notice or visit their GP until this is marked).
In stages 4 and 5 (too late- very poor prognosis!): 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. SO OFTEN NO SYMPTOMS AT ALL!!
- Regular monitoring of those at risk therefore very important; CVD, HT,
DM, genetically at risk individuals
How is imaging used to assess kidney function and what are the disadvantages of this as a diagnostic tool?
Imaging allows you to spot an obstruction - can tell you where by imaging whole urinary system)
Usually ultrasound (but could utilise CT/MRI):
Imaging of kidney, bladder, ureters, prostate gland –
Asseses size/ symmetry/ obstruction to urine flow anywhere?
Main disadvantages: expensive, difficult to assess extent of functional damage, also isn’t good for monitoring as you can’t use it often, also doesn’t tell you stage of damage
How is histology and microscopy used to assess kidney function and what are the disadvantages of this as a diagnostic tool?
Can assess both the medulla and the cortex.
Main disadvantages: Biopsy invasive, only a ‘snapshot’.
- Kidney damage can change very quickly
How can immunological techniques be used to assess kidney function and what are the disadvantages of this as a diagnostic tool?
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
Main disadvantage: only useful in specific diseases
- Mainly related to autoimmune disease, all they can do is prove, or rule
this out.
What is urinalysis?
Urine defined as:
fluid excreted by the kidneys, passed through ureters, stored in bladder, discharged through urethra.
Should be a response to what’s happening in your blood - hence no urine osmolality reference range!
In health: sterile, clear, amber, slightly acidic (pH 5.0-6.0), characteristic odour.
Anuria: <100 ml in 24 hr almost nothing, sign of obstruction?
Oliguria: far less than it optimal <400 ml in 24 hr, obstruction?
Polyuria: >3 L per 24 hr but changes based on body mass ( >50 ml/kg mass/24 hr = WEIGH THEM
What is filtered by the glomerulus?
Selective filter of blood passing through capillaries - macromolecules restricted by size, charge and shape.
Fibres 2nm apart but this increases if applied pressure falls – fibres separate, so more things can leak through.
- <5kDa molecules (e.g. inulin, urea, creatinine, glucose, electrolytes) - all
freely filtered - Proteins >66kDa and 3.5nm (e.g. albumin) generally retained by a
healthy glomerulus – so should not appear in urine
How can urine dipsticks be used to assess kidney function and what are the disadvantages of this as a diagnostic tool?
Look at protein levels, blood - neither should pass glomerulus into urine, and glucose, too much and it would be in urine.
Subjective to human error - semi quantitative (automated reader? Still depends on how long you have waited?)
Limitations:
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
Interferences:
Blood analysis – menstruation (+ve), vit. C (-ve)
Protein analysis – infected urine (alkaline, so will appear +ve for proteins), dilute urine (-ve)
What are ideal markers of kidney function?
Freely filtered
Not reabsorbed
Not secreted
Not metabolised in kidney (kidney cans make small proteins)
Not synthesised in the renal tubules/ kidney
What are the different exogenous markers used to assess kidney function?
Inulin (‘gold standard’)
- Metabolically inert sugar, provides good GFR estimation
- disadvantages:
- non-endogenous (intravenous administration)
- assay not widely available
- expensive - can’t use in everyone
Urea:
- end product of nitrogenous compound metabolism (esp. amino acids),
freely filtered at glomerulus.
- disadvantages:
- Some passive reabsorption in renal tubules
- Raised in GI bleeds/high protein diets, low in liver disease
Creatinine:
- product of muscle metabolism, fairly constant rate of production,
removed by glomerular filtration.
- Quick, cheap & convenient
- disadvantages:
- Interferences (e.g. Jaffe method – interference from ketones, bilirubin)
- GFR falls to <50ml/min before creatinine rises
Cystatin C:
- small protein produced by all nucleated cells - not affected by muscle
mass, age, gender or race.
- disadvantages:
- Affected by thyroid function and some drugs.
- expensive
NGAL (Neutrophil Gelatinase Associated Lipocalin):
‘Up and coming’ marker of acute kidney injury
How can the Glomerular Filtration Rate be used to assess kidney function and what are the disadvantages of this as a diagnostic tool?
Thought to be most reliable measurement of functional capacity –
?indicates number of functioning nephrons.
Most sensitive and specific marker of changes in overall renal function.
↓ GFR = kidneys doing less filtering so the plasma/serum creatinine increases, and the urine creatinine is reduced due to reduced clearance
How does creatinine clearance measure GFR?
Urine creatinine (in 24h period)
Serum/plasma creatinine (single sample at same time)
Clearance:
(CrCl ml min-1 ) = Urine creatinine mmol/L x Urine vol (mL)
Plasma/serum creatinine mmol/L x time (min)
What is eGFR?
175 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black)
4 variables used
- Serum creatinine
- Age: down w age
- Sex: men higher, more muscle mass?
- Ethnicity: black AC or not..?
Not to be used in
- AKI
- Children
- Pregnancy
- Malnourished
- Oedematous states (not fluid balanced)
- Muscle wasting diseases
- Amputees (less muscle mass)
What is proteinuria?
Variation due to: biology, posture, exercise, UTI, fever.
Proteinuria occurs in kidney disease due to either:
- increases in filtered load (increased glomerular vascular permeability)
or
- decrease in reabsorptive capacity (due to tubular damage).
Glomerular proteinuria – increased permeability means that larger and larger proteins are excreted, e.g. albumin, IgG. NON-SELECTIVE
Tubular proteinuria – decreased reabsorption of the freely filtered small proteins (e.g. RBP). These then appear in relatively higher quantities than albumin in the urine
24h protein excretion (<0.15g/24h)
Protein loss >3g/24h can result in ‘nephrotic syndrome’
- Protein:creatinine ratio (PCR)
- Albumin:creatinine ratio (ACR)
- Microalbumin (ability to detect albumin at low levels in urine)
Also make general assumptions.
- Assume standard creatinine consumption and excretion,
- Assumes male or female (midway through transition, or changed sex?)
How is proteinuria classified?
Overflow - too much going in - over saturation
Glomerular- the ‘sieve isn’t working, letting too much through
Tubular - glom working cannot be reabsorbed
What are the assumptions made in PCR and ACR?
Urine output 1.5L
Creatinine excretion 10mmol/day
Binary gender: male/female (not transgender or other)
How do the electrolytes vary with 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 1α hydroxylation 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 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). Or other proof, eg ultrasound.
What do NICE recommend for CKD?
Advise people not to eat any meat in the 12 hours before having a blood test for eGFR creatinine
Interpret eGFR-creatinine 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 eGFR-cystatin 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:creatinine ratio [ACR] less than 3 mg/mmol) or other marker of kidney disease
What are the different definitions for chronic kidney disease?
GF1: GFR >90 (normal or high)
GF2: GFR 60-89 (mildly decreased)
GF3a: GFR 45-60 (mildly to moderately decreased)
GF3b: GFR 30-44 (moderately to severely decreased)
GF4: GFR 15-29 (severely decreased)
GF5: GFR <15 (kidney failure)
If a patient falls into the 60-90 category then look at their albumin-creatinine ratio (ACR). <3mg/mmol albumin to creatinine in urine. >30mgs of albumin for every ml of creatinine is very serious CKD.
ACR 1 <3mg/mmol
ACR 2 3-30mg/mmol
ACR 3 >30mg/mmol
Diabetes Mellitus:
ACR <2.5mg/mmol
ACR <3.5mg/mmol
How is Acute Kidney Injury defined?
The reference serum creatinine should be the lowest creatinine value recorded within 3 months of the event. Comparison to a baseline value, not a value within the reference range!
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
Stage 1:
- SCr: increase ≥ 26μmol/L within 48hrs or increase ≥1.5 to 1.9 x
reference SCr
- Urine: <0.5 mL/kg/hr for > 6 consecutive hrs
Stage 2:
- SCr: increase ≥ 2 to 2.9 x reference SCr
- Urine: <0.5 mL/kg/ hr for > 12hrs
Stage 3:
-Scr: increase ≥354μmol/L or increase ≥3 x reference SCr or
commenced on renal replacement therapy (RRT)
- Urine: <0.3mL/kg/hr for > 24hrs or anuria for 12hrs
What are the NICE recommendations 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
