Preservative for urine urea collection?
Thymol, to avoid bacterial action
Interferences with urea method
Haemolysis increases urea and icterus decreases it
Causes of hypokalaemic metabolic alkalosis
Low Blood Pressure
Genetic diseases
- Bartter syndrome
- Gitelman syndrome
- Autosomal dominant hypocalcemia with hypercalciuria (ADHH)
Acquired diseases
- Diuretic use
- Vomiting
High Blood Pressure
Genetic disease
- Liddle Syndrome
- 11-beta-HSdehydrogenase inactivating mutation (SAME)
Acquired diseases
- Conn disease/secreting adenoma of the adrenal glands/bilateral hyperplasia
- Cushing disease/tumor of the adrenals
- Chronic administration of corticosteroid
- Natural licorice abuse
What is cystatin C
A cysteine protease inhibitor synthesised by all nucleated cells
Advantages of cystatin C over creatinine
Produced at a constant rate
Plasma concentrations unaffected by muscle mass, diet or gender
No known extra-renal elimination nor tubular secretion
EGFR equation exists for both adults and children
Common reference interval for 1-50 years
Potentially more accurate than creatinine
Potentially more reliable for detection of mild-mod impairment of kidney function
Better predictor of adverse outcome than eGFR using creatinine
Directly related to abnormal thyroid function (lower if hypothyroid, higher if hyperthyroid)
Uses of cystatin C measurement
- Assess glomerular function
- interpretable as a single numerical concentration or in calculation of GFR - Monitor renal function and progression of disease
- Risk predictor of poor outcome (death and kidney failure)
- Urinary cystatin C a marker of tubular dysfunction/damage
Limitations of cystatin C/pros of creatinine
Familiarity with creatinine
Confounded by thyroid dysfunction
Glucocorticoid treatment induces cystatin C production
Reported influences of age, gender, pregnancy, weight, height, genetic variation
Cystatin C methods
PETIA (turbidimetry)
PENIA (nephelometry)
Disadvantages of creatinine compared to cystatin C
Calculated eGFR unusable in children, AKI, individuals with muscle wasting
Wide normal reference interval and GFR may fall to half normal before serum creatinine concentration exceed upper reference limit
Dietary protein intake can increase creatinine in individuals with normal renal function
Widely used Jaffe method for creatinine determination non-specific
Why is urea inferior to creatinine as an indicator of renal function?
Considerably influenced by rate of nitrogen/protein turnover and hydration status
Markers of kidney dysfunction
Creatinine
urea
CystatinC
Albumin:creatinine ratio
eGFR
Neutrophil gelatinase associated lipocalin (NGAL)
alpha 1 microglobulin
Measured GFR
Definition of microalbuminuria
M: ACR >2.5mg/mmol
F: ACR > 3.5 mg/mmol
Definition of macroalbuminuria
M: ACR > 25 mg/mmol
F: ACR > 35 mg/mmol
Definition of neprotic range albuminuria
ACR > 300mg/mmol OR
PCR > 300g/mol OR
24hr urine protein > 3.5g/24hr
Preferred method for assessment of proteinuria?
First void spot urine ACR
Prognostic information from albuminuria/proteinuria?
Independent predictors of CKD progression, cardiovascular disease and all-cause mortality in both diabetic and non-diabetic individuals
Rationale for screening with UACR as opposed to UPCR or 24hr urine protein
- Performs as well as UPCR or 24 hr urine protein in predicting doubling of serum creatinine, commencement of RRT and all-cause mortality
- Strong evidence base
a) population studies show UACR predicts kidney and CV risks
b) intervention trials have shown renoprotective benefit associated with reduction in urinary albumin - Greater sensitivity
- Improved analytical precision at low concentrations
- Allows for assay standardisation
- Cost-effective
- Favoured by international best-practice guidelines
- Logistic difficulties with collection of 24 hr urine - inconveneint, incomplete collection, timing errors introduce inaccuracy
- Marked intra-individual variability in 24 hr urine protein results
Disdavantages of screening for proteinuria with UACR?
- May miss non-albumin proteinuria (multiple myeloma, Fanconi syndrome)
- Evidence base for CKD intervention strategies based on proteinuria is greater than it is for albuminuria
- Proteinuria traditionally measured in some specific clinical settings eg pre-eclampsia
Disadvantages of dipstick testing/screening for proteinuria?
- Poor sensitivity
- Operator dependency
- Limited evidence of cost effectiveness in high-risk populations
Why should sex-specific ACR cutoffs be used?
Creatinine excretion varies between men and women. Creatinine excretion is 40-50% higher in males, necessitating a lower ACR threshold for men. Note there is insufficient evidence to support ethnicity or age-specific cut-offs.
Factors other than CKD that can affect urinary albumin excretion?
High protein diet
Strenuous exercise
Circadian variation in protein excretion (higher in the afternoon)
UTI
CCF
Acute febrile illness
Menstruation/vaginal discharge
How is urinary ACR related to urinary protein excretion?
Microalbuminuria may not be detected as urinary protein.
Proportion of urinary protein accounted for by albumin increases as total proteinuria increases and if there is a glomerular rather than non-glomerular abnormality.
Relationship of urine ACR with 24 hr urine protein is non-linear and 24 hr urine protein and albumin excretion cannot be reliably predicted from urine ACR.
Causes of high cystatin c
Renal impairment
Hyperthyroidism
Obesity
Inflammation/infection/malignancy
Indication for urine cystatin c
Renal tubular damage
