NP5 Nephrology Assessment of Renal Function Essential Med Notes 2015

3. Estimate GFR using MDRD formula � most common way in which GFR is estimated (MDRD 7 equation) � complex formula incorporating age, gender, serum Cr, and African descent, but does not include weight

� GFR is reported as mL/min/1.73 m2 body surface area4. Estimate GFR using CKD-EPI equation

� the best current equation � calculated using serum Cr, age, sex, and race

Limitations of Using Serum Cr Measurements1. must be in steady state

� constant GFR and rate of production of Cr from muscles � sudden injury may reduce GFR substantially, but it takes time for Cr to accumulate and then re-establish steady state

� clinical correlation: in AKI, the rise in Cr is often delayed2. GFR must fall substantially before plasma [Cr] rises above normal laboratory range

� with progressive renal failure, remaining nephrons compensate with hyperfiltration � GFR is relatively preserved despite significant structural damage

3. plasma [Cr] is influenced by the rate of Cr production � lower production with smaller muscle mass (e.g. female, elderly, low weight)

� for example, consider plasma [Cr] of 100 µmol/L (1.13 mg/dL) in both of these patients • 20 yr old man who weighs 100 kg, GFR = 144 mL/min • 80 yr old woman who weighs 50 kg, GFR = 30.6 mL/min � clinical correlation: GFR decreases with age but would not be reflected as a rise in serum Cr due to the age-associated decline in muscle mass

4. tubular secretion of Cr increases as GFR decreases � serum Cr and CrCl overestimate low GFR � certain drugs (cimetidine, trimethoprim) interfere with Cr secretion

5. errors in Cr measurement � very high bilirubin level causes [Cr] to be falsely low � acetoacetate (a ketone body) and certain drugs (cefoxitin) create falsely high [Cr]

Measurement of Urea Concentration• urea is the major end-product of protein metabolism• plasma urea concentration reflects renal function but should not be used alone as it is modified

by a variety of other factors• urea production reflects dietary intake of protein and catabolic rate; increased protein intake or

catabolism (sepsis, trauma, GI bleed) causes urea level to rise• ECF volume depletion causes a rise in urea independent of GFR or plasma [Cr]• in addition to filtration, a significant amount of urea is reabsorbed along the tubule• reabsorption is increased in hypernatremic states such as ECF volume depletion• typical ratio of urea to [Cr] in serum is 1:12 in SI units (using mEq/L for urea and µmol/L for Cr)

Urinalysis• use dipstick in freshly voided urine specimen to assess the following:

1. Specific Gravity• ratio of the mass of equal volumes of urine/H2O • range is 1.001 to 1.030 • values <1.010 reflect dilute urine, values >1.020 reflect concentrated urine • value usually 1.010 in ESRD (isosthenuria)

2. pH• urine pH is normally between 4.5-7.0; if persistently alkaline, consider:

� RTA � UTI with urease-producing bacteria (e.g. Proteus)

3. Glucose• freely filtered at glomerulus and reabsorbed in proximal tubule • causes of glucosuria include

1. hyperglycemia >160-200 mg/dL (>9-11 mEq/L) leads to filtration that exceeds tubular resorption capacity

2. increased GFR (e.g. pregnancy) 3. proximal tubule dysfunction (e.g. Fanconi’s syndrome)

4. Protein• dipstick only detects albumin; other proteins (e.g. Bence-Jones, Ig, Tamm-Horsfall) may be missed • microalbuminuria (defined as ≥2.0 mg/mEq Cr in males and ≥2.8 mg/mEq Cr in females) is not

detected by standard dipstick (see Diabetes, NP28) • sulfosalicylic acid detects all protein in urine by precipitation • gold standard: 24 h timed urine collection for total protein

Clinical Settings in which Urea Level is Affected Independent of RenalFunction

Disproportionate Increase in Urea• Volume depletion (prerenal azotemia)• GI hemorrhage• High protein diet• Sepsis• Catabolic state with tissue breakdown• Corticosteroid or cytotoxic agents

Disproportionate Decrease in Urea• Low protein diet• Liver disease

Cystatin C Cystatin C is a protease which is completely filtered by the glomerulus and is not affected by muscle mass; it is not currently used in clinical practice, but may be a more accurate way to measure renal function in the future, particularly in DM

24 h Urine Collection• Discard first morning specimen• Collect all subsequent urine for the

next 24 h• Refrigerate between voids• Collect second morning specimenClarity: Cloudiness may indicate infectionColor: usually pale yellow or amber, but may be colorless (diabetes insipidus, excess water intake), bright yellow (due to riboflavin ingestion or vitamin tablets), or dark yellow (concentrated urine in intravascular volume depletion)

Estimating Urine OsmolalityLast 2 digits of the specific gravity x 30 = urine osmolality approximately (e.g. specific gravity of 1.020 = 600 mOsm)