Assessment Of Renal Function

Front 1

Functions of the kidney

Back 1

1. regulate water (BV, BP), electrolyte, acid-base balance

2. Excrete waste products of intermediary metabolism (urea, creatinine, uric acid, phosphate, sulphate, organic acid)

3. Production/elaboration of hormoens
(renin, EPO, 1,25(OH)2, vit D3)

Front 2

Parameters of
- renal blood flow
- GFR
- urine formation

Back 2

RBF: 1200 mL/min (~20% cardiac output)

GFR: 180 L/day, 110-140mL/min
(filtration fraction or GFR/RBF = 20%)

Urine formation: 1.5L/day, 1 mL/min

Front 3

how much water is resorbed by kidney?
- where does most water resorption occur?

Back 3

99% water in FILTRATE absorbed by kidney,
65% in PCT accomp. by Na+ and Cl- reabsorption

Front 4

What is the minimal urine vol per day? Why?

Back 4

400 mL/day
- because waste product: 550 mOsm/day
- max urinary conc. attainable is 1300-1400 mOsm/L
so min vol of urine: 550/1400 = 400 mL/day

Front 5

what is oliguria

Back 5

daily urinary output <400mL
→ azotaemia (abnormally high con of nitrogen-contaning compounds: urea, creatinine)
→ uremia (when azotemia becomes symptomatic)

Front 6

Aims of assessing renal function

Back 6

- best way is GFR: conventionally measured using technique of Clearance

Aims:
- assess severity/course of renal disease
- adjust dosage of meds primarily excreted by kidney

Front 7

What is GFR?

Back 7

Volume of glomerular filtrate produced by both kidneys per unit time

- Most sensitive parameter to reflect renal excretory function
- expressed in mL/min

Front 8

What is clearance? what is it used for?
- what is the ideal substance to estimate GFR?

Back 8

Clearance: vol of plasma from which a substance is completely cleared by kidneys per unit time

- estimates GFR of a particular substance
GFR = (Um x Vt)/Pm
Um: conc of substance M in urine
V: vol of urine/time [usually 24-hr collection]
Um x V: mass of M filtered/time
Pm: conc of M in plasma
(therefore GFR = vol of plasma filtered/time)

ideal substance to estimate GFR:
- freely filtered
- not reabsorbed, secreted, synthesized, metabolised (conc not altered by renal tubule cells
- creatinine almost fulfills all these requirements

Front 9

Clinical applications of GFR
- what contributes to GFR? [3]

Back 9

GFR depends on
- adequate no. of nephrons
- intact glomerular function
- normal renal PERFUSION

Front 10

Pathological conditions leading to decreased GFR
- what does low GFR indicate?

Back 10

- ↑plasma creatinine, urea
- secondary electrolyte & acid-base disturbance

Indications
- good index of chronic renal disease
- ↓GFR precedes renal failure: predicts TIME TO ONSET of renal failure

Front 11

how to mange GFR?

Back 11

- monitor changes to portrait progression of renal disease
- proper drug dosage: avoid potential drug toxicity

Front 12

WHAT IS PLASMA CREATININE? [5]

Back 12

- metabolic end-product of skeletal ms creatine
- not protein bound, non-polar, small (Freely filtered)
- not reabsorbed or metabolized.
- constant plasma conc provided ms mass, protein intake, renal function normal
- OVERESTIMATE: slightly secreted <5%. ↑in advanced renal failure

*plasma creatinine is inversely related to GFR

Front 13

Factors affecting creatinine generation [6]

Back 13

1. Aging ↓serum creatinine
2. Female sex ↓serum creatinine
3. Black ↑, Hispanic ↓, Asian ↓
4. Muscular ↑, Amputation ↓ (obesity no change)
5. Chronic illness (malnutrition, inflamm, deconditioning, neuromuscular disease) ↓
6. Vegetarian ↓, ingesting cooked meat ↑

Front 14

limitations of creatinine [4]

Back 14

1. can't detect mild ↓GFR: ~40-50%↓ before abnormal plasma creatinine lvl

2. Age, gender, ethnic-related (proportional to ms mass)

3. Overestimation: ↑renal tubular & GI mucosal secretion when blood lvl ↑

4. Analytical interference
- high bilirubin lvl → low creatinine
- high acetoacetate lvl → high creatinine

Front 15

Describe the use of plasma urea [3]
- how is urea measured? [2]

Back 15

- waste product of AA metabolism: synthesized by liver from ammonia & CO2
- excretory load depends on protein intake & metabolism
- underestimation: readily reabsorb back into circulation

Measurement:
- clearance dependent on urine flow rate
(↑UFR will ↓time of reabsorption, so ↓urea)
- in low GFR states: averaging CrCl & UrCl will give better estimation because CrCl overestimates, UrCl underestimates.

Front 16

limitations of plasma urea [2]

Back 16

- can't detect mild ↓GFR (~40% ↓ before abnormal plasma urea lvl shows

- subject to protein intake & metabolism
↓urea in liver dx & malnutrition (false neg.)
↑urea in high protien diet, GI bleed, tissue trauma, glucocorticoid, tetracycline (FP)

Front 17

What does RFT show?

Back 17

- Creatinine & Urea concentration in serum/plasma
*insensitive measures of GFR:
*plasma lvl can remain within ref ranges despite ↓GFR
*subject to various non-renal function related factors

Front 18

Cons of CrCl being used as estimation of GFR?

Back 18

- 24-hr urine collection: inconvenient, error-prone
- error-prone in timing of 24-hr urine collection
- measurement uncertainty up to 30%

Front 19

Formula prediction of GFR [3]
- what formulas are used? [4]

Back 19

- all based on plasma creatinine lvl
- diff formulas for adults/children
- ethnical different (may not apply to Asians: mainly from African-americans]

1. Cockroft & Gault: estimated CrCl
- depends on serum creatinine, age, weight, gender
- tends to overestimate ~16%

2. MDRD-eGFR: estimated GFR
- predicts GFR over wide range of values adjusted for body size (standardized to 1.73m^2)
- doesn't need body weight/timed urine sample

3. CKD-EPI formula

4. Schwartz formula in children
- include child's height

Front 20

What is the cockroft & gault formula?

Back 20

CrCl = (140-age) x BW/0.814 x plasma [creatinine] x 0.85 (if female)

Front 21

Limitations of creatinine based equations [3]
- what will ↑Cr [3]
- what will ↓Cr [4]

Back 21

- only good for steady state: not for acute renal failure
*rapid RF deterioration is underestimated by formulae
*stable renal function for 4 days

- hard if ms mass difficult to predict (late pregnancy, oedema)

- subject to interference by creatinine lvl
*↑Cr:
- Goulash effect (80% ↑Cr after eating 300g cooked beef)
- strenuous exercise
- drug inhibiting tubular Cr secretion (Trimethoprim, cimetidine, probenecid, amiloride, triamterine, spironolactone)

*↓Cr:
- rhabdomyolysis (severe ms wasting)
- amputee
- extreme body habitus
- liver dx, hyperbilirubinemai

Front 22

Conditions where clearance measurement is necessary [9]

Back 22

- extremes of age
- extremes of body habitus
- severe malnutrition, cachexia, inanition
- grossly abnormal ms mass
- high/low intake of creatinine/creatine
- pregnancy
- rapidly changing renal function
- prior to dosing (high toxicity drugs, excreted by kidney)
- prior to kidney donation

Front 23

What is cystatin C-based formula [6]
- clinical use

Back 23

Cystatin C:
- cysteine protease inhibitor
- low MW freely filtered
- synthesized by all nucleated cells, produced at constant rate
- not affected by ms mass, gender, diet
- no extra-renal routes of elimination
- reabsorbed/metabolized by PCT with MINIMAL amount present in urine

Clinical:
- ↑urinary excretion is marked for PCT injury
- promising but expensive

Front 24

Summary of GFR determination by all formulas

Back 24

1. Cr in blood is difficult to translate to GFR

2. eGFR by MDRD: most readily available (increasing application in drug-dosing decision

3. Cockroft & Gault: widely accepted for drug-dosing

4. CrCl by timed urine: for extremes of body composition. Faulty, inaccurate timing of urine collection contributes to error

5. GFR by infusion studies: gold standard
- use inulin (continuous IV drip because inulin not present in body)
but expensive and time-consuming, usu for research

Front 25

How to dx CRF? [2]
- staging [5]

Back 25

- kidney structural/functional abnormalities for >3 months

- Kidney damage presentation:
1. with/without ↓GFR (<60ml/min/1.73m^2)
2. proteinuria
3. tubular damage
4. imaging abnormalities

Staging:
1. >90 GFR: kidney damage with normal or ↑GFR
- CKD if other signs of kidney damage

2. 60-89 GFR: mildly ↓
- CKD if other signs of kidney damage

3. 30-59 GFR: moderately ↓
- CKD if >3 months

4. 15-29 GFR: severely ↓
- CKD if >3 months

5. <15 GFR (kidney failure)
- CKD if >3 months

Front 26

What enables a substance to be used to measure renal blood flow

Back 26

- freely filtered,
- not reabsorbed
- totally extracted/cleared from plasma after first pass through the kidney.

e.g. para-animohippurate clearance is used to calculate the effective renal plasma flow, eRPF