1. Renal function- basic data for students and residents
Department of Paediatrics
Section for Pediatric Nephrology
University Hospital Motol, Prague

2. Functions of the kidney
regulation e.g. homeostasis,
water, acid/base
excretion e.g. urea, creatinine
endocrine e.g. renin,
erythropoietin,
1,25 dihydroxycholecalciferol- conversion only in kidney!
The kidneys excrete the end products of metabolism, urea from amino acid breakdown, uric acid from purine (nucleic acids) metabolism and creatinine from the catabolism of creatine an amino acid found in muscle.
Homeostatic functions include the maintenance of water balance by regulating urine volume, acid base balance by altering hydrogen ion excretion, sodium balance by altering the rate of sodium reabsorption.
Endocrine functions include the secretion of renin from the JGA which influences aldosterone. Erythropoietin effects the rate of red cell production and 1,25-dihydroxycholecalciferol is the active form of vitamin D, effecting calcium homeostasis.
Patients with chronic renal disease and impaired renal functions will show defects in endocrine and excretory functions before the loss of homeostatic control. When the homeostatic functions cease then the patient is in renal failure and would die if there were no interventions.

3. Renal function tests detect renal damage monitor functional damage
help determine etiology
From a clinical perspective it is important to have test which would have these characteristics. No such test exists.
An early test to detect renal damage, for instance a simple strip test for haematuria is important in screening for heavy metal poisoning.
There is a clinical need to monitor a patient with renal disease and this is achieved by serial plasma measurements.
We need to know when to start dialysis in renal failure and laboratory tests assist the clinical decision making.
There are about a million nephrons in each kidney and this represents a considerable functional reserve. In renal disease about half the nephrons have to lose their functioning before the abnormality can be detected by conventional laboratory tests.

4. Laboratory tests of renal function
urine protein
urine glucose
hematuria
osmolality
glomerular filtration rate (GFR)
plasma creatinine
plasma urea
urine volume
urine urea
minerals in urine
I shall review the tests in the left column today. The measurement of urine protein is important in certain conditions, e.g.diabetes. The detection of substances such as red cells or glucose could be an early indicator of renal damage.

5. Kidney Function
A plumbers view

6. Kidney – basic data Urine excreted daily in adults: cca 1.5L
Kidney only ca 1% of total body weight, despite it
The renal blood flow= 20% of cardiac output
Plasma renal flow= PRF ca 600 mL/Min./1.73 M2
Reflects two processes
Ultrafiltration (GFR): 180 L/day
Reabsorption: >99% of the amount filtered

7. How do you know it’s broken?
Decreased urine production
Clinical symptoms
Tests

8. Where can it break? Pre-renal Renal (intrarenal)
Post-renal (obstruction)

9. Causes of kidney functional disorders
Pre-renal e.g. decreased intravascular volum
Renal e.g. acute tubular necrosis
Postrenal e.g. ureteral obstruction
Oliguria is a significant finding in a patient. An example is provided by Case 3 in the Chem Path tutorials. The traditional classification of causes is into prerenal, renal and postrenal. Usually the cause of the oliguria is obvious and can be appropriately managed.

10. Tests of renal function
glomerular filtration rate=GFR
plasma creatinine= Pcr
plasma urea-Purea
urine volume= V
urine urea- Uurea
cystatin C in plasma?
urine protein
urine glucose
hematuria
osmolality
I shall review the tests in the left column today. The measurement of urine protein is important in certain conditions, e.g.diabetes. The detection of substances such as red cells or glucose could be an early indicator of renal damage.

11. Renal Function Tests- Urine volumes
Adults:
1.5 L/24 h typical in health,
oliguria < 400 mL,
anuria < 100 mL,
polyuria > 3000 mL
Children: ca 1.5 ml/Kg of b.w./1 hour!
Urine volume depends on how much you drink and sweat. In health it is closely matched to water balance by the hormone ADH or vasopressin, AVP.
We define abnormally low urine volume as a 24 hour volume less than 400 mL. This is known as oliguria.
A patient is considered anuric when there is no or little urine, less than 100 mL/24 h.
There is no absolute definition for polyuria as some people can drink an awful lot and match it with a high urine output. If a patient has a urine volume greater than 3 litres per day and is not drinking then this is polyuria.

12. Principle of of Clearance
Some substances when filtered enter the tubules are not reabsorbed and so 100% excreted= GFR (inulin= gold standard for GFR, creatinine (but this one partially reabsorbed, particularly in uremia, then clearance <GFR
Some substances are filtered, enter tubules, and more of the substance is secreted enters the tubules by excretion. Clearance>GFR
Some substances are filtered, enter tubules, but are completely reabsorbed, so they did not reach the final urine (e.g. cystatin C)
I shall review the tests in the left column today. The measurement of urine protein is important in certain conditions, e.g.diabetes. The detection of substances such as red cells or glucose could be an early indicator of renal damage.

13. Glomerular filtration rate
Glomerular filtration= major physiologic responsibility of kidney, GFR used as index of overall excretory function
Methods:
clearence of inulin, creatinine, EDTA and DTPA (=both derivates of acetic acid), cystatin C
GFR= Ux x V (V=volum of urine/ 1 minute or 1 second)
P x x= clearence of substance used
Urea is easily measured. It has a wide reference range and the value increases after a meal.
Its concentration is increased in many different conditions which makes it sensitive to the presence of disease but a non-specific test.

14. Glomerular filtration rate
Also service of nuclear medicine dptm.
Follow up the inulin clearence, EDTA or DTPA clearence labelling the substances with chromium or Tcm99
Where will you catch the activity with detectors?
Never in the kidney or bladder area!!

15. Glomerular filtration rate
GFR in children, value always adapted to the BSA!! Ideal BSA in adults is 1.73m2
Schwartz equation : GFR= v x 0.808
Pcr (umol/L)
How to assess easy if plasma creatinine is OK?
Pcr max= Vcm x (v= body height in cm

16. Creatinine and Urea Plasma Concentration- hyperbolic correlation
Tendency in individual patients is more important than the one value, ever test if the hydration is OK. In patients with CRI always note also the BSA!
Lower limit today not 80 ml/Min. /1.73 m2 but 90 ml/Min./1.73 m2
pCr,
pUrea
Normal
range->
140 mL/min
(100%)
0 mL/min
(0%)
GFR 50%

17. Plasma urea (BUN) = BUN (blood urea nitrogen)
Urea: product of protein catabolism
Synthesized by liver, majority excreted by kidney, partially reabsorbed in tubuli
Plasma concentration increases with decreased GFR
Urea is easily measured. It has a wide reference range and the value increases after a meal.
Its concentration is increased in many different conditions which makes it sensitive to the presence of disease but a non-specific test.

18. Urea cycle aspartate CO2 NH3 Urea Cycle 3 ATP Urea
In health only about 60% of filtered urea is excreted the rest is reabsorbed passively by the renal tubules. The rate of urea reabsorption is variable and depends on the rate of tubular flow. More urea is reabsorbed if the flow rate is slow as there is more time for urea to diffuse into the peritubular capillaries.
Flow rate is slow when there is a decrease in RBF, following myocardial infarction for example. More urea is reabsorbed and plasma urea increases.
Many conditions result in renal hypoperfusion including fluid loss, circulatory insufficiency, renal artery stenosis
Urea

19. Enzymatic conductivity rate method for measuring urea
Urea + 3H2O
urease
Urease
solution
HCO3¯ + 2NH4 + OH¯
From a clinical perspective it is important to have test which would have these characteristics. No such test exists.
An early test to detect renal damage, for instance a simple strip test for haematuria is important in screening for heavy metal poisoning.
There is a clinical need to monitor a patient with renal disease and this is achieved by serial plasma measurements.
We need to know when to start dialysis in renal failure and laboratory tests assist the clinical decision making.
There are about a million nephrons in each kidney and this represents a considerable functional reserve. In renal disease about half the nephrons have to lose their functioning before the abnormality can be detected by conventional laboratory tests.

20. Urea in patients with kidney diseases
Useful test but must be interpreted with great care, urea plasma level is more than creatinine dependent on protein intake
Most useful when considered along with creatinine
High in high protein intake, low in severe liver dysfunction
Urea EF may be useful in pts. on diuretics

21. Plasma creatinine and renal functions
Creatine: main storage compound of high energy phosphate needed for muscle metabolism.
Creatinine: anhydride of creatine!
Creatine
Creatinine
(Waste product)
H2O
In most circumstances the measurement of plasma creatinine can provide a specific test of glomerular function.
The reference range is wide. A body builder may have a plasma creatinine at the top end and an old lady a value at the low end and this reflects muscle mass. Plasma creatinine should not be measured until 8 hours after a meal as there is some evidence that the concentration increases after meat ingestion.
Plasma creatinine concentration increases when GFR falls. The problem is that GFR has to fall quite a bit before plasma creatinine concentration reliably increases.
There are some important analytical interferences which you should check with the laboratory. A patient with ketoacidosis, jaundice or infection might have agents in the plasma which could invalidate the measurement of creatinine.
Overhead 1 follows

22. Plasma creatinine vs. GFR not linear, hyperbolic correlation!
[pCreat]
Change within an individual patient is usually more important than the absolute value
140 mL/min
(100%)
0 mL/min
(0%)
GFR

23. Jaffe´ reaction for measuring creatinine, simple, but better is enzymatic method
Creatinine + alkaline picrate solution
Bright orange/red colored complex
absorbs light at 485nm
(many interfering substances in blood
Can be minimized using rate method)
GFR is not often measured in clinical practice. It requires a patient to come to hospital. Currently people who are considering donating a kidney whilst they are alive have their GFR measured. Before administering a drug with potentially toxic effects some patients will require a GFR measurement before the chemotherapy. This enables the oncologist to calculate the exact dose of drug after estimating its elimination rate.
GFR used to be measured by calculating the clearance of inulin. Nowadays radioactive substances are used, either technetium labelled diethylenediaminetetra acetic acid DTPA or 51-chromium labelled EDTA ethylenediaminetetra acetic acid.

24. Analytical methods (Cr)
Normal range Pcr
Male mg/dL,
Female mg/dL
Be careful in children!!
Remember the max. plasma creatinine value!!

25. BUN: creatinine ratio Pre-renal disorders Renal disorders Post-renal
BUN:Cr ratio >20
Renal disorders
BUN: Cr nl but both elevated
Post-renal

26. Osmolality of urine Measures urine concentrating ability
Depends on # of particles, not size or charge
Largely due to ADH (anti-diuretic hormone)
Can reach maximum of 1200 mOsm/L
Normal range: mOsm/L, plasma
prior to collection, fluid intake restricted, first void submitted for evaluation
Measuring using the fact of freezing point depression

27. Standardized renal concentration capacity test
1. Voiding completely at 9 p.m. (WC)
2. Desmopressin administration (since 2006 as nasal spray). DDAVP is a Czech invention !!
3. Collection of urine (9 p.m. – 7 a.m.)
4. Testing of urine osmolality in this sample (not the morning urine only!)
5. The lower limit of normal value= mOsm/kg of urine
6. Short testing- Desmopressin, collection for 4 hours only= at least 900 mOsm/kg of urine

28. Modern dipsticks with multiplied zones:
Urine dipsticks
Strip impregnated with reagents for the substances in question within a urine sample
Substance level can be altered in the setting of pathology within the urinary tract
Measured substances:
Modern dipsticks with multiplied zones:
Protein, hemoglobin, glucose, urobilinogen, nitrite, leukocytes, specific gravity, and pH
Should be a tool everywhere on the level of primary care!!!