clinical biochemistry - lecture 6 investigation of renal
Post on 08-Feb-2022
2 Views
Preview:
TRANSCRIPT
Investigation of renal function (1)
• Functions of the kidney
- regulation of water, electrolyte and acid-base
balance
- excretion of the products of protein and nucleic
acid metabolism: e.g. urea, creatinine and uric
acid.
- The kidney are also endocrine organs,
producing a number of hormones, and are subject
to control by others.
Dr.F.AL-Quobaili
Clinical Biochemistry - Lecture 6
Glomerular function
Serum creatinine
-The glomerular filtration rate (GFR) is the
volume of plasma from which a given substance
is completely cleared by glomerular filtration per
unit time.
-GFR is 140 ml/min in healthy adult, it is
corrected to a body surface area (BSA) of 1.73
m2, so the units are ml/min/1.73m2.
Dr. F. AL-Quobaili
- Serum creatinine is used as a convenient but insensitive
measure of glomerular function. The reference range of serum
creatinine in adults is 55- 120 μmol/L. Consider an asymptomatic
person who shows a serum creatinine of 130 µmol/L.
- In young woman this might well be abnormal and requires follow up.
- In a muscular young man this is the expected result.
- In an elderly person this may simply reflect the physiological decline of
GFR with age.
Dr. F. AL-Quobaili
- Creatinine clearance
It is the volume of plasma that would have to be completely
`cleared` of creatinine during the time of collection in order to
give the amount seen in the urine.
Volume of plasma = UXV
P
U: urine creatinine concentration; V: volume of urine collected;
P: the plasma concentration of creatinine.
-Estimated GFR (eGFR)
The relatively poor inverse correlation between serum
creatinine and GFR can be improved by taking into account
some of the confounding variable, such as age, sex, ethnic origin
and body weight. The four-variable equation derived from the
Modification of Diet in Renal Disease (MDRD).
Dr.F.AL-Quobaili
Dr.F.AL-Quobaili
Cockcroft and Gault equation
Ccr (mls/min) = 140-Age x Weight (kg)
0.814 x Scr (mmol/l)
Note correction for Women x 0.85
Ccr (mls/min) = 140-Age x Weight X 0.85 (for female)
0.814 x Scr (mmol/l)
Example: Mr U., Age 20, weight 90kg, Scr 140
Estimated Ccr (mls/min) = 140-20 x 90
140 x 0.814
= 95
• Limitations of eGFR
Many hospital laboratories do not report a specific result
when the GFR is greater than 60 ml/min/1.73 m2.
eGFR is less accurate in patients with abnormal body
shape or mass, e.g. muscle wasting, amputees.
The GFR estimated by modification of diet in renal
disease (MDRD) formula is affected by consumption of
meat.
• eGFR- additional observations
To calculate GFR, it is easy to apply the MDRD equation.
Reduced glomerular function, is known to be associated
with cardiovascular risk and subsequent progression to
more sever renal failure.
Dr. F. AL-Quobaili
Dr. F. AL-Quobaili
- Other measures
• Cystatin C is a cysteine protease inhibitor produced by
all nucleated cells. It is a low- molecular- weight protein
(13 kDa) which is freely filtered by the glomerulus and
almost completely reabsorbed and catabolised by the
proximal tubules.
Serum levels of cystatin C are independent of weight,
height, muscle mass, age (over 1 year) or sex, and it has
a stable production rate.
Serum levels correlate well with GFR, performing at
least as well as creatinine, and being less subject to
confounding influences.
• Isotope tests
A number of isotope markers (e.g. 51 Cr-EDTA, 99Tc-DTPA)
are almost entirely cleared from the circulation by
glomerular filtration. They are injected or infused, and the
measurement of their disappearance from the circulation or
appearance in urine can be used to calculate the GFR.
Inulin clearance is widely regarded as the most accurate.
• Proteinuria
A small amount of albumin, usually less than 25 mg/24
hours, is found in urine. When larger amounts, in excess of
250 mg/24 hours, are detected, significant damage to the
glomerular membrane has occurred.
Albumin excretion in the range 25 - 300 mg/24 hours is
termed microalbuminuria.
Dr.F.AL-Quobaili
-To ensure that important constituents, such as water,
sodium, glucose and amino acids, are not lost from the
body, tubular reabsorption must be equally efficient.
- Compared with the GFR as an assessment of glomerular
function, there are no easily performed tests that measure
tubular function in a quantitative manner.
Dr.F.AL-Quobaili
Renal tubular function
Tubular dysfunction
- Some disorders of tubular function are inherited.
However, renal tubular damage is much more frequently
secondary to other conditions or insults.
Dr.F.AL-Quobaili
Investigation of tubular function
• Osmolality measurements in plasma and urine.
The function of tubules and collecting ducts to reabsorb
water, can be assessed by measuring urine concentration.
This is conveniently done by determining the osmolality,
and then comparing this to the plasma.
-If the urine osmolality is 600 mmol/kg or more, tubular
function is usually regarded as intact.
- When the urine osmolality does not differ greatly from
plasma (urine: plasma osmolality ratio ~ 1), the renal
tubules are not reabsorbing water.
Dr. F. AL-Quobaili
• The water deprivation test.
The causes of polyuria are summarized in this table.
- The normal physiological response to water deprivation is
water retention, which minimizes the rise in plasma
osmolality that otherwise be observed.
- The body achieves this water retention by means of AVP,
the action of which on the renal tubules may inferred
from a rising urine osmoality.
- If the urine osmolality rises to 600 mmol/kg or more in
response to water deprivation, diabetes insipidus is
effectively excluded.
- A flat urine osmolality response is characteristically seen
in diabetes insipidus.
- It should be noted that the water deprivation test is
potentially dangerous if there is severe inability to retain
water.
Dr. F. AL-Quobaili
Dr. F. AL-Quobaili
- The test must be terminated if more than 3 L of urine ispassed. An alternative approach, is to fluid restrictovernight and measure the osmolality of urine voided in themorning.
- If the urine osmolality fails to rise in response to waterdeprivation, desmopressin (DDAVP), a synthetic analogue ofAVP, is administered.
- In central diabetes insipidus, the renal tubules respondnormally to the DDAVP and the urine osmolality rises.
- Nephrognic diabetes insipidus is characterized by failure ofthe tubules to respond; the urine osmolality responsereamins flat.
• Urine pH and the acid load test
Renal tubular acidosis (RTA) may be characterized asfollows:
- Type I. There is a defective hydrogen ion secretion in the
distal tubule that may be inherited or acquired.
- Type II. The capacity to reabsorb bicarbonte in the
proximal tubule is reduced.
- Type III. Is a paediatric variant of type I renal tubular
acidosis.
- Type IV. Bicarbonate reabsorption by the renal tubule is
impaired as a consequence of aldosterone deficiency,
aldosternoe receptor defects, or drugs which block
aldosterone action .
If RTA is suspected, a fresh urine specimen should be
collected for measurement of urine pH. The normal response
to a metabolic acidosis is to increase acid excretion, and a
urine pH of less than 5.3 makes diagnosis of RTA unlikely as
the cause of the acidosis.
Dr.F.AL-Quobaili
- An acid load test involves administering ammonium
chloride (NH4Cl) (which makes the blood more acidic) and
measuring the urine pH in serial samples collected hourly
for about 8 hours. In response to the NH4Cl load, urine pH
normally falls to below 5.3 in at least one specimen.
- This test should not be performed in patients who are
already severely acidotic or who have liver disease.
• Specific proteinuria
Glomerular filtrate normally contains about 30 mg protein
/L. Less than 200 mg protein is normally excreted each
day (half of which is Tamm- horsfall mucoprotein, secreted
by tubular cells).
- Glomerular proteinuria occurs when the glomerulus
becomes abnormally leaky.
Dr.F.AL-Quobaili
-Tubular proteinuria occurs when the tubular reabsortption
of protein becomes defective.
Dr.F.AL-Quobaili
Glomerular and tubular proteinuria
Dr.F.AL-Quobaili
• Glycosuria
Glycosuria in the presence of a normal plasma glucose
occurs in proximal tubular malfunction causing a reduced
renal threshold. This can be benign (occur during
pregnancy), or a part of a more generalised disorder (the
Fanconi’s syndrome).
• Aminoaciduria
- Normally, the renal tubules reabsorb all the filtered
amino acids except for small amounts of glycine, serine,
alanine and glutamine.
- Amino aciduria may be due to disease of the renal tubule.Renal aminoaciduria may be due to impairment of one ofthe specific transport mechanisms (e.g. cystinuria).
Dr.F.AL-Quobaili
- Renal amino aciduria may also occur as a nonspecific
abnormality due to generalised tubular damage, together
with reabsorption defects affecting glucose or phosphate,
or both.
Specific tubular defects
- The Fanconi syndromeIt is term used to describe the occurrence of generalized
tubular defects such as renal tubular acidosis,
aminoaciduria and tubular poteinuria.
It may be inherited (e.g. in cystinosis) or secondary of
other disorders (e.g. Heavy metal poisoning, multiple
myeloma).
Acute renal failure
- In acute renal failure (ARF), the kidneys fail over a
period of hours or days. Chronic renal failure (CRF)
develops over months or years and leads eventually to
end-stage renal failure (ESRF).
Clinical Biochemistry - Lecture 4
Dr. F. AL-Quobaili
Aetiology
- ARF arises from a variety of problems affecting the
kidneys and/or their circulation.
Usually, urine output falls to less than 400 ml/24 hours,
and the patients is said to be oliguric or he may be anuric.
Kidney failure or uraemia can be classified as: Pre-renal,
post-renal and renal.
The first step in assessing the patient with ARF is to
identify any pre- or post-renal factors that could be readily
corrected and allow recovery of renal function.
The history and examination of the patient, drug history
and time course of the onset of the ARF, may well provide
important clues.
Biochemical findings in pre-renal uraemia include the
following:
• Serum urea and creatinine are increased. Urea is increased
proportionally more than creatinine because of its
reabsorption by the tubular cells.
• Metabolic acidosis: because of the inability of the kidney to
excrete hydrogen ions.
Dr.F.AL-Quobaili
Diagnosis
• Hyperkalaemia: because of the decreased glomerular
filtration rate and acidosis.
• A high urine osmolality.
Causes of post-renal uraemia include:
• renal stones
• carcinoma of cervix, prostate, or occasionally bladder.
Acute tubular necrosis
It may develop in the absence of pre-existing pre-renal or
post-renal failure. The causes include:
acute blood loss in severe trauma
septic shock
specific renal disease, such as glomerulonephritis
nephrotoxins, such as the aminoglycosides, analgesics or
herbal toxins.Dr. F. AL-Quobaili
Dr. F. AL-Quobaili
• Patients in the early stages of acute tubular necrosis may
have only modestly increased serum urea and creatinine
that then rise rapidly over a period of days.
It may be difficult to decide the reason for a patient`s
oliguria. The biochemical features are shown in this table.
Biochemical features in the differential diagnosis
of the oliguric patient
Intrinsic renal damagePre-renal failureBiochemical feature
> 40 mmol/L< 20 mmol/LUrine sodium
< 3:1> 10:1Urine/serum urea
< 11:1>15:1Urine/plasma osmolality
Important issues in the management of the patient with ARF
include:
Correction of pre-renal factors, if present, by replacement of
any ECF volume deficit.
Treatment of the underlying disease (e.g. to control
infection).
Biochemical monitoring. Assessment of body fluid volume,
serum creatinine and serum potassium.
Dialysis
There may be three distinct phases in the resolving clinical
course of a patient with acute renal failure (These are
illustrated in the following figure).
Dr.F.AL-Quobaili
Management
Recovery
Dr.F.AL-Quobaili
Chronic renal failure
Chronic renal failure (CRF) is the progressive irreversible
destruction of kidney tissue by disease which, if not treated
by dialysis or transplant, will result in the death of the
patient.
Patients may have few if any symptoms until the
glomerular filtration rate falls below 15 ml/minute (i.e. to
10% of normal function).
Consequences of CRF
Sodium and water metabolism
Most CRF patients retain the ability to reabsorb sodium
ions, but the renal tubules may lose their ability to reabsorb
water and so concentrate urine.
Dr. F. AL-Quobaili
Potassium metabolism
Hyperkalaemia is a feature of advanced CRF and poses a
threat to life.
Acid-base balance
As CRF develops, the ability of the kidneys to regenerate
bicarbonate and excrete hydrogen ions in the urine
becomes impaired.
Calcium and phosphate metabolism
The ability of the renal cells to make 1,25-dihydoxy-
cholecalciferol falls as the renal tubular damage
progresses.
- Calcium absorption is reduced and there is a tendency
towards hypocalcaemia.
- PTH is stimulated in an attempt to restore plasma
calcium to normal, and high circulating PTH may have
adverse effects on bone if this is allowed to continue (renal
osteodystrophy).
Dr. F. AL-Quobaili
Dr. F. AL-Quobaili
Erythropoietin synthesis
- Anaemia is often associated with chronic renal disease.
- The normochromic normocytic anaemia is due primarily to
failure of erythropoietin production.
Conservative measures involve:
• Dietary sodium restriction and diuretics may be required
to prevent sodium overload.
• Hyperkalaemia may be controlled by oral ion-exchange
resins (Resonium).
• Hyperphosphataemia may be controlled by oral aluminium
or magnesium salts.
• The administration of hydroxylated vitamin D metabolites
may prevent the development of secondary hyperpara-
thyroidism.
• Dietary restriction of protein, to reduce the formation of
nitrogenous waste products, may give symptomatic impro-
vement.
Dr.F.AL-Quobaili
Management
Most patients with CRF will eventually require dialysis, in
which case these conservative measures must be continued.
In contrast, after a successful kidney transplant, normal
renal function is re-established.
Haemodialysis and peritoneal dialysis will sustain life when
other measures can no longer maintain fluid, electrolyte and
acid-base balance.
Although transplant of a kidney restores almost all of the
renal functions, patients require long-term immunosuppr-
ession.
Dr.F.AL-Quobaili
Dialysis
Renal transplant
top related