Renal system lec 3

Clinical chemistry
5th stage
University of Baghdad-college of pharmacy
Dr. Zahraa Mohammed

Glomerular function tests

• increase in plasma urea and creatinine result

from decreased glomerular function
• Urea derived in the liver from protein ( from
diet or tissues)
• If the rate of production exceeds >> the rate
of clearance, plasma concentrations rise.
 increased plasma urea level

• The rate of production is accelerated by:

• a high-protein diet,
• absorption of a.a and peptides from digested
blood( haemorrhage into the GI lumen or soft
tissues),
• increased catabolism due to starvation,
• Tissue damage as in sepsis or steroid treatment.

Low plasma urea level

• due to increased GFR or haemodilution (common):
• – pregnancy (the commonest cause in young women),
• – over intravenous infusion (the commonest cause in hospital
patients),
• – ‘inappropriate’ ADH secretion (syndrome of inappropriate ADH
secretion, SIADH).
• due to decreased synthesis:
• – use of amino acids for protein anabolism during growth
especially in children,
• – low protein intake,
• – very severe liver disease (low amino acid deamination),
• – rarely inborn errors of the urea cycle (usually only occur in
infants).
 Creatinine
• mostly endogenous (derived from breakdown of
muscle creatine ).
• Plasma creatinine correlates with muscle mass,
95% of creatine occurring in skeletal muscle.
• The plasma creatinine concentration varies more
than that of urea during the day owing to
creatine intake in meals.
• sustained high-protein diets & catabolic states
affect the plasma concentration of creatinine less
than that of urea.

Creatinine
• The assay less precise than that of urea ( prone to
analytical interference by substances such as bilirubin,
ketone bodies and certain drugs)
• At time in which the plasma conc exceed the upper
plasma reference limit , the GFR, and ( the creatinine
clearance), reduced by ≈ 60%
• plasma urea concentrations rise faster than those of
creatinine with ↓ in GFR
• Urea reabsorbed at collecting duct at rate depend on
the amount filtered and the rate of luminal fluid flow
 GFR
• Ideal substance should be filtered by the
glomerulus, not reabsorbed from or secreted
into the tubules
• inulin closely fulfills the criteria.
• exogenous
• given either by constant infusion or by a
single injection followed by serial blood
sampling to enable the concentration at the
midpoint of the collection to be calculated

GFR
• endogenously substances such as creatinine,
(relatively constant production)
• The clearance acts as an approximation for
GFR:
 Creatinine clearances
• The modification of diet in renal disease (MDRD) formula can be used to estimate
GFR (eGFR)
• this formula of creatinine clearances used in clinical practice , also used to
titrate drug dosing in patients with renal impairment.
• This is calculated by the isotope dilution mass spectrometry (IDMS) traceable
MDRD equation recommended

• The equation not validated in the following groups:

• those under 18 years old, those acutely ill, patients with limb amputations,
pregnant women, the very elderly and the obese and malnourished.

Creatinine clearances
• ↑ muscle breakdown → higher plasma
creatinine concentration
• There may be increased muscle bulk in black
compared with white people.
• Individuals taking creatine supplements for
body building may show increased plasma
creatinine and also plasma creatine kinase
(CK).
 Cystatin C
• endogenous substance
• can be used as a marker of GFR
• Use of it may alleviate some of the problems
associated with creatinine clearance determinations.
• Better than endogenous compounds (such as
creatinine), , as is not secreted by the renal tubules and
does not return to the bloodstream after glomerular
filtration.
• ‘ideal’ endogenous marker for GFR, as blood
concentrations are independent of patient age and sex.

Renal tubular function tests

• impairs the adjustment of the composition
&volume of the urine with minimal effect on
the plasma urea or creatinine concentration.
• 1 .predominantly identify proximal tubular
dysfunction
• 2. predominantly identify distal tubular
dysfunction
 proximal tubular dysfunction

• ↓ isosmotic water reabsorption , countercurrent

multiplication &the ability to respond to ADH (A diluted
large volume urine )(polyuria)
• The tubules cannot secrete H+ & reabsorb bicarbonate (
alkaline urine with acidosis in the blood).
• Impaired the reabsorption of potassium, phosphate,
magnesium, urate, glucose and amino acids
● in plasma normal urea and creatinine concentrations (if
normal glomerular function) , Low bicarbonate concentration
with low pH (metabolic acidosis) Hypokalaemia,
hypophosphataemia, hypomagnesaemia and hypouricaemia
(Phosphaturia, glycosuria, uricosuria , generalized amino
aciduria)

proximal tubular dysfunction

• low-molecular-weight proteins such as retinol

binding protein, N-Acetyl-β-glucosaminidase
(NAG) & α1 –microglobulin (increased in the
urine because of reduced tubular reabsorption
and increased renal tubular secretion).
• Fanconi’s syndrom : detectable glycosuria,
phosphaturia and nonselective amino aciduria
&low molecular weight protein in urine
 RENAL STONE

• usually composed of metabolism products

present in normal glomerular filtrate, often at
concentrations near their maximum solubility
• can occur at any age
• the peak incidence at age 20–49 years.
• Males are affected more than females.

RENAL STONE
• The symptoms are related to their location (kidney,
ureter, or urinary bladder)
• Patients commonly present with acute, severe flank
pain ,often radiate to the abdomen and the groin,
testicle, or labia ,often associated with nausea and
vomiting

• Renal colic usually peaks within 90 to 120 minutes

• In infection , fever, chills, or other systemic signs of
sepsis (pyonephrosis or obstructive pyelonephritis) .
 RENAL STONE

• Patients often present with hematuria, 85%

of patients demonstrate at least microscopic
hematuria on urinalysis.

• Fever is rarely seen in renal colic,

• the presence of fever, pyuria, and
leucocytosis ( indicative of pyelonephritis)

High-risk factors

• Bone disorders
• Chronic diarrhea, malabsorption
• Diabetes, obesity (especially in women)
• Family history of kidney stones
• Gastrointestinal disease
• GI bypass surgery
• Gout
• Hyperparathyroidism
• Prior stones
• Renal tubular acidosis
• Sarcoidosis
 Conditions favouring renal calculus
formation
• 1. A high urinary concentration of one or more
constituents of the glomerular filtrate, due to:
• – a low urinary volume with normal renal function,
because of restricted fluid intake or excessive fluid loss
over a long period of time(particularly common in hot
climates) , this favours formation of most types of
calculi,
• – a high rate of excretion of the metabolic product
forming the stone, due either to high plasma and
therefore filtrate levels or to impairment of normal
tubular reabsorption from the filtrate.

Conditions favouring renal calculus

formation
• 2.Changes in pH of the urine, often due to
bacterial infection
• 3. Urinary stagnation due to obstruction to
urinary outflow or renal tract structural
abnormality.
• 4. Lack of normal inhibitors: urine normally
contains inhibitors
 chemical compositions
• crystals and noncrystalline phases [organic
material (the matrix)].
• The organic matrix consists of macromolecules
such as glycosaminoglycans (GAG's), lipids,
carbohydrates, and proteins. These molecules
play a significant role by promoting or inhibiting
the processes of kidney stone development .
• The matrix acts as a template.
• Albumin is the major component of the matrix of
all stone types

Natural inhibitors
• Inhibitors are substances which decrease the
processes required to stone formation .
• not work equally for everyone
• Inhibitors in urine includes
• small organic anions such as citrate
• small inorganic anions such as pyrophosphates
• multivalent metallic cations such as magnesium
• macromolecules such as osteopontin,
glycosaminoglycans, glycoproteins, urinary
prothrombin fragment-1, and Tamm–Horsfall proteins .
 Calcium salts calculi

• About 80 % of all renal stones .

• Precipitation is favoured by hypercalciuria,
• the type of salt depends on urinary pH and on the
availability of oxalate.
• In normal glomerular function ,hypercalcaemia causes
hypercalciuria .
• many subjects with these stone having normal plasma
calcium concentration
• due to hyperparathyroidism, renal calcium leak,
hyperoxaluria, hypomagnesemia, and hypocitraturia

Calcium salts calculi

• Any ↑ release of calcium from bone (as in actively

progressing osteoporosis, or in prolonged acidosis, in
which ionization of calcium is increased) causes
hypercalciuria; hypercalcaemia is unusual in such cases.
• Mostly, urinary pH of 5.0 to 6.5 promotes calcium
oxalate stones
• calcium phosphate stones occur when pH is greater
than 7.5 .
• The recurrence of calcium stone is greater than other
types of kidney stones
 Calcium salts calculi

• Hypercalciuria (daily urinary calcium excretion of more than

6.2 mmol in adult females and 7.5 mmol in adult males).
• Hyperoxaluria is a more important risk factor for formation of
renal stones than is hypercalciuria.
• Hyperoxaluria favours the formation of the very poorly
soluble calcium oxalate, even if calcium excretion is normal.
• The source of the oxalate may be derived exogenously from
the diet.
• Oxalate absorption is increased by fat malabsorption: calcium
in the bowel is bound to fat instead of precipitating with
oxalate, which is then free to be absorbed.

Calcium salts calculi

• Primary hyperoxaluria (rare inborn error)

expected in children with renal calculi
• There are two main types, 1 and 2, the former
being more common.
• Type 1 (more common) : due to deficiency of
alanine glyoxylate aminotransferase
• type 2 is due to deficient D-glycerate
dehydrogenase.
 Calcium salts calculi

• Calcium-containing calculi are usually hard, white

and radio-opaque.
• Calcium phosphate may form ‘staghorn’ calculi in
the renal pelvis
• calcium oxalate stones tend to be smaller and to
lodge in the ureters, where they are compressed
into a fusiform shape.
• Alkaline conditions favouring calcium phosphate
precipitation , stone formation are common in
patients with chronic renal infection.

Struvite stones
• Struvite or Magnesium Ammonium Phosphate
Stones
• About 10% of renal stones
• infection stones or triple phosphate stones.
• occurs among patients with chronic urinary tract
infections that produce urease, the most
common being Proteus mirabilis and less
common pathogens include Klebsiella
pneumonia, Pseudomonas aeruginosa, and
Enterobacter .
 Struvite stones
• Urease split/cleave urea to ammonia making
urine more alkaline which elevates pH
(typically > 7).
• Phosphate is less soluble at alkaline versus acidic
pH, so phosphate precipitates on to the insoluble
ammonium products, yielding to a large staghorn
stone formation .
• Occur in Women's more than the male.
• Escherichia coli is not capable of splitting urea
and is not associated with struvite stones

Uric acid stones

• About 8 %of renal calculi

• sometimes associated with hyperuricaemia, with
or without clinical gout.
• In most cases, no predisposing causes
• Precipitation is favoured in an acid urine.
• usually small, friable& yellowish brown ,
occasionally be large to form ‘staghorn’ calculi.
• radiolucent ( visualized by ultrasound)
 Cystine stones

• rare
• Cystine stones are due to an intrinsic metabolic
defect causing the failure of the renal tubules to
reabsorb cystine
• In normal subjects the concentration of cystine
in urine is soluble, but in homozygous cystinuria
this may be exceeded
• Like urate, cystine is more soluble in alkaline than
in acidic urine

Drug-Induced Stones

• accounts for about 1% of all stone types .

• Drugs such as guaifenesin, triamterene,
atazanavir, and sulfa drugs induce these stones.
• the protease inhibitor indinavir sulphate, (used
to treat HIV infection), increase the risk of
developing kidney stones .
• Other drugs may induce the formation of calculi
through its metabolic action by interfering with
calcium oxalate or purine metabolisms
renal stones