Biochemical Assessment of Renal Function Flashcards
Describe the kidneys?
paired retroperitoneal organs, bean-shaped,
weighing 120-170g
Describe the resting cardiac output that flows to the kidneys?
25% - 180L of filtrate but only 1-2L of
urine produced/day
What is the vasculature of the kidneys?
supplied by renal artery, drained by the renal
vein
Innervation of the kidneys?
renal plexus
What is the functional unit of the kidney?
nephron
Describe the structural components of the nephron?
- Glomerulus
- Proximal convoluted tubules
- Loop of Henle
- Distal convoluted tubules
- Collecting duct
Describe the functions of the different parts of the nephron?
- glomerulus - filtration
- proximal tubule - where main reabsorption occurs
- distal tubule - secretion
- collecting duct - water reabsorption
- loop of Henle - concentration of filtrate
What are the 3 basic renal processes?
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion
What are the endocrine functions of the kidneys?
- synthesis of hormones - 1,25-dihydroxyvitamin D3, renin and angiotensin and erythropoietin
- response to hormones
What are the excretory function of the kidneys?
- Protein metabolism
- NA metabolism
What are the homeostatic functions of the kidney?
- acid-base (isohydria)
- electrolyte (isoionia)
- fluid (isovolumia)
What is the metabolic function of the kidneys?
Gluconeogenesis during starvation
What does normal renal function depend on?
- number of functioning nephrons
- blood supply
- hormone secretion and feedback
Describe acute renal failure?
rapid loss of renal function
- usually but not always oliguric : (<400ml/24hr)
- retention of urea, creatinine, H+, K+, proteinuria
- potentially reversible
What is polyuria?
passing abnormally large amounts of urine
What is anuria?
failure of the kidneys to produce urine
What is oliguria?
urine output below normal
What is the cause of pre-renal ARF?
reduced renal perfusion
- blood loss, hypovolaemia
What is the cause of post-renal ARF?
ureteric/urethral obstruction
- stones or malignancy
What is the cause of renal ARF?
intrinsic kidney tissue damage
- glomerulonephritis, nephrotoxins
Describe chronic renal failure?
progressive irreversible destruction of
kidney tissue
- major effects of CRF are due to loss of
functional nephrons
- some patients may be asymptomatic until very
low levels of GFR
- most patients will require dialysis or
transplant
What is the purpose of renal functions tests?
- detecting presence of renal disease.
- assessment of progression of renal disease
- less valuable in determining the causes
of renal disease
What are the early indicators of chronic renal failure?
- Diabetes
- High blood pressure
- Cardiovascular disease
- Heamaturia or proteinuria
- Chronic use of known nephrotoxic agents
- Seriously sick patients
What are the types of renal function tests?
- glomerular function
- tubular function
What are glomerular function tests?
a measure of the filtration rate (GFR)
- index of number of functioning nephron
How are glomerular function tests done?
clearance tests : [urine in sample] & [plasma in sample]
What are the characteristics of the substances measured in glomerular function tests? i.e. an ideal marker
- endogenous substance
- freely filtered by the glomerulus
- not metabolized by the tubules
- [substance] remains constant during the period of urine collection
What is the clearance equation?
clearance = [urine] x flow rate/[plasma]
What is the gold standard for measuring GFR?
urinary inulin clearance
- inulin has all the properties of an ideal marker
NB: inulin - plant CHO
What is creatinine?
a product of energy (ATP) yielding reactions made by muscles as part of regular everyday activity
- phosphocreatine in muscles
- meets most of the criteria for an ‘ideal’ substance
- up to 10% Cr is actively secreted into the urine by renal tubules
What is the issue with a 24 hour timed urine collection period?
delays the availability of the result and increases the potential for collection errors
Which time period for urine collection is better: 24 or 12 hours?
they are both accurate
What are the problems with using Creatinine Clearance?
as the GFR falls, Cr Cl overestimates the true GFR because it is also secreted by the peritubular capillaries
- overestimates the GFR by 10 - 20%
What is the reference range for creatinine clearance?
~120ml/min in adults (gender dependent)
- decreases with age (6.5ml/min/1.73m2 for
each decade of life)
What is plasma creatinine?
the amount of creatinine in your blood
- an increased level may be a sign of poor kidney function
When is plasma creatinine used?
only useful when GFR is very low
- levels out of reference range when GFR has declined by
more than 50%
Plasma level are affected by?
- Muscle mass
- Diets
- Exercise
- Drugs
What is eGFRcr?
measures how much blood these filters clean every minute based on your body size - calculated GFR : when formulae have been used
What is the Cockcroft and Gault equation?
Ccr = (140 - age) x weight (kgs) x (0.85 if pt female)/0.81 x serum [creatinine]
What is MDRD study equation?
GFR (ml/min/1.73m2 = 175 x [Crs (micro mol) x0.0113] - 1.154 x [age] - 0.203 x [1.212 if black] x 0.742 if female]
- takes into account ethnicity but does not incorporate weight
What is the normal estimate of eGFR?
>60ml/min/1.73m2
Describe isotope labelled clearance?
- the most accurate, very expensive
- 99m Tc or 51Cr-EDTA
- 2 samples taken 1-3hrs after administration
- GFR calculated from plasma clearance
Urea is formed from?
AA ⇢ NH3 ⇢ urea
Describe plasma urea (BUN)?
- inferior to plasma [creatinine] as a measure of renal function - 50% of filtered urea is reabsorbed, more if flow rate decreases (dehydration) - affected more by diet than [creatinine]
What does a creatinine > 20 indicate?
pre or post renal azotemis
What is glomerular proteinuria?
Abnormal permeability of the glomerular capillaries to protein
What is selective glomerularlis?
only intermediate-sized proteins leak (<100kDa)
What is non-selective glomerular proteinuria?
range of differently sized proteins including larger proteins (Ig)
What is microalbuminuria?
small quantities of albumin in the urine ranging from 30 - 300 mg/24 hrs or spot urine 30- 300mg/L (2/3 visits over a 4 month period)
What are the levels of spot urine albumin in males and females?
Creat >2.5mg/mmol (male) or 3.5mg/mmol (female)
Microalbuminuria is an indication of?
- diabetes nephropathy
- vascular endothelial dysfunction
- hypertension
Describe the autoantibody test for renal function tests?
titres against self-destructive ab
- Anti-GBM + ANA
What are tubular function tests?
chemical analysis of urine
Renal tubular disorders may affect?
- ability to concentrate urine
- ability to excrete an appropriately acidified urine
- reabsorption of aa, gluc, phosp etc
What is urinalysis?
screening tool that tests for physical properties using dipstics
What physical properties are tested during urinalysis?
- Sg and osmolality
- pH, WBC
- Glucose
- Protein
- Ketones
- urobilinogen
- Nitrites
Describe the osmolality in a healthy person?
osmolality of urine is >3x the osmolality of serum (mmol/kg)
What do renal concentrating tests measure?
[urine] produced in response either to fluid deprivation or to IM injection of vasopressin (DDAVP).
Describe the process of fluid deprivation?
- Starting at 10pm, no fluid
- Urine/blood samples collected between 8am- 3pm the next day; pt weighed every 2hrs
- If weight loss of 3-5% of total body weight occurs, test should be stopped.
What is the normal reaction to fluid deprivation?
- No rise in plasma osmolality (285-295)
- Rise in urine osmolality to > 800
Describe the process of the DDAVP test?
- Pt allowed to drink a moderate amount of water after the fluid deprivation tests
- used to identify type/cause of DI
- IM injection of DDAVP given
- samples collected hourly for the next 3hrs
Describe the interpretation of the DDAVP test?
+ response = diabetes insipidus of HP origin
- response = nephrogenic diabetes insipidus
What are urinary acidification tests?
tests that assess the capacity of the tubules to produce an acid urine after induction of metabolic acidosis - useful in diagnosis of RTA
Describe the use of ammonium chloride in urinary acidification tests?
- 7g NH4Cl/100ml administered by mouth
- hourly collection of urine & arterial blood in the next 5hrs
- If urine pH does not fall below 5.3 in one sample ⇒ RTA type 1
What is reabsorptive proteinuria?
LMW proteins appear in urine (<70kDa)
What is secretory tubular proteinuria?
- Tamm-Horsfall protein (120kDa)
- N-acetyl β-glucosamidase
What is the interpretation of tubular proteinuria?
urine protein of >2.5g/day – Nephrotic syndrome
Describe Glycosuria, aminoaciduria & phosphoturia?
- described as Fanconi syndrome (acidosis is present)
- urine gluc >5mmol/L when plasma gluc is normal
- in children need to screen for IEM
How do you screen for IMD with reducing sugars?
using Clinitest tablets (except sucrose)
⇒ chromatography
How do you screen for IMD with amino aciduria?
- by TLC
- confirmed with HPLC
What are renal stones?
relative insolubility of urine constituents in water leading them to crystallize out – calculi
- radiological examination required to localize the stone, pts ‘cut for stone
What are the predisposing factors of renal stones?
- dehydration
- changes in urine pH
- specific microorganisms
What are the predisposing factors of renal stones?
- dehydration
- changes in urine pH
- specific microorganisms
State the metabolic and endocrine disturbances in chronic renal failure?
- Retention of nitrogenous waste products (uraemic toxins)
- Na, K & water imbalances
- Acid-base disturbance
- Ca2+,PO 4- , Mg2+& renal osteodystrophy
- Gonadal function
- Anaemia