measuring renal function Flashcards
what are the 2 reasons for measuring renal function?
1) identification of renal impairment in your patient
2) modification of dosages of drugs which are cleared by the kidneys
what are the 7 different types of patients at risk of renal failure?
1) extremes of age
2) polypharmacy
3) specific disease states
4) patients receiving long-term analgesia
5) transplant patients
6) drug therapy
7) patients undergoing imagine procedures
what are the 3 main ways to monitor a patients renal function?
1) patients clinical condition
2) modern imaging techniques
3) biochemical data
what is used for patient clinical condition?
- weight charts
- fluid balance charts
- degree of oedema
- results of urine dipstick testing
how are modern imaging techniques used?
- include macroscopic views of renal blood flow, filtration and excretory function
- some of these are used clinically but some ca only be currently used experimentally in the lab
what 3 types of scan fit into renography?
- gamma camera planar scintigraphy
- positron emission tomography (PET)
- single photon emission computerised tomography (SPECT)
what is biochemical data useful for?
identifying renal impairment
what types of blood markers are used for renal function?
- plasma or serum creatine (SCr)
- plasma or serum urea or blood urea nitrogen (BUN)
what are the key characteristics of creatine?
- breakdown of product of creatine phosphate in muscle
- generally produced at constant rate
- filtered at the glomerulus with some secretion into proximal tubule
- normal range in plasma: 40-120 micro mol/L
what is plasma creatine increased by?
- large muscle mass, dietary intake
- drugs which interfere with analysis
- drugs which inhibit tubular secretion
- ketoacidosis
- ethnicity
what is plasma creatine decreased by?
- reduced muscle mass
- cachexia/starvation
- immobility
- pregnancy
- severe liver disease
what are the key characteristics of urea?
- liver produces urea in the urea cycle as a waste product of protein digestion
- filtered at the glomerulus, secreted and reabsorbed in the tubule
- plasma urea described as BUN
what does BUN stand for?
blood urea nitrogen
what is the normal range of BUN?
2.5-7.5mmol/L
what level of BUN indicates moderate to severe renal failure?
> 20mmol/L
what is BUN increased by?
- high protein diet
- hyper catabolic conditions
- GI bleeding
- muscle injury
- drugs
- hypovolaemia
what is BUN decreased by?
- malnutrition
- liver disease
- sickle cell anaemia
- SIADH
what are the key features of an ideal marker of kidney function?
- naturally occurring molecule
- not metabolised
- only excreted by the kidney
- filtered but not secreted or reabsorbed by the kidney
what is an example of a substance that is freely filtered but not reabsorbed or secreted by the kidney?
inulin
what is an example of a substance that is freely filtered and partly or mostly absorbed by the kidney?
electrolytes
what is an example of a substance that is freely filtered but fully reabsorbed by the kidney?
glucose and amino acids
what is an example of a substance that is freely filtered, not reabsorbed but fully secreted by the kidney?
PAH
what is clearance?
the volume of plasma completely cleared of a given substance in unit time
what 3 basic functions does renal clearance provide information on?
- glomerular filtration (F)
- tubular reabsorption (R)
- tubular secretion (S)
what is the rate at which kidneys excrete solute into urine equal to?
the rate at which solute disappears from blood plasma
what is the equation for renal clearance?
Cx = Ux x V / P
what are some drawbacks of renal clearance?
- measuring clearance means measurement of overall nephron function
- this gives the sum of all transport processes occurring along nephrons
- no information is given about precise tubular sites or mechanisms of transport
what should the glomerular filtration rate be?
125mL/min
how is glomerular filtration rate measured?
- GFR can be measured clinically and used as an indication of renal function
- GFR can be estimated by measurement of clearance of creatine
- creatine is filtered and secreted into tubule
what is a more accurate estimation of renal function?
inulin clearance
how is inulin clearance used for measurement of GFR?
- it is freely filtered but it is not secreted and it is not absorbed
- therefore rate of excretion in urine equals the rate of filtration by the kidneys
- inulin clearance = GFR
- if a substance has clearance greater that inulin then it must also be being secreted; less means that it must be being reabsorbed or not filtered freely at the glomerulus
what is inulin?
inulin is a plant polysaccharide Mw 5200Da
what are the drawbacks of inulin clearance to measure GFR?
- inulin must be administered by IV to get relatively constant plasma or serum levels
- chemical analysis of inulin in technically demanding
- could use radio labelled compound instead
- however, these may also bind to proteins and distort results
- problems of IV infusion of GFR marker are avoided by using an endogenous substance with inulin-like properties
how does creatinine clearance work?
- creatinine is filtered at the glomerulus but some is secreted into the proximal tubule
- therefore using the equation above would actually over-estimate GFR by about 20% in humans
- however the colorimetry methods used to measure creatinine, under-estimate creatinine concentrations by about 20%
- luckily these 2 errors cancel each other out, and calculated creatinine clearance is approximately inulin clearance
what are the advantages to creatinine clearance?
- cheap, easy, reliable, used clinically
- avoids IV infusion, just requires venous blood and urine samples
how is creatinine usually produced?
by creatinine phosphate metabolism in muscle
how do you use PAH clearance to measure renal blood flow?
- if a substance is completely cleared from the plasma, its clearance rate will be equal to the renal plasma flow
- clearance of PAH - para-aminohippuric acid can be used to estimate this
- PAH another normally present in the blood
- when given, almost all cleared from kidney in one passage, some filtered in glomerulus and remainder secreted by proximal tubules
- around 10% by-passes tubule, travels from efferent arteries into peritubular capillaries an then venous renal blood, and is not secreted
- uncorrected value for PAH clearance often used: known as effective renal plasma flow
what are the biomarkers of renal disease?
- indicators of renal function such as plasma creatinine or BUN increase only after there is a significant loss of renal function: typically a 60% loss in renal function before plasma or creatinine or BUN increases
- urinary albumin/protein excretion can also be used as an indicator of chronic kidney disease
- currently a lot of research interest in identifying blood and urinary markers which increase in the early stages of renal failure and can be measured
what are the main proteins released into the plasma and/or urine to show renal disease?
- kidney injury molecule
- IL-18
- fatty acid binding proteins
- neutrophil gelatinise associated lipocalin
- cystatin C
