Case Eight - Case One Flashcards
what is AKI
sudden decline in renal function significant enough to produce uraemia, and also often oliguria
what is oliguria
a urine output of <400ml/day
what is a severe AKI defined as
a creatine level of >500umol/L
what is the incidence of AKI
The approximate incidence of AKI is 180 per 1 million; before the age of 50, this value is 17 per 1 million, but as high as 950 per 1 million in those over 80.§
what are the three main categories that causes of AKI be divided into
prerenal
intra-renal
post-renal
what is the most common cause of AKI in the hospital
sepsis
what what is the prerenal causes of AKI
impaired blood flow to the kidney
what may impaired blood flow to the kidney be a result of
hypovolaemia, decreased BP, decreased CO, or vascular disease
what are the clinical signs of prerenal causes of AKI
history of blood/fluid loss,
sepsis leading to vasodilation,
cardiac disease,
postural hypotension,
weak and rapid pulse with low JVP
what are the three intra-renal causes of AKI
- acute tubular necrosis (ATN)
- Nephrotoxicity
- renal parenchymal disease
what is ATN
by far the most common cause of AKI, where toxicity and or ischaemia results in decreased GFR
what is nephrotoxicity causes by
ahminoglycosides
what is renal parenchymal disease a result of
ATN
what are the investigations for AKI
urine dipstick
urine microscopy - red cell casts and red cells
Blood tests- U+E’s - particularly Cr and K+, FBC, free haemoglobin and myoglobin
Kidney function is monitored through urine output analysis and creatinine clearance monitoring – creatinine clearance monitoring is the ideal, i.e. it is a more precise indication of GFR than serum urea monitoring alone!
what is the official definition of AKI
Acute kidney injury is a sudden decline in renal function significant enough to produce uraemia, and also often oliguria – a urine output of <400ml/day, which is the minimum volume required to remove waste products from the blood.
what is the diagnosis criteria for AKI
- there is a rise of serum creatine of >26.5 in <48 hours
OR - there is a rise in serum creatine to >1.5x the baseline level which was previously known or assumed 7 days prior to the presentation
- there is a signifiant reduction in urine output compared to baseline
what is uraemia
a situation where there is enough urea in the blood to cause clinical symptoms, which may include anorexia and lethargy, and later, possible decrease in mental capacity leading to coma
what is the term azotaemia sometimes used for
sometimes used to describe levels of urea above normal but. not high enough to cause clinical signs
what is the mortality of those with an isolated AKI
5-10%
in those with other organ failure that then go into AKI, what is the mortality
50-70%
what are the three questions that need to be asked before diagnosing acute renal failure
- is the renal failure acute?
- is there a urinary tract obstruction?
- is there something rare that might be causing the AKI?
when should chronic renal failure be suspected (three things)
- there is co-existing diabetes
- there is increased blood pressure, and other signs of chronic disease
- small kidneys are apparent on ultrasound with increased echogenicity
what percentage of severe AKIs are due to obstruction
25% - most commonly causes by prostatic hypertrophy
what is the main test for obstruction
USS of the kidneys
renal USS will not detect obstruction but dilation of the calyces, and in 5% of cases, such dilation may not be detected, culminating in a false negative result
what are the three procedures that may be carried out in order to relieve an obstruction
catheritisation
percutaneous nephrostomy
surgery to allow impact of stents while consideration of how to treat the underlying cause is undertaken
what are the rare suspects that may cause an AKi
E.g. glomerulonephritis, vasculitis, or interstitial nephritis. Do a dipstick test on anyone with suspected AKI, and if there are any irregular findings, send off for urgent analysis. Often there will be haematuria and/or proteinuria.
what causes account for 80% of the cases
pre-renal failure and acute tubular necrosis
what antibiotics are contraindicated in sepsis with AKI
treatment with gentamicin or vancomycin as these are nephrotoxic agents
impaired blood flow to the kidney (pre-renal causes) may be a result of what
- hypovolaemia
- hypotension
- decreased CO
- vascular disease
- combinations of any of the above
how is the kidney able to maintain sufficient perfusion despite alterations in these conditions
through auto regulation, however in extreme circumstances, it cannot thus GFR will fail
what is this known as
prerenal uraemia
what drugs impair auto regulation and therefore may predispose to prerenal uraemia
ACE inhibitors and NSAIDs
what are the urine specific gravity and urine osmolarity tests
measures of the concentration of solutes in urine. they are quick and easy to carry out, but are unreliable in the presence of glycosuria or other unrelated conditions that disturb urine concentration
what are the kidneys particularly susceptible to
ischaemic damage and cholestatic jaundice
what conditions perpetuate renal ischaemia
gram-negative septicaemia, pre-eclamsia
what is treatment of ATN based on
increasing renal perfusion, while treating the underlying condition
how do ACE inhibitors damage the kidneys
they can lead to dilation of the efferent arteriole, thus lowering glomerular pressure, resulting in a reduced GFR. in patients with renal disease, this exacerbates the condition
how do NSAIDs damage the kidney
reduce prostaglandin production. prostaglandins are vasodilators - thus inhibition of their production may lead to vasoconstriction of the afferent arteriole, thereby causing reduced renal and reduced GFR
what is the first organ to be jeopardised when systemic circulation iOS compromised
kidneys
what is the well defined sequence of events that culminates in ATN
- rapid reduction in GFR followed by a rapid increase in serum creatine and urea
- extended period, typically 1-2 weeks where there is continued poor kidney function while serum creatinine and urea continue to rise
- finally, there is restoration of kidney function, where GFR rises, whilst serum creatine and urea fall
what is the combination of factors that exist in ATN
- intra-renal vasoconstriction
- tubular cell injury
what is intra-renal vasoconstriction due to
due to decreased vasodilation occurring in the presence of other factors, including endothelial damage e.g in trauma or in infection, where leukocyte activation and release of PGE2, EACh, and bradykinin occurs
what does ischaemia initiate and what does this lead to
ishcaemia initiates rapid utilisation of intracellular ATP stores, which, once depleted, will cause the cell to die by necrosis or apoptosis.
what will happen to adjacent cells
they all lose their adherent quality and desquamate
what does this lead to
RBCs are able to escape into the tubule, squishing together to form casts.
Casts can then block the renal tubule, forming a backup of tubular fluid
where is the necrosis the worst
in the loop of Henle - especially when it lies in a relatively poorly perfused medulla and the proximal tubule
what growth factors are released during cell injury to assist in the regeneration process
insulin-like growth factor, epidermal growth factor and hepatocyte growth factor
what are the three ways in which ischamia results in a reduction of GFR
glomerular contraction
back-leak of filtration
obstruction of the tubule
what does treatment of ATN essentially
involve keeping the patient alive until the condition rectifies itself
within what time period will AKI appear after taking a nephrotoxic drug
will appear within 2 weeks of taking a nephrotoxic drug
what are ahminoglycosides
class of antibiotics that are most commonly associated with nephrotoxicity
what are examples of ahminoglycosides
gentamicin, vancomycin, kanamycin, streptomycin
what’s renal parenchymal diseased a result of
acute tubular necrosis
what is kidney function monitored via
urine output analysis and creatine clearance monitoring
what are the signs of hypovolaemia
JVP
low BP
low urine output
poor tissue turgor
fast, weak pulse
what are the signs of fluid overload
raised BP
peripheral oedema
lung crepitations
gallop rhythm head on heart sounds
where will oedema always be particularly apparent in fluid overload
in the hips
what does the presence of small kidneys suggest
CKD
what should you also stop if creatinine is >150mmol/L
stop metformin also
what values in Hyperkalaemia are particually dangerous and what may they lead to
values above 6mmol/L and may lead to arrhythmias, particularly ventricular fibrillation or cardiac arrest
what will an ECG of VF show
tall tended T waves
small or absent P waves
wide QRS complex
asystole
sinus wave pattern
if VF is present, what is the imperative treatment
calcium gluconate
insulin
considering haemodialysis
what is calcium gluconate
cardio protective
give a 10ml dose of 10% of solution every 2 mins until the ECG improves
why is insulin given in VF
stimulates the uptake of glucose within the cell - and as glucose is taken up it is taken up in co-transport by potassium. giving insulin will lower the serum K+
when is haemodialysis considered
if the patient is anuric - producing no urine
what should be given if pulmonary oedema is present
venodilator - morphine
oxygen
loop diuretics
when should dialysis be considered
Pulmonary oedema
Persistent hyperkalaemia, i.e. K+ >7mmol/L
Severe metabolic acidosis, i.e. pH <7.2, or base excess <10
Uraemic encephalopathy
Uraemic pericarditis, aka “uraemic rub”
what do you treat acidosis with
sodium bicarbonate, this intervention will also help to lower the level of free potassium
what happens if sodium bicarbonate is administered too quickly
the patient may become hypocalcaemic, which often causes tetany
what do patients treated with haemodialysis require
70g protein daily to prevent negative nitrogen balance
once the patient has a normal fluid and electrolyte balance, what should fluid intake equal
fluid intake should equal urine output + vomit + fistula losses + 500ml extra allowance
what confirms acute tubular necrosis on urinalysis
muddy brown casts on urinalysis. renal tubular epithelial cells may also be seen
what do leucocytes on urinalysis suggest
infection
what do protein and blood suggest
acute nephritis
how is AKI prevented
Avoiding nephrotoxic medications where appropriate
Ensuring adequate fluid intake (including IV fluids if oral intake is inadequate)
Additional fluids before and after radiocontrast agents
what are the complications of AKIs
fluid overload, heart failure and pulmonary oedema
Hyperkalaemia
metabolic acidosis
uraemia which can leads to encephalopathy and pericarditis
what tool is used to screen for frailty
Rockwood Fraility Score
What is immediate management plan for sepsis
take lactate, urine output and blood culture
give IV fluids, antibiotics and oxygen
what is septic shock defined as
Septic shock is defined as ‘a subset of sepsis, which describes circulatory, cellular, and metabolic abnormalities which are associated with a greater risk of mortality than sepsis alone’. In hospital, we suspect septic shock when patients fail to respond to initial treatment – specifically, ‘sepsis with persistent hypotension despite fluid correction and inotropes and a serum lactate of greater than 2mmol/L’.
what is the most appropriate IV fluid therapy for initial resuscitation in a patient with sepsis
initial fluid resuscitation with a crystalloid given as a bolus over less than 15 mins
what are crystalloids
solutions containing small molecules in water (sodium chloride, glucose or Hartmann’s)
what are colloids
solutions with large molecular weight substances (e.g albumin, gelatine)
what does the choice and rate at which IV fluids are given depend on?
What is the aim of IV fluid therapy? (resuscitation, routine maintenance, replacement and redistribution)
What is the weight and size of the patient, and therefore what are the fluid requirements?
Are there ongoing losses?
Are there significant co-morbidities which may affect redistribution of fluids? (liver, renal and/or cardiac impairment etc)
what is the most appropriate antimicrobial for treatment of a likely urinary source of infection as per the BNF treatment summary
ceftriaxone
why is lactate raised in sepsis
raised as a result of tissue hypoxia in sepsis; as a result of widespread systemic inflammation, there is organ hypoperfusion and subsequently the cells turn to anaerobic metabolism, which produce lactate
what lactate value is considered a high risk criteria for sepsis
> 4mmol/L
what is mild hyperglycaemia in sepsis a result of
stress response from release of cortisol and cathecolamines by the body during sepsis
when should you urgently treat Hyperkalaemia
when the serum potassium exceeds 6.5 and/or there are ECG changes
what are the three priorities with regards to management of acute hyperkalamia
- protecting the cardiac membrane
- shifting potassium intracellularly
- stopping any contributing medications
what does IV calcium gluconate do
acts by reducing membrane excitatory effects of K on cardiac tissue rapidly, therefore reducing the potential for cardiac arrhythmias such as ventricular fibrillation, but has minimal effect on lowering serum K concentrations
what can you give to shift potassium intracellularly
give 10 units Insulin with 25g glucose (an example of a treatment regime for this would be 10 units Actrapid in 250mls of 10% dextrose at 50ml/hr for 5 hours (25g)
what else is given alongside insulin and glucose in severe, life-threatening Hyperkalaemia and when should it be avoided
nebuliser salbutamol 10-20mg is also given alongside insulin and glucose
avoid salbutamol if tachyarrhythmia present
what are some examples of potassium binders and what do these do
sodium zirconium cyclosilicate and patiromer
act by promoting potassium excretion for managing Hyperkalaemia in adults
what are the three main functions of the kidney
filter and excrete nitrogenous waste products
maintain acid base balance, by controlling reabsorption and excretion of electrolytes
produce certain hormones
what hormones does the kidney produce
erythropoietin, renin and calcitriol
why is creatinine in particular a useful marker of glomerular filtration
because it is completely filtered in the glomerulus
what is GFR proportional to
1/ creatinine
where does the RAAS system happen
in the juxtaglomerular apparatusw
how does it act to increase overall effective circulating volume
increasing reabsorption of sodium ions
vasoconstriction the efferent arterioles
what does histology of ATN show
sloughing of the renal tubular epithelium causing dilation and obstruction of tubules and some mild leukocyte infiltration
what are the 3 phases of ATN
- oligourio phase
- maintenance phase
- polyuric recovery phase
what is the oligourio phase
the kidneys produce less than 500mls of urine per day
the loss of the kidney’s homeostatic functions in AKI will mean that the kidneys are:
- unable to regulate acid-base balance, leading to Hyperkalaemia, fluid retention and metabolic acidosis
- unable to excrete metabolic waste products, leading to build up of urea and creatinine
what does this eventually lead to
multi-organ failure
why is clotting measured in a patient with sepsis
sepsis can be a cause of disseminated intravascular coagulation (DIC)
what is DIC characterised by
a clinical syndrome characterised by dysregulated coagulation
what happens in DIC
tissue factor is released into the bloodstream as a result of cytokine release, endotoxin release or endothelial damage, which activates the coagulation pathway
this widespread coagulation consumes clotting factors, which causes bleeding in a addition to microvascular thrombosis
what is the management of DIC
involves treatment of the underlying cause, and support blood product transfusion in life threatening bleeding
what is Stage 1 AKI
Creatinine:
1.5 – 1.9 times increase from baseline OR
> 26.5 µmol/l increase
Urine:
< 0.5ml/kg/h for 6 – 12 hours
what is Stage 2 AKI
Creatinine:
2.0 – 2.9 times increase from baseline
Urine:
< 0.5 ml/kg/h for > 12 hours
what is Stage 3 AKI
Creatinine:
3.0 times increase from baseline
OR
Increase in serum creatinine > 353.6 µmol/L
OR
In patients < 18 years, decrease in eGFR to < 35ml/min per 1.73m
Urine:
< 0.3ml/kg/h for > 24 hours OR
Anuria for 12 hours
what are the risk factors for developing an AKI
Risk factors for AKI:
Age 65 years or over;
History of AKI;
CKD (eGFR < 60mL/min/1.73m2);
Symptoms or history of urological obstruction, or conditions which may lead to obstruction;
Chronic conditions such as heart failure, liver disease, diabetes mellitus;
Neurological or cognitive impairment or disability (which may limit fluid intake because of reliance on a carer);
Sepsis;
Hypovolaemia;
Oliguria (urine output < 0.5 mL/kg/h);
Nephrotoxic drug use within the last week;
Exposure to iodinated contrast agents within the past week
what should you always remember to do in all patients with an AKI
obtain a urine dipstick
monitor urine output
compare the current renal function to historical records if available
why is urine dipstick important in AKI
> 3+ Proteinuria - indicates intrinsic renal disease
Send Urine PCR / MSU - if dipstick positive
If - ve - prob excludes intrinsic renal disease - Save time and money
If blood and protein +ve - consider glomerulonephritis
Dipstick positive for blood and no RBC - consider myoglobin
what drugs should be stopped in patients with AKI
Aminoglycosides (gentamicin)
ACE-inhibitors (ramipril)
ARBs (losartan)
Metformin
NSAIDs
Aciclovir
what drugs should be monitored carefully, adjusting dose or withholding deeding on eGFR
DOACs (apixaban)
Co-amoxiclav
Low molecular weight heparin (tinzaparin)
Sulphonylureas (gliclazide)
what opioids are considered safe to use in those with renal impairment
Opioids that are considered safer to use in those with renal impairment include oxycodone, fentanyl and hydromorphone; however, these patients are at high risk of opiate toxicity and adverse effects, and will require close monitoring, dose titration and input from specialist teams such as the pain team, renal team or the palliative care team.
what about furosemide
may actually improve renal function in patients who have AKI secondary to cardiorenal syndromes,
what is AIN
acute interstitial nephritis
this is a clinical syndrome characterised by inflammatory infiltrates in the renal intersitioum in response to a drug, infection or autoimmune process
An 80 year old gentleman with type 2 diabetes was started on ibuprofen for hip pain last week. His regular medications include amlodipine and atenolol for hypertension. Last year he was in hospital with pneumonia, and developed AKI during that admission. He has now presented to ED with a fall.
How many risk factors associated with AKI does he have?
5
Which factor does not affect estimated GFR?
weight
