Calculating AKI

Question 1

What can you monitor to know when renal impairment aka Acute Kidney Injury (AKI) occurs?

Answer 1

Increase in Serum Cr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours

Increase in Serum Cr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days

Urine volume <0.5 ml/kg/h for 6 hours.

Question 2

Give examples of drugs that can cause AKI

Answer 2

Candersartan dose increased leads to AKI- must have baseline serum creatinine level

Diuretics- removing them off this can allow patient to recover and rehydrating patient back up

Ibuprofen

Question 3

Define acute kidney injury

Answer 3

An abrupt decline in renal function, clinically manifesting as a reversible acute increase in nitrogen waste products

Microscopic level kidney is disturbed

Question 4

How can you tell by the serum creatinine the stages of AKI

Answer 4

Stage 1:
1.5-1.9 times baseline
≥0.3 mg/dl (≥26.5 micromol/l) increase

Stage 2:
2.0-2.9 times baseline

Stage 3:
3 times baseline
Increase in serum creatinine to ≥4.0 mg/dl (≥353.6 micro mol/l)
Initiation of renal replacement therapy
Patients of <18 years, decrease in eGFR to less than 35ml/minute per 1.73m2

Question 5

Describe the pre-renal cause of acute kidney injury?

Answer 5

Mechanism: Blood flow to the kidney is reduced which if not managed can cause ischaemic injury to the kidneys

Causes: Reduced blood pressure, hypovolaemia, dehydration, GI bleeding, sepsis, cardiac and liver failures, burn
Symptoms: dehydration, nausea and vomiting

Question 6

Describe the post-renal cause of acute kidney injury?

Answer 6

Mechanism: obstruction to outflow from kidneys

Causes: Benign prostatic hypertrophy (BPH), prostate cancer, renal calculi, retroperitoneal fibrosis

Question 7

Describe the intrinsic cause of acute kidney injury

Answer 7

Mechanism: damage to functional tissues of kidney

Causes: 
Acute interstitial nephritis (hypersensitivity reactions are often drug induced)
Myeloma
Rhabdomyolysis (developed from statins) 
Immunological renal disease (vasculitis)

Question 8

What are the exposures of patients with acute kidney injury

Answer 8

Exposures and susceptibilities 
Sepsis (reduced blood pressure) 
Critical illness
Circulatory shock-
Burns-
Trauma
Cardiac surgery
Major non cardiac surgery
Nephrotoxic drugs
Radiocontrast agents given to patients before scan can damage patient

Question 9

What are the susceptibilities of patients with acute kidney injury

Answer 9

Dehydration of volume depletion- develop infection or sepsis can develop AKI

Advanced age- kidneys slow down with age

Female gender

Black race

CKD- chronic kidney disease- not working as well as the should- includes donating a kidney is a risk factor

Chronic diseases like heart, lung or liver

Diabetes mellitus- linked with CKD- diabetic nephropathy

Cancer

Anaemia

Avoid giving patients anything that can cause AKI like ibuprofen- do not give to older patients as more at risk

Question 10

From the drugs, atenolol, indapamide, lisinopril, morphine, omeprazole, paracetamol, simvastatin, tramadol, warfarin, which one would you stop if patient had AKI?

Answer 10

1. Lisinopril- wouldn’t want because it could further increase risk (MAIN ONE)
2. Indapamide (thiazide like diuretic)- increase risk of dehydration (MAIN ONE)
3. Morphine opiates could accumulate and increase risk of respiratory depression
4. Atenolol- reduce blood pressure- may not stop suddenly but monitor it closely

Question 11

What are the pre-operatively based medicines given for a patient with AKI

Answer 11

1. Cefuroxime 1.5g stat

2. Gentamicin 160mg stat- nephrotoxic drug

Question 12

What is anuric

Answer 12

cannot produce urine

Question 13

Give examples of drug classes that cause AKI

Answer 13

NSAIDs- pre-renal
Amino glycosides
ACE inhibitors- pre-renal
ARBs- pre-renal
Diuretics- cause kidney perfusion and dehydration
Iodinated contrast agents- patient have before scans- acute interstitial nephritis

Question 14

How do NSAIDs and ACE inhibitors affect glomerular hydrostatic pressure and AKI?

Answer 14

Both cause pre-renal AKI
Reduce amount of blood that gets into for glomerular filrtation
Afferent arteriole- removes blood from glomerulus
Prostaglandins- vasodilator more blood flow to kidneys
NSAIDs stop this action

Efferent arteriole will constrict which means less blood is removed from the glomerulus and angiotensin II will vasoconstrict this
ACE inhibitors and ARBs stop this action

Question 15

How do you reducy e the risk of AKI through medicines optimisation

Answer 15

Stopping certain medicines
If patient feels unwell or have vomiting, diarrhoea, fever and sweat- they should stop taking regular medicine that may cause AKI
On sick days they should stop medicines like:
ACE inhibitors (pril), ARBs (-sartans), NSAIDs, Diuretics, Metformin- causes lactic acidosis

Question 16

36 hours after post operation, what should you do?

Answer 16

5L fluid intravenously since operation
Furosemide 160mg i/v single dose to remove fluid
Monitor fluid balance 
Serum potassium- affects heart
Serum Bicarbonate

Question 17

How are pharmacokinetics altered in renal impairment (AKI)?

Answer 17

All kinetic processes are affected

Absorption: may be affected due to gut oedema- affects drugs in gut

Distribution:
Odema = water increase drugs with low Vd will be affected- highly water soluble will be affected
Plasma proteins decrease- filter them when they shouldn’t and get excretion

Metabolism:
Kidneys have a metabolic function- reduced in AKI/CKD
Insulin is metabolised in kidney which is affected by AKI

Elimination:
Most significant effect when consider drug dosing

Question 18

How are pharmacokinetics especially elimination affected in AKI

Answer 18

Kidney involved in drug/metabolite elimination by glomerular filtration, renal tubular secretion and reabsorption

Renal impairment- all processes reduced

Extent to which drugs are affected depend on % active drug/metabolites are usually excreted

Dose adjustments are required to avoid accumulation and toxicity

Question 19

What drugs will be affected most depending on renal clearance and therapeutic index?

Answer 19

High renal clearance/wide therapeutic index- many antibiotics, only a problem with high IV doses- penicillin

High renal clearance/narrow therapeutic index
Amino glycosides, glycopeptides, digoxin
Dose adjustment- starting dose usually fine

Low renal clearance/narrow therapeutic index
Theophylline and Phenytoin- hepatic clearance, no toxic/active metabolites
Safe at full doses generally, monitor and titrate

Question 20

What are the ideal characteristics of a drug in renal impairment

Answer 20

1. Less than 25% excreted unchanged in urine
2. No active/toxic metabolites
3. No side effects
4. Levels/activity minimally affected by fluid balance or protein binding changes
5. Wide therapeutic margin
6. Not nephrotoxic- gentamicin is toxic
7. Does not interact with other drugs
8. LICENSED

Question 21

Describe dose modifications that take place for drugs given to patients with AKI

Answer 21

Renal impairment prolongs the half life of any renally excreted drug

1. Give a smaller dose at same dose interval
2. Give same dose at a longer interval- gentamicin and vancomycin
3. Loading dose may be needed to achieve steady state faster