Renal - L1 Assessing renal function

Question 1

Six subdivisions of renal function – 6

Answer 1

1. Regulation of extracellular fluid volume & BP
2. Regulation of blood Osmolarity - number of osmotically active particles per litre of fluid
3. Maintenance of ion balance (e.g., Na+, K+)
4. Homeostatic regulation of plasma pH (7.38 – 7.42) - secretion &/or reabsorption of H+ & HCO3-
5. Excretion of metabolic & other wastes - creatinine, urea, urobilinogen; hormones; drugs & xenobiotics
6. Hormone activity

Question 2

Creatinine – 3

Answer 2

1. Creatinine undergoes complete Glomerular filtration with little reabsorption – making it a useful indicator of glomerular filtration rate (GFR)
2. A metabolic waste product of Creatine metabolism in the muscles. It is different to Creatine.
3. Creatinine is higher in patients with higher muscle mass

Question 3

Algorithms for eGFR- 3

Answer 3

Cockcroft & Gault Formula (easily used)

Modification of Diet in Renal Disease (MDRD)

CKD-EPI (hard to use)

Question 4

Cockcroft & Gault Formula

Answer 4

Creatinine Clearance (CrCl)
CrCl = ((140-age)xWeight(kg)xF) / Serum Creatinine
F
1.04 – female
1.23 - male

Question 5

Adv & dis of using Cockcroft and Gault to estimate GFR - 4

Answer 5

1. Easy to calculate in practice
2. In use for many years – lots of evidence & experience in use for drug dosing. Most drugs still recommend based on CrCl
3. Based on limited variables
4. Increasing rates of obesity mean body weight is not an accurate measure of muscle mass – use adjusted or ideal body weight if obese/overweight

Question 6

Adv & dis of using MDRD to estimate GFR – 3

Answer 6

1. Gives a better estimation of GFR than Cockcroft & Gault
2. More difficult to calculate in practice
3. Not routinely used in clinical studies/publications to provide recommendations for drug dosing

Question 7

Adv & dis of using CKD-EPI to estimate GFR – 5

Answer 7

1. Superior to MDRD in estimating GFR
2. Very complex to calculate
3. Version available to use cystatin C instead of Creatinine for patients with low muscle mass – rarely seen in practice
4. Recommended by National Kidney Foundation & reported on most laboratory blood test reports
5. Little evidence in use for adjusting drug doses

Question 8

Kidney measurements - 2

Answer 8

eGFR refers to an estimate based on MDRD or CKD-EPI. Units are ml/min/1.73m2

CrCl or GFR refers to an estimate based on Cockcroft and Gault. Units are ml/min

Question 9

Which algorithm – 2

Answer 9

1. CKD-EPI (& previously MDRD): better estimates renal function - used to monitor disease progression, classify & identify renal impairment in CKD
2. Cockcroft & Gault used to establish safe doses for patients with renal impairment – preferred method of estimating renal function for dose decisions, particularly extremes of body weight, age & for medications with narrow therapeutic index which are renally cleared or nephrotoxic

Question 10

MHRA decision -5

Answer 10

1. eGFR is usually acceptable (CKD-EPI or MDRD)
2. eGFR can over-estimate in some cases
3. Overestimation leads to higher doses given compared to renal function risking drug accumulation & toxicity
4. Use CrCl when giving nephrotoxic drugs, elderly (>75), extreme muscle mass (BMI <18 or >40)
5. May need to use adjusted, ideal or actual body weight in obesity

Question 11

Drug dosing in obesity – 3

Answer 11

1. An area of research, some resources are available e.g. ClinCalc
2. Some medicines can be titrated to effect
3. Most important to prevent overdosing of toxic medicines or underdosing of critical medicines

Question 12

Clinical Implications Renal Impairment: Homeostasis – 4

Answer 12

1. Fluid overload
2. Metabolic acidosis
3. Sodium retention
4. Hyperkalaemia

Question 13

Complications of Impaired Renal Function: reduced endocrine function – 4

Answer 13

1. Anaemia
2. Renal Bone Disease
3. Hypertension
4. Increased cardiovascular risk

Question 14

Complications of Impaired Renal Function: reduced excretion – 7

Answer 14

1. Itching
2. Cramps
3. Restless leg syndrome
4. Nausea
5. Stress Ulceration
6. Drug Toxicity
7. Reduced Urine Output

Question 15

Things to consider with renal impairment – 4

Answer 15

1. Management of signs & symptoms of renal impairment
2. Management of underlying cause of renal impairment
3. Optimisation of ‘usual’ medications considering dose adjustments & contraindications
4. Approaches vary greatly depending on whether impairment is acute or chronic

Question 16

Renal impairment Stages – 5 (3A & 3B)

Answer 16

1 – eGFR >90 Kidney DMG (structural abnormalities, blood or protein in urine), normal or increased GFR.
2 – eGFR 60-89. Kidney DMG (same as stage 1),, mildly reduced GFR
3A – eGFR 45-59 Moderately reduced GFR & clear DMG
3B – eGFR 30-44 Same as stage 1
4 – eGFR 15-29 Severely reduced GFR & more damage for 3 months
5 - eGFR <15 Established kidney failure

Question 17

AKI – 4

Answer 17

1. Acute kidney injury (AKI) is a sudden reduction in kidney function over hours or days
2. It is not a physical injury to the kidney & usually occurs without symptoms, making it difficult to identify
3. Not a disease in itself - result of underlying pathology
4. Late diagnosis can miss opportunities for early treatment, reducing chance of recovery & prolonging treatment

Question 18

Stages of Acute Kidney Injury – 3

Answer 18

1 –
Serum creatinine: Rise >26mol in 48hrs or >1.5-1.9 x base SerumCr.
Urine output: <0.5ml/kg/hr for 6hrs

2 –
Serum creatinine: Rises >2-2.9 x base SerumCr
Urine output: <0.5ml/kg/hr for 12hrs

3 –
Serum creatinine: Rise >3 x base SCR or rise 354 umol/L or on renal replacement therapy
Urine output: <0.3ml/kg/hr for 24hrs or anuria (less than 100ml urine) for 12 hrs

Question 19

Kidney functions effected by acute change in overall function – 5

Answer 19

1. Regulation of acid/base balance
2. Regulation of fluid balance
3. Regulation of electrolytes
4. Filtration & Excretion of waste products (including drugs)
5. Production of urine

Question 20

Signs & Symptoms of AKI - 5

Answer 20

1. Acidosis
2. Oedema, reduced urine output
3. Hyperkalaemia – cardiac arrhythmias, muscle weakness, paralysis
4. Toxicity of medications with narrow therapeutic window e.g. Digoxin
5. Reduced urine output

Question 21

Risk factors of AKI – 14

Answer 21

1. Chronic Kidney Disease
2. Heart Failure
3. Liver Disease
4. Diabetes
5. Previous AKI
6. Oliguria (low urine output)
7. Neurological impairment
8. Hypovolaemia
9. Physical Disability
10. Cognitive Impairment
11. Use of nephrotoxic drugs/contrast
12. Sepsis
13. Deteriorating NEWS
14. Age 65+

Question 22

Causes of AKI – Pre, Renal, Pos & STOP

Answer 22

Pre-renal: hypoperfusion/ acute tubular necrosis
Renal: intrinsic renal disease
Post-renal: obstruction

S. Sepsis & hypoperfusion
T. Toxicity
O. Obstruction
P. Parenchymal kidney disease

Question 23

Medicines that can contribute to AKI Pre-Renal – 6

Answer 23

1. Diuretics
2. NSAIDs
3. ACE inhibitors
4. ARBs
5. Antihypertensives
6. Laxatives

Question 24

Medicines that can contribute to AKI Intrinsic: Acute interstitial nephritis - 7

Answer 24

1. NSAIDs
2. Aminoglycosides e.g. Gentamicin
3. PPIs
4. Aminosalicylates
5. Azathioprine
6. Diuretics
7. Vancomycin

Question 25

Medicines that can contribute to AKI Intrinsic: Acute Tubular Necrosis – 7

Answer 25

1. Gentamicin 2. Vancomycin 3. Contrast Media 4. Furosemide 5. NSAIDs 6. Rifampicin 7. Lithium

Question 26

Medicines that can contribute to AKI Methotrexate Intrinsic: Rhabdomyolysis - 5

Answer 26

1. Statins 2. Fibrates 3. Colchicine 4. Theophylline 5. Benzodiazepines

Question 27

Medicines that can contribute to AKI Post-Renal - 2

Answer 27

1. Anti-coagulants 2. Cytotoxic Chemotherapy

Question 28

Pharmacology of NSAIDs, ACEi and ARBs – 7

Answer 28

1. Consider the body’s normal response to a reduction in renal blood flow 2. Vasodilation of afferent blood vessels 3. Vasoconstriction of efferent blood vessels 4. ACE inhibitors & NSAIDs prevent body from achieving normal response 5. NSAIDs inhibit prostaglandin synthesis (prevents Vasodilation) 6. ACE inhibitors and ARBs cause vasodilation of efferent blood vessels 7. These result in hypoperfusion

Question 29

AKI Management - 6

Answer 29

1. Treat the cause 2. Optimise medications: Stop nephrotoxic & medications which exacerbate consequences of renal impairment 3. Review doses for other renally cleared drugs, especially if narrow therapeutic window 4. Maintain good hydration (avoid dehydration & avoid fluid overload = maintain euvolemia) 5. Treat electrolyte abnormalities & acidosis 6. Renal replacement therapy if necessary

Question 30

Prevention of AKI: Hospital setting - 5

Answer 30

1. ACEi /ARBs discontinued on administration of bowel preparations & consider withholding for 72 hours 2. Diuretics discontinued on administration of oral bowel preparations & withheld for 24 hours 3. Withhold ACEi/ARB peri-operatively – role of the pre-admission pharmacist 4. Monitor fluid balance – ensure good hydration 5. Withhold metformin for patients undergoing CT scans using contrast preparations

Question 31

Prevention of AKI: Recognising people at risk in the community – 2

Answer 31

1. Conditions leading to dehydration (for example, diarrhoea & vomiting) 2. Drugs with nephrotoxic potential (e.g. NSAIDs), with people who are at risk of acute kidney injury, particularly those who have eGFR <60 or disability which limits access to fluids

Question 32

Sick day rules – 5

Answer 32

Advice 1. Stay hydrated 2. Temporarily stop medication if unwell with fever or D+V Risks 3. Not evidence based 4. Risk of fluid overload in heart failure patients 5. May lead to poor compliance