W9.2_Renal Therapeutics Flashcards
1
Q
Define acute kidney injury (AKI). What are its complications and significance in hospital setting?
A
- Sudden episode of kidney failure/damage within few hours/days
- Can result in failure to maintain fluid balance, electrolyte level disturbances, and acid-based imbalances
- 20% of hospital admissions has AKI
2
Q
What the risk factors of AKI?
A
- Underlying CKD, history of AKI, reduction of urine output
- Age >65, dehydration
- Comorbidities, cancer, sepsis, neurological/cognitive impairment/disability, surgery
- Taking nephrotoxic medicines, recent use of iodine-based contrast media
3
Q
Explain the causes of AKI in terms of pre-renal, renal and post-renal causes.
A
- Pre-renal (80% of cases): inadequate perfusion of kidneys
- Volume depletion (diarrhoea, vomiting, excessive diuresis, haemorrhage, burns, inadequate intake)
- Reduction of cardiac output (heart failure, acute MI, sepsis, liver failure)
- Obstruction of renal arteries (renal thrombosis, renal stenosis)
- Medications that reduces blood pressure (ACE inhibitors, ARBs, NSAIDs, loop diuretics)
- Renal (intrinsic): structural damage to kidney, sustained drop in blood pressure
- Vascular (ex. vasculitis, thrombosis)
- Glomerular (ex. glomerulonephritis)
- Tubular (ex. ischaemia, rhabdomyolysis)
- Interstitial (ex. interstitial nephritis)
- Nephrotoxic medications
- Post renal: obstruction of urinary flow within renal tract
- Renal stones, enlarged prostate, deposition of crystals in tubules, tumours, blocked catheter
4
Q
What are the common symptoms of AKI and how is it diagnosed?
A
- Symptoms of AKI: may not be obvious/specific
- ex. reduced urine output, dark urine, tiredness/drowsiness, confusion, nausea and vomiting, swelling in legs/feet, itching, feeling thirsty
- Diagnosis: measure serum creatinine and compare to baseline (rapid rise)/fall in urine output for catheter
- Staged based on severity (1-3)
5
Q
Discuss the role of pharmacist in management of AKI.
A
- Medicines reconciliation: identity potential medication causes (thorough medication history including OTC, herbal medicines and recreational drugs)
- Ensure medicines appropriately withheld/stopped (withhold nephrotoxic medications on admission in patients with high risk of AKI, temporarily withhold that could compromise renal functions, recommend alternatives)
- Ensure all doses are amended accordingly and re-assess daily (use renal handbook)
- Fluid balance (advise IV fluids and IV medicines if required)
- Patient advice (discuss medication changes)
- Discharge planning (discuss restarting medications temporarily withheld, discuss medicines to avoid in future)
- Communication with other healthcare professionals (regarding medication changes, which medicines are being restarted and when)
6
Q
What are the medications typically reviewed when a patient exhibits renal impairment (6)? Explain sick day guidance and its appropiateness.
A
- Medications typically reviewed: ACE inhibitors, ARBs, NSAIDs, diuretics, metformin, some antibiotics
- Sick day guidance (may not be appropriate): teach patients how to manage their own medications if they become unwell to reduce risk of developing AKI
7
Q
Define and describe the characteristics of chronic kidney disease (CKD).
A
- Gradual decline in kidney function over a period of time
- Abnormal kidney function (eGFR<60mL/min/1.73m2)/structure for more than three months
- Substantially increase mortality risk, can lead to cardiovascular disease and other complications /end-stage kidney failure
- Asymptomatic initially, 10% of population have CKD, black and asian groups more likely
8
Q
What are the risk factors of CKD?
A
- Increasing age, smoking, family history, african/african-caribbean/asian background
- Hypertension, diabetes, cardiovascular disease, gout
- AKI, untreated urinary outflow tract obstruction, conditions with potential kidney involvement
9
Q
What are the possible causes of CKD?
A
- Conditions associated that affect kidney tissues (ex. hypertension, diabetes mellitus, hypercholesterolemia)
- Kidney infections
- Glomerulonephritis
- Taking nephrotoxic medications
- Conditions associated with obstructive kidney disease
- Multisystem diseases that may involve the kidney (ex. SLE)
- Hereditary history of kidney disease
10
Q
State the symptoms of CKD. How is staged or classified? What is the pharmacological aim for CKD management?
A
- Symptoms of CKD: may be initially asymptomatic
- Tiredness, trouble concentrating, poor appetite, trouble sleeping, muscle cramping at night, swollen feet and ankles, puffiness around the eyes, dry and itchy skin, often urination at night
- Staging and classification of CKD: increased ACR and decreased eGFR = more severe
- Pharmacological management of CKD: no cure, could only prevent/delay progression
11
Q
Regarding pharmacological management for CKD patients, describe the plans for hypertension management and cardiovascular risk.
A
- Hypertension management to aim for <140/90 mmHg (<130/80 for significant proteinuria):
- Lifestyle advice for ACR <30mg/mmol and ACE inhibitors/ARBs for >30 (beneficial effects on proteinuria and slows progression of CKD, but need to monitor K+ and renal function)
- Dihydropyridine calcium-channel blockers (may cause ankle swelling) and thiazide diuretics (for eGFR <30) might not be practical
- Resistant hypertension may develop
- Addressing cardiovascular risk:
- Atorvastatin 20mg OD for lipid modification (for eGFR <60)
- Antiplatelet drugs for secondary prevention of cardiovascular disease (but may increase bleeding risk)
- Dapagliflozin (SGLT2 inhibitors) given to give cardiovascular and kidney protection (can improve glycaemic control in type 2 diabetes too)
12
Q
Regarding pharmacological management for CKD patients, describe the plans for addressing diabetes, reducing infection risk, addressing anemia and renal bone disease risk.
A
- Addressing diabetes: start ACE inhibitor/ARB in proteinuria, tight control of hyperglycaemia to prevent/delay CKD progression
- Reduce infection risk: flu vaccine, covid vaccine, pneumococcal vaccine
- Addressing anaemia risk:
- CKD may develop anaemia due to reduced erythropoietin production -> reduce iron absorption
- Treatment: erythropoiesis stimulating agents (ESAs), iron (oral/IV), blood transfusion
- Addressing renal bone disease risk:
- Hyperphosphatemia (∵ X excrete), hypocalcaemia (∵ X activate vitamin D), secondary hyperparathyroidism (high PTH levels), disordered bone metabolism
- Treatment options: restrict phosphate intake, phosphate-binders, vitamin D supplementation, cinacalcet/etelcalcetide
13
Q
Regarding pharmacological management for CKD patients, describe any additional plans to regulate or prevent complications.
A
- Electrolyte regulation (hyperkalaemia, hyperphosphatemia)
- Fluid retention (may require diuretic)
- Gout (may require colchicine, allopurinol)
- Acid-base balance issues (may require sodium bicarbonate supplementation)
14
Q
Explain how medicines can be nephrotoxic and cause AKI. What are its risk factors? How is it prevented and what are the problems it poses to AKI patients?
A
- Nephrotoxic medicines: common cause of AKI
- Mechanisms: volume depletion, decreased renal perfusion, drug-induced glomerulonephritis, acute tubular necrosis (ATN), acute interstitial nephritis, obstructive uropathy
- Risk factors: >60 yo, renal impairment, volume depletion, sepsis, diabetes, heart failure
- Preventive measures: alternative medicines, correct risk factors, assess renal function before treatment, monitor renal function during treatment, avoid nephrotoxic combinations
- Problems: increased toxicity from drug/metabolite accumulation, increased sensitivity, poorer side-effects tolerance, lower effectiveness
15
Q
Explain the ADME considerations in patients with renal impairment. What should be done to minimise the risks?
A
- Absorption: significantly reduced for some oral medicines (due to uraemia, effects on gastrointestinal motility, hyperphosphatemia in CKD)
- Distribution: altered for some medicines (due to hydration status, protein binding, tissue binding)
- Metabolism: altered for some medicines (due to changes in phase I and II in CKD, vitamin D and insulin metabolism in kidneys)
- Excretion: altered for renally cleared medicines (reduced glomerular filtration and renal tubular secretion -> higher plasma concentration, reduced reabsorption -> higher concentration of medicines in urine)
- ∴ dosages might need to change
16
Q
What are the pharmacodynamic considerations in patients with renal impairment regarding uraemia?
A
- Increased sensitivity to CNS medicines (ex. benzodiazepines)
- Increased GI bleeding risk with irritant medicines (ex. NSAIDs)
- Increased hyperkalemia risk with potassium-sparing diuretics
17
Q
What is the role of pharmacist in medicines optimisation for patients with renal impairment?
A
- Dose adjustment, additional monitoring, knowing nephrotoxic medicines
- Dose adjustments: reduced total daily maintenance dose, reduce individual doses, increase interval between doses, different formulations (single dose X need to change)
- Alternative medicines: not nephrotoxic, wide therapeutic index, does not require renal metabolism/excretion of active form, low ADR profile, not highly protein bound, unaffected by fluid balance changes
- Using eGFR/eCrCl (not interchangeable) for treatment changes
- Monitor efficacy/effects, look for side-effects/increased sensitivity
18
Q
State the high risk medicines for patients with renal impairment (6).
A
- Nephrotoxic (ex. NSAIDs, aminoglycosides, methotrexate and other chemotherapeutic agents)
- Narrow therapeutic index medicines and excreted through kidneys (ex. digoxin, aminoglycosides, some chemotherapeutic agents)
- ACE inhibitors, ARBs
- Some antibiotics that can accumulate and cause seizures
- Pharmacologically active metabolites excreted through kidneys (ex. morphine)
19
Q
Explain the reasons for assessing renal function in patients. Why is creatinine is used in these tests?
A
- Routine screening/baseline bloods, at high risks, showing signs/symptoms of kidney disease, progression monitoring in CKD
- Creatinine is metabolic breakdown product of muscle (constant rate), can only cleared by kidneys, reabsorbed and secreted in small amount
20
Q
What are the ways to assess AKI and CKD in blood tests?
A
- Assessing AKI: measuring serum creatinine compared to baseline
- Assessing CKD: eGFR and eCrCl
- eGFR: CKD-EPI equation is used in lab reports/most patients, MDRD equation is less accurate when eGFR >60 and overestimates in elderly patients
- eCrCl: use ideal weight if obese, accuracy groups in some populations and does not take into account variations between races
- Cockcroft and Gault formula: eCrCl=((140-age) x weight/[plasma creatinine]) x 1.23 (male) or 1.04 (female)
21
Q
Regarding urinalysis, explain what urine dipstick is and the test components involved (7).
A
- Urine dipstick: initial screening to identify potential cause of renal dysfunction, test for blood, protein, leucocytes, nitrates, glucose
- Albumin creatinine ratio (ACR): ratio of albumin (mg) in urine to creatinine (mmol) in serum
- Protein creatinine ratio (PCR): ratio of protein (mg) in urine to creatinine (mmol) in serum
- Urine output: through 24-hour urine collection (to test urine creatinine clearance)
- Urea: waste product produced in liver -> filtered in kidneys, some reabsorption -> excreted in urine, high urea level could be due to dehydration or reduced eGFR
- Potassium: controlled by aldosterone (eliminate excess K+), renal dysfunction can get high levels
- Phosphate: can accumulate as kidney function declines
- Sodium: high sodium can indicate dehydration, low sodium can indicate oedema
22
Q
Explain the different personal and medicinal factors (3/3) in using different equations for renal function tests in dose adjustments.
A
- eGFR and eCrCl are not interchangeable
- Personal factors: use eCrCl when age >75, extremes of muscle mass, BMI <18 or >40
- Medicinal factors: use eCrCl if narrow therapeutic index and mainly renally excreted, nephrotoxic or high risk medications, dose management guidelines only provided in eCrCl
