W26 AKI + CKD Flashcards

Question

Renal (intrinsic renal toxicity)

Answer 1

1. Glomerular= Glomerulo-nephritis 2. Tubular= Acute tubular necrosis 3. Interstitial= Acute interstitial nephritis

Answer 2

* Drug induced glomerulonephritis (GN) * Immune mediated disease * Antigen-antibody complex accumulate within the glomerulus * Inflammatory response due to depositing immunoglobulins and complement in base membranes and blood vessels * Reduced GFR, salt and water retention, hypertension * Many drugs are known to cause GN

Answer 3

* Allopurinol * NSAIDs * Hydralazine * Penicillins * Sulfonamides * Gold * Rifampicin * Thiazide diuretics

Answer 4

* Acute tubular necrosis (ATN) can occur due to renal ischaemia or nephrotoxic agents or both * Direct toxic affect of drugs & metabolites * Can occur with normal doses but more likely with higher and prolonged dosing and in those with pre-existing renal disease, hypertension, heart disease & diabetes * Avoid nephrotoxic agents in high risk patients * May require renal replacement therapy (RRT) * Maintain adequate hydration and TDM where indicated

Answer 5

* Aciclovir * Aminoglycosides * Cephalosporins * Contrast media * Ciclosporin * Furosemide * Lithium * NSAIDs * Paracetamol * Tacrolimus * Vancomycin

Answer 6

*Highly cationic *Binds to the anionic phospholipid membrane of renal tubule cell *Endocytosis of gentamicin into renal tubule cell *Tubular damage and dysfunction are the main causes of renal insufficiency

Answer 7

* Acute interstitial nephritis (AIN) is a hypersensitivity reaction characterised by a fall in GFR within hours, days or months of exposure to a particular drug * Often associated with proteinuria & haematuria * Intestitium is infiltrated by inflammatory cells * Low-grade pyrexia, rash, arthralgia * AIN is thought to account for up to 15% of hospital admissions due to AKI

Answer 8

* Allopurinol * Amlodipine * Azathioprine * Bumetanide * Carbamazepine * Co-trimoxazole * Diltiazem * Erythromycin * Furosemide * Gentamicin * Lithium * Mesalazine * NSAIDs * Penicillins * Phenytoin * **Proton pump inhibitors** * Ranitidine * Rifampicin * Thiazides * Vancomycin

Answer 9

*PPI use is associated with an increased risk of AKI, CKD and progression to ESRD* *A delay in diagnosis and continued PPI use a contributory factor *Inflammatory process associated with the development of interstitial fibrosis *Incidence unknown but considered to be relatively rare *End-stage renal disease *Omeprazole most frequently implicated PPI *Relatively few reports with other PPIs but this may simply reflect volume of use *A class effect is suspected *Ranitidine has rarely been associated with AIN but is used as an alternative to PPIs

Answer 10

*Withdrawal of the PPI *Monitor renal function recovery *Corticosteroids sometimes used but no evidence of improved outcomes

Answer 11

* Obstruction to urine flow through the kidneys can be caused by a number of factors * Ureteric fibrosis * Renal calculi * Blood clots * Mechanical blockage * Prostatic hypertrophy or malignancy * Bladder tumour * All can occur with drug therapy

Answer 12

*Tubular blockage – crystalluria: * Tumour-lysis syndrome: uric acid crystals, sulphonamides, MTX, cisplatin, aciclovir *Tubular blockage - calcium nephropathy: * Over consumption of vitamin D & calcium containing antacids *Tubular blockage - myoglobin: * Statins (esp. with concurrent fibrates or enzyme inhibitors such as erythromycin)

Answer 13

* Dehydration * Diarrhoea * Chronic kidney disease * Liver disease * Heart failure * Infection/sepsis * Increasing age * Poly-pharmacy

Answer 14

* Nitrofurantoin * Thiazide and related diuretics e.g. chlortalidone, indapamide, bendroflumethiazide

Answer 15

* Antibacterial efficacy in UTI infection depends on the renal secretion of nitrofurantoin into the urinary tract * In patients with renal impairment, renal secretion of nitrofurantoin is reduced, which can result in treatment failure * Nitrofurantoin is therefore contraindicated in those with GFR <45 mL/min creatinine clearance (short courses can be used with caution between 30-44mL/min)

Answer 16

*Inhibits the renal tubular absorption of salt and water by its action at the beginning of the distal convoluted tubule *The effect on the kidney depends upon excretion into the renal tubule; efficacy falls with increasing renal impairment *Thiazide diuretics are unlikely to be of use once GFR<30 mL/min

Answer 17

* Trimethoprim * Amiloride * Spironolactone * Cimetidine * Administration in patients with renal impairment may increase creatinine without altering GFR

Answer 18

1. Determine the degree of renal impairment 2. If a drug is nephrotoxic or known to exacerbate kidney function, consider an alternative 3. Reduce dose or increase dosage interval (if necessary) to accommodate reduced renal clearance & alterations to kinetics 4. Consider the need to load the drug 5. For narrow therapeutic index drugs, monitor levels 6. For all drugs monitor for efficacy, safety & tolerability

Answer 19

They are the final common route of elimination for many drugs and drug metabolites 1. Glomerular filtration 2. Active tubular secretion 3. Passive tubular re-absorption

Answer 20

* Nausea, vomiting or diarrhoea associated with uraemia * Hypoproteinaemic oedema of the GI tract e.g. in nephrotic syndrome * Reduced intestinal motility and gastric emptying time e.g. uraemic neuropathy * Co-administration of chelating agents e.g. phosphate binders

Answer 21

* Changes in hydration state of the patient * Alterations in plasma protein binding * Alterations in tissue binding

Answer 22

* Drugs with a small volume of distribution (Vd) * E.g. Gentamicin in oedematous patients * Important with therapeutic drug monitoring * Particularly important when the state of hydration is fluctuating with the use of IV fluids, diuretics or intermittent renal replacement therapy (RRT)

Answer 23

* Requires therapeutic drug monitoring (TDM) * Unbound drug is pharmacologically active * In renal impairment, need to consider altered serum albumin concentration and decreased binding affinity

Answer 24

* Altered due to: * Hypoalbuminaemia * Uraemia, which will compete with drugs for binding to albumin * Clinically important for highly protein- bound drugs * A reduction in bound drug in plasma will result in a higher proportion of unbound, and therefore active drug in the plasma

Answer 25

* Phase I and II metabolism slower in CKD * Increase serum concentrations of the parent drug * Higher prevalence of adverse drug effects and toxicity * Kidney itself is also a site of metabolism for some drugs: -Insulin -Vitamin D

Answer 26

*Insulin is freely filtered in the kidney. Of the total renal insulin clearance, approximately 60% occurs by glomerular filtration and 40% by tubular secretion * In advanced renal failure there is a marked fall in insulin clearance * This may allow lower doses of insulin to be given or even the cessation of insulin therapy * Decreased calorie intake due to uraemia- induced anorexia, also may contribute to the decrease in insulin requirements

Answer 27

* Glomerular filtration * Renal tubular secretion

Answer 28

* In renal impairment these functions are reduced -Glomerular filtration – higher plasma levels -Tubular secretion - higher plasma levels * Extent to which drugs are affected depends on the % of active drug or metabolite that would normally be excreted by this route

Answer 29

* The half-life of morphine-6-glucuronide is increased from 3–5 hours in normal renal function to about 50 hours in end stage renal disease * Often avoid slow release oral preparations as any side effects may be prolonged

Answer 30

* The effect the drug has on the body * There are changes in the body’s response to drugs in renal impairment * Patients with uraemia have: -Increased sensitivity to drugs acting on the CNS e.g. benzodiazepines -An increased risk of GI bleeding with irritant drugs such as NSAIDs

Answer 31

* Cannot be measured directly therefore estimates are used: * eGFR -MDRD -CKD-EPI * GFR absolute * Creatinine clearance (CrCl) -Cockroft-Gault equation

Answer 32

* One of many molecules cleared by the kidneys that will accumulate in renal impairment * Glomerular filtration & secretion in proximal tubule * Product of muscle breakdown * Production fairly constant in people with stable diets * Production varies between individuals * Proportional to muscle mass and meat intake * May increase by up to 25% in individuals with normal kidney function following a meat containing meal * Important to consider age, sex, race & weight

Answer 33

* Modification of Diet in Renal Disease (MDRD) study group compared different methods of calculating GFR and found an equation with a good prediction of GFR * Age, sex, race (Caucasians, African Americans) * eGFR calculated automatically by laboratory * GFR measured in ml/min/1.73m2 * If BSA < 1.73m2, eGFR is likely to overestimate kidney function

Answer 34

* Using patient’s BSA will overcome this problem but requires an additional calculation * GFR absolute = (eGFR x BSA/1.73) E.g. * eGFR = 32ml/min/1.73m2 * BSA 1.5m2 * GFR absolute = 28ml/min

Answer 35

* Calculated using a different equation: Cockroft-Gault, which includes: * Age, bodyweight, serum creatinine, sex * Measures creatinine clearance in ml/min * Very accurate when used correctly

Answer 36

* Average build or height – actual body weight * Obese – adjusted body weight * Very muscular – actual body weight * Underweight – actual body weight

Answer 37

* CrCl overestimates GFR (15-20%) at normal kidney function due to tubular excretion of a small amount of creatinine which is unrelated to glomerular filtration and therefore not affected by changes in GFR * Tubular secretion usually maintained as glomerular filtration is lost * In advanced CKD this route can account for up to 50% of CrCl

Answer 38

* eGFR and CrCl not interchangeable * eGRF or CrCl OK for most drugs and for most patients of average build and height -GFR absolute -CrCl using appropriate body weight

Answer 39

* Not an exact science * Many reference sources are available with suggested doses but advice is not always consistent * Apply pharmacological knowledge * Limit the potential problems with adverse effects and toxicity

Answer 40

1. Determine the degree of renal impairment 2. If a drug is nephrotoxic or known to exacerbate kidney function, consider an alternative 3. Reduce dose or increase dosage interval (if necessary) to accommodate reduced renal clearance & alterations to kinetics 4. Consider the need to load the drug 5. For narrow therapeutic index drugs, monitor levels 6. For all drugs monitor for efficacy, safety & tolerability

Answer 41

* Loading doses may be required: * If therapeutic levels required quickly * Drugs that have a prolonged half-life in renal failure * E.g. Teicoplanin * Glycopeptide antibiotic * Bactericidal activity against aerobic and anaerobic Gram-positive bacteria including multi-resistant staphylococci

Answer 42

* Early identification key to limit progression and complications * Prevalence of CKD increases with age, DM, HTN and obesity * GFR & ACR independently related to mortality, CV events, progression to ESRD & AKI * Annual renal testing for patients with DM * Advice on when to refer to renal * Lifestyle advice: smoking cessation, exercise, healthy diet and weight loss * Anaemia management * Mineral and bone disorder management * Patient education

Answer 43

* RAAS inhibitors recommended for patients with proteinuria, diabetes & HTN to control blood pressure and proteinuria * SGLT2-i recommended for people with CKD + T2DM taking ARB or ACEi + ACR >30mg/mmol * Offer SGLT2-i if ACR 3-30mg/mmol * Statins: CKD considered highest risk group * Aspirin: recommended for 2° CVD prevention

Answer 44

* Large-scale placebo-controlled trials have demonstrated that sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces the risk of kidney disease progression and cardiovascular death * CREDENCE and DAPA-CKD trials demonstrated SGLT-2 inhibition’s efficacy at reducing risk of kidney disease progression in people with CKD, T2DM and albuminuric diabetic kidney disease * Subgroup analyses from DAPA-CKD suggest these benefits extend to certain types of albuminuric CKD, irrespective of the presence of DM.

Answer 45

*Recommended as an option for treating CKD in adults only if: * Add-on to optimised standard care including RAASi (unless c/i or n/t) * eGFR 25 to 75 ml/min/1.73 m2 and: * Have type 2 diabetes or * uACR ≥ 22.6 mg/mmol

Answer 46

* Measure serum CCa, phosphate, PTH and vitamin D levels in people with eGFR <30ml/min/1.73m2 * Offer bisphopshonates if indicated if eGFR >30ml/min/1.73m2 * Offer colecalciferol or ergocalciferol to treat vitamin D deficiency in people with CKD and vitamin D deficiency * If vitamin D deficiency corrected and symptoms of CKD– MBD persist, offer alfacalcidol or calcitriol if GFR <30ml/min/1.73m2 * If in doubt speak to a specialist

Answer 47

* ACKD services in Wales are coordinated from renal centres in secondary care * In SWW our renal anaemia team includes renal pharmacist and anaemia nurse specialists * CKD should be considered as a possible cause of anaemia when GFR <60ml/min/1.73m2 * More likely to be the cause if GFR is <30ml/min/1.73m2 (<45/min/1.73 m2 in patients with diabetes) and no other cause is identified

W26 AKI + CKD Flashcards

(71 cards)