MPharm Programme Acute Kidney Injury Alan M. Green 2017 Slide 1 of 47
Overview Renal Function What is it? Why does it matter? What causes it? Who is at risk? What can we (Pharmacists) do? How do you recognise and manage AKI? How can medicines be optimised in AKI? What resources are available? Slide 2 of 47
Publics knowledge of the kidneys 20 Study (Ipsos MORI poll) % of people who know their kidneys make urine? % of people interviewed who thought their kidneys had a role in processing medicines? % of participants who thought medicines could affect kidney health? Slide 3 of 47
Role of the Kidney Regulate water and electrolyte content in the body Retention of substances needed by the body Glucose, Protein Maintain acid/base balance Excrete waste products, water soluble toxic substances and drugs Endocrine functions Slide 4 of 47
Biochemistry Urea (ref. range serum Urea 3.0-6.5mmol/L) Produced when protein or a.a s are broken down in the liver. Urea is normally cleared by glomerular filtration and reabsorbed in the kidney tubules. Factors affecting Urea levels Urea Urea Dehydration Oedema Pregnancy Concurrent Infection Low protein diet Burns Gastric blood loss Liver function Chronic nutritional status Slide 5 of 47
Biochemistry Creatinine (ref. range 50-120 µmol/l) Produced continuously in muscle and is a function of muscle mass Waste product of muscle catabolism Predominantly cleared from the body via glomerular filtration Creatinine clearance often used to determine kidney function Plasma concentration of creatinine linked to both muscle mass and the kidneys ability to excrete creatinine Slide 6 of 47
It s just a number Slide 7 of 47
Calculating Renal Function Pt Gender Age Weight (Kg) Race SCr (µmol/l) GFR (ml/min/1.73m 2 ) 1 Male 25 80 Black 130 100 2 Male 75 80 White 130 48 3 Female 25 50 White 130 45 4 Female 75 50 White 130 25 Slide 8 of 47
Cockcroft-Gault CrCl (ml/min) = F x (0 age) x weight (Kg) Serum Creatinine (µmol/l) F = 1.04 (female) and 1.23 (male) Slide 9 of 47
egfr Modified Diet in Renal Disease egfr = 170 x (SCr) -0.999 x (age) -0.176 x (0.762 if female) x (1.180 if African American) x [Serum Urea Nitrogen] -0.170 x [Serum Albumin] +0.318 Slide 10 of 47
Estimating renal function Which formula to use in AKI? Cockcroft and Gault equation Modified Diet in renal disease 24 hour urine output Slide 11 of 47
Drug Dosing Practical suggestions: For the majority of drugs, egfr is suitable For narrow therapeutic index drugs, use egfr However correct for patients actual BSA OR GFR absolute = egfr x Actual BSA 1.73 If in doubt, and narrow therapeutic index drugs calculate CrCl via Cockcroft and Gault equation Slide 12 of 47
AKI or CKD? Mr Lincoln is 72 years old, weighs 65kg DHx Aspirin 75mg OD, Simvastatin 40mg ON, Perindopril 4mg OD, Metformin 500mg BD. U&E s on admission Na + 138 K + 4.2 Ur.2 Cr 268 Slide 13 of 47
Interpreting SCr Levels You need to know the patients BASELINE SCr levels to determine this, you can not determine it on ONE result! You need to see the trend. Slide of 47
Acute Renal Failure (ARF) Old terminology Do NOT use 'The abrupt transition from functioning kidneys to kidney function which is unable to accomplish biochemical homeostasis Slide 15 of 47
AKI conceptual model Slide 16 of 47
Acute Kidney Injury A rapid deterioration in renal function over hours or days Defined when one of the following criteria is met Serum creatinine rises by 26μmol/L within 48 hours or Serum creatinine rises 1.5 fold from the reference value, which is known or presumed to have occurred within one week or urine output is < 0.5ml/kg/hr for >6 consecutive hours KDIGO definition Slide 17 of 47
KDIGO Slide 18 of 47
Why is staging important? Increase in stage of AKI associated with increased risk of mortality and length of stay Early introduction of RRT as soon as a patient enters AKI stage 3, may be of benefit AKI stage 3 or complications arise then referral to critical care or renal team Slide 19 of 47
Why does it matter? NCEPOD 2009 Slide 20 of 47
Key Findings Current AKI management poor 50% of patients received good care Poor assessment of risk factors Unacceptable delay in recognising postadmission AKI 29% of patients had inadequacies in clinical management of AKI 33% of patients had inadequate investigations 20% of patients not referred to a nephrologist should have been Slide 21 of 47
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Why does it matter? 20% (1 in 5) of patients acutely admitted to hospital will develop AKI It s estimated that 30% of all AKI is because of medicines, with 5% of hospital inpatients developing drug induced renal impairment AKI is 100 times more deadly than MRSA infection Slide 23 of 47
Acute Kidney Injury 486-630 people per million per year will develop AKI 360,000 inpatient cases per year 210,000 have no history of CKD 75,000 110,000 preventable cases/year No one is safe! Cost very expensive % of AKI that starts in the community? Slide 24 of 47
Increased incidence and progression Ishani A et al. The Magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease and death. Arch Intern Med. 2011,171(3):226-233 Slide 25 of 47
AKI Outcomes Slide 26 of 47
Mortality and Morbidity Increased risk of morbidity and mortality Even small rises in SCr are associated with poorer outcomes Mortality >30% in the over 60s Estimated 20,000 30,000 deaths due to AKI are preventable Increases hospital length by 4.7 days on average 1000 00 patients start Long term RRT following AKI Slide 27 of 47
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Cost Due to longer hospitals stays, CCS admission more likely and increased risk of long term health problems AKI costs more than Lung cancer and bowel cancer Prevent 20% of AKI cases/year 87-124 million in the NHS in England Slide 29 of 47
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Recent evidence (In England) Kerr, Bedford, Matthews, O Donoghue 20 1.02 Billion inpatient cost related to AKI (Just over 1% of NHS total budget in 2010-11) Therefore preventing 20% of AKI cases/year 200 million saving/year Annual admissions with AKI is estimated at 830,000 Annual excess deaths associated with AKI could be over 40,000 Slide 31 of 47
What Causes it? Pre-renal (80%) Intrinsic (10%) Post-renal (10%) Slide 32 of 47
Causes STOP:AKI Sepsis and Hypoperfusion Toxcity Obstruction Parenchymal Kidney Disease Slide 33 of 47
Causes Pre renal Intrinsic Post renal Haemorrhage/GI Bleed Sepsis Caused by a substance or physiological process that damages functional tissues of the kidney Renal calculi Prostate Cancer Cardiac/Liver Failure Acute Interstitial Nephritis BPH Dehydration Acute Tubular Necrosis Retroperitoneal Fibrosis Hypovolaemia Burns Decreased BP Vascular disease Immunological renal disease Myeloma Rhabdomyolysis Retention Slide 34 of 47
3 R s kidney care Reducing Risk Early Recognition Right Response Slide 35 of 47
You need to know who is at RISK Advanced Age Sepsis, hypovolaemia and hypotension Diabetes mellitus, Heart failure, liver disease and atherosclerotic PVD CKD, Hx of AKI, Oliguria Surgical procedures Medication, Use of contrast media Low Albumin Slide 36 of 47
Reducing Risk (Prevention) Recognise and assess high risk pts Assess fluid status Avoid nephrotoxic agents Obtain baseline renal function Treat infection early Maintain effective circulatory volume Recognise and treat hypoxia Check for acidosis Slide 37 of 47
Early Recognition - How will I know Fluid balance chart Drug History U & Es Vital Signs Urine Dipstick Slide 38 of 47
Early Recognition (Detection) Monitor serum creatinine regularly in all adults, children and young people with or at risk of acute kidney injury. "If a tree falls in a forest and no one is around to hear it, does it make a sound?" Slide 39 of 47
Right Response (Management) Assess fluid status Avoid nephrotoxic agents Treat infection early Maintain effective circulatory volume Recognise and treat hypoxia Check for acidosis Slide 40 of 47
Medicines Optimisation: AKI Avoid nephrotoxic medicines Monitor RF when they are used Review nephrotoxic medicines E.g to prevent AKI in D&V Med r/v prior to surgery and radiological procedures requiring contrast media Temp/Permanently withdraw meds that affect kidney haemodynamics Review side effect profile of medicines Slide 41 of 47
Medicines optimisation: AKI Ensure medicines, and their doses, are appropriate for reduced renal function Ensure fluid volume used for drugs is appropriate Monitor potassium and review drugs that cause hyperkalaemia Slide 42 of 47
Drugs to look out for Consider Acute Nephrotoxic Drug Action (CANDA) Contrast Media Ace Inhibitors NSAIDs Diuretics ARBs Slide 43 of 47
TRIPLE threat NSAID, ACEI + Diuretic Slide 44 of 47
References to guide decision making Slide 45 of 47
Summary Common Harmful Costly Preventable/Treatable Slide 46 of 47
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