WEEK. MPharm Programme. Acute Kidney Injury. Alan M. Green MPHM13: Acute Kidney Injury. Slide 1 of 47

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1 MPharm Programme Acute Kidney Injury Alan M. Green 2017 Slide 1 of 47

2 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

3 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

4 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

5 Biochemistry Urea (ref. range serum Urea mmol/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

6 Biochemistry Creatinine (ref. range 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

7 It s just a number Slide 7 of 47

8 Calculating Renal Function Pt Gender Age Weight (Kg) Race SCr (µmol/l) GFR (ml/min/1.73m 2 ) 1 Male Black Male White Female White Female White Slide 8 of 47

9 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

10 egfr Modified Diet in Renal Disease egfr = 170 x (SCr) x (age) x (0.762 if female) x (1.180 if African American) x [Serum Urea Nitrogen] x [Serum Albumin] Slide 10 of 47

11 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

12 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

13 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 K Ur.2 Cr 268 Slide 13 of 47

14 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

15 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

16 AKI conceptual model Slide 16 of 47

17 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

18 KDIGO Slide 18 of 47

19 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

20 Why does it matter? NCEPOD 2009 Slide 20 of 47

21 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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23 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

24 Acute Kidney Injury people per million per year will develop AKI 360,000 inpatient cases per year 210,000 have no history of CKD 75, ,000 preventable cases/year No one is safe! Cost very expensive % of AKI that starts in the community? Slide 24 of 47

25 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): Slide 25 of 47

26 AKI Outcomes Slide 26 of 47

27 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 patients start Long term RRT following AKI Slide 27 of 47

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29 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 million in the NHS in England Slide 29 of 47

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31 Recent evidence (In England) Kerr, Bedford, Matthews, O Donoghue Billion inpatient cost related to AKI (Just over 1% of NHS total budget in ) 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

32 What Causes it? Pre-renal (80%) Intrinsic (10%) Post-renal (10%) Slide 32 of 47

33 Causes STOP:AKI Sepsis and Hypoperfusion Toxcity Obstruction Parenchymal Kidney Disease Slide 33 of 47

34 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

35 3 R s kidney care Reducing Risk Early Recognition Right Response Slide 35 of 47

36 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

37 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

38 Early Recognition - How will I know Fluid balance chart Drug History U & Es Vital Signs Urine Dipstick Slide 38 of 47

39 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

40 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

41 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

42 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

43 Drugs to look out for Consider Acute Nephrotoxic Drug Action (CANDA) Contrast Media Ace Inhibitors NSAIDs Diuretics ARBs Slide 43 of 47

44 TRIPLE threat NSAID, ACEI + Diuretic Slide 44 of 47

45 References to guide decision making Slide 45 of 47

46 Summary Common Harmful Costly Preventable/Treatable Slide 46 of 47

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Acute Kidney Injury in The Acute Oncology Patient

Acute Kidney Injury in The Acute Oncology Patient Dr Andrew Lewington BSc MEd MD FRCP Consultant Renal Physician/Honorary Senior Lecturer Leeds Teaching Hospitals Definition Definitions and terminology