Acute Kidney Injury. APSN JSN CME for Nephrology Trainees May Professor Robert Walker

Transcription

1 Acute Kidney Injury APSN JSN CME for Nephrology Trainees May 2017 Professor Robert Walker

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3 Kidney International (2017) 91, ; j.kint

4 Case for discussion 55year old woman with a 3 day history of severe gastrointestinal upset predominantly watery diarrhoea. No known previous history. Clinically hypotensive 90/50mmHg, tachycardic, JVP not visible lying flat. Weight is down by 3 kgs. Blood tests: ph 7.18, Creatinine 370umol/l, urea 25 mmol/l, HCO 3-14 mmol/l, K+ 6.7mmol/l, Na+ 130mmol/l. ECG demonstrates tented T waves.

5 Management options - priorities A: Lower K+ with insulin and dextrose is first priority B: Immediately replace fluid electrolyte losses with N-saline and NaHCO3 C: Needs urgent dialysis D: Slow fluid replacement over next 24 hours is more appropriate.

6 Objectives: Understand common presentations of acute kidney injury (AKI). Understand the basic pathophysiology of AKI

7 AKI: Definition An abrupt reduction in kidney function (within 48 hours) defined as: an absolute increase in serum creatinine of more than 22.4µmol/L OR a percentage increase in serum creatinine of more than 50% OR Oliguria of < 0.5 ml/kg/hr for > 6 hours Acute Kidney Injury Network Mehta et al. Critical Care :R31 doi: /cc5713

8 AKI: Causes rule of 3 Clinical Presentations: 1. Pre-renal: alterations in renal perfusion whatever the cause. Usually a feature of most forms of ARF. 3. Post-renal: obstruction. May occur from the tubules (uric acid precipitation) to the urethra (prostatic obstruction) 2. Renal: Toxic usually drugs, venom ischaemic - progression from reduced perfusion pressure immunologic injury acute GN, acute infection 2 1 3

9 A Bit of Physiology To be a good doctor one has to be a good physiologist. W Hall.

10 Acute Kidney Injury Altered Perfusion Kidney highly vascular with renal blood flow tightly regulated to maintain renal perfusion despite variations in systemic blood pressure.

11 Glomerular filtration Minor changes in perfusion pressure can reduce GFR Perfusion pressures closely regulated despite changes in systemic pressure - AUTOREGULATION

12 Normal Preservation of Kidney Function Vascular changes in glomeruli (vasoconstriction - vasodilation) Fine control of filtration pressure (myogenic and JG cells*) *Tubuloglomerular feedback changes in Na+ delivery sensed by the macula densa Changes in renin - angiotensin II, SNS (short term); aldosterone (long term) Link these mechanisms to changes in renal function that are seen clinically: oliguria, blood pressure, urinary sodium excretion.

13 Acute Kidney Injury Altered Perfusion Kidney highly vascular with renal blood flow tightly regulated to maintain renal perfusion despite variations in systemic blood pressure. Cardiovascular instability autoregulation compromised. Examples Major cause is Sepsis. Ischaemic heart disease, atherosclerosis & hypertension, renal impairment also associated with altered regulation.

14 Control of Renal Perfusion Normal Regulation from Tubulo-Glomerular Feedback mechanism and myogenic factors

15 A vascular system that regulates peripheral vascular resistance, blood pressure and glomerular filtration, while responding to the tubular load and reabsorption rate of NaCl. Kidney homeostasis = Blood pressure homeostasis = salt and water homeostasis Mediated by the Tubuloglomerular Feedback Mechanisms

16 Low Na+ High Na+ BP tends to fall BP is elevated

17 TGF: Luminal NaCl at the MD acts via NKCC2: LOW NaCl causes: Release of Renin (JG) Afferent Arteriolar Vasodilation Renin Ang II Efferent Arteriolar VasoConstriction Pgc GFR PT NaCl Reabsorption Raised Systemic BP (restoration to normal) HIGH NaCl causes: Suppressed Renin Afferent Arteriolar Vasoconstriction Efferent Arteriolar VasoDilation GFR, PT NaCl Reabsn, systemic BP returned to normal. These responses restore GFR = Autoregulation

18 Isolated glomerulus Tubuloglomerular feedback. J Peti-Peterdi. Physiology Video accessible at journal website Physiology Supplemental material for this article can be found at: org/cgi/content/full/24/2/88/dc1

19 renin Peti-Peterdi et al Physiology 2009

20 Direct imaging of renin enzyme activity in kidney Peti-Peterdi et al Physiology 2009

21 Myogenic constriction Vasoconstriction to increase perfusion pressure Contribution of pre-glomerular vessels important protective mechanism to prevent transmission of systemic pressures to glomeruli.

22 Myogenic oscillations afferent arterioles and glomerulus. J Peti-Peterdi. Physiology Video accessible at journal website Physiology Supplemental material for this article can be found at: cgi/content/full/24/2/88/dc1

23 Normal Control of Renal Perfusion Regulation from TubuloGlomerular Feedback mechanism and myogenic factors Balance between vasoconstricting hormones and vasodilating hormones These are being continously released at low doses in tonic fashion to maintain vascular tone. Vasoconstricting - AII, NorEpi & Epi (catecholamines) - SNS, AVP, endothelin Vasodilators - PGs, Nitric oxide

24 Note: not independent actions, rather final control of GFR is a balance of these actions. The Kidney: Eds: Harris Pollock Lawrence

25 Efferent arteriole TGF Renin release Pressure JG cells act as a pressure sensing area analagous to aortic barorecptors Afferent arteriole

26 Stress Response Pathophysiological Changes Decrease in pressure in afferent arteriole - renin release in < 1 sec. Directly constricts pre-glomerular & post-glomerular vessels Pressure dependent changes in RAS - major cause behind hypotensive resetting of RBF autoregulation. Peti-Peterdi Seeliger Physiology

27 Angiotensin II & RBF Directly constricts pre-glomerular & post-glomerular vessels. Now a pathophysiological response which results in marked reduction of renal perfusion. decreased GFR decreased blood flow in the vasa recta

28 Infusion 10ng Ang II into afferent arteriole. J Peti-Peterdi. Physiology 2009 Video accessible at journal website Physiology Supplemental material for this article can be found at: physiology.org/cgi/conte nt/full/24/2/88/dc1

29 Angiotensin II & SNS Increases NaCl reabsorption - proximal tubule also modify distal Na+/H+ channels distal tubule. An attempt to expand blood volume Distal NaCl load altered even at a constant filtered load. Linked to TGF mechanism Increases metabolism and decreases tissue oxygen tension.

30 Any form of cardiovascular instability SEPSIS O/A BP Pre admission BP

31 Alterations in renal haemodynamics Hypotensive insult Renal Blood Flow Role of vasa recta Medullary ischaemia Glomerular filtration rate vasoconstriction vs. vasodilation Acute tubular necrosis

32 NSAID Alterations renal haemodynamics NSAIDs Inhibition PG formation Vasculature & Macula Densa Renal Blood Flow Medullary ischaemia Glomerular filtration rate vasoconstriction vs. vasodilation Acute tubular necrosis

33 AKI: Pre-renal plus ATN AKI 2 1 3

34 AKI Renal injury Acute Tubular Necrosis (2) Normal glomerulus Normal TEC Dead TEC

35 Target Area for Early Ischaemic Injury Hypoxic Injury: 1. Tubules: Late proximal Tubules + MTAL rich in mitochondria and active in transport 2. Vascular Endothelium: Injured Cells undergo: necrosis apoptosis or sublethal injury

36 Bonventre J. J Clin Invest. 2011;121(11):

37 Post EH et al. Kidney International (2017) 91, 45 60

38 Bonventre J Clin Invest 2011 Bonventre J. J Clin Invest. 2011;121(11):

39 Acute Kidney Injury

40 AKI Case - Urinary biochemistry demonstrates a urinary Na+ 5mmol/l and osmolality of 650 mosm/kg Why is she hyperkalaemic? A: AKI reducing K+ excretion? B: AKI preventing inadequate HCO3- regeneration? C: intracellular acidosis is driving the hyperkalaemia?

41 AKI pathophysiology Renin Angiotensin aldosterone activation and SNS activation - sodium retention and potassium excretion Tissue hypoperfusion (volume depletion), anaerobic metabolism intracellular buffering Management is correction of abnormal pathophysiology.

42 Management Fluid replacement A: N-saline should not be used as will make acidosis worse B: With 3 kg weight loss, the 3 litre deficit should be replaced over 24 hours C: Needs to be catheterised to accurately measure urine output. D: Fluid replacement should be as fast as possible with close observation. E: D&C correct

43 Figure 2. Alterations in tubule cell structure after ischemic AKI Devarajan, P. J Am Soc Nephrol 2006;17: Copyright 2006 American Society of Nephrology

44 Recovery Phase AKI Important 25 50% mortality occurs in this period. Polyuria up 5-6L per 24 hrs Electrolyte abnormalities hypokalaemia, hyponatraemia. Polyuria - loss medullary concentration gradient lack response to AVP osmotic diuresis Recovery can take up to 28 days. On-going risk of mortality and subsequent CKD

45 Once in a while You may come across a place where everything is as close to perfection as you will ever need Place Brian Turner