A discussion about developments in AKI (Acute kidney injury) care Mark Thomas Jyoti Baharani Tarek Abdelaziz

Consultant Consultant Research Fellow

Dept of Renal Medicine, HEFT

Antje Lindenmeyer Zaheera Teladia

Lecturer Researcher

Primary Care Clinical Sciences, University of Birmingham

Comments on briefing welcome: [email protected] We have an Information leaflet, Consent form, Questionnaire and some Post Its for you!

Agenda      

Today is a mixture of CPD and Focus group The ‘Focus group’ is to ask what you want from our AKI services – this is part of our research We will record the discussion (anonymously) and would be grateful for your signed consent Alerting for acute kidney injury will be introduced for HEFT lab GP users in April. Telephone advice (as always) and online guidance (new) will be available. From June for 5 months only we are piloting a dedicated AKI outreach service [we will phone you] for patients in the Heartlands area only as part of the NIHR sponsored AKORDD study. 14/EM/0184 - NRES Committee East Midlands - approved 22/05/2014

Focus group • The aim is to find out how best to assist you as GPs in managing AKI patients • We have a very short 4 question questionnaire about the ‘mechanics’ of contacting you • The group is recorded – any discussion is anonymised • Participant information leaflet • Please sign and date your Consent – initial boxes

Introduction: AKI in the community • About 20% of all adult emergency admissions to hospital develop some degree of AKI • About 25% of those will die • Many of the cases will start in the community • It is the largest Cinderella condition in the NHS • We need to catch and treat it early • We want to talk to you briefly about this today: – plus a very short questionnaire and Post-It exercise

AKI in the UK Bedford et al BMC Nephrol 2014; Kerr et al Nephrol Dial Transplant 2014

• About 40,000 excess deaths per year in England – compare with 35,000 deaths from lung cancer in UK

• E Kent data – – – –

replot of data adults 6 months in 2009 excluded maternity & day case – 22% with AKI – marked rise in mortality with increasing stage

AKI amongst patients with data 100%

80%

78%

60%

40%

33% 26%

20%

15% 8% 2%

4%

3%

Stage 2

Stage 3

0% No AKI

Stage 1 AKI in patients

Mortality

Acute kidney injury (AKI – formerly acute renal failure): - a syndrome of many causes Any one patient will typically have more than one cause

‘Pre-renal’ AKI ~ 50-60%

Spectrum of injury with any cause of hypovolaemia

‘Renal’ or intrinsic AKI ~ 30%

‘Post Renal’ or Obstruction ~ 5-10% Tubular, ureteric, bladder or bladder outflow obstruction

Causes of intrinsic AKI: - Tubular cell injury (formerly acute tubular necrosis or ATN)

Ischaemia/ Hypotension – relative / absolute Vasoconstrictive drugs – NSAIDs, ACEi/ARBs Sepsis Toxins – aminoglycosides, contrast, myoglobin*

- Interstitial nephritis (allergic reaction to drugs e.g. certain antibiotics)

- Glomerulonephritis Uncommon but important -

Blood and protein on urine dipstick

Vascular disease e.g. Renovascular disease

Figure 2: Causes of acute kidney injury (AKI).

Note that AKI is now regarded as a spectrum of injury ranging from minimal to devastating. NSAIDs - Non steroidal anti-inflammatory drugs; ACEi – Angiotensin converting enzyme inhibitors; ARB – Angiotensin receptor blockers; * Rhabdomyolysis

RENAL BLOOD FLOW AUTOREGULATION: THE KIDNEYS CAN REGULATE THEIR BLOOD FLOW ACROSS A CERTAIN RANGE

Maximal vasodilation

Normal

Maximal vasoconstriction

Renal blood flow

Autoregulation range reset at higher levels of BP 60

80

100

(80/50)

(100/70)

(140/80)

120

140

(160/100) (200/110)

Mean arterial pressure MAP mm Hg Threshold below which renal hypoxia occurs is reset at higher level in chronic hypertension

Systolic blood pressure preceding onset of acute kidney injury with reference to baseline Mean ± standard error of mean: *two-way ANOVA

Liu Y L et al. Nephrol. Dial. Transplant. 2009;24:504-511

Nephrotoxins – something old, something new If in doubt check the Renal Drug Handbook

• • • • • • •

ACE inhibitors and ARBs NSAIDs – potentially including gels Aminoglycosides Calcineurin inhibitors – Ciclosporin etc. Iodinated contrast Aciclovir Warfarin with high INR and haematuria – glomerular bleeding and tubular obstruction

• Statins – recent use of high potency statins

Key points about the causes of AKI • The kidney is vulnerable to ischaemia • Vasodilatory prostaglandins and Angiotensin II help maintain GFR in the face of hypovolaemia • We are a high blood pressure society • Autoregulation – the kidney is used to BP in a certain range

• We should consider : “What is normal for my patient?”

AKI: a syndrome of many guises 400 AKI

350

Creatinine μmol/L

300

AKI with low muscle mass

250

Improving AKI with unknown baseline

200 150

ACKD with partial recovery

100 50

ACKD without recovery

0 Baseline

Day 0

Day 1

Day 2

Day 3

Day 7

Day 90

Effect of AKI on odds of death in multivariate analysis Chertow GM et al J Am Soc Nephrol 2005 Absolute rise in Creatinine

No rise

≥ 26 µmol rise

≥ 44 µmol rise

≥ 88 µmol rise

20

≥ 177 µmol rise

16.4

Odds ratio

15

15 9.7

10 5

20

6.5

4.1 1.0

0 No rise

10

2.0 25% rise

Relative rise in Creatinine

4.4 50% rise

6.5

7.9

5 0

100% rise

50% rise t o minimum of 177 µmol/l

Stage

Creatinine (Cr)

1

Rise of ≥ 26µmol/L within 48 hours or 50 - 99% Cr rise from baseline * (1.50-1.99

2

100 - 199% Cr rise from baseline * (2.00-2.99

3

baseline) baseline)

≥ 200% Cr rise from baseline * (≥ 3.00

baseline)

or (Current) Cr ≥ 354 µmol/L, with either: Rise of ≥ 26 µmol/L within 48 hours; or ≥ 50% Cr rise from baseline (i.e. baseline* of at least 236 µmol/L) or any requirement for renal replacement therapy

TABLE 1. THE INITIAL DETECTION AND STAGING OF ACUTE KIDNEY INJURY FOR ADULTS IN PRIMARY CARE (AFTER KDIGO1)

* Typically the rise is known (based on a prior blood test) or presumed (based on the patient history) to have occurred within 7 days;

note the National algorithm used by the Laboratory may look back up to 365 days

Risk of dialysis requiring AKI in inpatients Risk increases dramatically if the patient has a background of CKD 40.1

40

28.5

30 Odds ratio 20

10

6.5 1.0

2.0

>= 60 CKD 0-2

45-59 CKD 3a

0 30-44 CKD 3b

15-29 CKD 4