update on acute kidney injury - rcp london

Royal Derby Hospital

Dr Nick Selby

Associate Professor of Nephrology

Centre for Kidney Research and Innovation

Division of Health Sciences and Graduate Entry Medicine

University of Nottingham


Update on Acute Kidney Injury


5-15% of hospital admissions, mortality ~25% and >35% in AKI3

High incidence, poor outcomes

No specific therapies

Silent presentation, variation in

care


AKI is distributed across all specialties

Only 7.5% of patients under nephrology

Selby NM et al CJASN 2012; 7(4): 533


https://www.thinkkidneys.nhs.uk


AKI detection

Intranet Guidelines

Streamlined nephrology

referral Care bundles

Education programme


Better outcomes in patients with AKI care bundle

Kolhe NV, Staples D, Reilly T, Merrison D, Selby NM, et al. (2015) Impact of Compliance with a Care Bundle on Acute Kidney Injury Outcomes: A Prospective Observational Study. PLoS ONE 10(7): e0132279. doi:10.1371/journal.pone.0132279

Royal Derby Hospital What is AKI?

AKI stage Serum creatinine criteria Urine output criteria

1 An increase of more than 26mol/l above baseline (within 48hrs) OR An increase of more than or equal to 1.5 to 2 fold from baseline

<0.5mg/kg/hr for at least 6hours

2 An increase of more than or equal to 2 to 3 fold from baseline

<0.5mg/kg/hr for at least 12hours

3 An increase of more than 3 fold from baseline OR AKI with creatinine 355mol/l OR Initiation of RRT

<0.3mg/kg/hr for at least 24hours OR Anuria for >12hours

2727

782

636

Number of patients per annum sustaining each stage of AKI in 1000-bedded hospital

total: 4145

1. No mention of cause 2. What to do when no

baseline available? 3. Interpreting small

changes in creatinine in clinical practice

Royal Derby Hospital Why such small changes in creatinine?

• Even small changes in renal function are significant

• Multiple studies with same findings

• Findings persist after adjustment for co-morbidities

©2005 by American Society of Nephrology

Chertow G M et al. JASN 2005;16:3365-3370

26-35mol/l 88-167mol/l 44-80mol/l >176mol/l

>44µmol/l increase in s.creat – 6 fold increase in odds of death


Small changes in creatinine can reflect larger changes in GFR

CV

CV CV

20% drop in GFR

Royal Derby Hospital AKI and mortality: cause or association?

Summary:

• AKI indicates patient at higher risk of deterioration

• AKI is a clinical diagnosis: 1. Interpret small creatinine changes

to determine AKI

2. Determine cause of AKI

Selby et al CJASN 2012; 7(4): 533

24% mortality rate in patients with AKI

AKI is pro-inflammatory – causes distant organ dysfunction, acts as ‘force multiplier’ for acute illness

Scheel et al Kidney Int 2008; 74: 849

Royal Derby Hospital Causes of AKI

Pre-renal

• Hypotension

• Sepsis

• Volume depletion

• Bleeding

• CCF

• Hepato-renal syndrome

Intrinsic renal disease

• Tubular

Ischaemic ATN

Drugs/toxins/Contrast

Rhabdomyolysis

Tumour lysis

Tubulo-interstitial nephritis

Myeloma

• Vascular – large vessels

Renal artery thrombosis

Athero/Cholesterol emboli

Small vessels and glomeruli

GN or Vasculitis

HUS/TTP

Malignant BP

Post renal

• Bladder outflow

(including blocked catheter)

• Retroperitoneal disease

• Stones (rare)

OVERLAP


Relative proportions of causes of AKI

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pre-renal Obstruction GN/vasculitis TIN Atheroemboli

Perc

enta

ge

ATN Pre-existing CKD

Liano F; Pascual J. Kidney Int 1996 Sep;50(3):811-8.

*

* Includes toxic and ischaemic ATN

80-90% of AKI due to pre-renal, toxic or post-renal

causes


Efferent arteriole

Filtrate (urine)

Afferent arteriole

Pre-renal factors: response to renal hypoperfusion

Renin Angiotensin 1

Angiotensin 2

Aldosterone

Angiotensin 2 will cause vasoconstriction efferent > afferent; GFR maintained over range of arterial pressures Prostaglandins prevents afferent vasocontriction


Effect of ACEI and ARB

• Effect on angiotensin 2 on efferent vessels is lost

• Glomerular pressure decreases

• Filtration fraction falls

• GFR falls


Efferent arteriole

Filtrate (urine)

Afferent arteriole

Renin Angiotensin 1

Angiotensin 2

Aldosterone

NSAIDs inhibit the vasodilatory effect of PGI2 on afferent arteriole Unopposed vasoconstriction by angiotensin

NSAIDs effect in volume depletion


Case • 74yr old lady

• Admitted by GP: abnormal renal

function on routine bloods

• Felt well • No systemic or urinary symptoms • Good oral intake

• PMH:

Hyperlipidaemia Hypertension Recent Ix for weight loss, NAD

• DH: Amlodipine 5mg od Simvastatin 20mg od Omeprazole 20mg od

• Urine dip:

1+ protein only

• Other blood tests unremarkable

• Ultrasound kidneys: normal

6m ago

5wks ago

Now

Creatinine 82 87 246

What are the possible causes of AKI? Which is most likely?


ALWAYS DIP THE URINE

NAD

Pre-renal Post-renal Myeloma

Tubulo-interstitial dis (Renovascular)

Blood and protein

Still can be ATN, but raises the possibility of

inflammatory renal disease

e.g. vasculitis

Proteinuria (PCR>3)

(=Protein loss>3g per day)

Definitely glomerular

Urine dip is not to look for infection, it’s to help with diagnosis


Drug induced Tubulointerstitial nephritis

• Often occurs without classic symptoms • Sometimes – only clue is lack of other causes

plus temporal relationship with drug

• Urine dip: 1+ leuk, blood, protein Can be NAD

• Antibiotics, PPI, NSAIDs, diuretics, allopurinol, ++

• Diagnosis: usually needs renal biopsy prior to

steroid therapy


Mechanisms whereby a drug (or one of its metabolites) can induce acute interstitial nephritis

(A) The drug can bind to a normal component of the tubular basement membrane (TBM) and act as an allergen.

(B) The drug can mimic an antigen normally present within the TBM or the interstitium and induce an immune response that will also be directed against this antigen.

Allergen

Royal Derby Hospital Case

• 65yr old male • Undergoes primary PCI

for STEMI

• Contrast volume: 138ml

• BP 142/74, maintained

• Day 3 develops AKI: creatinine 294µmol/l (previously 116)

Other features: • Urine dip: NAD • Discomfort in toes: on

examination appear dusky

• Notable blood tests: • Eosinophils: 0.83x109/l () • C3 low

What are the possible causes of AKI? Which is most likely?


AKI and eosinophilia

• Acute TIN

• Cholesterol emboli

• Churg-Strauss syndrome

• DRESS syndrome

• Lymphoma

• Hypereosinophilic syndrome

• Schistosomiasis

• Vascular risk factors, AAA, vascular intervention (?anti-coagulation)

• Skin, AKI; sometimes abdominal symptoms, Hollenhorst plaque

• Treatment is largely risk factor modification

Cholesterol emboli

Royal Derby Hospital Case

• 67 year old man

• Brought to A+E

• Found at home on the floor

• House unkempt, empty whiskey bottles

• What would you expect to find in his urine?

Previous

Hb 14.1

WBC 18

Plt 163

Na 141

K 6.1 4.2

Ur 29 7

Creat 301 78

CCa 2.11

PO4 2.2

ALT 250

CK 24,670


Rhabdomyolysis

• +ve urinalysis blood, few RBC on microscopy

• Myoglobinuria absent in 25% patients with rhabdo

• Mx Recognise and treat fluid and

electrolyte disturbances Identify cause

Some less obvious causes e.g.: • Statins, precipitated by drug interactions • Viral infection • Hypothyoidism

Look out for compartment syndrome


Recreational drugs, poisoning and AKI

• Heroin, cocaine etc. Cocaine cut with levamisole – can induce ANCA assoc. vasculitis variant (MPO

and PR3 positivity)

• Ecstasy Rhabdo, circulatory collapse (seratonin syn), hyponatraemia (ADH release)

Fahal IH. BMJ 305: 29, 1992

• Legal highs Reports of Mephadrone (MCAT) causing AKI requiring dialysis

Rhidian BMJ Case Rep 2013

Bath salts (methylenedioxypyrovalerone, MDPV) - rhabdo Adebamiro Am J Kidney Dis. 2012 Feb;59(2):273

SPICE (synthetic cannabanoid) causing ATN Bhanushali Clin J Am Soc Nephrol 8: 523–526, 2013

• Poisoning:

Ethylene glycol: raised anion gap acidosis, raised osmolar gap, high lactate on ABG

Paracetamol (delayed presentation)


Indicators of ‘inflammatory’ AKI

ACTIVE URINE More than 2+ of blood and protein

VASCULITIC RASH

SYSTEMIC SYMPTOMS

Often present for months – myalgias, arthralgias, malaise

EPISTAXIS, SINUSITIS, HAEMOPTYSIS

Low platelets, high calcium, eosinophilia


IV Fluids and AKI

Which type?

How much?

How fast?


The SAFE Study Investigators. N Engl J Med 2004;350:2247-2256.

No benefit of colloids over crystalloids

Perel. Cochrane review 2013

No benefit with colloids Possible suggestions of harm Less of a difference in fluid volume than would have been anticipated


Myburgh JA et al. N Engl J Med 2012;367:1901-1911.

CHEST study: 6% HES versus Saline.


Perner A et al. N Engl J Med 2012;367:124-134.

Worse outcomes with 6% HES versus Ringers lactate – 6S trial


From ~1million patients, only 10% received one type of fluid only

• Retrospective database study

• Patients: SIRS needing >0.5L iv fluids

• Patients receiving saline were propensity matched to those receiving Ringers lactate or Plasmalyte

In-hospital mortality higher with saline 3.27 % vs. 1.03 %, p<0.001 No difference in AKI rates Similar study in post-surgical patients did report increased RRT

‘Toxicity’ of saline?


Chloride liberal versus restrictive approach

• Single ICU

• Switched from chloride liberal to chloride restrictive regime

• Less AKI, less RRT after the switch

• Number of limitations with this study

Yunos JAMA 2012; 308(15):1566-1572


Saline and renal perfusion

• 12 healthy males

• Randomised cross-over study 2L of IV fluid in 1hr

• MR with ASL used to measure perfusion that reduced with saline but not with Plasmalyte

Chowdhury Annals Surg 2012; 256 (1): 18–24

Perfusion Map


• Blinded cluster randomised controlled trial

• Saline versus Plasmalyte-148

• 4 ICUs in New Zealand

• Primary outcome: incidence of AKI

• Number of secondary endpoints and pre-planned subgroup analyses

• RRT was an exclusion criterion

• 2278 patients randomised

• 1162 versus 1116

• No differences between groups, generally low co-morbidity

• ~70% were post-operative

JAMA 2015;314(16):1701-1710


Results Median fluid volumes 2000 mL Mortality 7.6% versus 8.6%, p=0.4 No differences in any subgroups No difference in acidosis

Blinding failed No sample size calculation


Excess fluid associated with mortality

Adapted from Bouchard et al, Kidney Int 2009.

Adjusted odds ratio for death associated with fluid

overload at dialysis initiation = 2.07

Royal Derby Hospital Conclusions

• AKI is a major challenge; evidence emerging to support efforts to reduce variation in quality of AKI care

• AKI identifies patients at higher risk of adverse outcomes; need a holistic approach

• Clinical interpretation remains key and guides subsequent management: Is this AKI? What is the cause of AKI?

• The composition of fluid may affect the risk of AKI

No benefit of colloids Starch harmful Convincing evidence for saline avoidance remains elusive

• Fluid resuscitation should be weighed against potential for volume overload

[email protected] www.nottingham.ac.uk/research/groups/renal

update on acute kidney injury - rcp london

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