Acute kidney Injury(AKI) Dr Dana Ahmed Sharif Renal Physician MRCP UK/ MRCP London

Resource materials Davidson’s Principles & Practice of Medicine Kumar & Clark Clinical Medicine Oxford textbook of Clinical Nephrology Oxford handbook of Nephrology and hypertension Renal Association website( www.renal.org) K/DOQI guideline (www.kidney.org) AKI network ( www.akinet.org)

Renal function Kidney has many roles:

Renal function Kidney has many roles: - Excretory function

Renal function Kidney has many roles: - Excretory function - Osmolality regulation

Renal function Kidney has many roles: - Excretory function - Osmolality regulation - Acid base balance

Renal function Kidney has many roles: - Excretory function - Osmolality regulation - Acid base balance - BP regulation through salt and water balance

Renal function Kidney has many roles: - Excretory function - Osmolality regulation - Acid base balance - BP regulation through Salt and water balance - Hormone secretion ( Erythropoietin, Vit D3)

Definition of Acute Kidney Injury Acute usually reversible decline in renal function* Rapid time course( < 48 hrs) Reduction of kidney function: A- Rise in serum creatinine, defined by either: 1- absolute increase in serum creatinine of >0.3mg/dl( >26µmol/l) 2- % increase in serum creatinine of > 50% B- Reduction in urine output, defined as < 0.5ml/kg/hr for more than 6 hrs * Acute kidney injury network

Incidence of AKI* 500 ppm/year – UK ( up to 38,000/yr) Incidence of AKI needing dialysis 200 ppm/year Pre renal and acute tubular necrosis (ATN) accounts for 75% of the cases of AKI 7% of all hospital admissions( 65% of intensive care admission) Mortality: 5-10% in uncomplicated AKI 50-70% in AKI secondary to other organ failure( intensive care) > 50% in dialysis requiring AKI *Xue JL, Daniels F, Star RA et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 2006; 17: 1135–1142.

Acute kidney injury Pre renal Intrinsic Post renal - ↓ Effective renal blood flow: 1- Haemorrhage 2- Volume depletion 3- Low cardiac output 4- Sepsis 5- CCF 6- Cirrhosis - Arterial stenosis/Occlusion - Vasomotor: 1- NSAID 2- ACEI/ ARBs Intrinsic Post renal

Diagnosing pre-renal AKI Is the patient volume depleted?

Diagnosing pre-renal AKI Is the patient volume depleted? Is cardiac function good?

Diagnosing pre-renal AKI Is the patient volume depleted? Is cardiac function good? Is the patient septic?

Diagnosing pre-renal AKI Is the patient volume depleted? Is cardiac function good? Is the patient septic? History Examination Investigation

Diagnosing pre renal AKI History Examination : 1- Signs of Hypovolaemia: a- Low BP( and reduced pulse pressure) b- Postural BP drop ( a fall in systolic BP > 10mmHg) c- Sinus tachycardia and postural increase in heart rate ( increase in HR > 10 beat/min). d- Low JVP even when the patient is supine e- Cool peripheries and vasoconstriction f- Poor urine output

Diagnosing pre-renal AKI 2- Sings of hypervolaemia( high extracellular fluid): a- Increased circulating volume: - High BP - Elevation of the JVP b- Increased interstitial fluid: - Peripheral or generalized oedema - Pulmonary oedema (tachypnoea, tachycardia, third heart sound, basal crackles) - Pleural effusion - Ascites . Lab investigation: - Blood tests - urine: including urinary Na( low)

Case 1 67 yr man – IHD Admitted with D&V – O/E JVP not seen, BP 100/60 lying, 80/50 standing, pulse 105 bpm Creatinine 5.8 (0.7-1.2mg/dl) x2 IV access Given IV saline Catheterised and started on furosemide Function worsened and transferred to renal unit

What was the only helpful intervention 1- Inserting a urinary catheter 2- Inserting a CVP line 3- Administering IV fluids 4- Administering diuretics

What was the only helpful intervention 1- Inserting a urinary catheter 2- Inserting a CVP line 3- Administering IV fluids 4- Administering diuretics

Treatment of pre renal failure DO NOT put in a urinary catheter DO NOT GIVE DIURETICS – improving urine volume does not mean an improvement in renal function CVP line rarely needed – and certainly not substitute for clinical examination

Treatment of pre-renal failure Volume replacement Improve cardiac function in congestive cardiac failure

Treatment of pre-renal failure Volume replacement: fluid, blood, plasma expander… A- Resuscitate: - Hypotensive and tachycardic B- Replacement C- Maintenance

Treatment of pre-renal failure Volume replacement: fluid, blood, plasma expander… A- Resuscitate: - 0.9% Normal saline - be aware of fluid overload (high BP, RR, basal lung crackles and low satO2) - fluid challenge ( trial 200-300ml N saline IV in 10min, then re-assess, repeat if necessary) B- Replacement: depends on a- Degree of hypovolaemia b- Ongoing losses c- Whether oligo-anuric d- Cardiovascular status

Treatment of pre-renal failure A rough guide ( be aware of elderly and those with poor left ventricular function): - first litre over 2 hours, THEN REASSESS - second litre over 4 hours, THEN REASSESS - third litre over 6 hours, THEN REASSESS *Remember to add insensible loss, if not sure or think you over done it, stop all fluid and reassess the patient C- Maintenance: Once euvolaemic, and assume no other losses, match urine out put plus 30mls/hour (insensible loss may be higher if febrile)

Acute kidney injury Pre renal Intrinsic Post renal Vascular 1- Vasculitis 2- Thrombotic microangiopathy 3- Scleroderma renal crisis 4- Renal vein thrombosis 5- Cholesterol emboli Acute GN Glomerluo-nephritis Acute TIN tubulointestitial nephritis ATN acute tubular necrosis Post renal

Acute kidney injury Pre renal Intrinsic Post renal Vascular 1- Vasculitis 2- Thrombotic microangiopathy 3- Scleroderma renal crisis 4- Renal vein thrombosis 5- Cholesterol emboli Acute GN (Glomerluo-nephritis) Acute TIN (tubulointestitial nephritis) ATN acute tubular necrosis Ischaemic Nephrotoxic Post renal

Acute kidney injury Pre renal Intrinsic Post renal Vascular 1- Vasculitis 2- Thrombotic microangiopathy 3- Scleroderma renal crisis 4- Renal vein thrombosis 5- Cholesterol emboli Acute GN (Glomerluo-nephritis) Acute TIN (tubulointestitial nephritis) ATN acute tubular necrosis Ischaemic Nephrotoxic Endogenous 1- Haemoglobinuria 2- Myoglobinuria 3- Casts and Crystals Exogenous 1- Nephrotoxic drugs 2- Radiocontrast Post renal

Diagnosing Intrinsic Renal AKI Has pre-renal and post renal been excluded? History - Drug, Rash, joints, nose bleed, haemoptysis, hearing loss, claudication, IHD, diabetes, fever or night sweat, Recent infection Examination - Oedema, rash, mouth ulcer, hearing loss, uveitis, AF, ischaemic toe, bruits, evidence of scleroderma, prosthetic valve or stigmata of Endocarditis Laboratory investigations - Urine including microscopy for dysmorphic RBC, Protein, Bence Jones protein, protein/creatinine ratio or 24hr protein excretion - Blood – nephritic screen – ANA, dsDNA, ANCA, antiGBM, Immunoglobulines protein electrophoresis, Rh-factor, HBV, HCV, HIV, cryoglobulins, blood film, CK, C3,C4, ASO-titre , ESR and CRP . US kidneys . Renal biopsy

Criteria for distinction between pre-renal and intrinsic causes of renal dysfunction Urine specific gravity > 1.020 < 1.010 Urine osmolality(mOsm/Kg) > 500 < 500 Urine Na+ (mmol/l) < 20* > 40 Fractional excretion of Na+ < 1% > 1%** * Except in diuretics or dopamine ** remains low in contrast nephropathy and myoglobinuria

Case 2 What did they do right? 56 years old man Cough, haemoptysis and joint pain O/E JVP +6cm Creatinine 7.5mg/dl( 0.7-1.2) on admission IV access, started on IV fluid and diuretics- SOB worsened Transferred to renal unit after 1 week when renal function failed to improve

What was done correctly Omission of urine catheter Administered IV fluids and diuretics Transfer to renal unit after 1 week

What was done correctly Omission of urine catheter Administered IV fluids and diuretics Transfer to renal unit after 1 week

Treatment of intrinsic renal AKI GN – autoimmune – immune suppression/ plasma exchange Infective Bacterial Endocarditis – antibiotics Interstitial nephritis - Stop offending medication - Corticosteroids

Treatment of intrinsic renal AKI ATN - In-hospital mortality 19-37%* - Recovery could take up to 6 weeks** - Self correcting (full 60%, some 30%, dialysis 5-10%) - Very severe – permanent cortical necrosis * Oxford handbook of Nephrology and Hypertension 2009 ** Kumar and Clark/ Clinical Medicine July 2012

Acute kidney injury Pre renal Intrinsic Post renal Obstruction 1- Bladder out-let obstruction 2- Bilateral ureteral obstruction

Nature of Obstruction Outside - Tumours, prostate, retroperitoneal fibrosis, cervical Ca Within wall - Tumours, strictures Within lumen - Stones, tumours

Diagnosing post renal AKI History - pain, anuria, haematuria, prostatism Examination - palpable bladder, central abdo mass, PR, PV Observation Laboratory investigations - Urine - Blood - Imaging – US, CT

Treatment of Post renal AKI Obtain drainage of Urine - Bladder catheter – per urethra, suprapubic - Retrograde drainage - Antegrade drainage

Case 3 82 years old man Not passed urine for 20 hrs O/E: large bladder and prostate on PR Creatinine: 8.3 mg/dl USS- dilated bladder Urine catheter inserted, start to pass lots of urine Following day creatinine – 4.2 but then over subsequent days rises to 5.1 then 5.8 then 6.4. still passing lots of urine

What is the right intervention A- Restrict fluid to reduce urine output B- Give IV normal saline C- Remove catheter D- Investigate for other causes of renal failure

What is the right intervention A- Restrict fluid to reduce urine output B- Give IV normal saline C- Remove catheter D- Investigate for other causes of renal failure

Post recovery diuresis Occurs post resolution of AKI - Post relief of obstruction - Post ATN Important to check fluid status - Clinical exam - BP and pulse - Daily weight - Input and output chart Treatment – IV fluids replace electrolyte

Complication of AKI 64 years old man admitted with: Potassium 7.4 Urea: 90 Creatinine: 8.5

What is the first line treatment A- Insulin and dextrose B- IV calcium gluconate C- Ca+2 resonium D- Low potassium diet E- Dialysis

What is the first line treatment A- Insulin and dextrose B- IV calcium gluconate C- Ca+2 resonium D- Low potassium diet E- Dialysis

Other Complications of AKI Pulmonary oedema Acidosis Uraemia Other electrolyte disturbance such as hyerphosphataemia and hypocalcaemia

Who is a risk? Many cases of AKI should never occur in the first place 1- Elderly 2- Pre-existing renal disease 3- Surgery, trauma, sepsis or myoglobinuria 4- Diabetes 5- Volume depletion( Nil By Mouth, bowel obstruction, burn) 6- LV dysfunction 7- Nephrotoxic drugs 8- Cirrhosis (reduce arterial volume)

Common nephrotoxins NSAID Diuretics, ACEI, ARB2 especially in volume depleted patient Antibiotics, Aminoglycosides, Vancomycin Amphotericin B Immunosuppressant (ciclosporin, tacroliums) and chemotherapy (Cisplatin) IV contrast

Reducing risk perioperatively Three principles: 1- Avoid dehydration 2- Avoid nephrotoxins 3- Review clinical status and renal function those at risk Optimize volume status 1- No patient should go to theatre dehydrated 2- Review daily weight, input and output chart 3- Calculate losses especially those NBM ( use 0.9% N saline and NOT 5% Dextrose)

Reducing risk perioperatively Optimize blood sugar control in DM ( use sliding scale Catheterize those with prostate disease Avoid surgery if possible immediately after a contrast procedure Stop nephrotoxic drugs 24-48hrs preoperatively Review the patient EARLY postoperatively

Have you.. Have seen the result of K and acted appropriately? Assessed the patient’s volume status and treated pulmonary oedema or corrected hypovolaemia? Taken full history and examined patient head to toe? Excluded palpable bladder? Seen the patient’s regular drugs? And stopped nephro-toxins? Arranged urgent ultrasound(within 24hr)* Performed urine test and send for microscopy and MSU Checked acid-base status and intervened appropriately? Checked for any previous tests of renal function? Checked Hb, Calcium and Phosphate? Send blood for full nephritic and myeloma screen if you are suspecting intrinsic renal failure? * NCEPOD recommendation/ National Confidential Enquiry in to patient outcome and death. www.ncepod.org.uk

( Glomerluo-nephritis) Acute kidney injury Pre renal - ↓ Effective circulatory volume: 1- Haemorrhage 2- Volume depletion 3- Low cardiac output 4- Sepsis 5- CCF 6- Cirrhosis - Arterial stenosis/Occlusion - Vasomotor: 1- NSAID 2- ACEI/ ARBs Intrinsic Vascular: 1- vasculitis 2- Thrombotic microangiopathies 3- hypertensive emergencies Acute GN ( Glomerluo-nephritis) Acute TIN (tubulo-intestitial nephritis) ATN (acute tubular necrosis) Ischaemic Nephrotoxic Endogenous 1- Haemoglobinuria 2- Myoglobinuria 3- Myoglobin casts 4- Intratubular crystals Exogenous 1- Nephrotoxic drugs 2- Radiocontrast Post renal Obstruction 1- Bladder out-let obstruction 2- Bilateral ureteral obstruction

Summary 3 categories of AKI Simple clinical assessment will define which Be aware of life threatening complications and emergency treatment Recognise those at risk