AKI and CKD: Top ten facts for primary care physicians Richard Smith

KIDNEYS

CKD: Does it really matter? Richard Smith Consultant Nephrologist

www.renal.org/CKDguide/ckd.html http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4101902

The talk in one slide: Risk management Significant biochemical changes have no ‘immediate’ clinical correlate CKD(3) and AKI are associated with significant risk Recognise the patient at risk and manage this CKD(3): Confers significant cardiovascular risk and risk of AKI Progression to RRT is rare (1.3%) Progression to worse CKD (and therefore worse cardiovascular and AKI risk) is common

CKD: Does it really matter? 60 50 40 30 20 10 eGFR CKD3 CKD3 X CKD4 CKD4 RRT

CKD3: Does it really matter? 60 50 40 30 20 10 eGFR CKD3 X CKD4 RRT

Risks associated with CKD Cardiovascular Risk

Reduced kidney function is associated with a higher risk of CV events 1.0 1.4 2.0 2.8 3.4 Hazard ratio for CV event 1 2 3 4 ≥60 45-59 30-44 15-29 <15 eGFR (mL/min/1.73m2) Go 2004: pg 1301a 8.0-8.9 9.0-9.9 CKD3 Go 2004: pg 1300a pg 1301b Go 2004: pg 1297a Go et al. N Engl J Med 2004 351: 1296–1305 Tonelli et al. J Am Soc Nephrol 2006 17: 2034–2047 Eeg-Olofsson et al. J Internal Medicine 2010 268: 471–482 Khaw Nature Reviews Endocrinology 2009 5: 130-131 Go 2004: pg 1301a Go 2004: pg 1301a 1. Go AS et al. N Engl J Med. 2004;351:1296-305.

Age-related glomerulosclerosis is amplified by systemic atherosclerosis Kasiske BL. Kidney Int 1987; 31: 1153-1159

Risk factors for cardiovascular disease Risk factors for chronic kidney disease Hypertension Smoking Obesity Diabetes Dyslipidaemia Reduced GFR Proteinuria Hypertension Smoking Obesity Diabetes Dyslipidaemia Atherosclerosis Heart failure

SHARP: Major Atherosclerotic Events 5-year benefit per 1000 patients http://www.ctsu.ox.ac.uk/~sharp/

Risk of decline of GFR in elderly people 10,184 community-dwelling subjects aged 66 or over Decline in eGFR greatest in diabetic patients (2.1 and 2.7 ml/min/1.73m2/year in F and M respectively) Decline in eGFR in non-diabetic patients: 0.8 and 1.4 ml/min/1.73m2/year in F and M respectively Decline more likely if baseline eGFR <30 Hemmelgarn BR. Kidney International 2006: 29: 2155

CKD progression Steps to identify progressive CKD Obtain a minimum of three eGFR over not less than 90 days In new cases of reduced eGFR repeat within 2 weeks to exclude acute deterioration Slow progression by treating BP In CKD >140/90 mmHg In CKD and diabetes or ACR  70mg/mmol > 130/80 mmHg NOTES FOR PRESENTERS: Key points to raise: Acute deterioration of GFR may include acute kidney injury or initiation of angiotensin-converting enzyme inhibitor (ACE inhibitor)/angiotensin-II receptor blocker (ARB) therapy. An eGFR result less than 60 ml/min/1.73 m2 in a person not previously tested should be confirmed by repeating the test within 2 weeks. Focus on those where decline of GFR at observed rate would lead to renal replacement therapy within their lifetime by extrapolating the current rate of decline. Work with people who have the following risk factors for progression of CKD to optimise their health: cardiovascular disease; proteinuria; hypertension; diabetes; smoking; black or Asian ethnicity; chronic use of NSAIDS; urinary outflow tract obstruction. Additional information: People with CKD should be offered education and information tailored to the stage and cause of CKD, the associated complications and the risk of progression. The chronic use of NSAIDs may be associated with progression of CKD and acute use is associated with a reversible fall in GFR. Exercise caution when treating people with CKD with NSAIDs over prolonged periods of time. Monitor the effects on GFR, particularly in people with a low baseline GFR and/or in the presence of other risks for progression. For patients with access to the internet, the Renal Patient View system may provide a convenient means of accessing the results of their blood tests and information about their diagnosis and treatment. Recommendation 1.5.1 in full: Take the following steps to identify progressive CKD: Obtain a minimum of three GFR estimations over a period of not less than 90 days; in people with a new finding of reduced eGFR, repeat the eGFR within 2 weeks to exclude causes of acute deterioration of GFR – for example, acute kidney injury or initiation of ACE inhibitor/ARB therapy; define progression as a decline in eGFR of more than 5 ml/min/1.73 m2 within 1 year, or more than 10 ml/min/1.73 m2 within 5 years; focus particularly on those in whom a decline in GFR continuing at the observed rate would lead to the need for renal replacement therapy within their lifetime by extrapolating the current rate of decline.

Risks associated with CKD Acute Kidney Injury

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NICE Guidance 28th August 2013 The National Confidential Enquiry into Patient Outcome and Death found that only half of patients with AKI had received 'good' care Up to 30 per cent of cases of AKI can be prevented - that equates to at least 12,000 unnecessary deaths per year Inadequate assessment of risk factors in 24% of patients admitted with AKI Commonest risk factors not assessed were medication, co-morbidity and hypovolaemia

CKD3: Is it really CKD? 60 50 40 30 20 10 eGFR CKD3 X CKD4 RRT

Do not ignore eGFR 30-59ml/min until know direction of travel and significant causes ruled out

Diagnostic Criteria for Primary Care A rise in serum creatinine of ≥26.5 μmol/L in 48 hours A rise in serum creatinine of ≥50% in 7 days AKI stage 1: a rise in creatinine of ≥26.5 μmol/L or 1.5-1.9 × baseline AKI stage 2: a rise in creatinine of 2.0-2.9 × baseline AKI stage 3: a rise in creatinine of ≥3 × baseline or increase in creatinine to ≥353 μmol/L

Kidney medicine in primary care: BaNES 776 AKI spells over 12 months No differences between practices 19% of patients die in hospital 24% have diabetes 20% have diabetes and are >65 yrs old Case note review: Presentation usually with ‘other’ diagnosis Also 500 new referrals at Ipswich Hospital

Case 1 48 yr old man. Routine health check. Found to have eGFR of 35ml/min Referred for investigation of his “CKD 3” No previous eGFR Protein ++++ No haematuria BP 122/74 Renal biopsy demonstrated FSGS

Case 2 Mrs MA 74 year old eGFR 46ml/min/1.73m2 Dipstick of urine revealed + protein USS demonstrated ‘normal’ size kidneys Serum electrophoresis revealed a paraprotein with urinary BJP

Fact 1: Haematuria and proteinuria are flags for further investigation Fact 2: Combined renal length <20cm makes CKD likely Still need to exclude A/CKD

Case 3 Mr PS 80 year old ‘Stable’ IHD Not diabetic No ACEI Acutely SOB with possible rigor Few crackles L base Clarithromycin prescribed

24 hours later confused and hypotensive Emergency admission Treated as CAP according to hospital protocol Rx Vancomycin 1g x 2 Gentamicin 160mg x 2

48 hours later AKI diagnosed Baseline eGFR 42ml/min/1.73m2 Admission eGFR 22ml/min/1.73m2 ‘48h’ eGFR 12ml/min/1.73m2 4 week hospital admission Probably avoidable with recognition that patient likely to have CKD and risk conferred by this CKD

Case 4 74 year old male with 12 year history of T2DM presents to casualty unwell with lower abdominal pain. Known to have diverticular disease Most recent HbA1c 7.4% First thoughts? Rx Ramipril 5mg daily and Metformin 500mg bd

Case 5 74 year old male with 12 year history of T2DM presents to casualty unwell with lower abdominal pain. Known to have diverticular disease Rx Ramipril 5mg daily and Metformin 500mg bd Pyrexial. BP 130/74. Euvolaemic WCC 10.6x109/l CRP 48ng/ml eGFR 42ml/min with a potassium of 4.2mmol/l

Case 6 92 year old is seen in clinic having been found by GP to have ‘CKD4’ She is well with an eGFR of 26ml/min Rest of biochemistry is safe, urine reveals neither blood nor protein What do I do? USS shows echobright kidneys of 8.2cm and 8.4cm with no evidence of obstruction eGFR was 28ml/min in 2008

Fact 1: Haematuria and proteinuria are flags for further investigation Fact 2: Direction of travel is everything! Fact 3: Risk factors for AKI include age >65, diabetes, CVD and ACEI/ ARB Fact 4: Infection is a trigger for AKI in at risk patients even if not involving urinary tract

Case 7 A 36 yr old woman who has been previously fit and well and who rarely attends the surgery presents complaining of increased tiredness. She is an active sportswoman who has noticed reduction in exercise tolerance over 3 weeks such that she has struggled on hills when jogging. For 3 days she has had a sore throat, ‘painful’ fingers and noticed a few ‘red spots’ on her right thigh. On examination you confirm that she has a palpable non-blanching purpuric rash on her thigh. BP is 164/90 but examination is otherwise unremarkable. What do I do?

Case 7 A 36 yr old woman who has been previously fit and well and who rarely attends the surgery presents complaining of increased tiredness. She is an active sportswoman who has noticed reduction in exercise tolerance over 3 weeks such that she has struggled on hills when jogging. For 3 days she has had a sore throat, ‘painful’ fingers and noticed a few ‘red spots’ on her right thigh. On examination you confirm that she has a palpable non-blanching purpuric rash on her thigh. BP is 164/90 but examination is otherwise unremarkable. What do I do Dipstick of urine revealed blood ++ and protein ++

Fact 1: Dipstick of urine is your get. out of jail free card Fact 1: Dipstick of urine is your get out of jail free card. Particularly if hypertension.

Case 8 78 year old with stable CKD3. Rx Ramipril 5mg daily eGFR June 2011 47ml/min April 2014 41ml/min Cares for terminally ill husband therefore deferred R hip replacement What pain killers would you recommend? Pharmacist recommended Ibuprofen 400mg daily 4th July 2014 16ml/min Stopped Brufen 14th July 2014 39ml/min

X Fact 5: NSAID/COX inhibitors/COX-2 inhibitors Fact 6: Consider stopping ACEI/ARB Even in patient with stable kidney function if ‘at risk’ Fact 7: Restart ACEI/ARB when acute event resolved Patients who need ACEI/ARB should not be deprived of them because of undue concerns about AKI

Fact 8: Stop metformin if risk of AKI Fact 9: Metformin can be used in CKD3 Avoid in CKD3b if significant risk of AKI

Kidney medicine in primary care: 7 minutes Recognition and Prevention of AKI Is this an at risk patient? Age >65 years Vascular disease DM ACEI/ARB CKD Is glomerular perfusion threatened ? Hypotension or sepsis NSAID/COXi/COX-2i

Fact 10: Slides and more info available at www.clinimeded.co.uk Wales Deanery CPD for GPs http://gpcpd.walesdeanery.org/ Clinical Acute Kidney Injury Quiz: http://www.doctors.net.uk