Dr Simon Roe Consultant Nephrologist April 2015

Transcription

1 Chronic Kidney Disease and AKI an update Dr Simon Roe Consultant Nephrologist April 2015

2 CKD and AKI CKD- Definition Risk Factors NICE Guidance- What s new 2014 egfr measurement- limitations and interpretation Diagnosis and who to test When to do renal USS GFR Categories Progression Management AKI- Including General rules, Lifestyle and Pharmacotherapy Definition Risk factors Recognising risk Rules for management (incl. sick day rules)

3 Outline Why is CKD important 2014 NICE CKD guidelines what s new Management of CKD AKI what s the relevance for primary care

4 What is CKD? Chronic kidney disease is defined as: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m 2 for 3 months with or without evidence of kidney damage OR Evidence of kidney damage (without decreased GFR) for 3 months: albuminuria haematuria after exclusion of urological causes structural abnormalities

5 The Burden of CKD to the NHS Chronic Kidney Disease is an epidemic worldwide 8.5% people in UK have CKD 1.3% of all NHS spending is on CKD 50% of this goes on the 2% of the CKD population that require dialysis and transplantation Overall RRT incidence rate stabilised at 108 pts/million/yr Late presentation rates have dropped from 24% to 19% over the last 6 years (but still show variability 13-23% for EM units)

6 Causes of Established Renal Failure Primary diagnosis in UK patients who started dialysis in 2013 Hypertension 8% Uncertain 15% Other 18% GN 14% Polycystic 8% Vascular 5% Diabetes 25% Pyelo 7% Diabetes and hypertension/ vascular diseases are leading causes of ESRD UK Renal Registry 2014 report

7 People at increased risk of CKD Eight major risk factors for CKD Diabetes High blood pressure Age over 60 years Smoking Obesity Family history of kidney disease Ethnic minorities Established cardiovascular disease 95% of patients with CKD 3 are also on hypertension, diabetes or CHD registers

8 Variability in Care Evidence based guidelines exist for managing CKD in primary care but evidence of inconsistency of care Variation in CKD prevalence Variability in achievement of key treatment priorities BP QOF vs NICE targets Variation in late presentation How much of this variability is unwarranted?

9 CKD Prevalence by CCG England

10 NICE guidelines 2014 what s new? Investigations for CKD Enzymatic creatinine assay use CKD-EPI equation to estimate GFR Cystatin C to confirm stage 3A CKD Revised classification GFR and ACR categories Definition of progression Relationship with AKI

11 Limitations of egfr measurements egfr is an ESTIMATE!! Increasing uncertainty at values >60ml/min Based on serum creatinine Measurements subject to variation eg. recent vigorous exercise, large meat meal, extremes of muscle mass, lab variation/delays, drugs (trimethoprim) Not valid in AKI, children, pregnancy, dialysis Always confirm with 2nd blood test

12 Changes to lab GFR estimating equation Levey AS et al. Ann Int Med 2009;150: NICE 2014 recommends that labs use the CKD-EPI formula to calculate egfr instead of the MDRD formula 12 Advise patients not to eat meat in the 12 hours before a blood test for egfr

13 Making a Diagnosis of CKD New finding of egfr <60 Repeat within 1-2 weeks Exclude acute kidney injury Review previous U&E results Review drugs eg NSAIDS Exclude UTI, palpable bladder etc Urine dipstick for haematuria Send urine for ACR Only label as CKD if at least 2 abnormal readings over 3 months

14 Who to test for CKD? Offer annual egfr and ACR if: Diabetes Hypertension Previous acute kidney injury Cardiovascular disease Structural renal disease, stones or BPH Family history Stage 5 CKD or hereditary renal disease Haematuria or proteinuria Multisystem disease with potential renal involvement Monitor GFR in people prescribed nephrotoxic drugs eg lithium, CNI, NSAIDS

15 When to do a renal ultrasound Accelerated progression of CKD Visible or persistent invisible haematuria Symptoms of urinary tract obstruction Family history of polycystic kidney disease and aged over 20 GFR <30ml/min (GFR category G4 or G5) Considered by a nephrologist to require a renal biopsy

16 16 GFR Categories in CKD

17 A higher profile for albuminuria

18 Prognostic significance of abnormal ACR Albuminuria was linearly related to events along its entire distribution An ACR >3 is not normal and is associated with a higher risk of CKD, AKI, cardiovascular mortality, all cause mortality, even if GFR normal These effects are independent of GFR and independent of traditional cardiac risk factors Adapted from Levey et al, 2010, Kidney International Blue normal/ mild ACR Green moderate ACR Red severe ACR

19 Proteinuria and urine A/PCR Urine dipstick semi-quantative Depends on concentration; sticks detect >0.3g/l protein Spot urine albumin or protein: creatinine ratio Good correlation with 24hr urine protein ACR more sensitive than PCR at low levels Use ACR in diabetes and CKD If ACR 3-70mg/mmol confirm with early am sample Urine Protein Urine PCR (mg/mmol) Urine ACR (mg/mmol) Category > 3 Proteinuria 0.5g/day > 50 > 30 Severe proteinuria > 1g > 100 > 70 Heavy proteinuria > 3g > 300 > 220 Nephrotic

20 Integration of GFR and albuminuria when evaluating risk No CKD (88%) Mild risk (9.2%) Moderate risk (2%) High risk (<1%) Based on 4 meta-analyses of 45 cohorts with 1.5million individuals, studying 5 endpoints 20 Levey, Eckardt, Gansevoort et al, KI 2011

21 Rising currency of Cystatin C A low molecular weight cysteine protease inhibitor- produced by all nucleated cells Filtered at the glomerulus and not reabsorbed Serum concentration mainly determined by GFR Inflammation, thyroid disease, and steroids may affect levels Less dependent on race and body mass Potential uses: Confirming stage 3a CKD (egfr ml/min) NICE: Consider using Cystatin C to confirm CKD in patients with egfr and ACR <3mg/mmol Assessing for CKD in malnourished patients BUT not widely available in UK; cost implications

22 Progression of CKD Small fluctuations in GFR are common and not necessarily indicative of progression Accelerated progression is defined as: a drop in GFR category accompanied by a 25% or greater drop in GFR from baseline over 12 months a sustained decline in egfr of more than 15ml/1.73m 2 /year this group is at increased risk of progression to established kidney failure Increased confidence in assessing progression with more serum creatinine measurements and longer follow-up

23 Guide to frequency of monitoring by GFR and albuminuria category

24 Management of Patients with CKD Identify patients with CKD Treat reversible causes Reduce cardiovascular risk Delay progression Treat complications Dialysis preparation

25 Outcome for patients with CKD Patients with CKD are more likely to die than require dialysis Stage GFR (ml/min) RRT Death % 19.5% % 24.3% % 45.7% 27,998 CKD patients followed for 5 years Keith DS, AIM 2004;164: CKD is an independent and major risk factor for cardiovascular disease

26 Life style measures Smoking cessation Weight management Target BMI kg/m 2 Physical activity At least 30 min 5 days per week

27 Adequate BP management delays the progression of CKD 160/95 If blood pressure is consistently below target, the GFR loss per year would be reduced by 80% Bakris et al., Am J Kid Disease, 2000

28 Management - hypertension Treatment target <140/90mmHg (SBP range ) If CKD and diabetes or ACR >70mg/mmol <130/80mmHg (SBP range ) ACE inhibitors first line Diabetes (microalbuminuria) or proteinuria All patients under 55 years Calcium channel antagonist or diuretic 2nd line Thiazide-like if egfr>30, loop if egfr<30

29 Pharmacotherapy ACE inhibitors/arbs* should be offered to the following: Diabetic Nondiabetic Nondiabetic ACR (mg/mmol) >3 >30 >70 PCR (mg/mmol) >50 >100 Need to confirm CKD No Yes Yes Need to confirm high BP No Yes No ACE inhibitors are first line treatment for all Change to ARB only if ACE not tolerated

30 Prescribing ACE I and ARB safely Check baseline egfr and K + (start if K <5 only) Avoid NSAIDs and other K + drugs if possible Avoid combination of ACE and ARB Repeat egfr and K weeks after initiation and after each increase in dose If egfr/k + change excessive repeat and? refer (?RAS) Review other causes/drugs;?stop ACE Stop if K + >6, consider low K diet or loop diuretic Allow 30% creatinine / 25% in egfr

31 Lipid lowering therapy Offer atorvastatin 20mg to all patients with CKD (NICE Lipid Guideline 2014) SHARP Study Lancet 377: , 2011 Simvastatin 20mg + ezetimibe 10mg vs placebo 9,000 patients CKD and dialysis, 4.9 yrs 17% reduction in major atherosclerotic events No effect on progression of CKD Prevent events per 1000 over 5 years Well tolerated

32 Optimal glycemic control prevents progression of CKD 32 Study HbA 1C goals New ACR (3-30mg/mmol) ACR progression (>300mg/g) ADVANCE 6.5% vs 7.3% 9% less 30% less Target HbA1C of ~7% (53 mmol/mol) recommended to prevent or delay progression of diabetic renal disease ACCORD 6.3% vs 7.6% 21% less 32% less VADT 6.9% vs 8.4% 32% less 37% less Patel A et al. NEJM 2008;358: Ismail-Beigi F et al. Lancet 2010;376: Duckworth W et al. NEJM 2009;360:129-39

33 Medicines management Review medications (eg NSAIDS) Trimethoprim may increase creatinine Metformin stop if egfr <30-40 Consult BNF or SPC for new medications Use egfr for dose adjustment except at extremes of weight Vaccinate - Hep B, pneumonia, influenza

34 Management - Bone disease Use bisphosphonates if indicated in stage 1-3 Check calcium, phosphate and PTH if egfr <30 If PTH high (>2x normal range) check Vitamin D and treat deficiency (25OH Vit D <50nmol/l) Stage 3-4 CKD use cholecalciferol Stage 4-5 CKD use 1-alfacalcidol Dietary phosphate restriction

35 Management Anaemia More common if GFR <45 or diabetes Rule out other causes eg iron deficiency Consider Rx if Hb < g/l Consider iron deficiency - Ferritin <100µg/l Trial of oral iron If no response refer for IV iron No evidence to support normalisation Hb, ESA/EPO improves QoL

36 Acute Kidney Injury -Everybody s problem

37 What is AKI? An abrupt decline in renal function. Defined by: an acute rise in serum creatinine OR a fall in urine output

38 Number of patients per annum sustaining each stage of AKI in a 1000 bed hospital Definition of AKI AKIN Stage Serum creatinine criteria Urine output criteria 1 An increase of more than 26µmol/l above baseline 2727 OR An increase of more than or equal to 1.5 to 2 fold from baseline <0.5mg/kg/hr for at least 6hours An increase of more than or equal to 2 to 3 fold from baseline 3 An increase of more than 3 fold 636 from baseline OR Serum creatinine >355 µmol/l with total: an acute rise of at least 45 µmol/l OR 4145 Initiation of RRT <0.5mg/kg/hr for at least 12hours <0.3mg/kg/hr for at least 24 hours OR Anuria for >12hours

39 Electronic Alerts for AKI

40 and why does it matter? AKI is common 16-18% of hospital admission AKI is serious mortality/ LOS, CKD AKI is expensive Probably > 500M/yr to NHS

41 AKI is relevant to primary care and all specialities Half to 2/3rds of AKI cases are community derived Porter C, Devonald M. NDT 2014;(0):1-6 Over 92% of AKI cases are admitted as an emergency

42 AKI is sub-optimally managed June 2009 AKI avoidable in 14% Only 50% received good care Post admission AKI: poor recognition and care 24% did not receive adequate senior review 85% did not have documented evidence of critical care outreach involvement

43 Prevention AKI in Primary Care Recognition & management Follow up after AKI

44 Cause and risk of AKI Risk factors CKD + albuminuria Diabetes CCF PVD Chronic Liver disease Previous AKI Age >75 ACEI/ARB/NSAIDS/diuretics Aminoglycosides Triggers Sepsis or infection Hypovolaemia Hypotension Post-op Iodinated contrast Medication

45 Albuminuria and CKD are both independent risk factors for AKI Grams et al, J Am Soc Nephrol, 21: , 2010

46 Prevention: Recognise the risk Medicines Management Medicines reconciliation and review Sick day rules IV contrast Close monitoring Repeat U+E s During acute illness After starting high risk medication Hydration

47 Sick day rules - Consider for patients at increased risk of AKI - Primary & secondary care Rule 1 Hydration Rule 3 Avoid NSAIDS Patients & carers Rule 2 Omit ARB/ACEI/diuretics (Metformin) Rule 4 Monitor renal function

48 Case study 78yrs old female CKD 3A (baseline 160), CCF, on ramipril, bisoprolol and furosemide Becomes unwell with symptoms of UTI and vomiting Scenario 1 Poor oral intake Continues to take medication Seen by out of hrs Rx trimethroprim Seen by GP D5 UE s : Na 149, K6.3, Ur38, Cr 500 Admitted to hospital Scenario 2 Contacts GP/community matron Keep hydrated Pill holiday for 48hrs Rx- amoxycillin/antiemetic UE Creat 180 GP review 48hrs Creat 168, clinical improvement

49 Drugs and AKI Very common cause/ contributor to AKI Various mechanisms Pre-renal (diuretics, ACE-I and ARBs, NSAIDs) Direct tubular toxicity (aminoglycosides, contrast agents) Interstitial nephritis allergic (antibiotics, NSAIDs, PPIs and many more drugs)

50 Trimethoprim Trimethoprim inhibits tubular secretion of creatinine Increase serum creatinine Apparent AKI Creatinine normalises after cessation Hyperkalaemia Less effective at lower egfr

51 Management of AKI Fluid management and resuscitation Medication review Stop nephrotoxic medication Early antibiotics for sepsis Undertake relevant investigations Importance of urine dip Hospital / nephrology referral when needed

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53 CKD Prevalence (%) CKD Prevalence by Practice Westdale Lane Surgery C84033 Oakenhall Medical Pract C84095 Unity Surgery C84150 Stenhouse Medical Centre C84026 The Willows Medical Centr C84612 The Calverton Practice C84047 Trentside Medical Group C84010 Whyburn Medical Practice C84124 Park House Medical Centre C84709 Peacock Health C84133 Torkard Hill Medical Ctre C84053 Newthorpe Medical Practice C84131 West Oak Surgery C84696 The Ivy Medical Group C84646 The Jubilee Practice C84613 Giltbrook Surgery C84667 Highcroft Surgery C84055 Plains View Surgery C84115 Apple Tree Medical Practice C84125 Daybrook Medical Practice C84066 The Om Surgery Y00026 Nottingham North And East CCG 16.0% 14.0% 12.0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0% NHS NOTTINGHAM NORTH AND EAST CCG: Chronic Kidney Disease Age Specific Prevalence (%) Prevalence (England) ---- Prevalence (East Midlands SCN) -. _

54 AKI Causes 54 Pre-Renal/ ATN (70-80% of cases) Drugs / TIN Renal Immunological renal diseases Post-Renal Obstruction (5-10% of cases) Myeloma

55 Effects of ACE, ARB & NSAIDs on renal perfusion in hypovolaemia Hypovolaemia efferent arteriolar vasoconstriction maintains glomerular perfusion pressure ACE/ARB blocks this effect of angiotensin 2 on efferent arteriole Glomerular pressure falls GFR falls Prostaglandins cause afferent arteriolar vasodilatation; blocked by NSAIDs

56 Referral NICE AKI Guideline Nephrology: Discuss AKI management with a nephrologist as soon as possible (and within 24 hours) if one of the following is present: Potential diagnosis requiring specialist treatment (for example, vasculitis or glomerulonephritis) Complications associated with AKI Patients with renal transplant and AKI AKI with no clear cause Inadequate treatment response Stage 3 AKI egfr is less than < 30 ml/min/1.73 m 2 after AKI episode CKD stage 4 or 5 Renal replacement therapy: Refer adults, children and young people immediately for RRT if any of the following are not responding to medical management: Hyperkalaemia Metabolic acidosis Symptoms or complications of uraemia such as pericarditis or encephalopathy Fluid overload +/- pulmonary oedema