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How to improve outcomes in Chronic Kidney Disease

How to improve outcomes in Chronic Kidney Disease. Paul Cockwell Consultant Nephrologist Queen Elizabeth Hospital Birmingham. CKD is usually present in association with other chronic conditions. Heart of Birmingham PCT – Relative risk of death b ased on known comorbidities.

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How to improve outcomes in Chronic Kidney Disease

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  1. How to improve outcomes in Chronic Kidney Disease Paul Cockwell Consultant Nephrologist Queen Elizabeth Hospital Birmingham

  2. CKD is usually present in association with other chronic conditions

  3. Heart of Birmingham PCT – Relative risk of death based on known comorbidities Hazard Ratio of Death 6 1 4 5 3 0 2 Number of co-morbidities

  4. Aims of the lecture • To discuss risk stratification in CKD • Outline the current evidence base for the management of CKD • Discuss the relevance of AKI to CKD

  5. Estimated prevalence of CKD in the UK is 13.5% - based on single tests • 6% with stage 3-5 CKD (eGFR <60 ml/min) • 9% with albuminuria

  6. eGFR – brief summary • aMDRD– current internationally accepted standard for reporting kidney function when the eGFR is abnormal (<60 ml/min) • aMDRD factors 4 variables – age, sex, ethnicity and creatinine – to provide an eGFR • CockroftGaulteGFR – often used for drug dose adjustment • CG and MDRD eGFR are not equivalent • CKD EPI eGFR – a new generation eGFRs that may supersede MDRD

  7. Beware of the (inaccuracy) of eGFR eGFR is not accurate when ≥ 60 mL/min Greatest accuracy at 30–59 mL/min; even then ‘90% of eGFRs within 30% of iGFR’!! Poggio et al. J Am Soc Nephrol. 2005; 16: 459–466

  8. The Health improvement Network (THIN): 6.7 million patients from 426 primary care centres in the UK. CKD 3-5 prevalence 2005-2009. Jain, Calvert, Cockwell, McManus – under review

  9. For patients with an eGFR <60 ml/min delta eGFR is as important as the overall value

  10. Proteinuria When the term proteinuria is used people are usually referring to albuminuria Albuminuria in clinical practice is now measured by a urinary Albumin Creatinine Ratio

  11. An ACR of 100 = an AER of 1g/d

  12. The CKD classification system

  13. The Health improvement Network (THIN): 6.7 million patients from 426 primary care centres in the UK. Age stratified prevalence of CKD 3-5 in 2009. Jain, Calvert, Cockwell, McManus – manuscript under review

  14. The CKD classification system

  15. eGFR threshold and risk of Death or ESKD O’Hare et al, JASN 2007

  16. Risk of ESKD in respect of eGFR and proteinuria ACR 30+ mg/mmol ACR 3-29 mg/mmol ACR < 3mg/mmol Adapted from Levey et al KI 2011

  17. Primary Care CKD • Risk stratification • BP management • Primary and secondary prevention of CVD • Monitoring • Referral into and communication with secondary care

  18. Secondary Care - Nephrology • Manage the established renal failure pathway • Enhanced monitoring and counseling • Prepare for dialysis • Assess for kidney transplantation • Manage secondary complications of kidney disease • Anemia of CKD (ESA, functional iron deficiency) • Secondary hyperparathyroidism

  19. Secondary Care non-nephrology • Management of comorbidity • Drug dosing and toxicity • Management of AKI • Sense check for primary care • Referral to secondary care nephrology

  20. http://www.nice.org.uk/Guidance/CG73

  21. Overall supporting information for the management of CKD Minimising the risk for people with CKD of progression of CKD and Cardiovascular disease (CVD) • The BP target for non-proteinuric CKD without diabetes is <140/85 • The BP target for diabetes and CKD is <130/80 • The BP target for proteinuric CKD (ACR>30) without diabetes is <130/80 • ACE inhibitors or ARBs should be used in all people with diabetes and with microalbuminuria (ACR>3.5 mg/mmol in men and 2.5 mg/mmol in women) and all people without diabetes with an ACR>30 even if BP<130/80. • The dose of ACEi/ARB should be used at the maximum tolerated. ACEiand ARBs should not be used in combination. • If there is an eGFR decline of >25% on introduction of an ACEi/ARB or dose increase of an ACEi/ARB then the drug should be stopped and advice should be obtained from secondary care nephrology • Primary and secondary prevention of CVD should be optimised; statins, anti-platelet drugs, and warfarin are not contraindicated in CKD. • NSAIDs should not be used Management of complications of CKD • People with CKD and a Hb < 10g/dl, who have had other causes of anaemia excluded should be considered for treatment of anaemia associated with CKD. Advice should be obtained from secondary care nephrology. • Please refer any uncertainties about bone chemistry through the advice and guidance portal

  22. eService (request) From: Vanessa Miller Sent: Monday, March 05, 2012 1:13 PM To: Paul Cockwell Cc: Barbara Joyce Subject: A&G Please see the attached advice and guidance request. This young lad came to see me with testicular pain.   As part of the assessment I dipsticked his urine which came up as showing marked proteinuria.    Subsequent ACR came back as slightly elevated at 6.6.   I saw him on a further two occasions and his urine remained positive on dipstick.   His renal profile came back normal;  creatinine 88, and urea 3.8.   CRP was also normal at 10 and he is normotensive with blood pressure of 117/68.       There is no family history of renal disease. I would be grateful for your opinion as to whether this needs any further investigation. Yours sincerely,

  23. eService (reply) Dear Thanks for the referral. This is probably orthostatic (postural) proteinuria. I would diptest or ACR the urine on an early morning specimen (first urine pass of the day) - if -ve or trace +ve reassure him. Orthostatic proteinuria is common in male adolescents and usually goes by the age of 30. If positive let me know and we should probably review him to make sure that there is no glomerular lesion. Best wishes Paul (Cockwell) ________________________________________

  24. Labelled CKD 139,176 Confirmed CKD 108,911 Miscoded 60705 Appropriately coded 78471 Uncoded 30,440 THIN and QOF CKD1 Jain, Calvert, Cockwell, McManus – under review

  25. Is this important? – Probably If you have CKD and are on the register vs not on the register • You have better BP control • If you have diabetes, you have a better HbA1c

  26. MAP (mmHg) 95 98 101 104 107 110 113 116 119 0 -2 r = 0.69; P < 0.05 -4 -6 GFR (mL/min/year) Untreated HTN -8 -10 -12 130/85 140/90 -14 Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics • Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996. • Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996. • Klahr S, et al. N Eng J. Med 1994. Bakris GL. Hypertension. 1997. • Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997. • Lebovitz H, et al. Kidney Int. 1994. www.hypertensiononline.org Bakris GL, et al. Am J Kidney Dis.2000;36(3):646-661. ,

  27. Accurate measurement of BP is crucial Validated BP – BPTru

  28. Standard clinic BPs vsBPTru

  29. BP management – NICE guidelines

  30. ACEior ARBs and the kidneys – the evidence base • People with diabetes and and ACR> 2.5  (men) or 3.5  (women) irrespective of BP • Non-diabetic people with CKD and hypertension and ACR >30 • Non-diabetic people with CKD and ACR > 70 mg/mmol irrespective of BP • No evidence for dual blockade

  31. In high risk groups ACEi/ARBs provide a 20% risk reduction in ESKD From Weir, NephSap; Vol 5 No 10, 2011

  32. ACE inhibitors and glomerular function Glomerular pressure PGC Efferent dilatation Proteinuria

  33. Interstitial capillary density and renal outcome

  34. Statins – the SHARP study • History of chronic kidney disease • not on dialysis: elevated creatinine on 2 occasions • Men: ≥1.7 mg/dL (150 µmol/L) • Women: ≥1.5 mg/dL (130 µmol/L) • on dialysis: haemodialysis or peritoneal dialysis • Age ≥40 years • No history of myocardial infarction or coronary revascularization • Uncertainty: LDL-lowering treatment not definitely indicated or contraindicated

  35. SHARP: Major Atherosclerotic Events 25 Risk ratio 0.83 (0.74 – 0.94) Logrank 2P=0.0022 20 Placebo 15 Eze/simv Proportion suffering event (%) 10 5 0 0 1 2 3 4 5 Years of follow-up

  36. SHARP: Cause-specific mortality Event Eze/simv Placebo Risk ratio & 95% CI (n=4650) (n=4620) Coronary 91 (2.0%) 90 (1.9%) Other cardiac 162 (3.5%) 182 (3.9%) 7.4% SE 8.4 Subtotal: Any cardiac 253 (5.4%) 272 (5.9%) reduction (p=0.38) Stroke 68 (1.5%) 78 (1.7%) Other vascular 40 (0.9%) 38 (0.8%) 7.3% SE 7.0 Subtotal: Any vascular 361 (7.8%) 388 (8.4%) reduction (p=0.30) Cancer 150 (3.2%) 128 (2.8%) Renal 164 (3.5%) 173 (3.7%) Other non-vascular (7.6%) 354 (6.7%) 311 8.6% SE 5.8 Subtotal: Any non-vascular 668 (14.4%) 612 (13.2%) increase (p=0.14) Unknown cause 113 (2.4%) 115 (2.5%) 1.9% SE 4.2 Total: Any death 1142 (24.6%) 1115 (24.1%) increase (p=0.65) 0.6 0.8 1.0 1.2 1.4 Eze/simv better Placebo better

  37. SHARP: Major Atherosclerotic Events by renal status at randomization Risk ratio & 95% CI Eze/simv Placebo (n=4650) (n=4620) Non-dialysis (n=6247) 296 (9.5%) 373 (11.9%) Dialysis (n=3023) 230 (15.0%) 246 (16.5%) Major atherosclerotic event 526 (11.3%) 619 (13.4%) 16.5% SE 5.4 reduction (p=0.0022) No significant heterogeneity between non-dialysis and dialysis patients (p=0.25) 0.6 0.8 1.0 1.2 1.4 Eze/simv better Placebo better

  38. Key points!! Around 50% of the increased mortality risk associated with conventional risk factors However patients with CKD are less likely to be optimally treated for risk factors than patients without CKD With advanced CKD there is an increasing association with non-traditional risk-factors

  39. Non-traditional risk factors and an evidence base • Spironolactone – RCTs in process • Bicarbonate – RCT in process • Phosphate – phosphate binder RCT being commissioned • Allopurinol – strong supportive evidence – needs an RCT!!

  40. A major risk factor for CKD is AKI Mehta et al, Crit Care, 2007

  41. Impact of AKI on Hospital Mortality Multivariate analysis • Acute kidney injury, mortality, length of stay and costs in hospitalized patients • 19,982 patients admitted to academic medical centre • 9,205 patients with >1 creatinine results Chertow et al. J Am Soc Nephrol. 2005; 16: 3365–3370

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