Chronic Kidney Disease

Maarten Taal

Royal Derby Hospital and University of Nottingham

United Kingdom

Outline

• CKD epidemiology update

• Estimating GFR: – CKD-EPI equation – Cystatin C

• Revised CKD Classification System (KDIGO 2012 and NICE 2104)

• Risk Prediction in CKD: – Renal – Cardiovascular

CKD Epidemiology

CKD Stage 1-5 Prevalence

Bruck K et al. JASN 2015 ePub

Health Survey for England 2009: CKD 1-5 prevalence 12.3% Fraser SDS et al. JPubHealth 36: 577–586; 2014

Variation not explained by prevalence of: • Diabetes • Hypertension • Obesity

Jha V et al. Lancet 382: 260-72; 2013

Annual incidence of ESKD

Global and regional mortality from 235 causes of death for 20 age

groups in 1990 and 2010: a systematic analysis for the Global

Burden of Disease Study 2010

Lozano R. Lancet 380: 2095 – 2128; 2013

Estimating GFR

MDRD Equation

Giles, P. D et al. BMJ 334:1198-1200; 2007

eGFR = 2.59 x (serum creatinine) -1.154 x (age) -0.203 x (0.742 if female) x (1.21 if African American)

CKD-EPI Equation

Levey et al. Ann Int Med 150:604-612; 2009

MDRD vs. CKD-EPI

Levey et al. Ann Int Med 150:604-612; 2009

CKD-EPI and Reclassification

Matsushita et al. JAMA 307:1941-51; 2012

CKD-EPI and Risk prediction

Matsushita et al. JAMA 307:1941-51; 2012

Net Reclassification Improvements

Cystatin C

• Small protein produced by all nucleated cells

• Filtered by glomerulus

• No tubular secretion

• Almost completely reabsorbed and catabolised by tubule cells

• Not affected by muscle mass or gender

• Is affected by: obesity, thyroid status, diabetes, corticosteroids, inflammation, smoking

NICE Clinical Guideline 182: 2014

1.1.14 Consider using eGFRcystatinC at initial diagnosis to confirm or rule out CKD in

people with:

• an eGFRcreatinine of 45–59 ml/min/1.73 m2, sustained for at least 90 days and

• no proteinuria (albumin:creatinine ratio [ACR] less than 3 mg/mmol) or other marker

of kidney disease.

NICE Clinical Guideline 182: 2014

1.1.15 Do not diagnose CKD in people with:

• an eGFRcreatinine of 45–59 ml/min/1.73 m2

and

• an eGFRcystatinC of more than 60ml/min/1.73 m2 and

• no other marker of kidney disease.

Cystatin C vs. Creatinine vs. Both: Bias

Inker et al. NEJM 367:20-9; 2012

Cystatin C vs. Creatinine vs. Both: Accuracy

Inker et al. NEJM 367:20-9; 2012

Cystatin C for Risk Prediction: Death

Shlipak et al NEJM 369:932-43; 2013

Cystatin C for Risk Prediction: ESKD

Shlipak et al NEJM 369:932-43; 2013

Cystatin C for Risk Prediction: NRI

Shlipak et al NEJM 369:932-43; 2013

Cystatin C - Problems:

• Currently available in only 3 labs in UK

• Much more expensive

• Prediction data compared Cystatin C to a single Creatinine eGFR

• More data required:

– eGFR-C study

– Renal Risk in Derby study

CKD Classification

NICE CKD Classification 2008

eGFR and UACR as Risk Factors

Gansevoort et al. KI 80:93-104; 2011

Van der Velde et al. KI 79:1341-42; 2011

Risk Prediction in CKD

Renal Risk

• eGFR 51 (CKD 3)

• 84y female

• No previous illness

• BP 125/65

• UACR 1.6mg/mmol

• Category G3a A1

• eGFR 51 (CKD 3)

• 52 year male

• Type 2 DM

• BP 160/95

• UACR 365mg/mmol

• Category G3a A3

Renal Risk Scores

• Patients with CKD stage 3-5

• Risk Factors:

– Age

– Gender

– eGFR

– Albuminuria

– Albumin

– Calcium

– Phosphate

– Bicarbonate

• Outcome: ESKD

• AUC 0.917

Tangri N, JAMA 305:1553-9, 2011

KFRE Validation

Tangri N et al. JAMA. 2016;315(2):164-174.

External validation: • 31 cohorts • 721,357 people • 30 countries • 4-Variable KFRE • C statistic = 0.88 • Correction factor to

improve calibration for non-N.American populations

KFRE Risk Calculator

http://kidneyfailurerisk.com/

Renal Risk

• eGFR 51 (CKD 3)

• 84y female

• No previous illness

• BP 125/65

• UACR 1.6mg/mmol

• 5Year ESKD risk = 0.2%

• eGFR 51 (CKD 3)

• 52 year male

• Type 2 DM

• BP 160/95

• UACR 365mg/mmol

• 5Year ESKD risk = 7.5%

CV Risk Prediction in CKD

• Framingham underestimates CV risk in CKD

• QRISK2 includes CKD but as a binary variable

• Meta-analysis: 637 315 individuals from 24 cohort studies

• Selected participants without CVD at baseline

• Considered eGFR and UACR as risk factors in addition to Framingham risk factors

• Risk assessed over 5 years

Matsushita K. Lancet Diabetes Endocrinol 2015

Matsushita K. Lancet Diabetes Endocrinol 2015

General Population Cohorts

CKD Cohorts

Summary

• CKD remains prevalent in 10-20% of adults • The CKD-EPI equation is more accurate and has

less bias than the MDRD equation • The role of cystatin C for estimating GFR is not yet

clear • The new CKD classification promotes a risk-based

approach to management • The KFRE provides an evidence-based tool for

ESKD risk prediction • GFR and UACR add predictive value to traditional

Framingham cardiovascular risk factors