Morbidity & Mortality from

Chronic Kidney Disease

Dr. Lam Man-Fai (林萬斐醫生)Honorary Clinical Assistant Professor

MBBS, MRCP, FHKCP, FHKAM,

PDipID (HK), FRCP (Edin, Glasg)

Hong Kong Renal Registry Report 2012

1. An increasing trend of patients on dialysis was noted

2. In 1996, incident rate was 95.1 patients per million

populations (pmp) vs 157pmp in 2011

3. 1115 new patients were accepted into RRT programs

4. The total number of patients treated increased from 3312 in

1996 to 8510 in 2013

5. Overall, there were

3573 patients (43.6%) on peritoneal dialysis (PD)

1246 patients (15.2%) on hemodialysis (HD)

3378 patients (41.2%) were living with a functioning

renal transplant

Cardiovacular mortality • Elderly patients with CKD are 13 fold more

likely to die than reach advanced CKD

• CVD being the major cause for mortality

• CKD patients likely to have DM, HT,

hyperlipidemia

• CVD risk factors in CKD associate with both

ESRD & mortality (Life’s Simple 7)• Blood Pressure, cholesterol & glucose

• Smoking, physical activity, diet & BMI

Muntner P et al. JASN 2013,24

Graded and Independent Relationship Between Estimated

Glomerular Filtration Rate (GFR) and CVD Outcomes*

*Adjusted for baseline age, sex, income, education, coronary disease, chronic heart failure, stroke or transient ischemic attack,

peripheral artery disease, diabetes, hypertension, dyslipidemia, cancer, hypoalbuminemia, dementia, liver disease, proteinuria, prior

hospitalizations, and subsequent dialysis requirement. Shastri S et al. Am J Kidney Dis 2010; 56: 399-417

Glomerular Filtration Rate (GFR)

Vol of blood filtered across glomerulus per unit time

Best single measure of kidney function

Normal 100-130 ml/min

Determined by:

• Net filtration pressure across glomerular basement

membrane

• Permeability and surface area of glomerular basement

membrane

Creatinine Clearance

Measure serum and urine creatinine levels and

urine volume and calculate serum volume

cleared of creatinine

Same issues as with serum creatinine, except

muscle mass

Requirements for 24 hour urine collection adds

variability and inconvenience

serum

urine

serum Cr

VCr

Cr

timeunitexcretedcreatinineCrCl

][

][

][

/

eGFR by MDRD FormulaMathematically modified serum creatinine with

additional information from patients age, sex

and ethnicity

eGFR = 30849.2 x (serum creatinine)-1.154 x

(age)-0.203

(if female x (0.742))

Other risk factors for CVD• Albuminuria

• Low eGFR (< 60ml/min)

• Stage of CKD

• CVD mortality risk 3 fold higher in CKD 4

• Risk of developing CHF, AF, IHD, PVD &

stroke, increased by 2 fold if GFR < 60

• Endothelial dysfunction

• Chronic inflammation

• Anaemia

• Sympathetic hyperactivitySantoro A et al. Kidney Blood Press Res 2014 39

Dose-dependent Linear relationship

between LDL-C reduction & CV events

Updated International Guidelines on Chronic

Kidney Disease

1. In adults aged ≥50 years with eGFR <60 ml/min/1.73 m2 but not treated with chronic

dialysis or kidney transplantation (GFR categories G3a–G5), we recommend

treatment with a statin or statin/ezetimibe combination. (1A)”

2. In adults aged ≥50 years with CKD and eGFR ≥60 ml/min/1.73 m2 (GFR categories

G1–G2), we recommend treatment with a statin. (1B)”

3. In adults aged 18–49 years with CKD but not treated with chronic dialysis or kidney

transplantation, we suggest statin treatment in people with one or more of the

following 2A):”

Known coronary disease (myocardial infarction or coronary revascularization)

Diabetes mellitus

Prior ischemic stroke

Estimated 10-year incidence of coronary death or nonfatal myocardial infarction

>10%

Marcello Tonelli. Lipid management in chronic kidney disease: synopsis of the kidney disease: improving global outcomes. 2013 Clinical Practice Guideline

Accessed on 2013

KDIGO 2013 on Lipid Management of CKD

Updated International Guidelines on Chronic

Kidney Disease

KDOQI CLINICAL PRACTICE GUIDELINE FOR

DIABETES AND CKD: 2012 UPDATE

We recommend using LDL-C lowering medicines, such as statins or

statin/ezetimibe combination, to reduce risk of major atherosclerotic

events patients with diabetes and CKD, including those who have received

a kidney transplant. (1B)”

KDOQI. KDOQI Clinical Practice Guideline for Diabetes and CKD. 2012 Update. Am J Kidney Dis. 2012;60(5):850-886

Recommended dose of statins & ezetimibe in

CKD patients

KDOQI 20121

KDIGO 20132

Agents No CKD or stage

1-2

CKD stage 3 CKD stage 4-5

Ezetimibe 10 mg 10 mg 10 mg

Agents eGFR G1-G2 eGFR G3a-G5, including patients

receiving dialysis or who had a kidney

transplant

Atorvastatin

Any dose

approved for

general population

20

Rosuvastatin 10

Simvastatin /

ezetimibe20 / 10

Simvastatin 40

1. KDOQI. KDOQI Clinical Practice Guideline for Diabetes and CKD. 2012 Update. Am J Kidney Dis. 2012;60(5):850-886

2. Marcello Tonelli. Lipid management in chronic kidney disease: synopsis of the kidney disease: improving global outcomes. 2013 Clinical Practice Guideline

Accessed on 2013

Gout and comorbidities

• Kidney disease

• Cardiovascular disease

• Metabolic syndrome

– Hypertension

– Obesity

– Dyslipidaemia

– Type 2 diabetes

Weaver Al, et al. Cleve Clin J Med 2008;75(suppl5):S9-S12.

Gout

• An inflammatory arthritic condition occurs when

urate crystals accumulate in joints and other

tissues

• Gout is not a minor disease since it may induce

disability, severe nephropathy and increases

cardiovascular risk

Ru L-B. Imm Cell Biol 2010;88:20-23. Lukas E, et al. Eur J Heart Fail 2002;4:403-410.

Richette P, et al. Lancet 2010;375:318-328.

Nephron and Urate Excretion

Glomeruli provide nearly complete filtration of urate

The filtered urate is: Reabsorbed to the

extent of 99% of the load

Secreted or reabsorbed again

Only 10% of uratefiltered by glomerulus is finally excreted but has been reabsorbed & secreted by renal tubules

Gout overproduction +/- underexcretion of urate

Kidneys remove

uric acid from the

blood for excretion

out of the body

6.8 mg/dL (0.4 mmol/L)

threshold for solubility

at 37C

Serum urate

Baburaj K. Gout [PowerPoint slides]. 2010. Available at: http://www.hillingdongp.org.uk/documents/Gout.pdf. Accessed 29 May 2012.

10% of urate filtered

Causes of Hyperuricaemia & Gout

If sUA is higher than 6mg/dL (360umol/L), the pain intensity and

the frequency of gouty attack will be higher, while the pain will

sustain longer, more painkiller is needed, more harm to kidneys.

Hyper-uricaemia

Gout Attack

Painkiller

Impaired

Renal

Function

Hyperuricaemia and hypertension

• 20 - 40% hypertensive patients have hyperuricaemia

• Prevalence of HT among gouty patients is between 25 - 50%

• Serum urate levels predict the later development of HT

• Normative Aging Study showed serum urate level independently

predicted development of HT

• MRFIT study showed normotensive men with hyperuricaemia at

baseline had an 80% excess risk of developing HT compared to

those who did not have hyperuricaemia

Edwards NL. Curr Opin Rheumatol 2009;21:132-137.

Perlstein TS, et al. Hypertension 2006;48:1031-1036.

Krishnan E, et al. Hypertension 2007;49:298-303.

Feig DI, et al. N Engl J Med 2008;359:1811-1821.

Uric acid mediated hypertension

Menon V et al. Am J Kidney Dis. 2005;45(1): 223-232.

CVD

CKD

TraditionalCardiovascularRisk Factors

Non-traditionalCardiovascularRisk Factors

CKD Is a Risk Factor for CVD and CVD May Be a Risk Factor for the Progression of CKD

The Root of Gout Treatment:

Urate-lowering

Urate-lowering

therapyHyper-

uricaemia

Gout Attack

Painkiller

Impaired

Renal

Function

Early, Multifactorial Intervention Is Both

Renoprotective and Cardioprotective

BP

Glycaemia

Lipids

Proteinuria

(angiotensin II)

Lifestyle

Bowman’s capsuleImproved

glycaemic control1

Optimisation of BP:

<130/80 mmHg1

<140/80 mmHg4

Lipid level reduction1-3:

LDL <2.59 mmol/L (100 mg/dL)1;

<1.8 mmol/L (70 mg/dL) high risk1

Weight loss/exercise1,2

Smoking cessation1-3

Dietary salt restriction2

1. National Kidney Foundation. Am J Kidney Dis. 2007;49(Suppl 2):S42-61. 2. American Diabetes Association. Diabetes Care.

2004(Suppl 1);27:S79-S83. 3. Perkins BA, et al. N Engl J Med. 2003;348(23):2285-2293. 4. American Diabetes Association.

Diabetes Care. 2013;36(Suppl 1):S11-S66

Glomerulus

Loop of

Henlé

Collecting tubule

Renal

tubule

Renin-angiotensin

system (RAS)

blockade1:

ACE inhibitors or

ARBs

Thank you for your attention