Morbidity & Mortality from Chronic Kidney...
Transcript of Morbidity & Mortality from Chronic Kidney...
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