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 CrCl creatinineexcreted [ Cr] serum / unit time [ Cr] urine [ Cr] serum V
egfr by MDRD Formula Mathematically 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 hyperactivity Santoro 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 KDIGO 2013 on Lipid Management of CKD 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
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 2012 1 Agents No CKD or stage 1-2 KDIGO 2013 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 20 Rosuvastatin Any dose approved for 10 Simvastatin / general population ezetimibe 20 / 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 urate filtered 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 10% of urate filtered Serum urate 6.8 mg/dl (0.4 mmol/l) threshold for solubility at 37 C Baburaj K. Gout [PowerPoint slides]. 2010. Available at: http://www.hillingdongp.org.uk/documents/gout.pdf. Accessed 29 May 2012.
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. Hyperuricaemia Impaired Renal Function Gout Attack Painkiller
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.
Uric acid mediated hypertension Feig DI, et al. N Engl J Med 2008;359:1811-1821.
CKD Is a Risk Factor for CVD and CVD May Be a Risk Factor for the Progression of CKD CKD Traditional Cardiovascular Risk Factors Non-traditional Cardiovascular Risk Factors CVD Menon V et al. Am J Kidney Dis. 2005;45(1): 223-232.
The Root of Gout Treatment: Urate-lowering Urate-lowering therapy Hyperuricaemia Impaired Renal Function Gout Attack Painkiller
Early, Multifactorial Intervention Is Both Renoprotective and Cardioprotective BP Optimisation of BP: <130/80 mmhg 1 <140/80 mmhg 4 Improved glycaemic control 1 Glomerulus Bowman s capsule Glycaemia Renal tubule Proteinuria (angiotensin II) Renin-angiotensin system (RAS) blockade 1 : ACE inhibitors or ARBs Loop of Henlé Lipid level reduction 1-3 : LDL <2.59 mmol/l (100 mg/dl) 1 ; <1.8 mmol/l (70 mg/dl) high risk 1 Lipids Collecting tubule Weight loss/exercise 1,2 Smoking cessation 1-3 Dietary salt restriction 2 Lifestyle 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
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