The CKD problem• Clinically silent in the early stages• Cost of renal disease can be extreme to health care service• Effects of renal disease can be extreme on patient• Treatments now available to slow progression• Need an “early warning” system for CKD
Diseases of the Kidney• Diabetes• Hypertension• Atherosclerosis• Glomerular diseases All global renal diseases• Toxins – Gentamicin affect glomerular – NSAIDS filtration rate (GFR) – Compound analgesics• Inherited diseases• Tubular disorders
Definition of CKD• Kidney damage for 3 months – Defined by structural or functional abnormalities of the kidney, with or without decreased glomerular filtration rate (GFR)• Reduced GFR for 3 months• New staging for chronic kidney disease (CKD) is primarily based on kidney function.National Kidney Foundation (NKF). Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.
• Glomerular Filtration Rate is the volume of fluid passing through the glomerulus in a given period of time.• Influenced by renal perfusion pressure, renal vascular resistance, glomerular damage, post-glomerular resistance.• “Normal Range” approx 90 - 150 mL/min – Approx 170 L per day• A larger healthy person has a higher GFR – Can be reported as 90 - 150 mL/min/1.73m2• Values fall with increasing age
Other reasons for estimating the GFR• Monitoring progression of CKD• GFR estimates are used for drug dosing decisions – Dosing of renally excreted drugs – Avoiding nephrotoxic drugs• Risk factor for cardiovascular disease mortality• Renal involvement in systemic diseases, such as diabetes mellitus or SLE
Why are CKD/ESRD Patients Predisposed to CV Disease? CKD/ESRDANEMIA INFLAMMATION plus CaP deposition LVH/CHF LIPIDS HTN CAD and PVD CV DISEASE AND DEATH
Why are CKD/ESRD Patients Predisposed to CV Disease?• 30-50% of ESRD patients have INFLAMMATION (increased CRP, increased IL-6, decreased albumin) – Increased CRP is a primary marker for inflammation predicting cardiovascular disease in normal adults – Increased CRP is the primary marker for increased cardiovascular mortality on dialysis• CKD/ESRD patients have metastatic calcification (coronary arteries) because of secondary hyperparathyroidism and elevated PO4 levels.
Bagaimana hubungan antara hipertensi dengan CKD ?
Distribution of hypertensives (65-89 years) MEN WOMEN ISOLATEDISOLATED SYSTOLICSYSTOLIC 59.3% 63.6% 30.3% 27.7% 10.4% 8.7% COMBINED COMBINED ISOLATED ISOLATED DIASTOLIC DIASTOLIC Framingham study
Factors Affecting Blood Pressure Blood Cardiac TotalPressure = Output X Peripheral Resistance Amount of blood ejected per minute Blood flow through blood vessels
Prevalence of HTN in CKD 80% of patients with glomerulonephritis and 30% of patients with chronic interstitial disease are hypertensive.
Aggressive BP Control, Proteinuria andCKD Progression – what is the optimal BP for CKD? 0 <1 gm/D 1-2.9 >3 gm/D -2 gm/D -4 Mean fall <125/75 in GFR -6 (ml/min/yr) * <140/90 -8 * -10 Klahr S et al, N Engl J -12 Med 330:877, 1994 GOAL BP<125/75 if >1 gm proteinuria
Angiotensin II plays a central role in organ damage Atherosclerosis* Stroke Vasoconstriction Vascular hypertrophy Endothelial dysfunction HypertensionA II LV hypertrophy Fibrosis Remodeling Heart Failure Death Apoptosis MI GFR Proteinuria Renal Failure Aldosterone release Glomerular sclerosis *Preclinical data. LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.