Presentation is loading. Please wait.

Presentation is loading. Please wait.

1 Concepts of Renal Injury & CKD Prevention Dhavee Sirivongs, M.D. September 15, 2005 Lecture Hall 1 Faculty of Medicine, KKU.

Similar presentations


Presentation on theme: "1 Concepts of Renal Injury & CKD Prevention Dhavee Sirivongs, M.D. September 15, 2005 Lecture Hall 1 Faculty of Medicine, KKU."— Presentation transcript:

1

2 1 Concepts of Renal Injury & CKD Prevention Dhavee Sirivongs, M.D. September 15, 2005 Lecture Hall 1 Faculty of Medicine, KKU

3 2 Early Stage CKD has been neglected? High compensatory kidneys No annual check up Clinical presentation appears at CKD V Patients are high tolerant No doctor concern, no GFR calculation No public awareness Etc.

4 3 Concepts Critical mass of the kidney Genetic factor Environmental insults, include. drugs In-body factors: Ht Progressive nature of kidney disease & kidney

5 4 CKD: pathophysiology original insult destroyed most nephron The rest of nephron was hypertrophy as compensatory process Non-immunological insults destroy glomeruli & tubules Immunological insults destroy glomeruli & tubules Proteinuria destroys the tubule via oxidation Obstructive nephropathy induces glomerular and intersitium invasion of wbc

6 5 Nephron Loss to Critical number Acute process Chronic process Unrecovery ARF Trauma Surgical Immunological (SLE) Metabolic (DM) Mechanical (OU)

7 6 Mechanisms of Renal Injury Immunological insults (direct) & proteinuria (indirect): SLE, NS Non-immuno insults (direct) & proteinuria (indirect): DM, acetaminophen, pregnancy related Obstructive nephropathy (tubular dilatation, jncreased luminal pressure, glomerulosclerosis

8 7 Collagen type IV

9 8 Lupus nephritis

10 9

11 10 Lupus nephritis

12 11 Lupus nephritis

13 12 Obstructive nephropathy

14 13

15 14

16 15 Nephron Loss to Critical number Wear & Tear Hemodynamic Hypertrophy Fibrotic changes Etc. Progressive nephron loss CKD V ESRD Factors: Hypertension, Smoking, Drugs, Pre-renal

17 16 Markers of renal injury Microalbuminuria/Proteinuria Urinary sediments: hematuria, pyuria Clinical index: Nocturia (poor concentrating ability), Hypertension FEMg ?

18 17 Glomerular hypertension Renal injury Reduced number of nephrons Systemic hypertension SCARRING Autoregulation* * Lost in diabetes Brenner, Meyer, Hostetter, N Engl J Med, 1982 A unifying hypothesis for the progressive nature of renal disease

19 18 Proteinuria/Microalbuminuria The current number one marker for renal injury (also the marker for CVS morbidity/mortality)

20 19 ProteinuriaHypertension

21 20 PODOCYTE DYSFUNCTION IN RESPONSE TO PROTEIN LOAD Increased glomerular permeability to proteins ACEi / AIIRA Podocyte protein accumulation Proteinuria Cytoskeleton rearrangement Gene activation Loss of differentiated phenotype TGF-  Slit diaphragm dysfunction Prosclerosing activation of mesangial cells Podocyte detachment Foot process effacement Permselective dysfunction GLOMERULOSCLEROSIS Ang II Abbate et al., Am J Pathol, 2002

22 21

23 22 Mechanism of Proteinuria

24 23 AlbuminuriaHypertension Renal deterioration Renal Injury Tubular injury Glomerular injury

25 24 Conclusive concept Known causeUnknown cause Treatable causeDiseased kidney CKD 1 CKD 2 CKD 3 CKD 4 CKD 5 Normal kidney Markers of Kidney damage

26 25 Life style modification Adequate fluid intake Low salt diet Proper protein diet Adequate rest Stop smoking Exercise Etc.

27 26 Pharmacological approach Angiotensin converting enzyme inhibitor (ACE-I) Angiotensin receptor blocker (ARB)

28 27 Concept of ACE-I/ARB Usage ใช้แนวคิด “ เศรษฐกิจพอเพียง ลด ความฟุ้งเฟ้อ ”

29 28 REIN: ACE-I IS MORE RENOPROTECTIVE THAN CONVENTIONAL THERAPY IN NON-DIABETIC RENAL DISEASE % of patients without doubling of baseline creatinine or ESRF Follow-up P= – - 20 – 0 – 20 – 40 – 60 – % Reduction in Proteinuria Diastolic Blood Pressure (mm Hg) 100 – 90 – 80 – 70 – 60 – Ramipril Conventional therapy Gisen group; Lancet 1997

30 29 3 MONTHS PROTEINURIA REDUCTION PREDICTS LONG-TERM GFR DECLINE The REIN study Ramipril Overall Conventional * Corrected for GFR > 3 gr/24 h  GFR (ml/min/month) 3 years  proteinuria * ( percent change vs.baseline) 3 months Perna et al., J Am Soc Nephrol, 2000

31 GFR (ml/min/month) Ramipril  GFR = ± 0.54  GFR = ± 0.50  GFR = ± 1.12  GFR = ± 0.87 Ramipril Conventional CORE FOLLOW-UP Ruggenenti et al., Lancet, 1998

32 31

33 32 Decrease in Mean Blood Pressure (mm Hg) + 2 – 0 – - 2 – - 4 – - 6 – - 8 – - 9 – - 10 – + 40 – + 20 – 0 – - 20 – - 40 – - 60 – % Reduction in Proteinuria p <.001 % with Doubling of Baseline Creatinine + ESRD + death Losartan Conventional therapy Brenner et al, N Engl J Med., NS RENAAL: ARB IS BETTER THAN CONVENTIONAL THERAPY IN TYPE 2 DIABETIC NEPHROPATHY

34 33 6 MONTHS PROTEIN/CREATININE RATIO REDUCTION PREDICTS RENAL AND CARDIOVASCULAR EVENTS The RENAAL study ESRD CV events Heart failure RENAAL Study group, 2002 Hazard ratio (95 % C.I.) Decreased risk Increased risk

35 34 Prevention of progression and remission strategies for chronic kideny diseases Stop activities of the insult(s) Save the the rest of nephrons –Life style modification eg. Stop smoking –Pharmacological approach, to control hypertension, intraglomerular pressure, protein/microalbuminuria Ideal drugs: ACEI, ARB

36 35 ISN: Activities on CKD prevention Canada: Symposium on CKD prevention yearly since 2002 Mexico 2003: The Ensenada Conference on Renal Disease in Minorities Groups, with Emphasis on the Americas Italy 2004: Bellago conference: Prevention of Renal Disease in the Emerging World: Toward global Health Equity Hong Kong 2004: CKD Prevention Pre-congress WCN 2005, Singapore

37 36 ISN: Prevention strategies Detecting those at risk of developing CKD Preventing the onset of CKD in susceptible individuals by altering lifestyle Detecting those with early stage CKD Preventing progression of CKD by intervention Developing and applying diagnostic guidelines including albuminuria and estimated GFR as well as therapeutic guidelines Raising awareness with the general public, policymakers and physicians Creating funds and facilities for global assistances

38 37 กิจกรรม CKD prevention ใน ไทย คณะอนุกรรมการป้องกันไตวายเรื้อรัง สมาคม โรคไตฯ แผนงานป้องกันภาวะไตวายแบบบูรณาการ สัมมนาอายุรแพทย์โรคไต แนวปฏิบัติเพื่อชะลอการเสื่อมของไต อบรมวิทยากรพยาบาล โครงการศึกษาอัตราการเสื่อมของไต อบรมแพทย์และพยาบาลใน 5 พื้นที่ใน 5 ภาค กย. 48 เผยแพร่ความรู้ให้กับประชาชน 5 ธค. 48 กลุ่มวิจัยโรคไต เรื้อรัง คณะ แพทยศาสตร์ ม. ขอนแก่น ก่อตั้งตั้งแต่ ปี พ. ศ. 2544

39 38 End of the session

40 39 Loss of Kidney Mass

41 40 A META-ANALYSIS IN 840 TYPE 1 AND TYPE 2 DIABETIC PATIENTS WITH INCIPIENT AND OVERT NEPHROPATHY AND PRESERVED RENAL FUNCTION Change in proteinuria (%) Change in GFR (%/year) Modified from Weidmann et al., Nephrol Dial Transpl, 1995

42 41

43 42

44 43 Cause/Etiology Pre-clinical evidences Clinical evidences Lab. evidences

45 44 NEPHRON NUMBER IN 10 MIDDLE-AGED WHITE HYPERTENSIVES AND 10 MATCHED NORMOTENSIVES Keller et al., N Engl J Med, 2003 Mean glomerular volume (10 -3 /mm 3 ) Nephron number per kidney (x 1,000) HP 0 1,000 1,500 2,000 2, N ( ) 1,429 (1,130-1,627) * * p < 0.001

46 45 HALTING THE PROGRESSION OF CHRONIC NEPHROPATHIES: The negleted issue of residual proteinuria Lowest < 1.5 g/24 h Middle g/24 h Highest ≥3.5 g/24 h  GFR (ml/min/month) 3 years Ruggenenti et al., J Am Soc Neph, 2000 Tertiles Proteinuria Residual proteinuria (6 months)


Download ppt "1 Concepts of Renal Injury & CKD Prevention Dhavee Sirivongs, M.D. September 15, 2005 Lecture Hall 1 Faculty of Medicine, KKU."

Similar presentations


Ads by Google