A Comprehensive Approach to Kidney Disease and Hypertension

1. A Comprehensive Approach to Kidney Disease and Hypertension Dr. Eddy Susatyo, SpPD SubBagGinjaldanHipertensi IlmuPenyakitDalam RSI ARAFAH/ RSUD Rembang

2. Ginjal FungsiGinjal • Regulasi volume cairan • Regulasikeseimbanganelektrolit • Regulasikeseimbanganasamdanbasa • Regulasitekanandarah (RAAS) • Regulasieritropoesis • Ekskresisampahmetabolik • Metabolisme vitamin D • Sintesis prostaglandin

5. ApapenyebabGagalGinjal ?

6. Akut GagalGinjal Kronik

7. Chronic • CKD: Chronic Kidney Disease • Acute • ARF: Acute Renal Failure • AKI: Acute Kidney Injury • Acute Classification • Pre-renal • Renal • Post-renal

9. 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

10. Diseases of the Kidney • Diabetes • Hypertension • Atherosclerosis • Glomerular diseases • Toxins • Gentamicin • NSAIDS • Compound analgesics • Inherited diseases • Tubular disorders All global renal diseases affect glomerular filtration rate (GFR)‏

12. 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

13. 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

14. Estimate of GFR • Measured GFR • Serum creatinine • Creatinine clearance • Formulae based on serum creatinine • Cockcroft and Gault • MDRD • Other • EgCystatin C All based on measurements of serum creatinine

15. Abbreviated MDRD Study Equation GFR (mL/min/1.73 m2) = 186.3  SCr-1.154  Age-0.203 0.742 (if female)  1.210 (if African American) Equations for Estimating GFR Cockcroft-Gault Equation (140 – Age)  Weight in kg Ccr = (mL/min)‏  0.85 if female 72  SCr MDRD = Modification of Diet in Renal Disease; Ccr = creatinine clearance. Levey et al. Ann Intern Med. 2003;139:137-147.

17. 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.

18. Prevalence of CKD

19. Other Glomerulonephritis 10% 13% Diabetes Hypertension 50.1% 27% The Most Common Causes of CKD Primary Diagnosis for Patients Who Start on Dialysis

20. STAGES OF CKD INCREASED RISK NORMAL DAMAGE LOW GFR RENAL FAILURE CKD DEATH COMPLICATIONS

21. Bagaimanadengan Anemia Renal ?

22. Anemia Rates Increase as Levels of CKD Severity Progress 10 15 15 8 17 62 8 9 43 5 20 14 100 Anemia Prevalence (%)‏ Hgb Values 80 11-12 g/dL 10-11 g/dL 60 <10 g/dL 40 20 0 <2 2-2.9 3-3.9 ≥4 Creatinine (mg/dL)‏ Chronic Kidney Disease (CKD) Progression Hgb = hemoglobin. Kausz et al. Dis Manage Health Outcomes. 2002;10:505-513.

23. Normal GagalGinjal

28. Chronic kidney disease (CKD) Anemia is an expected complication of CKD Treatment Increased cardiovascular morbidity recombinant human erythropoietin (r-HuEPO) Left Ventricular Hypertrophy (LVH) Congestive Heart Failure (CHF)

29. Diambil : Jerome Rossertdkk, Nephrol Dial Transplant (2002) 17: 359–362

31. CKD/ESRD ANEMIA INFLAMMATION plus CaP deposition LVH/CHF LIPIDS HTN CAD and PVD CV DISEASE AND DEATH Why are CKD/ESRD Patients Predisposed to CV Disease?

32. Why are CKD/ESRD Patients Predisposed to CV Disease? • 30-50% of ESRD patients haveINFLAMMATION(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 havemetastatic calcification (coronary arteries)because of secondary hyperparathyroidism and elevated PO4 levels.

33. Bagaimanahubunganantarahipertensidengan CKD ?

34. Distribution of hypertensives (65-89 years) ISOLATED SYSTOLIC ISOLATED SYSTOLIC COMBINED COMBINED ISOLATED DIASTOLIC ISOLATED DIASTOLIC Framingham study

35. Factors Affecting Blood Pressure Total Peripheral Resistance = X Blood Pressure Cardiac Output Amount of blood ejected per minute Blood flow through blood vessels

38. Prevalence of HTN in CKD 80% of patients with glomerulonephritis and 30% of patients with chronic interstitial disease are hypertensive.

41. Aggressive BP Control, Proteinuria and CKD Progression– what is the optimal BP for CKD? * * Klahr S et al, N Engl J Med 330:877, 1994 GOAL BP<125/75 if >1 gm proteinuria

42. Angiotensin II plays a central role in organ damage Atherosclerosis* Vasoconstriction Vascular hypertrophy Endothelial dysfunction Stroke Hypertension A II LV hypertrophy Fibrosis Remodeling Apoptosis Heart Failure MI Death GFR Proteinuria Aldosterone release Glomerular sclerosis Renal Failure *Preclinical data. LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.

43. Renin Angiotensin Aldosterone System Non-ACE pathways(eg, chymase)‏ • Vasoconstriction • Cell growth • Na/H2O retention • Sympathetic activation Angiotensinogen AT1 Angiotensin I Renin Angiotensin II ACE AT2 Aldosterone • Vasodilation • Antiproliferation(kinins)‏ Cough,angioedema Benefits? Inactivefragments  Bradykinin

44. Increased angiotensin II Decreased vasodilatory prostaglandins Low GFR

45. How About Renal Osteodystrophy

46. Bone Disease in CKD • Metabolic abnormalities • Hyperphosphatemia • Hypocalcemia • PTH elevation

47. Bone Disease in CKD • Renal Osteodystrophy • Osteomalacia / osteitis fibrosis cystica / osteosclerosis • Metastatic calcification • Vascular!

48. Bone Disease in CKD • Renal Osteodystrophy

50. Maturnuwun