A Comprehensive Approach to Kidney Disease and Hypertension Dr. Eddy Susatyo, SpPD SubBag Ginjal dan Hipertensi Ilmu Penyakit Dalam RSI ARAFAH/ RSUD Rembang

Ginjal Fungsi Ginjal Regulasi volume cairan Regulasi keseimbangan elektrolit Regulasi keseimbangan asam dan basa Regulasi tekanan darah (RAAS) Regulasi eritropoesis Ekskresi sampah metabolik Metabolisme vitamin D Sintesis prostaglandin

Apa penyebab Gagal Ginjal ?

Akut Gagal Ginjal Kronik

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

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

All global renal diseases affect glomerular filtration rate (GFR)‏ 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)‏

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

Estimate of GFR Measured GFR Serum creatinine Creatinine clearance Formulae based on serum creatinine Cockcroft and Gault MDRD Other Eg Cystatin C All based on measurements of serum creatinine

Equations for Estimating GFR 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) 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.

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.

Prevalence of CKD

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

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

Bagaimana dengan Anemia Renal ?

Anemia Rates Increase as Levels of CKD Severity Progress 100 Anemia Prevalence (%)‏ 62 15 10 Hgb Values 80 11-12 g/dL 43 8 15 10-11 g/dL 60 <10 g/dL 40 20 8 17 14 9 5 20 <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.

Normal Gagal Ginjal

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)

Diambil : Jerome Rossert dkk, Nephrol Dial Transplant (2002) 17: 359–362

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

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) ISOLATED SYSTOLIC ISOLATED SYSTOLIC COMBINED COMBINED ISOLATED DIASTOLIC ISOLATED DIASTOLIC Framingham study

Factors Affecting Blood Pressure Total Peripheral Resistance = Cardiac Output X 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.

Klahr S et al, N Engl J Med 330:877, 1994 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

A II 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.

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

Decreased vasodilatory prostaglandins Increased angiotensin II Low GFR

How About Renal Osteodystrophy

Bone Disease in CKD Metabolic abnormalities Hyperphosphatemia Hypocalcemia PTH elevation

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

Bone Disease in CKD Renal Osteodystrophy

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