Gangguan sistem urologi fokus gagal ginjal Dr. Eddy Susatyo, SpPD FinaSIM RSU dr. Sutrasno Rembang

STRUCTURE OF THE KIDNEYS

Chronic Kidney Disease ?

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

How About the Function of Renal ?

Fungsi ginjal Regulasi volume cairan tubuh Regulasi keseimbangan elektrolit Regulasi keseimbangan asam basa Regulasi tekanan darah (RAAS) Ekskresi sampah metabolik Regulasi erithropoesis Metabolisme vit D Sintesis prostaglandin

RAAS Brain ADH Renin Angiotensin II Kidney Na+ excretion H2O excretion Lung Ang II Angiotensin I Adrenal Angiotensinogen Aldosteron RAAS Hepar

The Most Common Causes of CKD Glomerulonefritis Penyakit ginjal herediter Hipertensi Uropathy obstruktif Infeksi Nefropati diabetik

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

Pe Reabs Na Hipertrofi sel renal Pe eksr sisa metab Ggn konstentrasi urin Pe ekskr kalium Penurunan GFR Ggn fs ekskresi Pe ekskr PO4 Pe ekskr ion H CKD Ggn Reproduksi Ggn Imun Ggn fs non ekskresi  prod eritropoetin Pe abs Ca

JENIS PEMERIKSAAN PENUNJANG Urinalisis Evaluasi Fungsi Ginjal Evaluasi Serologis Pemeriksaan Radiologis Biopsi Ginjal

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

CKD Progresses in Stages Defined by Kidney Function: GFR 300,000 <15 Kidney failure 5 80 400,000 15-29 Severe decr in GFR 4 1520 7,600,000 30-59 Mod dec. in GFR 3 1060 5,300,000 60-89 Mild decr. in GFR 2 1180 5,900,000 90 Kidney damage normal incr. GFR 1 Patients/ Nephrologist Prevalence GFR Description CKD Stage 20 Million People With CKD (1 in 9 adults) in the United States, Many More at Risk *Estimated maximal load of kidney failure patients/nephrologist. Adapted from NKF. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.; Coresh et al. Am J Kidney Dis. 2003;41:1-12; and Wish. Nephrol News Issues. 1999;13:23, 27, 53.

Clinical Features – CKD 3-5 Unintentional weight loss Nausea, vomiting General ill feeling Fatigue; Headache; Frequent hiccups Generalized itching (pruritus) Increased or decreased urine output Need to urinate at night, polyuria Easy bruising or bleeding

Clinical Features – CKD 3-5 Blood in the vomit or in stools Decreased alertness; Muscle cramps Seizures; Agitation; Hypertension Peripheral sensory neuropathy Breath fetor; Loss of appetite; Uremic frost on the skin Uremic pericarditis, CHF

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

Considerations for Patients with CKD? CVD Anemia Altered bone & mineral metabolism Complications Higher level of proteinuria Higher BP Poor glycemic control Smoking Hyperlipidemia Drug use Diabetes Hypertension Older age Family history of CKD Racial or ethnic minority Other: low income, minimal education, kidney-mass reduction, known kidney disease Progression Factors Susceptibility Risk Factors Levey et al. Ann Intern Med. 2003;139:137-147. USRDS. 1999 Annual Data Report. Available at: www.usrds.org.

What Are Progression Factors for CKD? Elevated creatinine may indicate CKD, but not all creatinine elevation is irreversible Key progression factors include Elevated blood pressure (BP)‏ Proteinuria Poorly controlled glucose in patients with diabetes Excess protein intake. NSAIDs, contrast, aminoglycosides, other Levey et al. Ann Intern Med. 2003;139:137-147.

2-year Follow-Up of Medicare Patients: Focus on Diabetes, CKD or Both + DM, - CKD - DM, +CKD + DM, + CKD Medical Cohort CKD identified as ICD-9-CM diagnosis code, includes CKD from diabetes, hypertension, obstructive uropathy, and other diagnosis codes reported on USRDS ESRD registration forms. ESRD = end-stage renal disease; DM = diabetes mellitus; ICD-9-CM = International Statistical Classification of Diseases, 9th Revision, Clinical Modification. Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31.

LVH Increases With CKD Progression LVH at Baseline (%)‏ 80 60 40 20 50-75 25-50 <25 Dialysis Start eGFR (mL/min/1.73 m2)1 eGFR = estimated glomerular filtration rate. 1. Levin et al. Am J Kidney Dis. 1999;34:125-134. 2. Foley et al. J Nephrol. 1998;11:239-245.

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.

Specific Interventions for Complications of CKD Adequate energy intake 11-12 g/dL LDL-C <100 mg/dL (70?) TG <150 mg/dL HDL-C >40 mg/dL CKD stage 3 = 35-70 pg/mL 4 = 70-110 pg/mL < 130/80 mm Hg preprandial glucose 90-125 mg/dL A1C <7% Target Goals Dietary modification Reach Hgb goal Maintain lipids to target PTH control BP control Glycemic control Intervention Dyslipidemia Anemia Malnutrition Secondary HPT Hypertension Diabetes Complication A1C = glycosylated hemoglobin; HPT = hyperparathyroidism; PTH = parathyroid hormone; LDL-C = low-density lipoprotein cholesterol; TG = triglycerides; HDL-C = high-density lipoprotein cholesterol; Hgb = hemoglobin.

Summary: Clinical Actions for Progressive Stages of CKD Kidney replacement if uremia present <15 or dialysis Kidney failure 5 Prepare for kidney replacement Evaluate and treat complications 15-29 Severe  GFR 4 *All actions for prior stages 30-59 Moderate  GFR 3 Estimate progression 60-89 Kidney damage with mild  GFR 2 Diagnose and treat comorbid conditions Address progression factors Reduce/control CVD risk factors 90 Kidney damage with normal or  GFR 1 Evaluate for CKD Reduce/control CKD risk factors 90 with CKD risk factors At increased risk Risk Action* GFR (mL/min/1.73 m2)‏ Description CKD Stage *Actions for each progressive stage of CKD also include all the actions for prior stages. NKF. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.

Cause of death in dialysis patients

Decisions in renal replacement Pre-dialysis care Active treatment - Peritoneal dialysis (PD) - Haemodialysis (HD) - Transplantation Conservative (non-dialytic) care. Symptom management.

Penatalaksanaan CKD Uremia : diit protein 0,6 – 0,8 gr / kg bb / hari Ditujukan untuk mengurangi gejala klinik , mencegah komplikasi , mencegah progresifitas CKD, mempersiapkan initiasi dialisis Uremia : diit protein 0,6 – 0,8 gr / kg bb / hari Hiperkalemia : diit rendah kalium ; 60 – 80 meq/hari Asidosis metabolik : diit rendah protein / fosfat; HCO3 Stop rokok Kontrol lipid ( preparat statin ) HbA1C < 7 % Hipertensi Anemia Osteodistrofi renal Komplikasi kardiovaskuler

How Do We Know if a Patient is Adequately Dialyzed? K/DOQI Guidelines Define Adequate Dialysis as: KT/V = 1.2 or greater URR = 65% or greater

URR% - Urea Reduction Ratio : the percentage of urea removed during the treatment KT/V : Formula utilizing dialyzer urea clearance, treatment time and total body fluid

Example URR URR% = Ur pre – Ur post x 100% Ur Pre 35/50 = 70/100 = 70% Initial (predialysis) urea level: 50 mg/dL The postdialysis urea level: 15 mg/dL The amount of urea removed: 50 mg/dL–15 mg/dL = 35mg/dL URR% = Ur pre – Ur post x 100% Ur Pre 35/50 = 70/100 = 70% Recommended a minimum URR of 65 percent. The URR is usually measured only a month.

Acute kidney injury in Sepsis ? How About Acute kidney injury in Sepsis ?

Critical ill patient potentially AKI

AKI in ICU  5 –25% Mortality AKI 40-80%

< 0,5ml/kg per jam untuk >6jam Klasifikasi/staging AKI modifikasi RIFLE Stadium kriteria kreatinin kriteria urin output 1. Risk serum kreatinin meningkat > 0,3 mg/dl atau meningkat lebih dari 150-200 % dari awal < 0,5ml/kg per jam untuk >6jam 2. Injury serum kreatinin meningkat sampai > 200% sampai 300% dari data awal < 0,5 ml/kg per jam untuk 12 jam 3. Failure serum kreatinin meningkat > 300%, (serum kreatinin > 4mg/dl dengan peningkatan akut 0,5mg/dl, indikasi untuk renal replacement therapy <0,3 ml/kg per jam x 24 jam atau anuria x 12 jam Mehta RL. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007 Loss Persistent renal failure for >4 weeks ESRD Persistent renal failure for >3 months Murray PT, Palevsky PM. Nephrology Self Assesment Program , Vol 6, No 5, Sept 2007

Ischemia-reperfusion Complement activation (PMN, endothelial cells…) Sepsis Ischemic insult Nephrotoxic insult Ischemia-reperfusion Endotoxin release Complement activation + Pro-inflamatory mediators Anti-inflamatory mediators - Oxygen free radicals Arachidonic acid metabolities Cellular activation (PMN, endothelial cells…) Nitric oxide Proteases Heat shock proteins Chemokines Endothelins Platelet activating factor  Urinary KIM-1, NAG Acute kidney injury  Serum creatinine  Urine output  GFR Pathogenic mechanism of sepsis related acute kidney injury

Schrier et al, J Clin Invest 2004, 114:5-14 Effects of ischemia on renal tubules in the pathogenesis of ischemic AKI Schrier et al, J Clin Invest 2004, 114:5-14

Renal Protection Renal protection, there is damage before any symptom MAP> 65 mmHg CVP 8-12 mmHg (no ventilator) 12-15 mmHg (ventilator) Urine > 0,5ml/BW/hour SaO2 >70% Koloid ,albumin ?

Tight control of blood glucose Intensive insulin therapy  sepsis by 45% Blood glucose 80-110 mg/dl  morbidity and mortality Mechanism :  bacterial phagocytosis and antiapoptotic effect of insulin

Matur Nuwun