Evidence-Based MedicineA CKD patient with dyslipidemiaReported by R2 Instructed by Dr.

Our Patient40:150,:60,(BMI:26.7 Kg/m2) (GFR: 20.2 ml/min):135/85 mmHg,14,;

HemogramHb: 10 g/dl, Hct: 31%.UrinalysisProtein (+),RBC: 2/HPF,WBC:3/HPF. Our Patient

Our PatientBiochemistry: Uric acid: 6.0 mg/dlTriglyceride: 180 mg/dlTotal cholesterol: 225 mg/dl HDL: 40 mg/dl LDL: 140 mg/dlAC sugar: 100 mg/dlElectrolyte: Cr: 3.5 mg/dlNa: 138 mEq/L K: 4.0 mEq/LAlb: 4.0 g/dl Ca: 8.8 mg/dl P: 4.8 mg/dl

,,.??Our Patient

5As of EBMAsk : ask an answerable questionAcquire : track down the best evidenceAppraisal : validity, impact, applicabilityApply : to patients problemAudit : effectiveness

Ask an answerable questionPatient : CKD, PredialysisDyslipidemiaProteinuriaIntervention : Lipid lowering medicationComparison : Without lipid lowering medicationOutcome : All cause mortalityRenal outcome

Acquire track down the best evidenceGuidelinePrimary journal or databaseSecondary journal or database

Acquire track down the best evidenceGuidelinePrimary journal or databaseSecondary journal or database

Published Guideline

GuidelineCountryYearStage of CKDLipidTreatmentKDOQIUSA2003Stage 3,4,51.LDL 100-1292.LDL > 1303.TG > 200 & non-HDL > 1301.TLC2.TLC+low dose statin3.TLC+low dose statinCARIAustralia2005CKD PtTC > 166LDL > 100TG > 200Initiate statin if LDL > 100

Other GuidelinesEBPG (2002) : Dialysis patientBRA (2002) : Dialysis patientCSN (2005) : No guideline available

Ask an answerable questionPatient : CKD, PredialysisDyslipidemiaProteinuriaIntervention : StatinComparison : Without statinOutcome : All cause mortalityRenal outcome

Acquire track down the best evidenceGuidelinePrimary journal or databaseSecondary journal or database

Secondary Database

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. - Level 1aHMG CoA reductase inhibitors (statins) for kidney transplant recipients. - Level 1aHMG CoA reductase inhibitors (statins) for dialysis patients. - Level 1aEffect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease. - Level 2bA randomized trial of the effect of statin and fibrate therapy on arterial function in CKD. - Level 1bAcute effect of simvastatin on inflammation and oxidative stress in chronic kidney disease. - Level 2b

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. - Level 1aHMG CoA reductase inhibitors (statins) for kidney transplant recipients. - Level 1aHMG CoA reductase inhibitors (statins) for dialysis patients. - Level 1aEffect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease. - Level 2bA randomized trial of the effect of statin and fibrate therapy on arterial function in CKD. - Level 1bAcute effect of simvastatin on inflammation and oxidative stress in chronic kidney disease. - Level 2b

Acquire track down the best evidenceGuidelinePrimary journal or databaseSecondary journal or database

Primary Database

Appraisal Validity, Impact, aPplicability

CochraneStatin for people with CKD not requiring dialysisVBMJEffect of statins with CKDX

Potentially relevant articlesMedLine : 146EMBase : 367Cochrane : 70Total : 583Full text analysis : 62Included : 28(58 report)Complete : 26(52 report)Ongoing : 2(6 report)Studied excluded : 521Search overlap; Not RCT/review article; RCT, outcome not appropriate; Duration < 8wksStudied excluded : 4Non RCT/ review article : 3Duration < 8 wks : 1

Medline:Pre-Dialysis : 146Dialysis : 32Transplant : 68EMBase:Pre-Dialysis : 367Dialysis : 67Transplant : 118Cochrane:Pre-Dialysis : 38Dialysis : 14Transplant : 19Full text analysis : 68Pre-Dialysis : 146Dialysis : 32Transplant : 6850 trial, 54 comparison, 30144 PtPre-Dialysis : 26Dialysis : 11Transplant : 17Excluded : 801Search overlap : 104Not RCT/review : 693Duration < 8wks : 4Excluded : 16Duplicate reportsDuration < 8wksNon RCT

Text bookUnpublished trialNot english onlyExpert CochraneVVunclearVBMJVVVV

CochraneBMJInclusion1. RCT, quasi RCT2.Statin to Placebo/No/ Statin3.CKD - KDOQI a.Stage 3,4 b.Stage 1,2 + Proteinuria4.Baseline Cr > 1.4mg/dl5.Duration > 8wks1. RCT, quasi RCT2. Statin to Placebo/No/Statin3. CKD - KDOQI a. RRT b. Stage 3-5 c. Stage 1,2 + Proteinuria4. Baseline Cr > 1.4mg/dl5. Duration > 8wksExclusion1. ESRD2.Impaired liver function3.Elevated CPK4.Combination treatment1. Undefined renal impairment2. Impaired liver function3. Elevated CPK4. Combination treatmentOutcomeRhabdomyolysisDouble of serum Cr Allograft rejection

Allocation concealmentAdequate(A)Unclear(B)Inadequate(C)BlindingInvestigatorParticipantsassessorAnalysisIntention-to-treat analysisYesNoNo statedFollow up% of excluded

Forest Plot

Forest PlotCochran chi-square ( Cochran Q )Definite heterogeneity : P < 0.05Possible heterogeneity :No Statical significant, Q/df > 1 Heterogeneity unlikely :No Statical significant, Q/df < 1

Apply to patients problemAll Cause MortalityCVRenal outcomeGFR ProteinuriaCochraneBMJCochraneCochraneCochraneBMJBMJBMJ

Cochrane

Others

ConclusionStatins have benefit in improving mortalityStatins can improving proteinuria but cant ameliorate the progression of the GFR

Statin

For your attention

Q & AMeta-analysis versus Clinical trial ?quasi - Randomized control trial ?Heterogeneity of studies ?MESH term ?Level of evidence of guidelines ?

All Cause Mortality

All Cause Mortality

CV Mortality

CV Mortality

Renal - CrCl

Renal Proteinuria