Patient Background. Physical Exam. Updates in Diabetic Renal Disease and Prevention of Progression

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1 Updates in Diabetic Renal Disease and Prevention of Progression, F.A.C.O.I Clinical Associate Professor of Medicine Philadelphia College of Osteopathic Medicine Chair: Division of Nephrology Metropolitan Nephrology Associates Patient Background 60 y/o AA male evaluated for T2DM Diagnosed during routine examination in PCP s office. Random glucose 243 mg/dl. Symptoms of polyuria, polydipsia, polyphasia. PMH: HTN, hyperlipidemia, obesity PSH: appendectomy, cardiac stent Medications: Lisinopril 10 mg/daily, Zocor 20 mg/daily, metformin 500mg/daily, atenolol 50 mg/daily FamHx: Father; deceased, MI at 50. Mother and Sister; T2DM. SocHx: Smoker, 15 pack years. Alcohol, infrequently. Factory worker. Physical Exam BP: 134/84 HR: 84 Resp: 16 BMI: 34 Neck: supple, no goiter Heart: 84 per minute, S4+ Lungs: clear Extremities: reduced pinprick b/l, no peripheral edema Eyes: dilated exam background retinopathy changes May 4-7,

2 Labs at Diagnosis Hgb 13.8 Hct 36% Hgb A1C: 8.6% Na: 132 K: 3.8 Cl: 104 CO2: 26 BUN: 31 Cr: 2.2 egfr: 62 cc/min UA: trace protein, no RBC s Course of Therapy Initiated metformin 500mg/BID, added to his regimen of Lisinopril, Zocor and Atenolol. Hgb/A1C reduced 8.1% What are your multiple courses of therapy? May 4-7,

3 No. of dialysis patients (thousands) Updates in Diabetic Renal Disease and Prevention of Progression Diabetes: The Most Common Cause of ESRD Primary Diagnosis for Patients Who Start Dialysis Other Glomerulonephritis Diabetes 50.1% 10% 13% Hypertension 27% No. of patients Projection 95% CI , , , r 2 =99.8% United States Renal Data System. Annual data report May 4-7,

4 Diabetic Nephropathy A microvascular complication of diabetes marked by albuminuria and a deteriorating course from normal renal function to ESRD. Type I DM 20-30% of patients develop microalbuminuria, less than half progress to overt nephropathy Incidence of ESRD is 45% at 30 years. Type II DM Up to 63% of patients develop DN, depending on ethnicity Leading Cause of ESRD by overall populations Expansion of mesangial matrix with diffuse and nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) Thickening of glomerular and tubular BM Arteriosclerosis and hyalinosis of afferent and efferent arterioles Tubulointerstitial fibrosis Pathology Natural History May 4-7,

5 Chronic Renal Insufficiency Cohort Study (CRIC) Over 20 million Americans have CKD Progression to ESRD and cardiovascular disease consequences are well recognized as major causes of morbidity and mortality CRIC is a major epidemiologic study of a CKD cohort CRIC Multicenter, observational cohort study that enrolled nearly 4000 participants from at seven clinical centers in the US Mean egfr was 43 ml/min at study entry Ethnically diverse Excluded PKD, bone marrow or solid organ transplant, and NYHA class III/IV Heart Failure More than 50 articles published since existence CVD in CKD CRIC Mineral and Bone disorders CKD in Hispanic Population Cognitive impairment Biomarkers Vascular pathology Future focus on genomic associations, new biomarkers, and expanding understanding of morbidity of kidney disease beyond ESRD and CVD May 4-7,

6 CKD Screening CKD generally asymptomatic until late stages and awareness is low among patients. Majority due to DM and HTN Screening and monitoring by PCP could lead to earlier intervention and improvement in clinical outcomes USPSTF CKD Screening Insufficient evidence to support routine screening in asymptomatic adults (those without DM, HTN, or CVD) No studies assessed harm of screening for CKD ACP No evidence to support screening for CKD stages 1-3 in adults with no risk factors Inconclusive evidence regarding periodic laboratory monitoring in patients with CKD 1-3 Screening the general population has not been shown to be cost-effective NKF CKD Screening Assess risk of CKD in all patients and those perceived to be high risk BP Serum creatinine levels Urinary albumin/creatinine ratios (ACR) Urine for erythrocytes and leukocytes ADA Annual screening of all patients with DM with urinary ACR and serum creatinine measurements JNC HTN patients should be screened with UA and creatinine measurement Urinary albumin measurement optional before starting HTN therapy May 4-7,

7 Walking the dog Global Projections for the Diabetes Epidemic: World 2007=246 M 2025=380 M 54% NA 28.3 M 40.5 M 43.0% SA/CA 16.2 M 32.7 M 102% EUR 53.2 M 64.1 M 20% AFR 10.4 M 18.7 M 80% EM/ME 24.5 M 44.5 M 82% SEA 46.5 M 80.3 M 73% WP 67.0 M 99.4 M 48% M=million; AFR=Africa; EM/ME=Eastern Mediterranean and Middle East; EUR=Europe; NA=North America; SA/CA=South and Central America; SEA=South-East Asia; WP=Western Pacific. International Diabetes Federation. Diabetes Atlas. 3rd ed. Available at: May 4-7,

8 CKD Diagnosis and Classification abnormalities of kidney structure or function present for greater than 3 months with implications for health Markers of damage Albuminuria (ACR > 30mg/g) Sediment abnormalities Electrolyte abnormalities due to tubular disorders Histologic abnormalities Structural abnormalities found on imaging History of Kidney Transplantation Decreased GFR GFR < 60 ml/min/1.73m CKD Diagnosis and Classification Newly published Kidney Disease Improving Global Outcomes (KDIGO) diagnosis and classification of CKD Our Example patient egfr stage 2 with serum creatinine of noted 2.2 mg/dl Cause CKD Classification based on presence or absence of systemic disease (i.e. SLE, DM) Anatomic location (glomerular, tubulointerstitial, vascular, cystic, and congenital diseases) egfr Prior KDOQI stages are maintained now adding 3a (45-59 ml/min per 1.73 m) and 3b (30-44 ml/min per 1.73 m) Albuminuria A1 <30 mg/g A mg/g A3 > 300mg/g May 4-7,

9 CKD Classification Low Risk (Green) Moderately Increased Risk (Yellow) High Risk (Orange) Very High Risk (Red) Prognosis of CKD KDIGO Clinical Practice Guidelines Kidney Int Suppl 3: 1-150, 2013 A1 A2 A3 Normal to mildly increased Moderately increased Severely increased <30 mg/g mg/g >300 mg/g G1 G2 G3a G3b G4 G5 Normal or High Mildly decreased >90 Green Yellow Orange Green Yellow Orange Mild to moderately decreased Yellow Orange RED Moderately to severely decreased Orange RED RED Severely Decreased Kidney Failure RED RED RED <15 RED RED RED May 4-7,

10 Risk Factors for CKD Progression DM with A1C Diet Obesity Hypertension Cardiovascular Abnormalities FGF-23 and Phosphate Acute Kidney Injury Race and Socioeconomic Status Nephrolithiasis Other considerations Solitary cysts or solid lesions Isolated microscopic hematuria Erythropoiesis Stimulating Agents May 4-7,

11 Risk Factors for CKD Progression Hypertension Goal BP for established CKD < 130/80 Observation and post hoc analysis data Systematic review of 2300 CKD patients, included MDRD study, REIN-2 trial, and AASK trial BP target < /75-80 compared to target of <140/90 showed no benefit Upadhyay, et al. Systematic Review: BP target in CKD and proteinuria as an affect modifier. Ann Int Med 154: , 2011 May 4-7,

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14 Systolic Blood Pressure Intervention Trial (SPRINT) Compare SBP <120 vs. 140mmHg in delaying CKD progression in HTN patients over age 50 Risk Factors for CKD Progression HTN Ambulatory Blood Pressure Monitoring (ABPM) Possibly more useful than clinic BP measurements 436 Italian CKD patients mean egfr 43 ml/min Elevated BP, non dippers, reverse dippers had increase risk for composite endpoints of death or ESRD Prognostic role of ABPM in patients with nondialysis CKD. Arch Int Med 171: , Risk Factors for CKD Progression HTN Proteinuric CKD (>300 mg/d) RAAS inhibition superior to other antihypertensive agents Systematic review 85 RCTs (nearly 22,000 patients) showed no benefit of combination of ACEI and ARB No benefit in preventing ESRD, progression of proteinuria (micro macro) Maione A, et al. ACEI ARB and combined therapy in patients with micro- and macroalbuminuria and other CV risk factors: systematic review of RCTs. Nephrol Dial Trans 26: May 4-7,

15 Goals National Guidelines recommend an HbA 1 C less than 6.5%-7% to prevent vascular complications Optimal Glycemic Targets for Patients with DM and CKD have not been fully established since prior landmark trials excluded those Stage 3? Importance of tight control in ESRD population Microalbuminuria < 30mcg/mg Diagnosis Early vs. Late Referral Multidisciplinary Care CKD Care Conservative Care vs. Renal Replacement Therapy in Elderly May 4-7,

16 CKD Care Early referral associated with better outcomes in CKD patients No RCTs (data from large systematic review and meta analysis) Early referral group Lower overall mortality-difference persisted for 5 years Shorter hospitalization Higher rates of initiation of PD Decreased use of temporary catheters for HD (3 fold higher rates of permanent access) KDIGO Work Group 2012 Clinical Practice Guidelines Kidney Int Suppl 3: 1-150, CKD Care Renal Replacement Therapy vs. Conservative Care Elderly patients with multiple co morbidities have poor prognosis on RRT Multidisciplinary approach for decisions to initiate RRT in those over 75 years old with multiple co morbidities Recent data suggests conservative care should strongly be considered Educate regarding minimal survival differences with RRT in certain patient populations May 4-7,