The Effect of Chronic Kidney Disease CKD on

The Effect of Chronic Kidney Disease (CKD) on the Cardio. Vascular System Lesley C. Dinwiddie MSN, RN, FNP, CNN February 24 th, 2011

Thanks to the Cardinal Chapter for giving me the opportunity to increase awareness about the underdiagnosed and under-treated public health threat that is Chronic Kidney Disease (CKD) plus Cardio. Vascular Disease!

Disclosures ICEER – Institute for Clinical Excellence, Education, and Research – nurse organized, nonprofit group promoting education about CKD Acknowledgement of Patricia Mc. Carley, RN, MSN, NP, co-creator of this presentation. Consultant for Teleflex Medical, Hemosphere, Surg. Pro, and Genentech – no conflicts of interest to disclose for this presentation.

Overall Objective Explain the scenario of chronic kidney disease (CKD) and the effect of cardiovascular disease (CVD) in the patient with chronic kidney disease.

What is the leading cause of Mortality in our CKD patient population?

Focused Objectives • Describe the link/the synergy between patients with CKD and CVD. • Teach how to recognize patients at risk for CKD, review screening for CKD and assessment of e. GFR. • Discuss factors related to progression and slowing of progression of CKD and CVD. • Identify complications of CKD and strategies to improve outcomes.

How you see this all depends on your perspective!

NKF-KDOQI Staging Classification of CKD Stage Description GFR 1 Chronic kidney damage with normal GFR >90– 120 m. L/min/1. 73 m 2 2 Mild GFR 60– 89 m. L/min/1. 73 m 2 3 Moderate GFR 30– 59 m. L/min/1. 73 m 2 4 5 15– 29 m. L/min/1. 73 m 2 Severe GFR <15 m. L/min/1. 73 m 2 or Dialysis Kidney failure e. GFR (m. L/min/1. 73 m 2) * May be normal for age National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

CASE 1 • Mary is a 70 year old female with history of CKD, type 2 diabetes mellitus, twenty year history of hypertension, CHF, hyperlipidemia, and CAD with recent history of MI and angioplasty. • Patient presents to the office • Chief complaint: “shortness of breath”

CASE 1 – cc: “shortness of breath” Assessment in the office: – BP 118/50 P-112 R-24 T-97. 4 – Alert & oriented x 3 – No neck vein distention or apparent edema – Lungs – crackles in bases – RRR, SEM III/VI – No focal neurological deficits – Meds: lisinopril, furosemide, clopidogrel, aspirin, isosorbide, carvedilol, glipizide, and rosiglitazone, atorvastatin

CASE 1 – cc: “shortness of breath” What are your differential diagnoses? Does the fact that this patient has CKD affect your choice of diagnoses?

CASE 1 – cc: “shortness of breath” • CARDIOVASCULAR DISEASE – MI – Arrhythmia • CHF • Anemia • OTHER

CASE 1 – cc: “shortness of breath” Cardiovascular Disease ? ? - MI - Arrhythmia Patient with recent MI and angioplasty and…… CKD.

Cardiovascular Outcomes Worsen with CKD Progression VALLIANT TRIAL 3 -Yr Follow-Up by e. GFR Levels in Post-MI Patients Estimated Event Rate (%) P<0. 001 N = 14, 527 e. GFR (m. L/min/1. 73 m 2) 75 60 -74 45 -59 <45 CHF = congestive heart failure; CV = cardiovascular. Anavekar et al. N Engl J Med. 2004; 351: 1285 -1295.

CASE 1 – cc: “shortness of breath” • MI symptoms in patients with CKD: • 4, 482 patients seeking care for AMI - community wide study involving 11 medical centers in Worchester, MA during 4 study years (1997, 1999, 2001, 2003) Patients with CKD were less likely to report chest pain, arm pain, shoulder pain, while being more likely to report shortness of breath Sosnov, J et al. AJKD. 2006. 47(3); 378 -384.

Prevalence of IHD in the General Population and CKD CV Disease General Population CKD Ischemic Heart Disease 8 - 13% 15 % (transplant) 40% (CKD stage 5) Sarnak et al. Circulation. 2003. 108; 2154. IHD admissions are 2 -2. 5 times higher in the CKD population USRDS, 2004 Annual Report MI remains in our diagnoses

CVD and CKD – Morbidity • Cardiac arrhythmia admission rates are 2 times as common in CKD population USRDS, 2004 Annual Report • 269 patients with stable CHF - longer PQ and QRS intervals were inversely related to e. GFR (cardiac-event free survival rate 51% in pts with CKD vs 81% in those without CKD) Bruch, C et al. Int J of Cardiol. 2007. 118(3): 375 -380.

CASE 1 – cc: “shortness of breath” Cardiovascular Disease ? ? MI or arrhythmia • Shortness of breath – YES Exam reveals - RRR • MI – possible – must continue to consider in the differential and evaluate further

VASCULAR SYSTEM WABeresford Elastic/conducting arteries Large veins Heart Veins Lym Node pha ti cs Muscular/distributing arteries Venules Postcapillary venules Arterioles Capillaries

CASE 1 – cc: “shortness of breath” Congestive Heart Failure? Cardio-Renal Syndrome* – “ A syndrome in which the heart OR kidney fails to compensate for the functional impairment of the respective organ, resulting in a vicious cycle that will ultimately result in decomposition of the entire circulatory system. ” Boerrigter, G. Current Heart Failure Rep. 2004: 1(3); 113 -120. CRS “occurs through multiple mechanisms that demonstrate the complex interaction between the two organs” Elhassan and Schrier 2010 ASN Kidney News

CASE 1 – cc: “shortness of breath” Congestive Heart Failure? “A pathologic condition where combined cardiac and renal dysfunction amplifies progression of the individual organ to astounding morbidity and mortality. ” Bongartzr, Eur Heart J, 2995 “A Fatal Dance of Two Noble Organs” Burl, D, UCDavis, 2008.

The Cardiorenal Syndrome: Which Came First— the Chicken or the Egg? By Elwaleed Elhassan, MD, and Robert Schrier, MD http: //www. asn-online. org/publications/kidneynews/archives/2010/sep/KN_sep 2010. pdf

Classification and Pathophysiology of CRS • Acute cardiorenal syndrome (type 1) - Acute worsening of heart function leading to kidney injury and/or dysfunction • Chronic cardiorenal syndrome (type 2) -Chronic abnormalities in heart function leading to kidney injury and/or dysfunction • Acute renocardiac syndrome (type 3) -Acute worsening of kidney function leading to heart injury and/or dysfunction http: //www. asn-online. org/publications/kidneynews/archives/2010/sep/KN_sep 2010. pdf

Classification and Pathophysiology of CRS • Chronic renocardiac syndrome (type 4) - Chronic kidney disease leading to heart injury, disease, and/or dysfunction • Secondary cardiorenal syndrome (type 5) - Systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney http: //www. asn-online. org/publications/kidneynews/archives/2010/sep/KN_sep 2010. pdf

High Prevalence of CKD in Patients Hospitalized with Acute Decompensated HF Cardiorenal Syndrome ADHERE N = 118, 465 Percent of Patients Acute Decompensation Heart Failure National Registry e. GFR <90 60 -89 30 -59 15 -29 < 15 ml/min/1. 73 m 2 Heywood, JT et al. J Card Fail. 2007. Aug 13(6); 422 -230.

Prevalence of LVH in the General Population and CKD Congestive Heart Failure? Patient has long history of hypertension – LVH often the intermediate step resulting in impaired LV filling, increased ventricular stiffness, and CHF CV Disease LVH (ECHO) General Population 8 - 13% CKD 25 – 50% (stage 2 – 4) 75 - 85% (stage 5) Sarnak, M et al. Circulation. 2003: 108(17) 2154 -2169

CASE 1 – cc: “shortness of breath” Congestive Heart Failure? • Patients with CKD have volume 10 - 30% increase in volume in absence of edema Palmer, BF, N Eng J of Med, 2002: 347; 1256 -1261 • Common LIFE THREATENING DX!!! (CHF admissions 5 x higher in CKD) USRDS, 2004 Annual Report

CASE 1 – cc: “shortness of breath” Congestive Heart Failure? • Rosiglitazone may aggravate edema and CHF O’Connor AS, Schelling JR. Am J Kid Dis. 2005. 46(4): 766 -773 • Volume overload not clearly evident on exam • Lungs with evidence of possible fluid so CHF still in differential

CASE 1 – cc: “shortness of breath” Anemia secondary to GI bleed or CKD?

Anemia Signs and Symptoms Central Nervous System • Fatigue • Depression • Impaired cognitive function Gastrointestinal System • Anorexia • Nausea Vascular system • Low skin temperature • Pallor of skin, mucous membranes and conjunctivae Immune System • Impaired T-cell an macrophage function Cardiorespiratory system • Exertional dyspnea • Tachycardia, palpitations • Cardiac enlargement, hypertrophy • Increased pulse pressure, systolic ejection murmur • Risk of cardiac failure Genital Tract • Menstrual problems • Loss of libido Ludwid H, et al Semin Oncol 1998, 25(Suppl 7); 2 -6.

Pathophysiologic Consequences of Anemia in CKD: Effects on the CV System Reduced Hemoglobin Reduced O 2 Delivery Increased Cardiac Workout Dilated Cardiomyopathy - LVH Ischemic Heart Disease Congestive Heart Failure Angina Pectoris Myocardial Infarction Adapted from Metivier et al Nephrol, Dial, Transpl. 2000; 15 Suppl 3: 14 -18.

Correction of Anemia in Patients with CKD and CHF N = 84 Before After P Value Hgb (g/dl) 10. 4 13. 1 < 0. 05 NYHA 3. 89 2. 53 < 0. 05 VAS fatigue/ SOB index 8. 6 2. 8 < 0. 05 No. of days Hospitalizations 3. 38 0. 16 < 0. 05 . Silverberg, DS. Perit Dial Int. 200 l. ; 21 Suppl 3 ; S 236 -240.

CASE 1 – cc: “shortness of breath” Anemia secondary to GI Bleed or CKD? • Clopidogrel and aspirin – as high as 30 % incidence of bleeding - increased risk in elderly, women, and patients with reduced kidney function uptodate. com Stool for occult blood negative

ANEMIA Erythropoietin deficiency is the most common cause of anemia in CKD. Erythroid marrow X Iron Erythropoietin RE cells RE = reticuloendothelial Red blood cells O 2 delivery Adapted from: Harrison, F In Principles of Internal Medicine. 1998: 334.

Prevalence of Anemia (%) Anemia Starts Early in CKD and Worsens with Disease Progression 100% N = 1, 658† 10% 80% 33%-36% 30%-32. 9% < 30% 15% 60% 15% 8% 40% 20% 17% 9% 5% 14% 8% 62% 67. 5% 43% 20% 0% <2 2 -2. 9 3 -3. 9 >4 Serum Creatinine Level (mg/d. L) *Start of Dialysis (n=131, 484) †Kausz AT, et al. Dis Manage Health Outcomes. 2002; 10(8): 505 -513. *Obrador GT, et al. J Am Soc Nephrol. 1999; 10: 1793 -1800.

Anemia and CHF

CASE 1 – cc: “shortness of breath” FINAL DIAGNOSES Labs: Troponin < 0. 03 µg/L Hgb 8. 2 g/dl Chest X-ray - enlarged heart, pulmonary edema • Anemia of CKD • CHF secondary to anemia

CKD in CVD “…proper management of CVD is different and more complex in patients with CKD” Brosius, FC et al. Circulation. 2006; .

CVD Events, Hospitalization and Death are Common in CKD Age-Standardized Rate of Cardiovascular Events (per 100 person-yr) END Points: CV Events, Hospitalization Death Estimated GFR (m. L/min/1. 73 m 2) Go, et al. , 2004

Cardiovascular Disease is Prevalent in CKD % Male Patients Framingham Heart Study Normal SCr (n=2591) Elevated SCr (1. 5– 3. 0 mg/d. L n=246) CVD CHD CHF LVH Culleton. Kidney Int. 1999; 56: 2214.

Percent of Patients with CKD Chronic Kidney Disease is Prevalent in CVD 60 45% 40 33% N= 23% 20 N= 14527 68000 CAD = Coronary artery disease ACS = Acute Coronary Syndrome CHF = Chronic heart failure 431 0 ACS CAD GFR < 60 CRCL < 60 VALLIANT Heart and 60 Soul CRCL< < 60 CHF GFR < 60 DIG. 60 In HF Ix, JH et al, JASN, 2003 Anavekar, NS et al, NEJM, 2004 Shilpak, et al, JASN, 2004

CKD and CVD • 37, 173 individuals screened 2000 -2003 in Kidney Early Evaluation Program (KEEP) • Ave age 52. 9, h/o DM, HTN, or CKD on survey • Followed (max 47. 7 months) “Anemia, (decreased) e. GFR, and microalbuminuria were independently associated with CVD, and when all 3 were present, CVD was common and survival was reduced. ” Mc. Cullough, PA et al. Arch. Of Int Med. 2007. .

CVD and CKD • 13, 826 individuals screened between 1987 – 1990 (Atherosclerosis Risk in Community Study and the Cardiovascular Health Study) • Ave age 57. 6 • Followed at 3 year intervals (average of 9. 3 years) • BP and Cr. were measured to track decline in kidney function independently “Cardiovascular disease is associated with kidney function decline and with the development of kidney disease. ” Elsayed, E et al. 2007. Arch. Of Int Med. 2007. .

Traditional Risk Factors for Cardiac Disease Traditional • • • Hypertension Diabetes Age Smoking Dyslipidemia Obesity Inactivity Family History LVH Sarnak. Am J Kidney Dis. 2000; 35(suppl 1): S 117 Block. Am J Kidney Dis. 1998; 131: 607 Kitiyakara. Curr Opin Nephrol Hypertens. 2000; 9: 477

Risk Factors for Cardiac Disease in Patient with CKD Traditional • • • Hypertension Diabetes Age Smoking Dyslipidemia Obesity Inactivity Family History LVH Non-Traditional (Kidney) • • • GFR < 60 ml/min Proteinuria/hypoalbumin Anemia Inflammation ( CRP) Oxidative stress Hyperhomocysteinemia Disorders of mineral metabolism Fluid overload Uremic toxins Electrolyte imbalance Malnutrition Thrombogenic factors Sarnak. Am J Kidney Dis. 2000; 35(suppl 1): S 117 Block. Am J Kidney Dis. 1998; 131: 607 Kitiyakara. Curr Opin Nephrol Hypertens. 2000; 9: 477

Microalbuminuria: Independent Predictor of Combined End Points CV Death, MI, and Stroke: The HOPE Trial Variable Microalbuminuria Hazard Ratio 1. 59 Cr >1. 4 mg/dl 1. 40 CAD 1. 51 PVD 1. 49 Diabetes Mellitus 1. 42 Male 1. 20 Age 1. 03 Waist-hip Ratio 1. 13 Mann et al, Ann of Intern Med, 2003

Proteinuria is Associated with Adverse CV Outcomes – LIFE study Adjusted Hazard Ratio N= 7143 <2. 2 mg/g >83. 3 mg/g Watchtell et al, Ann of Intern Med, 2003

Albuminuria Prevend Study • In a population-based study (subset n = 9000) the presence of albuminuria enhanced the predictive value of ST-T segment changes in a resting ECG for all-cause and CVD mortality. • The impact of the presence of microalbuminuria on all-cause mortality was greater than other more traditional cardiac risk factors including hypertension, hypercholesterolemia, cigarette smoking, obesity, and diabetes. Diercks et al, JACC, 2002

Microalbuminuria – CV Risk Factor? • Despite the fact that the Framingham study established in 1984 that proteinuria is an important risk marker of CV mortality in the general population, albuminuria has never been added to the list of important CV risk factors. Kannel, A Heart J, 108, 1984 • Confirmed by Arnlov et al, persons with normal BP, without DM and normal GFR – microalbuminuria is a strong predictor of CV outcome. Arnlov et al, Circulation, 2005

Albuminuria — So WHAT? LIFE STUDY Reducing Proteinuria independent of BP decreased CVD risk (endpoints CV mortality, stroke, MI) Ibsen, et al, Hypertension 45, 2005 PREVEND-II Patients with albuminuria treated with fosinopril decreased CV events compared to patients on pravastatin Asselbergs et al Circulation 110, 2004 RENAAL Patients treated with ARB showed significant decreased risk of CV endpoints with any decrease in albuminuria. de. Zeeuw, et al , KI, 2004.

Chronic Kidney Disease is a Risk Factor for Cardiovascular Disease Sarnak et al. Circulation. 2003; 108: 2154 -2169.

CASE 2 Case: – Diane, 63 -year-old , 66 -kg body weight – Hospitalized March & April, Hct 16%, GI work-up negative, Transfused – May, Adm. with weakness Hct 27. 5%, K+ 6. 9 mg/dl, Creatinine 1. 3 mg/dl – Nephrology consult

CASE 2 Case: – What if any level of kidney disease? None Mild (GFR 60 -90) Moderate (GFR 30 - 60) Severe (GFR 15 -30) Kidney failure (GFR <15)

CASE 2 Use Prediction Equation MDRD formula (simplified) Case: – 63 -year-old, non-African American, female SCr = 1. 3 mg/d. L • Formula result: – e. GFR= 44 m. L/min/1. 73 m 2 Stage 3 Moderate Kidney Disease

Estimate GFR from Prediction Equations • Cockcroft-Gault equation (www. clinicalculator. com/english/nephrology/cockcroft/cc. htm) Cr. Cl (ml/min) = [(140 – age) x IBW (kg)]/(72 x SCr) x (. 85 if female) • MDRD equation (www. kidney. org/professionals/kdoqi/gfr_calculator. cfm) GFR (ml/min/1. 73 m 2 ) = 186 x (SCr)-1. 154 x (age)-0. 203 x x (0. 742 if female) x (1. 210) if African-American Cockcroft, DW and Gault, MH. . Nephron. 1976; 16: 31 -41. . . Levey et al, J AM Soc Nephrol. 2000; 11: 155 A.

Serum Creatinine Is Inaccurate in Predicting Kidney Function SCr e. GFR CKD Stage Age Gender Race (mg/d. L) (m. L/min/1. 73 m 2 ) 20 M B 1. 3 91 1* 20 M W 1. 3 75 2* 55 M W 1. 3 61 2* 20 F W 1. 3 56 3 40 F B 1. 3 48 3 F W 1. 3 44 3 63 (Case 2) B = black; W = all ethnic groups other than black; *With evidence of kidney damage. Duncan, L et al. Nephrol Dial Transplant. 2001; 16(5): 1042 -1046 National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. .

What is Chronic Kidney Disease? Kidney damage (structural or functional*) or GFR < 60 ml/min/1. 73 m 2 for greater than 3 months * structural – i. e cysts, obstruction functional – hematuria, proteinuria National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. .

NKF-KDOQI Staging Classification of CKD Stage Description GFR 1 Chronic kidney damage with normal GFR >90– 120 m. L/min/1. 73 m 2 2 Mild GFR 60– 89 m. L/min/1. 73 m 2 3 Moderate GFR 30– 59 m. L/min/1. 73 m 2 4 5 15– 29 m. L/min/1. 73 m 2 Severe GFR <15 m. L/min/1. 73 m 2 or dialysis Kidney failure e. GFR (m. L/min/1. 73 m 2) * May be normal for age National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

CKD by Diagnoses (Simplified) • Diabetic kidney disease • Non-diabetic kidney diseases Vascular diseases (Hypertension) Glomerular diseases Tubointerstitial diseases Cystic diseases • Diseases in Transplant … Always Pursue Etiology National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Eliminate Reversible Causes Acute Renal Failure (ARF) • May be superimposed on CKD • Evaluate and correct potentially reversible causes of a kidney injury: - Decreased renal perfusion – hypovolemia, hypotension, or drug induced (ACEi, ARB) - Nephrotoxic agents - Acute interstitial nephritis - Urinary tract obstruction - Heart failure, liver disease - Other Schieppati, A et al. In: Primer on Kidney Disease. 2005: p. 444.

CKD IS A PROGRESSIVE DISEASE Timely evaluation and treatment may improve outcomes Stage e. GFR 1 2 Kidney Damage Mild Kidney Function 120 90 3 Moderate Kidney Function 60 4 Severe Kidney Function 30 5 Kidney Failure 15

The Chronic Kidney Disease Epidemic CKD Affects 12% of the US Population CKD Stage e. GFR (m. L/min/1. 73 m 2) ≥ 90 60 -89 30 -59 15 -29 <15 e. GFR = estimated glomerular filtration rate. *2003. Coresh et al. J Am Soc Nephrol. 2005; 16: 180 -188; United States Renal Data System (USRDS) 2005 Annual Data Report. Available at: www. usrds. org; USRDS 2005 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U. S. government. Available at: www. usrds. org. Accessed December 6, 2005.

CKD Patients Are More Likely to Die Than Progress to ESRD Percentage Who Remained Event-Free vs. Death vs. Developed ESRD During 5 -Year Follow-Up 100% % of Patients 15% 16% 7% 10% 80% 28% 60% 75% 63% 64% 20% 40% 1% 20% 0% 10% Stage I 20% 24% Stage III Disenrolled Event-free RRT Died N= 27, 000 Totals Stage 2 -4 46% 3. 1% RRT 24. 9 % Die Stage IV Keith D, et al. J Am Soc Nephrol. 2002; 13: 620 A.

Screening and Detection of CKD Screening is the beginning of a complex management process for CKD. • WHO to screen? – identify risk factors • HOW to screen? - History - Measure BP and glucose - Urinalysis – hematuria, proteinuria - Measure urinary albumin or protein excretion - e. GFR - use prediction equation • WHEN to screen? National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Identify Risk Factors: Individual Predictors of New-Onset Kidney Disease Developing CKD Odds Ratio Risk of WHO to screen? Community Based Population N = 2585 Baseline Exam 1978 -82; FU- 18 yrs. Fox et al JAMA, 2004; 291(7): 844 -50.

Risk Factors for CKD - Early Detection • • Diabetes WHO to screen? Hypertension • Aging (>60 years old)* • Racial-ethnic background (African American, Native American, Asian American, Pacific Islander, Latin American, Hispanic) • Family history of kidney disease National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. *Coresh, J et al, Am J Kidney Dis, 2003; 41(1): 1 -12. .

Risk Factors for CKD - Early Detection WHO to screen? • Tobacco Use • Low Income/Education/ Poor access to healthcare • UTI, Urinary stones, lower UT obstruction • Autoimmune disease • ARF – recovery • Neoplasia • Anemia • Insulin resistance • • • Reduced kidney mass High-protein diet Hyperlipidemia Atherosclerosis Obesity Nephrotoxin exposure – NSAIDS – Contrast dye • Hazardous chemical or environmental exposure National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. Fox et al JAMA, 2004; 291(7): 844 -50. Mohanram, A et al. Kidney Int. 2004; 66: 1131 -1138. Kurella, M et al. J Am Soc Nephrol. 2005; 16: 2134 -2140.

WHO to screen? “…all patients with CVD should be screened for CKD” Brosius, FC et al. Circulation. 2006; .

Screening and Detection of CKD HOW to screen? • History – clues (i. e. recent infections, symptoms during urination, skin rash, arthritis, heart failure, family history, medications) • Blood pressure –high blood pressure is both a risk factor and an early complication, often first sign of kidney damage • Abnormal serum glucose – early factor • Urinalysis – hematuria or proteinuria National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Measure Urinary Albumin or Protein Excretion HOW to screen? • Untimed, “spot” urine for albumin- or protein-tocreatinine ratio (first-morning-void preferred) • 24 - hour urine collection for microalbumin, or protein acceptable (note: measure creatinine also to determine if collection is accurate) • Advantages of random urine vs. 24 hour urine: lower cost and ease of collections National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Screening for Microalbuminuria, Albuminuria or Proteinuria HOW to screen? • Microalbuminuria: 30 - 300 mg of albumin/g of creatinine (. 03 -. 30) • Macroalbuminuria: > 300 mg albumin/g of creatinine (. 30) • Proteinuria: > 200 mg protein/g creatinine (. 20) National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. National Kidney Foundation. Am J Kidney Dis. 2007; 49(suppl 2): S 1 -S 179.

Glomerular Filtration Rate (GFR) HOW to screen? • GFR – Best overall index of kidney function in health and disease • Normal GFR varies according to age, sex, and body size • Normal – 120 to 130 m. L/min/1. 73 m 2 in young adults, declines with age • Estimate GFR from prediction equations National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. .

Screening and Detection of CKD WHEN to screen? • Measure annually for microalbuminuria in patients at risk for CKD (including pts with CVD) • Measure for microalbuminuria in patients with DM - at diagnosis for type 2 diabetes - after 5 years for type 1 diabetes • Measure serum creatinine annually in patients at risk for CKD and calculate e. GFR (automatic on many labs and required by law in some states) National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266. www. cdc. gov/MMWR? PDF? wk/mm 5610. pdf.

What Would Your Strategy Be to Slow Progression of CKD? Stage e. GFR 1 2 Kidney Damage Mild Kidney Function 120 90 3 Moderate Kidney Function 60 4 Severe Kidney Function 30 5 Kidney Failure 15

Targets for Treatment - CKD Early Detection of CKD Delay progression Prevent complications BP Control Anemia Treat Proteinuria Malnutrition DM/BS control Avoid Nephrotoxins Treat Dyslipidemia Bone Disease Acidosis Treat comorbidities Prepare for RRT Cardiovascular disease Educate patient Hypertension Select RRT modality Diabetes Determine access and initiate dialysis in a timely fashion Lifestyle Adapted from Pereira, B. . Kid Int. 2000; 57: 351 -365.

Delay Progression: Targets: Hypertension and Proteinuria • Hypertension is an independent variable that predicts long-term decline in kidney function • Proteinuria is also an independent variable that predicts long-term decline in kidney function • Both are targets to reduce CKD progression National Kidney Foundation. Am J Kidney Dis. 2004; 43(suppl 1): S 1 -S 290. .

Lower Mean BP Results in Slower Rates of Decline in GFR (Diabetics and Non-Diabetics) MAP (mm. Hg) GFR (m. L/min/year) 95 0 98 101 104 107 -2 110 113 116 119 r = 0. 69; P < 0. 05 -4 -6 Untreated HTN -8 -10 -12 -14 130/85 140/90 Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996. Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996. Klahr S, et al. N Eng J. Med 1994. Bakris GL. Hypertension. 1997. Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997. Lebovitz H, et al. Kidney Int. 1994. Slide source: hypertensiononline. org Bakris GL, et al. Am J Kidney Dis. 2000; 36(3): 646 -661.

Delay Progression: Targets: Hypertension and Proteinuria GOAL: With Proteinuria 130/80 mm Hg or lower (NKF)) Without Proteinuria 130/80 mm Hg DM/CKD (JNC VII, NKF)) GOAL: Proteinuria < 500 – 1000 mg/day Urine protein-to-creatinine ratio <. 5 – 1. 0 National Kidney Foundation. Am J Kidney Dis. 2004; 43(suppl 1): S 1 -S 290. Chobanian et al, , JAMA, 2003; 289: 2560 -2572.

Delay Progression: Targets: Hypertension and Proteinuria Lifestyle modifications Weight Loss 10 kg loss 5 -20 mm Hg DASH Diet rich in fruit vegetables 8 – 14 mm Hg Low-sodium Diet Restrict sodium intake 2 – 8 mm Hg Physical Activity 30 minutes/day most days 4 – 9 mm Hg Moderate alcohol 2 drinks/day men 2 – 4 mm. Hg consumption 1 drink/day/women Chobanian et al, JAMA. 2003; 289: 2560 -2572.

Renoprotection with ARB Type 2 Diabetes: RENAAL † ** 28% * 25% 16% * P = 0. 02 † P =0. 006 **P =0. 002 Brenner. N et al. N Engl J Med. 2001; 345: 861.

CALM: Reductions from Baseline in Urinary Albumin: Creatinine Ratio (Week 24) 0 – 10 Change in Urinary Albumin: Creatinine Ratio, % – 20 – 30 * – 40 † – 50 † – 60 Candesartan 16 mg Lisinopril 20 mg Both *P = 0. 05 from baseline. †P < 0. 001 from baseline. Mogensen CE et al. BMJ. 2000; 321: 1440– 1444.

Slow Progression: Target: Hypertension and Proteinuria Increased risk of side-effects in patients with CKD • At start up or change in ACE inhibitor/ARB dose, check creatinine and potassium within 2 weeks • If e. GFR decreases > 30% over 4 months then decrease or discontinue ACEi/ARB. Consider renal artery stenosis (RAS) • IF K+ , dietary counseling, diuretics, HCO 3 replacement, avoid herbals National Kidney Foundation. Am J Kidney Dis. 2004; 43: S 1 -S 290

Slow Progression: Target: Hypertension and Proteinuria Increased risk of side-effects in patients with CKD • Avoid CCBs - Dihydropyridine, effective in lowering BP but can cause increased proteinuria • Extreme caution with Aldactone and K+ sparing meds • NSAIDS – block prostaglandin metabolism, +) ( renin - aldosterone - K aldosterone - sodium retention, exacerbate volume overload, and nephrotoxicity National Kidney Foundation. Am J Kidney Dis. 2004; 43: S 1 -S 290

Slow Progression Target: Diabetic Kidney Disease Complication RR (95% CI) Risk p Value Reduction Cardiovascular end point 0. 47 (0. 24 -0. 73) 53% . 008 Nephropathy 0. 38 (0. 17 -0. 87) 61% . 003 Retinopathy 0. 42 (0. 21 -0. 86) 58% . 02 Gaede, et al, N Engl. J Med. 2003; 348(5): 383 -393.

Slow Progression Target: Diabetic Kidney Disease • Reduce BP to <130/80 mm. Hg • Use multiple antihypertensive drugs (ACE inhibitor, ARB, diuretic, CCB, beta-blocker) • Maximal reduction of proteinuria • Treat hyperlipidemia (LDL <100 mg/d. L) • Stop cigarette smoking American Diabetes Association. Diabetes Care 2008; 31(suppl 1): S 1 -S 42 National Kidney Foundation. Am J Kid Dis. 2007; 49(suppl 2): S 1 -S 179.

Slow Progression Target: Diabetic Kidney Disease • Insulin half-life prolonged with decreased GFR • Treatment cautions in CKD: Adjust all agents to avoid hypoglycemia No Metformin (e. GFR < 40 ml/min/1. 73 m 2) - lactic acidosis Sulfonylureas accumulate in kidney failure (glipizide preferred agent) Glitazones may aggravate edema and CHF O’Connor, AS & Schelling, JR. Am J Kid Dis. 2005; 46(4): 766 -773. American Diabetes Association. Diabetes Care 2008; 31(suppl 1): S 1 -S 41

Slow Progression: Target: Avoid Nephrotoxins • • NSAIDs are potentially nephrotoxic Avoid other nephrotoxins – iodinated radiocontrast, aminoglycosides, amphotericin B, cyclosporin, tacrolimus, ? colas • Prevention of contrast induced nephropathy - oral N-acetylcysteine (600 mg) before and after; sodium bicarbonate infusion (154 meq/L – 3/m. L/kg/hr 1 before and 6 hours post National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Slow Progression: Target: Dyslipidemias • • Consider patients with CKD in highest risk group for development of atherosclerotic CVD Evaluate at presentation of CKD, after a change in status, and annually Treatment targets – LDL < 100 mg/d. L – Triglycerides < 150 mg/d. L – non-HDL < 130 mg/d. L Use statins initially, also consider fibrates National Kidney Foundation. Am J Kidney Dis. 2003; 41(suppl 3): S 1 -S 91.

Delay Progression: Target: Lifestyle Changes • Stop smoking • Exercise • Sodium restriction 2 - 3 g/day of sodium • Fluid restriction • Potassium restriction – low K+ diet if elevated • Consider dietary protein restriction: – Microalbuminuria: 0. 8 g/kg/day – Decreasing GFR: 0. 6 g/kg/day . National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Targets for Treatment - CKD Early Detection of CKD Delay progression Prevent complications BP Control Anemia Treat Proteinuria Malnutrition DM/BS control Avoid Nephrotoxins Treat Dyslipidemia Metabolic Bone Disease Acidosis Treat comorbidities Prepare for RRT Cardiovascular disease Educate patient Hypertension Select RRT modality Diabetes Determine access and initiate dialysis in a timely fashion Lifestyle Adapted from Pereira, B. . Kid Int. 2000; 57: 351 -365.

Disturbances of Ca++, PO 4, PTH, and Vitamin D Decreased Vitamin D Receptors and Ca-Sensing Receptors PTH Ca++ Bone Disease Serum P Fractures Bone pain Marrow fibrosis Erythropoietin resistance 1, 25 D Calcitriol Systemic Toxicity CVD Hypertension Inflammation Calcification Immunological Renal Failure Ca = calcium; CVD = cardiovascular disease; P = phosphorus; SHPT = secondary hyperparathyroidism. Courtesy of Kevin Martin, MB, BCh.

Vascular Calcification and CKD Patient Without CKD Patients With CKD Rib Ca Deposition Vertebra Intimal Calcification Secondary to Atherosclerosis EBCT Indicating Coronary Calcification Medial Calcification Secondary to CKD EBCT=electron beam computed tomography. Raggi P. Clin Nephrol. 2000; 54: 325 -333.

Vascular Smooth Muscle Cell Na Pi Increasing Phosphate NPC Cbfa-1 Pi SMC genes alkaline phosphatase AP Ca/P loaded matrix vesicles calcium-binding proteins collagen-rich ECM Matrix Mineralization Giachellli, CM, AJKD , 2001

EBCT Scores and Cardiovascular Risk in the General Population Mayo Clinic EBCT Guidelines EBCT Score Plaque Burden Implication for CV Risk Recommendations <10 Minimal Low Reassurance, education 11 -100 Definite, mild Moderate Counseling for primary prevention; daily ASA 101 -400 Definite, moderate Moderately high >400 Extensive High Institute risk factor modification and secondary prevention Institute aggressive risk factor modification EBCT=Electron Beam Computed Tomography CV=Cardiovascular Rumberger JA, Brundage BH, Rader DJ, Kondos G. Mayo Clin Proc. 1999; 74: 243 -252.

Risk of Cardiovascular Calcification is Increased in Dialysis Patients Non-dialysis, no CAD (N=22) Non-dialysis, CAD (N=80) Dialysis (N=49) 2500 Mean total 2000 coronary 1500 artery calcium score* 1000 500 High CV risk† 0 28 -39 40 -49 50 -59 Age (years) 60 -69 *Determined by electron beam computed tomography (EBCT) CAD=Coronary Artery Disease † Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Am J Kidney Dis. 1996; 27: 394 -401.

Framingham Heart Study: Coronary Artery Calcification (CAC) Increase as GFR Declines *Median CAC (solid lines) and interquartile GFR ranges (boxes) are presented. • 319 subjects (162 men/157 women) from the Framingham Heart Study who were free of symptomatic cardiovascular dise • Coronary artery calcification (CAC) was evaluated by electron-beam computed tomography( EBCT) • Correlation was significant when adjusting for age, sex, body mass index, hypertension and total cholesterol

Treat Disorders of Bone and Mineral Metabolism • Check i. PTH and (25)OH D 2 levels annually starting in stage 2 CKD • Treat low (25)OH D 2 levels with ergocalciferol 50, 000 IU q mon x 6, cholecalciferol 1000 IU/day • Treat i. PTH with activated Vitamin D • Monitor Ca and PO 4 levels and keep in normal ranges for lab National Kidney Foundation. . Am J Kidney Dis. 2003; 42(suppl 3): S 1 -S 201.

Annual CVD Mortality (%) Cardiovascular Disease Mortality General Population vs. ESRD Patients 100 10 1 GP Male GP Female GP Black 0. 1 GP White Dialysis Male 0. 01 Dialysis Female Dialysis Black Dialysis White 0. 001 25 -34 35 -44 45 -54 55 -64 66 -74 75 -84 >85 Age (years) GP: General Population. Foley RN, et al. Am J Kidney Dis. 1998; 32: S 112 -S 119.

Target: Cardioprotection Initiate cardioprotective measures at diagnosis of CKD • Traditional risk-factor reduction Control BP and blood sugars, treat dyslipidemias, stop smoking, increase physical activity, and manage weight. • Nontraditional CKD-related risk factor reduction Decrease proteinuria, treat anemia and mineral and bone disorders, control volume overload, and correct electrolyte imbalances. National Kidney Foundation. Am J Kidney Dis. 2002; 39(suppl 1): S 1 -S 266.

Early Recognition of CKD and Collaboration between Cardiology and Nephrology Nephrologist Stage 3 1 2 Kidney Damage Mild Kidney Function Moderate Kidney Function 120 90 60 4 Severe Kidney Function 30 5 Kidney Failure 15 e. GFR Primary Care, Endocrinologist, Cardiologist Adapted from K/DOQI Guidelines For Bone Metabolism and Disease 2003, Bone Care market research.

CKD and CVD Have One, Screen for the Other!!! • Pts with CVD have increased risk for CKD and should be screened annually. • Aggressively manage CVD and CKD risk factors and slow progression of two diseases.

Thank You! You are not just Nephrology Nurses – you are RNs who interact with our patients’ families, the public and other RNs who care for our CKD patients long before either they, or we, know they have CKD!You can make a difference!

Please email me: lesleyd@nc. rr. com