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The Effect of Chronic Kidney Disease (CKD) on the CardioVascular System

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

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The Effect of Chronic Kidney Disease (CKD) on the CardioVascular System

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

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

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

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

  5. What is the leading cause of Mortalityin our CKD patient population?

  6. 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 eGFR. • Discuss factors related to progression and slowing of progression of CKD and CVD. • Identify complications of CKD and strategies to improve outcomes.

  7. How you see this all depends on your perspective!

  8. NKF-KDOQI Staging Classification of CKD eGFR (mL/min/1.73 m2) * May be normal for age National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl 1):S1-S266.

  9. 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

  10. 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”

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

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

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

  14. Cardiovascular Outcomes Worsenwith CKD Progression VALLIANT TRIAL 3-Yr Follow-Up by eGFR Levels in Post-MI Patients P<0.001 N = 14,527 eGFR (mL/min/1.73 m2) 75 Estimated Event Rate (%) 60-74 45-59 <45 CHF = congestive heart failure; CV = cardiovascular. Anavekar et al. N Engl J Med. 2004; 351:1285-1295.

  15. 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) CASE 1 – cc: “shortness of breath” • 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.

  16. Prevalence of IHD in the General Population and CKD 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

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

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

  19. VASCULAR SYSTEM WABeresford Elastic/conducting arteries Large veins Heart Node Muscular/distributingarteries Veins Lymphatics Venules Arterioles Capillaries Post-capillary venules

  20. Congestive Heart Failure? CASE 1 – cc: “shortness of breath” • 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

  21. Congestive Heart Failure? CASE 1 – cc: “shortness of breath” • “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.

  22. 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_sep2010.pdf

  23. 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 Classification and Pathophysiology of CRS http://www.asn-online.org/publications/kidneynews/archives/2010/sep/KN_sep2010.pdf

  24. 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 Classification and Pathophysiology of CRS http://www.asn-online.org/publications/kidneynews/archives/2010/sep/KN_sep2010.pdf

  25. High Prevalence of CKD in Patients Hospitalized with Acute Decompensated HF Cardiorenal Syndrome ADHERE Acute Decompensation Heart Failure National Registry N = 118,465 Percent of Patients eGFR <90 60-89 30-59 15-29 < 15 ml/min/1.73m2 • Heywood, JT et al. J Card Fail. 2007. Aug 13(6); 422-230.

  26. 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 Sarnak, M et al. Circulation. 2003: 108(17) 2154-2169

  27. Congestive Heart Failure? CASE 1 – cc: “shortness of breath” • 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 5x higher in CKD) • USRDS, 2004 Annual Report

  28. Congestive Heart Failure? CASE 1 – cc: “shortness of breath” • 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

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

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

  31. Pathophysiologic Consequences of Anemia in CKD: Effects on the CV System Reduced Hemoglobin Reduced O2 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.

  32. Correction of Anemia in Patientswith CKD and CHF . Silverberg, DS. Perit Dial Int . 200l.; 21Suppl3 ; S236-240.

  33. Anemia secondary to GI Bleed or CKD? CASE 1 – cc: “shortness of breath” • 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

  34. X Iron Erythropoietin Erythroid marrow RE cells O2 delivery Red blood cells ANEMIA Erythropoietin deficiency is the most common cause of anemia in CKD. RE = reticuloendothelial • Adapted from: Harrison, FIn Principles of Internal Medicine. 1998:334.

  35. Anemia Starts Early in CKD and Worsens with Disease Progression 33%-36% 100% 30%-32.9% < 30% N = 1,658† 10% 80% 15% 60% Prevalence of Anemia (%) 15% 8% 40% 17% 67.5% 62% 8% 9% 43% 20% 5% 20% 14% 0% < 2 2-2.9 3-3.9 > 4 *Start of Dialysis (n=131,484) Serum Creatinine Level (mg/dL) †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.

  36. Anemia and CHF

  37. FINAL DIAGNOSES CASE 1 – cc: “shortness of breath” • 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

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

  39. CVD Events, Hospitalization and Death are Common in CKD Age-Standardized Rate of Cardiovascular Events(per 100 person-yr) END Points: CV Events, HospitalizationDeath Estimated GFR (mL/min/1.73 m2) Go, et al., 2004

  40. Cardiovascular Disease is Prevalent in CKD Framingham Heart Study Normal SCr (n=2591) % Male Patients Elevated SCr (1.5–3.0 mg/dL n=246) CVD CHD CHF LVH Culleton. Kidney Int. 1999;56:2214.

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

  42. 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) eGFR, and microalbuminuria were independently associated with CVD, and when all 3 were present, CVD was common and survival was reduced.” CKD and CVD McCullough, PA et al. Arch. Of Int Med. 2007. .

  43. 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 CVD and CKD “Cardiovascular disease is independently associated with kidney function decline and with the development of kidney disease.” Elsayed, E et al. 2007. Arch. Of Int Med. 2007. .

  44. Traditional Risk Factorsfor Cardiac Disease • Traditional • Hypertension • Diabetes • Age • Smoking • Dyslipidemia • Obesity • Inactivity • Family History • LVH Sarnak. Am J Kidney Dis. 2000;35(suppl 1):S117 Block. Am J Kidney Dis. 1998;131:607 Kitiyakara. Curr Opin Nephrol Hypertens. 2000;9:477

  45. Risk Factors for Cardiac Disease in Patient with CKD • 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 • Traditional • Hypertension • Diabetes • Age • Smoking • Dyslipidemia • Obesity • Inactivity • Family History • LVH Sarnak. Am J Kidney Dis. 2000;35(suppl 1):S117 Block. Am J Kidney Dis. 1998;131:607 Kitiyakara. Curr Opin Nephrol Hypertens. 2000;9:477

  46. Microalbuminuria: Independent Predictor of Combined End Points CV Death, MI, and Stroke: The HOPE Trial Mann et al, Ann of Intern Med, 2003

  47. Proteinuria is Associated withAdverse CV Outcomes – LIFE study N= 7143 <2.2 mg/g >83.3 mg/g Adjusted Hazard Ratio Watchtell et al, Ann of Intern Med, 2003

  48. Albuminuria Prevend Study • In a population-based study (subset n = 9000) the presence of albuminuria enhanced the predictivevalue of ST-T segment changes in a restingECG for all-cause and CVD mortality. • The impact of the presence of microalbuminuriaon 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

  49. 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. • Confirmed by Arnlov et al, persons with normal BP, without DM and normal GFR – microalbuminuria is a strong predictor of CV outcome. Kannel, A Heart J,108,1984 Arnlov et al, Circulation, 2005

  50. Albuminuria — So WHAT? LIFE STUDY Reducing Proteinuria independent of BPdecreased 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. deZeeuw, et al , KI, 2004.

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