WORKSHOP #6: LA DISFUNZIONE VENTRICOLARE OCCULTA E NON: - Nella Patologia renale. Luigi Tarantini Osp. San Martino - (Belluno)

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1 WORKSHOP #6: LA DISFUNZIONE VENTRICOLARE OCCULTA E NON: - Nella Patologia renale Luigi Tarantini Osp. San Martino - (Belluno)

2 Il paziente con Malattia Renale Cronica è il paziente ad alto rischio CV (1) Foley RN et Al. Am.J.Kidney Dis 1998

3 Il paziente con Malattia Renale Cronica è il paziente ad alto rischio CV (2) Rate of Hospitalization* ,54 Hospitalization 144,61 86,75 45,26 17,22 Rate of cardiovascular event* CV Events 21,8 11,29 2,11 3,65 36,6 Rate of death from any cause* Death From Any Cause 11,36 4,76 0,76 1,08 14, <15 egfr (ml/min/1.73 m2) < <15 egfr (ml/min/1.73 m2) egfr (ml/min/1.73 m2) egfr = estimated glomerular filtration rate *Age-standardized rates per 100 person-years N=1,120,295 ambulatory adults Adapted from Go AS et al. N Engl J Med. 2004;351:

Il paziente con Malattia Renale Cronica è il paziente ad alto rischio CV (3) Age- and gender-adjusted risk to develop a cardiovascular event (defined as a fatal or nonfatal myocardial infarction or

4 Il paziente con Malattia Renale Cronica è il paziente ad alto rischio CV (3) Age- and gender-adjusted risk to develop a cardiovascular event (defined as a fatal or nonfatal myocardial infarction or cerebrovascular accident) and to develop a renal event in the PREVEND cohort during 7 yr of follow-up. *P 0.05 versus patients with a urinary albumin excretion 15 mg/d. Ron T. Gansevoort and Paul E. de Jong JASN 2009

Staging of Chronic Kidney Disease Stage 1 2 3 Description Kidney damage with normal or elevated GFR+ some evidence of kidney damage reflected by microalbuminuria, proteinuria, and hematuria as well

5 Staging of Chronic Kidney Disease Stage Description Kidney damage with normal or elevated GFR+ some evidence of kidney damage reflected by microalbuminuria, proteinuria, and hematuria as well as radiologic or histologic changes Kidney damage with mildly decreased GFR + some evidence of kidney damage reflected by microalbuminuria, proteinuria, and hematuria as well as radiologic or histologic changes Moderately decreased GFR 3A: GFR B: GFR GFR ml/min/1.73 m Severely decreased GFR Kidney failure <15 or dialysis The suffix p to be added to the stage in proteinuric patients (proteinuria >0.5 g/24h) as proposed by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines 2013

6 Serum Creatinine mg/dl Renal Function: Serum Creatinine vs. Glomerular Filtration Rate Stage 5 (Renal Failure) Stage 4 (RD severe) Stage 3 (moderate RD) Stage 2 (mild RD ) Stage 1 (Normal) B 3A Glomerular Filtration Rate ml/min x 1.73m 2

8 Prevalence of CKD Contributors* Cystic kidney disease 4.6% Urologic disease 2.8% Other known cause 10.2% Unknown cause 3.9% Missing cause 1.2% Glomerulonephritis 16.2% Hypertension 24.2% Diabetes 36.9% *Based on 2005 data United States Renal Data System 2007 Atlas. Bethesda, MD: National Institutes of Health National, National Institute of Diabetes & Digestive & Kidney Diseases, 2007.

Mild Renal Insufficiency mediates early cardiac

After 4 Weeks Sham group Uninephrectomy Cardiac

apoptosis* (% Tunel Nuclei +) MBP (mmhg) 89.8 2.

2 RBF (ml/min) 8.0 0.7 4.7 0.6** *P< 0.01 **P< 0.

9 Mild Renal Insufficiency mediates early cardiac apoptosis, fibrosis and diastolic dysfunction After 4 Weeks Sham group Uninephrectomy Cardiac fibrosys* (picrosirius Staining %) Cardiac apoptosis* (% Tunel Nuclei +) MBP (mmhg) GFR (ml/min) RBF (ml/min) ** *P< 0.01 **P< 0.05 Martin F.L. et Al. Am. J. Physiol. Regul integr. Comp. Physiol. In press

10 Mild Renal Insufficiency mediates early cardiac apoptosis, fibrosis and diastolic dysfunction *P< 0.05 Martin F.L. et Al. Am. J. Physiol. Regul integr. Comp. Physiol. In press

11 CKD and CVD risk Factors Traditional risk factors Age Male gender Diabetes mellitus Smoking Hypertension Dyslipidemia Hyperhomocysteinemia Inflammation Oxidative stress Non traditional risk factors Anemia Sympath. nervous system activation oxidative stress and inflammation Protein glycation and carbamylation Endothelial dysfunction Coagulation disorders Disturbances of mineral metabolism Uremic toxins Protein-energy wasting

Urine phosphate (mg/24 hours) 1,25-dihydroxyvitamin D (pg/ml) Urine calcium (mg/24 hours) Alterations in Mineral Metabolism Occur in Early Stages of CKD Steady decline in urine phosphate excretion

12 Urine phosphate (mg/24 hours) 1,25-dihydroxyvitamin D (pg/ml) Urine calcium (mg/24 hours) Alterations in Mineral Metabolism Occur in Early Stages of CKD Steady decline in urine phosphate excretion Progressive depletion of 1,25(OH) 2 D 3 Decline in urine calcium excretion n= CKD1 14 *P<0.05 CKD2 vs CKD3 P<0.05 CKD3 vs CKD4 * CKD2 75 CKD3 180 CKD Stage CKD4 43 CKD5 7 (n=319) n= CKD1 15 *P<0.05 CKD2 vs CKD3 P<0.05 CKD3 vs CKD4 P<0.05 CKD4 vs CKD5 * CKD2 87 CKD3 221 CKD Stage CKD4 156 CKD5 43 (n=522) n= CKD1 14 *P<0.05 CKD2 vs CKD3 P<0.05 CKD3 vs CKD4 * CKD2 74 CKD3 179 CKD Stage CKD4 43 CKD5 7 (n=317) Shading=statistical significance between levels. Urine phosphate excretion decreases and leads to phosphate retention 1,25D production decreases, leading to 1,25D depletion and contributing to elevated PTH Urine calcium excretion decreases, impacting calcium balance Adapted from Craver L, et al. Nephrol Dial Transplantation. 2007;22:

13 Hypovitaminosis D, PTH and mortality JS Chen Clinical Endocrinology 2008

14 Patients (%) Progressive Vitamin D Deficiency in CKD 100 Prevalence of 1,25(OH) 2 D 3 and 25(OH)D 3 deficiency by GFR (OH)D 3 <15 ng/ml 1,25 (OH) 2 D 3 <22 pg/ml (n=61) (n=117) (n=230) (n=396) (n=355) (n=358) (n=204) <20 (n=93) GFR level (ml/min) Adapted from Levin A, et al. Kidney Int. 2007;71:31-38.

Phosphorus Homeostasis Bone Health Growth &

Apoptotic Anti-angiogenic Prostate, Colon,

Immunomodulatory Effects Multiple Sclerosis Type

Psoriasis Rheumatoid Arthritis Inflammatory

Effects Renin-Angiotensin Regulation Decreased

stimulation of pancreatic insulin production)

15 Kidney Physiologic Effects of Vitamin D Throughout the Body 25(OH)D Major Circulating Metabolite Colon Prostate Breast, etc. 1,25(OH) 2 D Biologically Active Calcium and Phosphorus Homeostasis Bone Health Growth & Regulation Antiproliferation Prodifferentiation Apoptotic Anti-angiogenic Prostate, Colon, Breast Cancers etc. Immunomodulatory Effects Multiple Sclerosis Type 1 Diabetes (via ß-islet cell destruction) Psoriasis Rheumatoid Arthritis Inflammatory Bowel Disease Periodontal Disease Cardiovascular Effects Renin-Angiotensin Regulation Decreased Risk for: Hypertension Type II Diabetes (via stimulation of pancreatic insulin production) Heart Failure Neuromuscular Effects Muscle Mass Muscle Strength Better Balance Adapted from: Holick MF. Mayo Clin Proc. 2006;81:

16 IPERFOSFOREMIA

17 Kidney International 2002

18 PTH and Vascular Calcification KR Neves Kidney International 2007

19 PTH as a CV risk factor in moderate CKD A Lishmanov Int Urol Nephr 2011

Ventricular relaxation Ventricle mass left atrial volume Δ Blood

20 The relevance of ventricular-arterial interaction in HFPEF and Myocardial ischemia end-systolic load ventricular wall stress Ventricular relaxation Ventricle mass left atrial volume Δ Blood Pressure Diastolic Blood Flow myocardial ischemia Rafey M. Clev. Clin. Med. J. 2009

21 The relevance of arterial stiffness for kidney function Renal Myogenic Response: Kinetic Attributes and Physiological Role Loutzenhiser R et Al Circ. Res. 2002

22 M.L. Maschio 52 aa. PA 160/100, BMI 35, glicemia 112 mg/dl, Trigliceridi 220 mg/dl, Col. HDL 44 mg/dl, Creatinina : 1.6 mg/dl (GFR 55 ml/min 1.73 mq)

23 The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events:Multiethnic Study of Atherosclerosis Agarwal S. et Al. Cardiol Res Pract. 2012;2012: Epub 2011 Jul 26.

24 Left Ventricular Hypertrophy in Nondiabetic Predialysis CKD 50% 75% Paoletti E. et aal. American Journal of Kidney Diseases, 2005

25 Left Ventricular Hypertrophy in Nondiabetic Predialysis CKD Paoletti E. et aal. American Journal of Kidney Diseases, 2005

26 PredictedLVM = - 55:37 + (6.63 X height 2.7 ) + ( stroke work) 18.1 X sex Massa inappropriata: massa osservata > 28% massa predetta J. Of Hypertension 2011

27 Calcificazioni Ipertrofia concentrica Dilatazione atriale Sin.

28 Stenosi dinamica intraventricolare Insuff. mitralica

29 La disfunzione renale quale fattore di rischio di scompenso cardiaco Framingham Physician Health Study Lam Circulation 2010 Dhinga circ. Heart Fail 2011

30 The Natural History of Preclinical Diastolic dysfunction: a population based study Rochester Mayo Clinic RSV: Right Ventricle systolic pressure GFR: Glomerular filtration Rate Vogel et Al. Circulation Heart Failure in press

31 CKD e Aterosclerosi coronarica Nakano, T. et al. Am. J. Kidney Dis. 55, (2010)

32 CKD e Aterosclerosi coronarica(2) RD Stage 1-2 RD Stage 3A RD Stage 3B RD Stage 4-5 Nakano, T. et al. Am. J. Kidney Dis. 55, (2010)

33 Diagnosis of coronary artery disease in patients with advanced chronic kidney disease Johnston Heart 2008

34 Bisogna avere in sé il caos per partorire una stella che danzi. Friedrich Nietzsche Grazie dell attenzione!!!!

Cardiovascular Disease in CKD. Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center

Cardiovascular Disease in CKD. Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center Cardiovascular Disease in CKD Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center Objectives Describe prevalence for cardiovascular disease in CKD