Cardio Renal Disease. Dr. Rajasekara Chakravarthi Head, Dept of Nephrology CARE Hospitals Hyderabad

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1 Cardio Renal Disease Dr. Rajasekara Chakravarthi Head, Dept of Nephrology CARE Hospitals Hyderabad

2 PREVALENCE OF CVD IS HIGH CAD LVH CHF (CLINICAL) (ECHO) (CLINICAL) GENERAL POPULATION 5-12% 20% 5% CKD NA 25-50% NA HEMODIALYSIS 40% 75% 40% PERITONIAL DIALYSIS 40% 75% 40% RENAL TRANSPLANT 15% 50% NA SARNAK AND LEVEY AJKD 2000, 35:

3 Def: _ Cardio renal syndrome - a relatively normal kidney is dysfunctional because of a diseased heart, with the assumption that in the presence of a healthy heart same kidney performs normally.

4 DEF: _ Cardiorenal syndrome, general definition: a pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ

5 CRS type 1 (acute CRS). _ Type 1 CRS is characterized by a rapid worsening of cardiac function, leading to acute kidney injury (AKI)

6 _ Acute heart failure (HF) may be divided into 4 subtypes: _ hypertensive pulmonary edema with preserved left ventricular (LV) systolic function _ acutely decompensated chronic HF _ cardiogenic shock, and _ predominant right ventricular failure

8 Type II: chronic cardiorenal syndrome. _ Chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and potentially permanent chronic kidney disease

10 Type III: acute renocardiac syndrome _. Abrupt worsening of renal function (e.g. acute kidney ischaemia or glomerulonephritis) causing acute cardiac disorder (e.g. heart failure, arrhythmia, ischaemia)

12 Type IV: chronic renocardiac syndrome _. Chronic kidney disease (e.g. chronic glomerular or interstitial disease) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events

14 Type V: Secondary cardiorenal syndrome _ Systemic condition (e.g. diabetes mellitus, sepsis) causing both cardiac and renal dysfunction

16 Current Approaches to managing Cardiorenal Dysfunction Neurohormonal antagonists Other vasoactive therapies - Positive ionotropes - Natriuretic peptides Agents that target the kidney - Vasopressin - Adenosine antagonists Renal replacement therapy (Ultrafiltration) Mechanical circulatory support

17 Current Options May Have Undesirable Clinical Impacts _ Favorable aspects of diuretic therapy Increases urine output; reduces total body volume in majority of patients 4 _ Adverse aspects of diuretic therapy Direct activation of renin-angiotensin-aldosterone system 3,10 Enhanced myocardial aldosterone uptake 12 Loss of K, Mg, Ca, secondary myocyte Ca loading 12 Indirect reduction of cardiac output 10,11 Increased total systemic vascular resistance 11 Reduced natriuresis 8 and GFR 7,9 Associated with increased morbidity and mortality 2,5,6

18 Furosemide Monotherapy Causes Significant Decline in Renal Function (GFR) Change in GFR after IV furosemide 80 mg in CHF GFR (% Change) Placebo IV furosemide Urine Output (ml) 0 8 h Gottlieb et al. Circulation. 2002;105:1348.

19 Relief for Acutely Fluid Overloaded Patients With Decompensated Congestive Heart Failure The RAPID-CHF Trial Bart et al. J Am Coll Cardiol. 2005;46:

20 Early Ultrafiltration in Patients With Decompensated HF and Observed Resistance to Intervention With Diuretic Agents The EUPHORIA Trial

21 Ultrafiltration versus IV Diuretics for Patients Hospitalized ized for f Acute Decompensated Congestive HF: A Prospective Randomized Clinical Trial UNLOAD Trial Costanzo MR et al. J Am Coll Cardiol. 2007;49:

22 Conclusions Early ultrafiltration produces greater weight loss than IV diuretics, without changes in renal function An early ultrafiltration strategy reduces 90-day Percentage of patients requiring rehospitalization for HF Number of HF rehospitalizations Days of rehospitalization for HF Emergency department and unscheduled office visits Costanzo MR et al. J Am Coll Cardiol. 2007;49:

23 WHY ULTRAFILTRATION? _ PATIENT effective control of symptoms - early control of symptoms - short hospital stay - no requirement for ICU - diuretic side effects HOSPITAL - faster turnaround time - less requirement ICU bed - day heart failure clinic (like CRF)

24 Pathophysiology IL 1 IL 6 ANP MDF (Myocardial depressant factors) Removed by UF

25 Renal function and survival in CHF _ Most powerful predictor mortality in CHF _ 1906 pts Crcl.. < 44 ml/min (CG equation) mortality risk 2.85 (P= <0.001) _ RF stronger predictor factor than Na, K, Mg, EF or NYHA Class _ N terminal ANP - Hillage et al Circulation 102: ; 2000

26 Evolution of CRRT SLOW IHD 1993 CVVHDF 1988 IHD 1960 Cytokine control SCUF CAVH CAVHD CAVHDF SCUF 1977 CAVH 1978 CVVHD 1986 CAVH D 1984 Uraemic control All of the above CVVH 1985 CAVHDF 1984 CHF Control SCUF CAVH CVVH Paganini et al Seminars in dialysis vol9, No.2 (Mar-Apr)1996;

27 AIM OF THE STUDY _ Role of CAPD in refractory congestive heart failure at our centre during the period _ Prospective study continued till date

28 Inclusion Criteria _ Refractory heart failure _ Severe systolic dysfunction (EF<35%) _ No possibility of surgical treatment _ No response to the best medical therapy available (fluid decongestive therapy) _ Adequate socio financial support

29 MATERIALS & METHODS _ 21 patients with severe congestive heart failure refractory to optimal pharmacological therapy _ All patients had NYHA class IV with varying stages of CKD III-IV _ CAPD prescription is based on the amount of UF needs to be achieved _ The total follow up ranged between 6 months to 2 years _ Statistical analysis : paired student t test

30 Clinical and technical Data Pt. Gend er Age Diagnosis PD Prescription Ultra-filtration PD Follow- up (months) Peritonitis episodes 1 M 63 Ischaemic CMP One Icodextrin nocturnal exchange F 54 RHD+MVR One Icodextrin nocturnal exchange + 1.5% one exchange F 60 Ischaemic CMP One Icodextrin nocturnal exchange + 1.5% one exchange F 57 Ischaemic CMP One Icodextrin nocturnal exchange + 2.5% one exchange M 63 Ischaemic CMP One Icodextrin nocturnal exchange M 58 Ischaemic CMP One 2.5% exchange per day M 57 Ischemic CMP Three 2.5% exchange per day M 59 Ischemic CMP One 2.5% exchange per day M 70 Ischemic CMP Two 2.5%exchnage per day M 63 Ischemic CMP Three 2.5% exchange

31 RESULTS _ Of the 21 patients studied 17 were males and 4 were females _ The mean age was yrs _ There was a significant improvement in NYHA class IV to II in 4 patients and NYHA class IV to III in 1 patient NYHA class IV to I in 1 patient (p=0.0006) _ We have observed significant improvement in quality of life, reduction in morbidity and decreased hospitalization rates (p=0.0010) _ Only one patient had an episode of peritonitis during the follow up

32 Table summarizing our experience at Care Hospitals Pt. Gende r Age Diagnosis Ejection Fraction % Before After Renal egfr CKDstages Hospitalisation days (before) Hospitalisatio n days (after) 1 M 63 Ischaemic CMP F 54 RHD+MVR F 60 Ischaemic CMP F 57 Ischaemic CMP M 63 Ischaemic CMP M 58 Ischaemic CMP M 57 Dilated cardio myopathy M 59 RHD M 70 Dilated cadio myopathy M 63 Dilated cadio myopathy

33 Change in the functional class NYHA Grade NYHA(before) NYHA(after) p= Patients

34 Number of Hospitalisation Days Number of Days Hospitalisation days(before) Hospitalisation days(after) p= Patients

35 Improvement in LV Ejection fraction Ejection Fraction % Ejectiuon fraction(before) Ejection fraction(after) Patients

36 CONCLUSION _ Independent of the renal functions peritoneal dialysis appears to be a promising therapeutic option for patients with refractory CHF _ Peritoneal Dialysis offers significant improvement in quality of life, reduction in morbidity and decreased hospitalization rates in patients with refractory CHF _ One exchange (Dextrose/ Icodextrin) is sufficient enough for achieving fluid balance

37 Definition of CIN _ CIN is most commonly defined as: an acute impairment of renal function following the use of CM with an increase in serum creatinine (SCr) of 44.2 µmol/l (0.5 mg/dl), or as an increase of 25% from baseline within 72 h after Intravascular CM administration In the absence of an alternative etiology ESUR, European Society of Urogenital Radiology Thomsen HS. Curr Opin Urol. 2007;17:70-76.

38 CIN adversely affects survival for many years after the episode Brown JR et al. Circulation 2007; 116: Abs 1689.

39 Are We Failing to Identify Patients With Renal Impairment Because of How We Screen for Them? Age, y Normal SCr Patients with Abnormal egfr Yes 1.2% Yes 12.6% 70 Yes 47.3% Duncan L et al. Nephrol Dial Transplant 2001; 16:

41 Estimating Kidney Function Cockcroft Gault: estimates creatinine clearance (ml/min) (140-age) x weight (kg) 72 x SCr (mg/dl dl) x 0.85 (if female) 4-variable MDRD: estimates GFR (ml/min/1.73 m 2 ) x SCr x age x (0.742 if female) x (1.21 if black) 6-variable MDRD: estimates GFR (ml/min/1.73 m 2 ) 170 x (SCr x 0.011) x (age) x (SUN x 2.801) x (SAlb x 0.1) x (if African-American) x (if female) Coritsidis GN. Available at: Lamb EJ et al. J Am Geriatr Soc 2003;51: ;Grubb A et al. Clin Chem 2005;51 (8):

42 Stages of CKD Adapted from the National Kidney Foundation K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease; Evaluation, Classification, and Stratification.

43 The CIN Risk Index CIN Risk Factors and Scores Risk Factors Hypotension Presence of an intra-aortic balloon pump Congestive heart failure Age >75 years Anemia Diabetes Chronic kidney disease Volume of contrast agent used Integer Score (SCr( >1.5 mg/dl dl) 2 (GFR 40 60) 4 (GFR 20 40) 6 (GFR <20) 1 per each 100 cc 3 Reference: Mehran R et al. J Am Coll Cardiol. 2004;44:

45 Algorithm for Management of Patients Receiving Iodinated CM Calculate egfr Assess CIN risk egfr <30 ml/min egfr ml/min Discontinue NSAIDs, other nephrotoxic drugs, metformin egfr 60 ml/min Discontinue metformin Hospital admission Nephrology consultation Dialysis planning* Other strategies as for egfr ml Serial SCr and electrolytes Intravenous volume expansion Consider choice of contrast medium Limit contrast volume (<100 ml) Consider pharmacological treatment SCr before discharge or within h Good clinical practice * Plans should be made in case CIN occurs and dialysis is required IV isotonic crystalloid ml/kg/h for 3 12 h before and 6 24 h after the procedure Consider potentially beneficial agents (theophylline, statins, ascorbic acid, PGE 1 ); 45 none Adapted from McCullough PA, et al. Am J Cardiol. 2006;98[Suppl]:2K-4K. approved for this indication

46 Fluids What? _ 0.9% saline significantly reduced contrast nephropathy compared to 0.45% saline (0.7% vs. 2% ; P =0.04) USE ISOTONIC CRYSTALLOIDS Mueller C et al: Arch Intern Med 2002; 162: _ Hydration with isotonic sodium bicarbonate decreased the incidence of contrast nephropathy compared to 0.9% saline (1.7% vs. 13.6%; P = 0.02) Merten GJ et al: JAMA 2004; 291:

47 _ Check e GFR _ Stop ACEI /ARB/ ARB s /DRI s _ Stop Metformin _ Stop diuretics _ No NSAID S _ IV hydration NS 1 ml /kg/hr/12-24 hrs (pre & post) If HF _ ml/kg/hr/12-24 hrs (pre & post) - Maintain I/O check - IV Na HCo 3? - NAC mg 3 doses (Vol( of contrast, type of contrast) - Check S. Creatinine 48 hrs

48 Society Society Recommendations: Type of CM for High-risk Patients Isosmol ar Low- osmolar ACC/AHA/SCAI 2007 (PCI) ACC/AHA 2007 (UA/NSTEMI) Hungarian Society of Nephrology 2007 National Kidney Foundation (K/DOQI) 2005 Norwegian Society of Nephrology 2004 German Cardiac Society 2004 ESUR 2005 French Radiologic Society 2004

51 As medicine is practised in the 1990s the pt with heart disease and renal disease are frequently managed by physicians who are interested in only one of the two organ systems. In circumstances when the pt is visited by both, the physicians frequently take opposite points of view and make therapeutic recommendations that are principally designed to preserve a single organ system. Packer M Cardio Renal Disease (II Ed) 1992 PP III - VI

53 ANEMIA MANAGEMENT IN CKD Critical links : CKD CVD Anemia Adverse consequences of anemia Anemia and clinical outcomes 1) observational studies 2) Interventional trials Challenges of targeting higher hb Trends in anemia management Epoetin vs. Darbepoetin

54 Heart Failure after MI- Benefit beyond Hemoglobolin from Erythropoetin _ Erythropoetin Induces Neovascularization and Improves Cardiac Function in Rats with Heart Failure after Myocardial Infarction. - Van der Meer et al. J Am Coll Cardiol 46: , 2005 _ Editorial Eberhard Ritz J Am Soc Nephrol 5: 2-7, 2006 _ High dose Epo - A Limitation

55 Volume overload Primary stimulus Pressure overload Increased diastolic pressure - Increased diastolic stress Increased systolic pressure + - Increased systolic stress Series addition of new sarcomeres Parallel addition of new myofibrils Chamber enlargement Wall thickening Eccentric hypertrophy Concentric hypertrophy

56 Initial insult Hypoxia Oxidative stress GLOMERULAR INJURY proteinuria INTERSTITIAL FIBROSIS Glomerular hypertension/ hypertrophy GLOMERULO- SCLEROSIS Hypoxia Oxidative stress Tubular dysfunction REDUCED NEPHRON NUMBER Destruction of capillaries Hypoxia Oxidative stress Epoetin? Tubular destruction

57 CKD-MBD Ca X P > 55 PTH Phosphate binders Calcinimetics Vit D analogues Ca containing Non Ca containing Sevelamer Lanthanum

Contrast Induced Nephropathy

Contrast Induced Nephropathy O CIAKI refers to an abrupt deterioration in renal function associated with the administration of iodinated contrast media O CIAKI is characterized by an acute (within 48 hours)