CARDIORENAL SYNDROME IN PATIENTS WITH HEART FAILURE IN KANO. A DISSERTATION SUBMITTED TO THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF FELLOWSHIP OF THE COLLEGE IN INTERNAL MEDICINE (CARDIOLOGY). BY DR MUHAMMAD NAZIR SHEHU M.B, B.S [B.U.K.] 2002 DEPARTMENT OF MEDICINE AMINU KANO TEACHING HOSPITAL, KANO. MAY 2014 i DECLARATION I hereby declare that this work is original unless otherwise acknowledged. This work has not been presented to any other College for Fellowship and has not been submitted elsewhere for publication. Signature---------------------------- Date---------------------- DR MUHAMMAD NAZIR SHEHU May 2014 ii CERTIFICATION I SUPERVISORS’ CERTIFICATION This study reported in this Dissertation was done by the candidate under our supervision. We also supervised the writing of the Dissertation. SUPERVISOR 1. SIGNATURE/DATE:……………………………………………….. Professor SA Isezuo (FMCP) Professor of Medicine and Consultant Physician/Cardiologist, Usman Danfodiyo University Teaching Hospital,Sokoto. 2. SIGNATURE/DATE:……………………………………………….. Professor B. N. Okeahialam, (FWACP). Professor of Medicine and Consultant Physician/Cardiologist, Jos University Teaching Hospital, Jos, Plateau State, Nigeria. 3. SIGNATURE/DATE:------------------------------------------------------- DR M. M. BORODO (FMCP) Associate Professor of Medicine and Consultant Physician/Gastroenterologist, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria. iii CERTIFICATION II HEAD OF DEPARTMENT’S CERTIFICATION This is to certify that this work was undertaken by Dr----------------------------------------------- in the Department of Medicine Aminu Kano Teaching Hospital Kano. Head of Department’s Name: ………………………………………………………….. Signature and Date …………………………………………………………………….. iv DEDICATION This work is dedicated to my parents, late Alhaji Muhammadu Abua and Hajiya Hasiya Muhammad, and my grandfather, late Alhaji Shehu Kurfi. v ACKNOWLEGDEMENT All gratitude belongs to the Almighty Allah, who spares my life and made it possible for me to undergo this training. My profound appreciation goes to Professor SA Isezuo, Professor BN Okeahialam and Dr MM Borodo for their continued thorough supervision and guidance throughout this work. My gratitude goes to all the doctors and other staff of Medicine Department of AKTH for their encouragement and support during the course of my training and in carrying out this work. I thankfully acknowledge Professor AG Habib, Dr MU Sani, Dr Aliyu Abdu and Dr Bappa Adamu for their support and contributions to this Dissertation. I extend my special thanks to the Head of Medicine Department Jos University Teaching Hospital, Professor E. N. Okeke and the entire staff of the department for their contributions. My thanks go to all the people that assisted me in doing this work, in particular Mallam Hamisu, Mallam Bashir and Mallam Lawan Na’iya, staff of Health Records Department of AKTH. Equally appreciated are the staff of Community Medicine Department, Dr AU Gajida, Dr MU Lawan and Muhammad Usman Jos for assisting me in statistics. I am especially indebted to my sponsors and employers, Katsina State Government through the Health Services Management Board (HSMB), Katsina. My thanks go to the Board Chairman, Dr Salisu Banye, the General Manager, Dr Aliyu El-ladan and the Director Medical Services, Dr Bashir Abdullahi. I wish to express my sincere gratitude to my wife Hadiza, my children Bashir and Fadimatu, my elder brother Sunusi and the entire extended family members for their support and patience during the period of my residency training. vi TABLE OF CONTENTS Title page………………………………………………………………… I Declaration………………………………………………………………. II Certification I……………………………………………………………. III Certification II…………………………………………………………… IV Dedication………………………………………………………………… V Acknowledgement……………………………………………………….. VI Table of Contents………………………………………………………… VII Abbreviations…………………………………………………………….. VIII List of Tables and Figures…………………………………………………X Abstract…………………………………………………………………… XI CHAPTER ONE: INTRODUCTION…………………………………1 CHAPTER TWO: LITERATURE REVIEW------------------------------------6 CHAPTER THREE: MATERIALS AND METHODOLOGY-------------35 CHAPTER FOUR: RESULTS………………………………………… 44 CHAPTER FIVE: DISCUSSION…………………………………… 62 LIMITATIONS OF THE STUDY…………………67 CONCLUSION---------------------------------------------68 RECOMMENDATIONS………………………… 69 REFERENCES…………………………………………………………… 70 APPENDICES..…………………………………………………………… 88 vii LIST OF ABBREVIATIONS ACE-I- Angiotensin converting enzyme inhibitors. ADHF- Acute decompensated heart failure. AF- Atrial fibrillation. AKI- Acute kidney injury. AKTH- Aminu Kano Teaching Hospital. ARBs- Angiotensin receptor blockers. ARD- Advanced renal disease. AST- Aspartate transaminase. BNP- Brain natriuretic peptide. BP- Blood pressure. BUN- Blood urea nitrogen. CAD- Coronary artery disease. CHF- Congestive heart failure. CK- Creatinine Kinase. CKD- Chronic kidney disease. CK-MB Creatinine Kinase - myocardial band. CRS- Cardio-renal syndrome. CVP- Central venous pressure. DCM- Dilated cardiomyopathy. DM- Diabetes mellitus. ECG- Electrocardiography EDTA- Ethylene Diamine Tetrachloroacetic acid eGFR- Estimated glomerular filtration rate. viii GFR- Glomerular filtration rate. HDL- High density lipoprotein. HF- Heart failure. HHD- Hypertensive heart disease IHD- Ischaemic heart disease. IL- Interleukin. JVP- Jugular Venous Pressure. LDH- Lactate dehydrogenase. LDLc- Low density lipoprotein cholesterol. LV- Left ventricle. LVEF- Left ventricular ejection fraction. LVH- Left ventricular hypertrophy. NYHA-New York Heart Association. PND- Paroxysmal nocturnal dyspnoea. RI- Renal impairment. SBP- Systolic blood pressure. SCr- Serum creatinine. SNS- Sympathetic nervous system. RAAS- Renin-angiotensin-aldosterone system. TC- Total Cholesterol. WBC- White blood cell count. WRF- Worsening renal function. ix LIST OF TABLES AND FIGURES Page Table I: Criteria for CRS classification 40 Table II: Baseline clinical characteristics of all 170 patients 45 Table III: Comparison of the clinical characteristics among patients. 46 Table IV: Comparison of the laboratory parameters among patients. 51 Table V: Comparison of electrocardiographic findings among the patients. 53 Table VI: Comparison of echocardiographic findings among patients. 54 Table VII: Comparison of clinical variables among patients with and without CRS 58 Table VIII: Mortality and duration of hospital stay. 59 Table IX: Comparison of deceased and survivors of CRS. 61 Figure 1: Pathophysiology of CRS 13 Figure 2: Heart and kidney interaction 17 Figure 3: Mechanism by which anaemia can cause heart failure and CRS 19 Figure 4: Age group and sex distribution of the participants. 47 Figure 5: Classification of CRS among the group. 48 Figure 6 Types of CRS found among the patients. 49 Figure 7: Aetiology of HF among the study patients. 55 Figure 8: Medication received by the patients. 56 Figure 9 Echocardiographic image of DCM. 91 Figure 10: Echocardiographic image of HHD. 92 Figure 11: Echocardiographic image of rheumatic mitral valve stenosis. 93 Figure 12: Electrocardiographic tracing of DCM. 94 Figure 13 Electrocardiographic tracing of HHD. 95 Figure 14 Electrocardiographic tracing of acute myocardial infarction. 96 x ABSTRACT Background: The combination of heart failure and renal impairment often defined as cardiorenal syndrome (CRS) has an important prognostic implication among patients with heart failure. It is currently recognized as an independent predictor of morbidity and mortality among the population of patients with heart failure. Objectives: The main aim of this study was to determine the prevalence, predictors and outcomes of CRS among patients admitted with HF in medical wards of Aminu Kano Teaching Hospital, Kano, Nigeria. Methods: The study was cross-sectional in design. Patients aged 18 years and above who satisfied the inclusion criteria were consecutively recruited over a period of 11 months. Detailed history and physical examination as well as relevant baseline blood chemistry, full blood count, urinalysis, eGFR, electrocardiography, echocardiography and renal ultrasound scan were carried out. Urinary protein creatinine ratio was determined in those with proteinuria. Serum creatinine, urea and electrolytes were measured at presentation and repeated once during heart failure therapy. Heart failure and CRS were defined and classified using appropriate criteria. Data analysis was done using univariate and multivariate analyses. Results: Of the 170 patients studied, 100 (58.8%) were females and 70 (41.2%) were males. Mean age of patients was 49.6 ± 18.74 years. One hundred and twenty four (72.9%) patients had CRS, with 54%, 28% and 18% of them having mild, moderate and severe form of CRS respectively. Patients in NYHA class IV HF symptoms were more than 2 times at risk of developing CRS (95% CI=1.008-4.526, RR=2.135, P= 0.048), while those older than 40 years had more than 3 times risk of having CRS (95% CI=1.797-8.582, RR= 3.927, P=0.001). Patients with CRS had significantly higher mortality rate compared to those without the syndrome (25% vs13% P= 0.031). There was no significant difference in the duration of hospital stay between patients with and those without CRS (17.86±13.11 vs. 15.85±13.46 P= xi 0.378). Serum creatinine of ≥170µmol/L and serum urea of >20mmol/L were the identified predictors of mortality (95% CI, 1.098-6.243 RR= 2.618, p= 0.030 and 95% CI, 1.106-6.757, RR= 2.734 and p=0.029 respectively).