Hypertension and Kidney Disease - ECAB 9788131223420, 9788131231975, 8131231976

Table of contents :
Front cover
Title page
Copyright
ECAB Clinical Update:Nephrology
Hypertension andKidney Disease
About the Authors
Contents
ECAB Clinical Update InformationHypertension and Kidney Disease
ELSEVIER CLINICAL ADVISORY BOARD (ECAB)INDIA
STATEMENT OF NEED
HYPERTENSION AND KIDNEY DISEASE
TARGET AUDIENCE
Educational Objectives
DISCLAIMER
DISCLOSURE OF UNLABELED USES
DISCLOSURE OF FINANCIAL RELATIONSHIPSWITH ANY COMMERCIAL INTEREST
RESOLUTION OF CONFLICT OF INTEREST
CONTENT DEVELOPMENT COMMITTEE
ENQUIRIES
Introduction
Renal Artery Stenosis
Abstract
Keywords
Introduction
Etiologies
History, Experimental Models, and Pathogenesis of Hypertension in Ras
Clinical Features
Investigations
Anatomical Diagnosis
Duplex Ultrasound Scanning23
Arteriography and Digital Subtraction Angiography27
CT Angiography30
Magnetic Resonance Angiogram30,31
Investigations to Assess Functional Significance
Captopril Scintigraphy32
Renal Vein Renin Ratio33
Diagnostic Approach: An Overview
Unilateral Renal Artery Stenosis
Bilateral Renal Artery Stenosis
Management
Medical vs. Surgical Therapy
Conclusion
Childhood Hypertension: Emerging Concepts
Abstract
Keywords
Introduction
Prevalence of Primary and Secondary HypertensioN in Children
Childhood Hypertension: Techniques and Terms
Hypertension
Pre-hypertension
Masked Hypertension
White-Coat Hypertension
Etiology
Comorbid Factors
Clinical Presentation
Evaluation
Initial Evaluation
Additional Evaluation
Target End-Organ Damage Evaluation
Management of Pediatric Hypertension
Non-pharmacologic: Lifestyle Modifications
Pharmacologic
Hypertension and Progression of CKD
Hypertensive Emergencies
Surgery
Length of Therapy
Conclusion
Hypertension and Chronic Kidney Disease
Abstract
Keywords
Introduction
CKD and Hypertension: Global and Indian Disease Burden
CKD as Etiology of Hypertension
Hypertension as Etiology of CKD
Patient Assessment: Principles and Overview
Salient Points in Assessment and Planning Management
Proteinuria and Hypertension in CKD
Dyslipidemia and Hypertension
Metabolic Syndrome and Hypertension
Hypertension and Hyperuricemia in CKD
Target BP Levels Recommended in CKD Patients
Ambulatory BP Monitoring in CKD Patients
Management of Hypertension in CKD Patient
Lifestyle Modifications
Pharmacotherapy of Hypertension in CKD
RAAS Blockers
Diuretics
Calcium-Channel Blockers (CCB)
-Adrenergic Blockers
-Blockers
Monitoring BP in CKD Patients
Special Case Scenarios
Hypertension in Hemodialysis Patients
Resistant Hypertension
Post-transplant Hypertension
Conclusion
Case Studies Hypertension and Chronic Kidney Disease
Case 1
Case 2
Essential Hypertension: Pathogenesis and Pathophysiology
Abstract
Keywords
Introduction
Mechanism of Blood Pressure Control
Central Role of Kidney in Genesis of Essential Hypertension
Risk Factors for Development of Essential Hypertension
Genetics
Congenital Effects
Metabolic Syndrome and Obesity
Insulin Resistance and Hyperinsulinemia in Hypertension
High-Sodium and Low-Potassium Diets
Hyperuricemia
Stress
Physiological Alterations in Genesis of Essential Hypertension
Sympathetic Overactivity
Baroreceptor Dysfunction
Cardiac Output Alterations
Autoregulation
Peripheral Resistance
Cell Membrane Alterations
Endothelial Dysfunction
Renin-Angiotensin-Aldosterone System
Altered Renal Physiology in Hypertension
Resetting of Pressure Natriuresis
Sensitivity to Sodium
Acquired Natriuretic Hormone
Acquired Tubulointerstitial Disease as a Unifying Hypothesis in the Pathogenesis of Salt-Dependent Hypertension131
Conclusion
Prevention of Hypertension in Kidney Disease
Abstract
Keywords
Introduction
Global Burden of Hypertension
Hypertension Scenario in The Developing World
Increasing Prevalence in Developing World: Why?
Long-Term Risk of Hypertension
Hypertension Awareness, Treatment, and Control in Kidney Disease
Pre-hypertension: Is It Relevant?
Importance of Systolic Blood Pressure
Prevalence of Hypertension in Renal Disease
Chronic Kidney Disease: The Global Scenario
Chronic Kidney Disease: The Indian Scenario
"Treat Kidney To Cure Heart": The Relationship Between Ckd and Cvd
Starategies For Prevention of Hypertension in Kidney Disease
Preventive Strategies at the Community Level
Role of Primary Care Physician
Early Detection and Control of Modifiable Risk Factors
Early Detection and Control of Diabetes
Control of Obesity and Other Metabolic Risk Factors
Lifestyle Modification
Avoidance of Smoking
Reduced Salt Intake
Avoidance of Excessive Alcohol Consumption
Increased Physical Activity
Conclusion
Other Books in This Series

Citation preview

ECAB Clinical Update: Nephrology

Hypertension and Kidney Disease

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ECAB Clinical Update: Nephrology

Hypertension and Kidney Disease Suresh C. Tiwari Soumita Bagchi Sanjeev Gulati R.P. Mathur Madhivanan Sundaram Rahul Grover Umesh Gupta Vikram Kalra

Editor

Suresh C. Tiwari

ECAB Clinical Update: Nephrology

A division of Reed Elsevier India Private Limited

Copyright © 2010 Elsevier Mosby, Saunders, Churchill Livingstone, Butterworth Heinemann and Hanley & Belfus are the Health Science imprints of Elsevier. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying recording or otherwise, without the prior permission of the copyright holder. Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures, equipment, and the use of drugs become necessary. The authors, editors, contributors, and the publisher have, as far as possible, taken care to ensure that the information given in this text is accurate and up-to-date. However, readers are strongly advised to confirm that the information, especially with regard to drug dose/usage, complies with current legislation and standard of practice. Opinions expressed in this book are those of the authors and do not necessarily reflect those of Elsevier India Pvt. Ltd., the editors, or sponsors. Elsevier India Pvt. Ltd. assumes no liability for any material published herein. The publisher does not endorse the quality or value of the advertised/sponsored products described therein. Please consult full prescribing information before issuing prescriptions for any products mentioned in this publication. ISBN 978-81-312-2342-0 Published by: Elsevier, a division of Reed Elsevier India Private Limited Registered Office: Gate No. 3, Building No. A-1, 2 Industrial Area, Kalkaji, New Delhi - 110019 Corporate Office: 14th Floor, Tower 10B, DLF Cyber City, Phase-II, Gurgaon 122002, Haryana Printed at Solar Print Process Pvt Ltd., New Delhi

ECAB Clinical Update: Nephrology ELSEVIER CLINICAL ADVISORY BOARD MEMBERS Dr. D.S. Rana MD MNAMS (Nephrology)

Dr. Bharat V. Shah MD DNB

Sr. Consultant - Nephrologist Chairman, Dept. of Nephrology Sir Ganga Ram Hospital, New Delhi.

Anil Clinic, B-4, Shilpa Apartment, A-G Link Road, Chakala, Andheri (E), Mumbai. Lilavati Hospital & Research Centre, Bandra Reclamation, Bandra (W), Mumbai. Nanavati Hospital, S.V. Road, Vile Parle (W), Mumbai.

Dr. S.C. Tiwari MD DM FAMS FISN FGSI FIMSA Director of Nephrology & Transplant Medicine Fortis Institute of Renal Sciences Fortis Escort Heart Research Institute, New Delhi Former Professor & HOD, Nephrology, All India Institute of Medical Sciences, New Delhi.

Dr. Amit Gupta MD DNB Professor, Department of Nephrology, SGPGI, Lucknow.

Dr. Vivekananda Jha MD DM Additional Professor of Nephrology, Coordinator, Stem Cell Research Facility, Postgraduate Institute of Medical Education and Research, Chandigarh.

Dr. Vijay Kher MD DM FAMS Director of Nephrology & Renal Transplant Medicine, Fortis Healthcare Flt. Lt. Rajan Dhall Hospital, New Delhi.

Dr. H. Sudarshan Ballal MD (Med) Board Certified in Medicine, Nephrology & Critical Care (USA)

Head, Department of Nephrology Director, Manipal Institute of Nephrology & Urology, Manipal Hospital, Bangalore. Clinical Professor of Medicine, Kasturba Medical College, Manipal and Mangalore, MAHE (Deemed University).

Dr. Sanjay Kr. Agarwal MD FRCP DNB FIMSA MNAMS FISN FICP

Professor & Head Department of Nephrology, All India Institute of Medical Sciences, New Delhi.

Hypertension and Kidney Disease CONTRIBUTORS Dr. (Prof.) Suresh C. Tiwari Dr. Soumita Bagchi Dr. Sanjeev Gulati Dr. Vikram Kalra

Dr. R.P. Mathur Dr. Madhivanan Sundaram Dr. Rahul Grover Dr. Umesh Gupta

EDITOR Dr. (Prof.) Suresh C. Tiwari

ELSEVIER INDIA Clinical Education and Reference Division DIRECTOR Vidhu Goel

HEAD - MEDICAL SOCIETIES, AGENCY AND GOVT. RELATIONS Tarun Choudhry

HEAD, CLINICAL SPECIALTIES, SOUTH ASIA Dr. Shveta Dhamija

CONTENT MANAGER Dr. Arundhati Kar

CONTENT DESIGNER AND EDITOR Shravan Kumar

EDITORIAL OFFICE Elsevier, a division of Reed Elsevier India Private Limited 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon, Haryana – 122002, India. Telephone: + 91-124-4774444 Fax: + 91-124-4774100 E-mail: [email protected]

About the Authors A pioneer in renal care, Dr. S.C. Tiwari comes with a vast experience at the All India Institute of Medical Sciences (AIIMS) where he had served as Professor and Head of the Department of Nephrology. The Nephrology Department, under his leadership was rated the best in India for three consecutive years, according to a national survey. After 30 long years of meritorious term at AIIMS, Prof. Tiwari decided to move on and took premature retirement. Dr. Tiwari’s career is marked by unmatched excellence that got acknowledged in various ways. From being a Fellow of the National Academy of Medical Sciences, Indian Society of Nephrology, Geriatric Society of India to Best Nephrologist award from Vice-President of India, his accomplishments are too many. As an administrator, he has held positions of significance. He has been President of Indian Society of Haemodialysis; President, Indian Society of Nephrology; Chairman, Hospital Management Board, AIIMS; Member, Academic Committee, AIIMS, to name a few. He is also on the Advisory Board of UPSC and ICMR. As a Visiting Professor, Dr. Tiwari has been at the Albert Einstein College of Medicine, Winthrop University Hospital, Mineola and Long Island Jewish Medical Center, New York, US, University of Minnesota, Hennepin County Medical Center, Minneapolis, US as well as at the University of Manitoba, Winnipeg, Canada. He also has to his credit more than 275 national and international publications to date. In addition to his continued academic and educational endeavors, he is leading the Department of Nephrology & Transplant Medicine as Director in Fortis Institute of Renal Sciences and Fortis Escort Heart Research Institute, New Delhi. Dr. Soumita Bagchi is currently Consultant in Nephrology and Renal Transplantation Department in Rockland Hospital, New Delhi. She has a wide base of experience in renal transplant and dialysis beginning from All India Institute of Medical Sciences where she

ECAB Clinical Update: Nephrology   n   About the Authors

acquired her DM degree through Batra Hospital and Medical Research Centre where she was a Junior Consultant. She has many publications in eminent national and international journals to her credit and has been an active orator in various Nephrology conferences as well. Her areas of special interest include prevention of chronic kidney disease and its adverse outcomes and renal transplantation. Dr. Sanjeev Gulati is currently the Associate Director at Fortis Institute of Renal Sciences and Transplantation, New Delhi. He was previously working as Additional Professor in Nephrology at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow. He has also had the privilege of working as an Associate Professor in Nephrology at the prestigious McMaster University, Hamilton, Canada. He is qualified in adult and pediatric nephrology and has authored more than 130 scientific papers published in indexed journals including NEJM, Kidney International, and American Journal of Kidney Diseases. He has also authored 15 chapters in various textbooks (including the prestigious Oxford Textbook of Nephrology and Comprehensive Pediatric Nephrology). He has received several awards for his outstanding research from the Indian Council of Medical Research, Indian Academy of Pediatrics, Indian Society of Nephrology, Australian College of Pediatrics, Royal College of Pediatrics and Child Health UK, Royal College of Physicians and Surgeons of Canada, and the Japanese Society of Nephrology. He is a reviewer for several prestigious journals like Pediatrics, American Journal of Kidney Diseases, Pediatric Nephrology, and Indian Pediatrics. He has been in the Executive Committee of the Indian Society of Nephrology, Indian Society of Pediatric Nephrology, Peritoneal Dialysis Society of India, and Indian Society of Organ Transplantation. His areas of special interest include renal transplantation and kidney diseases in children. Dr. R.P. Mathur is the Director of Nephrology and Renal Transplant Medicine at Rockland Hospital, New Delhi. He began his journey in the field of medical sciences with two Gold Medals in Final MBBS at JLN Medical College, Ajmer and was in Merit List of University of Rajasthan in all three professional examinations in MBBS. He is

About the Authors   n   ECAB Clinical Update: Nephrology

also the recipient of prestigious National Scholarship. The title of “ISN Scholar” was conferred upon him by International Society of Nephrology after Fellowship in Clinical Nephrology at Manchester Institute of Nephrology & Transplantation, where he worked with Professor Sir Neter Mallick and Professor Ram Gokal, the renowned international icons in the field of Nephrology and CAPD. His other international assignments were associated with Apollo Hospitals and Ministry of Health, Government of Saudi Arabia. Dr. Mathur established Department of Nephrology at Western Railway Head Quarter Hospital at Mumbai in 1984. He has been a Post Graduate Teacher and Examiner for Diplomat National Board and served on important positions in the Zonal Chapters of Indian Society of Nephrology and Associations of Physicians of India. Dr. Mathur is an aluminus of All India Institute of Medical Sciences and Fellow of Indian College of Physicians. He has contributed chapters on kidney diseases in various medical books and presented papers in various national and international conferences and delivered guest lectures. His areas of special interest are prevention and retardation of progression of Chronic Kidney Disease. Dr. Madhivanan Sundaram is currently working as an Assistant Professor in Christian Medical College, Vellore. He has secured several distinctions as an undergraduate student and was the recipient of API Gold Medal in Internal Medicine during his postgraduation. He graduated in Nephrology from CMC, Vellore in 2007 and secured DNB the following year. In his fledgling career, he has five publications so far. He was awarded the JCM Shastry prize for the Best Outgoing Postgraduate during his DM. His areas of interest include chronic kidney disease, hemodialysis and peritoneal dialysis as well as bone and mineral metabolism.

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Contents ECAB Clinical Update Information.......................................... i Introduction...............................................................................1 Dr. (Prof.) Suresh C. Tiwari

Renal Artery Stenosis�����������������������������������������������������������������6 Dr. Madhivanan Sundaram and Dr. (Prof.) Suresh C. Tiwari

Childhood Hypertension: Emerging Concepts��������������������������30 Dr. Sanjeev Gulati

Hypertension and Chronic Kidney Disease�������������������������������49 Dr. Soumita Bagchi and Dr. Umesh Gupta

Essential Hypertension: Pathogenesis and Pathophysiology����������������������������������������������������������������������74 Dr. Vikram Kalra, Dr. Rahul Grover, and Dr. (Prof.) Suresh C. Tiwari

Prevention of Hypertension in Kidney Disease����������������������109 Dr. R.P. Mathur

Other Books in This Series�����������������������������������������������������129

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ECAB Clinical Update Information

Hypertension and Kidney Disease ELSEVIER CLINICAL ADVISORY BOARD (ECAB) INDIA ECAB is an endeavor of Elsevier, the leading publishing house worldwide in health sciences, with an aim to develop relevant content in clinical specialties and make them easily available to the medical professionals of India. In the first year of its inception, ECAB included clinical specialties like diabetes, cardiology, gastroenterology, and obstetrics & gynecology. In the second phase, ECAB extended its endeavor to four more clinical specialties, i.e., orthopedics, pediatrics, nephrology, and medicine. The aim of this concept is to explore the experience and learning of some of the eminent medical professionals of India and south-east Asia in their respective fields in addition to Elsevier’s own existing resources to create content, which is available in the form of various products and services for utilization by the Indian clinical practitioners. This concept is the first of its kind in the Indian medical scenario, and ECAB will extend this to every clinical discipline in the near future to serve the information needs of the Indian medical fraternity.

STATEMENT OF NEED Nephrology is a superspeciality that requires knowledge of a wide range of clinical presentations. Because of the involvement and interrelation of the various organ systems, it takes longer to acquire the pattern recognition and to be able to recognize rare presentations of common conditions and rare conditions that may be serious and difficult to diagnose. In this age, where at times there seems to be an overabundance of information, it is important for the practicing clinician to have an authoritative source of quality advice and genuine practice wisdom. Keeping in mind the requirements of the society, the practitioners need to update themselves on the current approach and the wide variety of choices now available. India has a distinct need for comprehensive programs i

ECAB Clinical Update: Nephrology   n   Information

that fit into the Indian context of the situation. It has to be a continuous process, which approaches the problem on the basis of the experience of the specialists in India who are among the stalwarts in this field. In its quest to better approach the topic, Elsevier has pooled its existing resources with those of the internationally acclaimed nephrologists of India who have chosen to apply their rich clinical knowledge and expertise to serve the Indian patients. This book provides a useful basis from which to view new perspectives in nephrology, coupled with the more traditional protocols. It will be a valuable learning tool and reference point for the many professionals engaged in nephrology work.

HYPERTENSION AND KIDNEY DISEASE Hypertension is fast becoming a pandemic of enormous proportions, and along with its sequelae such as cardiovascular and cerebrovascular adverse events it is a leading cause of morbidity and mortality worldwide. The intimate interrelationship of hypertension and kidney changes has already been established for quite some time now, but the exact mechanisms and causality are still being discovered. The role of kidney as evidenced by subtle changes in the initiation of even the so-called “primary hypertension” is increasingly being scrutinized. The effects of established renal causes that induce hypertension such as renal artery stenosis are well established. Even the pediatric population is no longer immune to this potentially debilitating condition. This book will help the reader to understand the intricacies of the genesis of hypertension and its effects on the kidney. It explores the various established guidelines and newer promising aspects in diagnosis and management of hypertension and the kidney changes that lead up to it as well as the changes induced in the kidney as a result of hypertension. Newer emerging concepts in the treatment of hypertension in the pediatric population have also been described in this book. The chapters on hypertension and chronic kidney disease and prevention of hypertension in kidney disease enlighten the reader about the benefits of timely management of the condition to prevent its progression to end-stage kidney disease, which requires expensive

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and invasive interventions not suitable to majority of population in a developing country like ours. The chapters in this book aim to guide the practitioner to diagnose and manage hypertension in the setting of suspected, diagnosed, or established kidney disease with special reference to practical experience of the same in India. The authors have put together the most relevant facts about the disease complex for an easy comprehension and understanding of the same by practitioners and students across the specialty.

TARGET AUDIENCE This book is intended for the Indian Nephrologists, advanced practitioners, and other healthcare professionals interested in the treatment of kidney and related disorders.

Educational Objectives Readers will find the contents of this book helpful to understand: •

the role of kidney in initiation and progression of hypertension;

•

the mechanisms underlying the development of primary hypertension;

•

the changes induced in kidney as a result of sustained uncontrolled systemic hypertension;

•

the effects of renal artery stenosis on hypertension and its management protocol;

•

the unique facets of childhood hypertension and its implications as well as management;

•

the vicious cycle of interrelation between hypertension and chronic kidney disease;

•

the means and importance of prevention of hypertension in patients suffering from established or suspected kidney diseases.

DISCLAIMER The content and views presented in this educational activity are those of the contributors and do not necessarily reflect the opinions or recommendations of the whole ECAB or Elsevier. The content has iii

ECAB Clinical Update: Nephrology   n   Information

been prepared based on a review of multiple sources of information, but is not exhaustive of the subject matter. Readers are advised to critically evaluate the information presented, and are encouraged to consult the available literature on any product or device mentioned in the content.

DISCLOSURE OF UNLABELED USES This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the Food and Drug Administration. Please consult relevant literature for information about approved uses.

DISCLOSURE OF FINANCIAL RELATIONSHIPS WITH ANY COMMERCIAL INTEREST As a provider of credible content, Elsevier requires that everyone is in a position to: control the content of an educational activity, disclose all relevant financial relationships with any commercial interest, and identify and resolve all conflicts of interest prior to the educational activity. The ECAB defines “relevant financial relationships” as any amount occurring within the past 12 months. Financial relationships are those relationships in which the individual benefits by receiving a salary, royalty, intellectual property rights, consulting fee, honoraria, ownership interest (e.g., stocks, stock options, or other ownership interest, excluding diversified mutual funds), or other financial benefit. Financial benefits are usually associated with roles such as employment, management position, independent contractor (including contracted research), consulting, speaking and teaching, membership on advisory committees or review panels, board membership, and other activities for which remuneration is received or expected. The ECAB considers relationships of the person involved in the educational activity to include financial relationships of a spouse or partner. For an individual with no relevant financial relationship(s), the participants must be informed that no relevant financial relationship(s) exist.

RESOLUTION OF CONFLICT OF INTEREST The ECAB has implemented a process to resolve conflict of interest for each book. In order to help ensure content objectivity, independence, and

iv

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fair balance, and to ensure that the content is aligned with the interest of the intended audience, the ECAB has the evaluation of content done by those members of ECAB who are not directly involved in the project.

CONTENT DEVELOPMENT COMMITTEE Dr. (Prof.) Suresh C. Tiwari MD DM FAMS FISN FGSI FIMSA Dr. Soumita Bagchi MD DM (Nephrology) Dr. Sanjeev Gulati MD DNB (Ped) DM DNB (Nephro) FIPN FIAP FRCPC (Can) MNAMS FISN

Dr. Vikram Kalra MD DM (Nephrology) Dr. R.P. Mathur MD DM (Nephrology) FICP Dr. Madhivanan Sundaram MD (Int Med) DM (Nephro) DNB (Nephro) Dr. Rahul Grover MD DM Dr. Umesh Gupta MD DM (Nephrology) Dr. Shveta Dhamija MBBS Dr. Arundhati Kar DNB Shravan Kumar

ENQUIRIES For content related enquiries, please contact us at [email protected].

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Introduction Hypertension is both a cause and effect of kidney disease. The kidney facilitates the initial elevation of blood pressure and in turn may suffer its consequences. On the other hand, presence of kidney disease may be the underlying undetected cause of hypertension in a given patient. Hypertension is one of the most important independent risk factors for development of kidney disease. It is in fact a key factor in the progression of chronic kidney disease (CKD). Additionally, the presence of renal disease is also a strong risk factor for cardiovascular morbidity and mortality. A significant proportion of patients with CKD die of cardiovascular adverse events even before reaching end-stage renal disease (ESRD). Hypertension and proteinuria are the major determinants of renal disease progression as well as cardiovascular morbidity and mortality. Therefore, adequate control of hypertension is the single most important intervention not only to retard the progression to CKD but also to reduce the cardiovascular risk. Essentially, it implies, “Treating the kidney to cure the heart!” Hypertension is not a single disease entity; rather it is a disease complex arising from multi-factorial etiology with different presentations depending on the interaction of the various factors that lead to it. Understandably, the condition cannot be treated by a single approach. The treatment has to be tailored according to the specific individual and etiological characteristics. This book addresses the various causes and presentations of this condition and outlines the recommended treatment protocols best suited to control each. Atherosclerotic Renal Artery Stenosis (ARAS) is a common, but often under-diagnosed and under-treated entity that is a potentially curable form of hypertension and renal disease in elderly population. A strong index of suspicion is needed in patients who exhibit evidence of atherosclerosis in other vascular systems, such as history of transient ischemic attacks, cerebrovascular stroke, ischemic heart disease, or 1

ECAB Clinical Update: Nephrology

Introduction

peripheral vascular disease. It is important to correctly diagnose ARAS not only for proper management of the condition but also to avoid the use of ACE inhibitors or ARBs, which are likely to have deleterious consequences in patients with bilateral kidney involvement. It is not “essential” to have hypertension! The age related rise in systolic BP is responsible for increased incidence and prevalence of hypertension with advancing age. Isolated systolic hypertension needs to be adequately controlled to reduce the morbidity and mortality associated with renal and cardiovascular diseases. Although it is seen more commonly in the elderly population, the seeds of hypertension may be sown in childhood itself. Hypertension and early stages of kidney disease usually go undetected in children in the absence of any regular health screening program and reluctance on the part of doctors to record children’s BP as a routine. The common conditions like posterior urethral valves and vesicoureteric reflux are often detected only when renal failure has already set in. It is important to pay attention and evaluate urinary symptoms, recurrent urinary tract infections, and growth retardation in children. All children above 3 years of age should have BP recording during their annual medical check-up. Especially in the pediatric population, and also in the general population, a single reading of high blood pressure may or may not diagnose hypertension. The entities like white coat hypertension and masked hypertension cannot be ignored. Wherever indicated, the use of ambulatory BP monitoring should be encouraged. Ambulatory BP monitoring (ABPM) provides round the clock information about BP levels during daily activities and sleep. Ambulatory BP readings are usually lower than office readings but correlate better with target organ injury. In majority of healthy persons, BP drops by 10–20% during night. Absence of nocturnal reduction in BP is associated with increased risk of cardiovascular events. Patients in whom ABPM has recorded BP >135/85 mmHg are nearly twice as likely to have a cardiovascular event as those with 24-hours mean BP 80% stenosis, presence of renal dysfunction, and poorly controlled hypertension (even on treatment with anti-hypertensives) are subjected to intervention if kidneys are more than 7.5 cm in length. Those who have flash pulmonary edema or worsening symptoms following ACE-inhibitor are also candidates for intervention. The more The more stenosed kidney or the side that is more dependent on renin pathway (detected by captopril scintigraphy or renal vein renin ratio) is usually managed first.

stenosed kidney or the side that is more dependent on renin pathway (detected by captopril scintigraphy or renal vein renin ratio) is usually managed first. Medical management alone is considered for elderly subjects and those who have milder stenosis, good control of blood pressure, significant co-morbidities, and preserved renal function.

MANAGEMENT Renal artery stenosis is claimed to be a reversible cause of hypertension. However, the patients are not always picked up early in the natural history of the disease. Thus, blood pressure may not actually be reversed following relief of obstruction. However, control of blood pressure may be significantly improved following intervention. The two goals of treatment of RAS are firstly, to control hypertension and secondly to control progression of renal insufficiency. 16

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The options available for patients with RAS are surgical treatment, percutaneous angioplasty, stent placement, and medical treatment.1 More than one modality may have to be chosen for effective control of blood pressure and cure. Older surgical treatments have now been replaced by endovascular interventions. Unilateral nephrectomy in patients with small poorly functional kidney (but having severe hypertension), renal autotransplantation, and bypass surgeries are the main surgical procedures still carried out. The procedures are made cumbersome by the presence of collaterals and atherosclerosis of the involved arteries. Advances in interventional radiology have made percutaneous procedures easy. Balloon angioplasty is commonly performed in most centers. Fibromuscular dysplasia is potentially curable with angioplasty. In RAS due to fibromuscular dysplasia, the blood pressure is usually ACE-inhibitors are acceptable in unilateral RAS and may be the drug of choice. However, they are contraindicated in bilateral RAS as they may precipitate severe renal failure.

well-controlled following the intervention, and relapse of the problem rarely occurs. Repeat procedures may be needed in only about 25% of cases.34 Restenosis is a common problem following angioplasty alone (without stenting) in atherosclerotic RAS. Implanting a stent after dilatation results in long lasting control. Antiplatelet therapy is recommended following stent placement. Stent re-stenosis may occur and so the patients have to be monitored periodically.35 Percutaneous revascularization is recommended for patients with hemodynamically significant RAS and accelerated hypertension, resistant hypertension, malignant hypertension, hypertension with an unexplained unilateral small kidney, and hypertension with intolerance to medication.36 Medical management consists of use of various antihypertensive agents alone or in combination. Aggressive blood pressure control, atherosclerotic risk factor modification, and use of antiplatelet therapy are indicated once the condition is diagnosed. The availability of powerful antihypertensive drugs has made blood pressure control easier than in the past. ACE-inhibitors and ARB deserve special mention 17

ECAB Clinical Update: Nephrology

because of their intervention in the pathophysiological cascade of RAS. ACE-inhibitors are acceptable in unilateral RAS and may be the drug of choice. However, they are contraindicated in bilateral RAS as they may precipitate severe renal failure. There may be a transient worsening of renal function following introduction of these drugs, which usually settles down. Calcium-channel blockers, beta-blockers, and alphablockers may also be used for control of blood pressure.36

Medical vs. Surgical Therapy The controversy as to whether endovascular intervention is superior to medical therapy has still not been settled. Trials that have been done to address this problem have very small sample size as well as methodological fallacies. In a meta-analysis published recently, hypertension was cured in only 20% and 10% respectively following Where hypertension is refractory to medical therapy, there is weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. Balloon angioplasty appears to be safe and shows fewer cardiovascular and renovascular complications.

stenting and PTRA (percutaneous renal angioplasty), but improved control of blood pressure occurred in 49% and 53% patients, respectively. Renal function improved or stabilized in about 30% and 40% and worsened in 20% and 30%, respectively. There was no response in about 30% of patients in both groups.37 The Dutch Renal Artery STenosis Intervention Cooperative (DRASTIC) study is the largest randomized study performed so far incorporating 106 patients.38 Patients with atherosclerotic renal artery stenosis were randomized to balloon angioplasty (n = 56) versus antihypertensive medication (n = 50). Three months after randomization, 22 patients from the medication group underwent balloon angioplasty in an intention-to-treat analysis. No difference in blood pressure was found between the groups after 3 months, nor after 12 months of followup, although there was a small medication-sparing effect of balloon 18

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angioplasty. Renal function after angioplasty was slightly better in the angioplasty group than in the medication group, and improvement of the renal scintigram occurred more often after angioplasty. The authors concluded that angioplasty offered little advantage over medical management. A systematic review done by Cochrane group compared the role of intervention to medical management.39 Three large studies by Plouin et al., Webster et al., and Van jaarsveld et al. were included for this systematic review. The authors came to the consensus that “available data are insufficient to conclude that balloon angioplasty is superior to medical therapy in lowering blood pressure of people with renal artery stenosis and pharmacologically controlled blood pressure. Where hypertension is refractory to medical therapy, there is weak evidence that balloon angioplasty lowers blood pressure more effectively than medical therapy. Balloon angioplasty appears to be safe and shows fewer cardiovascular and renovascular complications”. Thus with the present level of knowledge, it is difficult to categorize patients to medical or surgical therapy. Clinician’s experience is still to be deployed for finalizing one or the other mode of therapy. Large randomized trials are required to study this important problem. Trials like CORAL, RAVE, and ASTRAL are underway to study the usefulness of these two methods of management.40–42 Rational decisions should be taken with understanding of the pathogenetic concepts, clinical features, and outcome of investigations.

CONCLUSION Renal artery stenosis is an important clinical condition. Atherosclerosis is the commonest cause. Early identification of this problem can result in cure in a significant proportion of patients. Astute clinical skills have to be applied to diagnose this problem (Table 1).43 Prudence has to be applied when investigations are chosen to diagnose the condition (Figure 1). As treatment options are controversial, medical and surgical intervention procedures have to be judiciously selected and combined to give the best benefit to patients to control blood pressure and to preserve renal function. 19

20

Intervention

Medical management

BRAS

MRA/CTA

Deterioration of renal function

Solitary kidney

Bilateral disease

Malignant hypertension

Flash pulmonary edema

Resistant hypertension

Consider intervention

Size >7.5 cm

Poor control and/or progression

Re-evaluation

Stable renal function, controlled BP

Lifestyle changes, antihypertensive drugs with other supportive drugs

Functional assessment—Blood pressure, renal size, renal function

Doppler evaluation

Figure 1. Management approach to renal artery stenosis.

Significant

Not significant

Captopril angiogram

MRA/CTA

URAS

Clinical evidence of RAS

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Table 1. Testing for Renovascular Hypertension43 Low index of suspicion (should not be tested) Borderline hypertension Mild to moderate hypertension Moderate index of suspicion (non-invasive tests recommended) Severe hypertension (diastolic blood pressure >120 mmHg) Hypertension refractory to standard therapy, excluding ACEinhibitor or ARB Abrupt onset of sustained, moderate to severe hypertension at age 50 years Hypertension with a suggestive abdominal or flank bruit Moderate hypertension (diastolic blood pressure >105 mmHg) in a smoker or evidence of occlusive vascular disease or unexplained but stable serum creatinine elevation Normal blood pressure in a hypertensive smoker or recently diagnosed moderate to severe hypertensive patient on ACEinhibitor or an ARB treatment High index of suspicion (consider proceeding directly to arteriography) Severe hypertension (diastolic blood pressure >120 mmHg) with either progressive renal insufficiency or refractory hypertension even with aggressive treatment, particularly in a patient who has been a smoker or who has other evidence of occlusive arterial disease Accelerated or malignant hypertension (grade III or grade IV retinopathy) Hypertension with recent elevation of serum creatinine, either unexplained or reversibly induced by an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker Moderate to severe hypertension with incidentally detected asymmetry of renal size

REFERENCES 1. 2.

Textor SC. Current approaches to renovascular hypertension. Med Clin North Am 2009;93:717–32. Don BR, Schambelan M, Lo JC. Endocrine hypertension. In: Greenspan FS, Gardner DG, eds. Basic and Clinical Endocrinology 7th ed. United States of America: The McGraw-Hill companies; 2004:432.

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3.

4.

5.

6. 7. 8.

9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

19. 20.

21. 22.

22

Balk E, Raman G, Chung M, et al. Effectiveness of management strategies for renal artery stenosis: a systematic review. Ann Intern Med 2006;145: 901–12. Fava C, Minuz P, Patrignani P, Morganti A. Renal artery stenosis and accelerated atherosclerosis: which comes first? J Hypertens 2006;24: 1687–96. Kendrick J, Chonchol M. Renal artery stenosis and chronic ischemic nephropathy: epidemiology and diagnosis. Adv Chronic Kidney Dis 2008; 15:355–62. Plouin PF, Perdu J, La Batide-Alanore A, Boutouyrie P, Gimenez-Roqueplo AP, Jeunemaitre X. Fibromuscular dysplasia. Orphanet J Rare Dis 2007;2:28. Panja M, Mondal PC. Current status of aortoarteritis in India. J Assoc Physicians India 2004;52:48–52. Glodny B, Glodny DE. John Loesch, discoverer of renovascular hypertension, and Harry Goldblatt: two great pioneers in circulation research. Ann Intern Med 2006;144:286–95. Pickering TG. Renovascular hypertension: etiology and pathophysiology. Semin Nucl Med 1989;19:79–88. Atlas SA, Rosendorff C. The renin-angiotensin system--from Tigerstedt to Goldblatt to ACE inhibition and beyond. Mt Sinai J Med 1998;65:81–6. Skott O, Jensen BL. Cellular and intrarenal control of renin secretion. Clin Sci (Lond) 1993;84:1. Basso N, Terragno NA. History about the discovery of the renin-angiotensin system. Hypertension 2001;38:1246–9. Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med 2008;264:224–36. Bastl CP, Hayslett JP. The cellular action of aldosterone in target epithelia. Kidney Int 1992;42:250–64. Textor SC. Pathophysiology of renovascular hypertension. Urol Clin North Am 1984;11:373–81. Brown JJ, Davies DL, Morton JJ, et al. Mechanism of renal hypertension. Lancet 1976;1:1219–21. Safian RD. Atherosclerotic renal artery stenosis. Curr Treat Options Cardiovasc Med 2003;5:91–101. Krijnen P, van Jaarsveld BC, Steyerberg EW, Man in’t Veld AJ, Schalekamp MA, Habbema JD. A clinical prediction rule for renal artery stenosis. Ann Intern Med 1998;129:705–11. Kumar SC. Bilateral renal artery stenosis presenting as flash pulmonary edema. J Assoc Physicians India 2006;54:651–4. Eipper DF, Gifford RW Jr, Stewart B, Alfidi RJ, McCormack LJ, Vidt DG. Abdominal bruits in renovascular hypertension. Am J Cardiol 1976;37: 48–52. Sharma BK, Jain S, Suri S, Numano F. Diagnostic criteria for Takayasu arteritis. Int J Cardiol 1996;54 Suppl:S141–7. Bosmans JL, De Broe ME. Renovascular hypertension: diagnostic and therapeutic challenges. JBR-BTR 2004;87:32–5.

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23. Riehl J, Fritz A, Sieberth HG. The use of duplex sonography in the diagnosis of renal artery stenosis. Eur J Med Res 1997;2:14–22. 24. Olin JW. Role of duplex ultrasonography in screening for significant renal artery disease. Urol Clin North Am 1994;21:215–26. 25. Olin JW, Piedmonte MR, Young JR, DeAnna S, Grubb M, Childs MB. The utility of duplex ultrasound scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 1995;122:833–8. 26. Radermacher J, Chavan A, Schäffer J, et al. Detection of significant renal artery stenosis with color Doppler sonography: combining extrarenal and intrarenal approaches to minimize technical failure. Clin Nephrol 2000;53:333–43. 27. Geisinger MA, Pohl MA. Renal angiography. In: Jacobson HR, Striker GE, Klahr S, eds. Principles and Practice of Nephrology St. Louis: Mosby Year Book; 1965:55. 28. Hillman BJ. Digital radiology of the kidney. Radiol Clin North Am 1985;23: 211–26. 29. Liss P, Eklöf H, Hellberg O, et al. Renal effects of CO2 and iodinated contrast media in patients undergoing renovascular intervention: a prospective, randomized study. J Vasc Interv Radiol 2005;16:57–65. 30. Josephs SC. Techniques in interventional radiology: renal CT angiography. Tech Vasc Interv Radiol 2006;9:167–71. 31. Potthast S, Maki JH. Non-contrast-enhanced MR imaging of the renal arteries. Magn Reson Imaging Clin N Am 2008;16:573–84. 32. Leiner T, Michaely H. Advances in contrast-enhanced MR angiography of the renal arteries. Magn Reson Imaging Clin N Am 2008;16:561–72. 33. Maisey M. Radionuclide renography: a review. Curr Opin Nephrol Hypertens 2003;12:649–52. 34. Rabbani MA, Zaidi A, Ahmad B, et al. Pre-operative renal function and selective renal vein renin levels as markers of favourable outcome in renovascular hypertension. J Pak Med Assoc 2007;57:178–81. 35. Alhadad A, Mattiasson I, Ivancev K, Gottsäter A, Lindblad B. Revascularisation of renal artery stenosis caused by fibromuscular dysplasia: effects on blood pressure during 7-year follow-up are influenced by duration of hypertension and branch artery stenosis. J Hum Hypertens 2005;19:761–7. 36. Zeller T, Rastan A, Rothenpieler U, Müller C. Restenosis after stenting of atherosclerotic renal artery stenosis: is there a rationale for the use of drugeluting stents? Catheter Cardiovasc Interv 2006;68:125–30. 37. Hirsch AT, Haskal ZJ, Hertzer NR, et al. American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. J Am Coll Cardiol 2006;47:1239–312.

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38. Leertouwer TC, Gussenhoven EJ, Bosch JL, et al. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology 2000;216:78–85. 39. van Jaarsveld BC, Krijnen P, Pieterman H, et al. The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group. N Engl J Med 2000;342:1007–14. 40. Tobe SW, Atri M, Perkins N, Pugash R, Bell CM. Renal atherosclerotic revascularization evaluation (RAVE study): study protocol of a randomized trial [NCT00127738]. BMC Nephrol 2007;8:4. 41. Cooper CJ, Murphy TP, Matsumoto A, et al. Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: rationale and design of the CORAL trial. Am Heart J 2006;152:59–66. 42. Mistry S, Ives N, Harding J, et al. Angioplasty and STent for Renal Artery Lesions (ASTRAL trial): rationale, methods and results so far. J Hum Hypertens 2007;21:511–5. 43. Mann SJ, Pickering TG. Detection of renovascular hypertension. State of the art: 1992. Ann Intern Med 1992;117:845.

24

Case Studies

Renal Artery Stenosis CASE 1 A 25-year-old male presented with complaints of high blood pressure that required four drugs for control. As part of secondary evaluation Doppler was done, which showed a doubtful left renal artery stenosis (resistive index 0.33 and peak systolic velocity of 190 cm/s in the mid left renal artery) (Figure 1). It was confirmed with an MRA (Figure 2). Captopril angiogram showed decline in glomerular filtration rate (GFR) on the left kidney post captopril (Figure 3). Because of his young age, requirement of many drugs for blood pressure control, and positive captopril test, he was advised intervention (2k1c model requiring intervention. Reason: Severe hypertension, young age, positive captopril scintigraphy).

Figure 1. Renal Doppler: Borderline high peak systolic velocity (191.5 cm/s) at the mid segment of left renal artery. As the resistive index was also low, renal artery stenosis was suspected. 25

ECAB Clinical Update: Nephrology

Figure 2. Magnetic resonance angiogram in the same patient (anterior left view): Stenosis of the left main renal artery just distal to the origin. 220 200 180 160 140 120 100 80 60 40 20 0

0

2

4

6

8

10 12 14 16 18 20

280 260 240 220 200 180 160 140 120 100 80 60 40 20 0

0

2

4

6

8

10 12 14 16 18 20

Figure 3. Pre- and post-captopril images. The second image shows a decline in glomerular filtration rate in the left kidney (blue trace). This indicates dependence of renin–angiotensin axis in the preservation of glomerular filtration of the involved kidney.

CASE 2 A 54-year-old renal allograft recipient after 5 years of renal transplantation presented with worsening hypertension and mild graft dysfunction. Doppler showed transplant renal artery stenosis. He was managed with increase in anti-hypertensive drugs. As he was waiting for his intervention, he developed an acute onset of breathlessness with accelerated blood pressure. He needed ventilation and intravenous 26

Case Studies

Sundaram and Tiwari

nitroglycerine for blood pressure control. After stabilization, he underwent angioplasty and stenting (Figure 4) (1k1c model requiring intervention. Reason: Severe and resistant hypertension, solitary renal status, worsening of renal function, and flash pulmonary edema).

Figure 4. Renal artery stenosis involving the origin of transplant renal artery before and after intervention. Note the irregularity in the first image and the stent in the second.

CASE 3 A 28-year-old girl was told to have mild blood pressure. She was taking one drug for blood pressure control, and her renal function was normal. On evaluation with Doppler, it was found that her right kidney is not visualized and there was evidence of left renal artery stenosis (Figure 5). C-reactive protein was normal. She was subjected to an MRA, which showed stenosis involving the suprarenal and infrarenal segments of aorta (Figure 6). There was a stenosis in the left main renal artery. The right renal artery was not visualized. DTPA renogram showed non-functional right kidney (Figure 7). Arteriography was performed, which showed mild stenosis in the left renal artery without significant gradient across the stenosis. The aortic narrowing was also not significant. She was advised medical management only (1k1c model not requiring intervention. Reason: Mild hypertension, no significant anatomical stenosis, normal renal function).

27

ECAB Clinical Update: Nephrology

Figure 5. Doppler showing increased peak systolic velocity in the mid segment of left renal artery (267 cm/s)—evidence of renal artery stenosis.

Figure 6. Stenosis involving the left main renal artery with stenosis of supra- and infra-renal aortic segments. The right renal artery and kidney are non-traceable.

28

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400

Counts / sec

300

200

100

0 0

10

20 min

30

40

Lt kidney Rt kidney Rt BRG Lt BRG

Figure 7. DTPA renogram showing good function of the left kidney with non-functioning right kidney.

29

Childhood Hypertension: Emerging Concepts Dr. Sanjeev Gulati

MD DNB (Ped) DM DNB (Nephro) FIPN FIAP FRCPC (Can) MNAMS FISN

Associate Director, Dept. of Nephrology Fortis Institute of Renal Sciences and Fortis Escort Heart Research Institute, New Delhi

ABSTRACT:  Hypertension  often  begins  in  childhood,  and  children  can  inherit  the  tendency  from  one  or  both  parents.  A  child  is  said  to  be  hypertensive  if  the  average  systolic  blood  pressure  (SBP)  and/or  diastolic  blood  pressure  (DBP)  is  more  than  the  95th  percentile  for  gender,  age,  and  height  on  more  than  three  occasions.  For  measurement  of  blood  pressure,  the  mercury sphygmomanometer remains the method of choice. All  children  beyond  3  years  of  age  should  have  a  yearly  blood  pressure evaluation during their routine check‐ups.  The prevalence of persistent secondary hypertension in children  is  about  0.1%,  and  renal  disease  predominates  in  this  group.  Most  acute  hypertension  in  childhood  is  due  to    

30a

glomerulonephritis.  Chronic  hypertension  is  most  commonly  associated  with  renal  parenchymal  disease,  and  only  a  small  proportion  has  underlying  conditions  like  renovascular  hypertension,  pheochromocytoma,  or  coarctation  of  the  aorta.  The extent of evaluation depends on the age of child, severity of  hypertension,  extent  of  end‐organ  damage,  and  the  long‐term  risk  factors  for  the  individual  patient.  Medical  management  needs  to  be  initiated  promptly  for  even  persistent  mild  hypertension  as  soon  as  it  is  detected  in  a  child.  Education,  anticipatory  guidance,  early  detection,  accurate  diagnosis,  and  effective  therapy  may  help  to  improve  the  long‐term  outcomes  of  children  and  adolescents  affected  by  this  potentially  debilitating and possibly fatal condition.   

KEYWORDS:  Childhood  hypertension,  ambulatory  blood  pressure, automated oscillometric  devices,  small cuffs,  essential  hypertension, syndrome X, white‐coat effect.   

30b

Childhood Hypertension: Emerging Concepts Dr. Sanjeev Gulati

MD DNB (Ped) DM DNB (Nephro) FIPN FIAP FRCPC (Can) MNAMS FISN

Associate Director, Dept. of Nephrology Fortis Institute of Renal Sciences and Fortis Escort Heart Research Institute, New Delhi

INTRODUCTION Hypertension is perhaps one of the commonest human diseases with an estimated worldwide prevalence of one billion. Data from the third NHANES (National Health and Nutritional Assessment Survey) survey reveals that in United States, one-third of the people were unaware of this problem and another one-third had BP control below the established goals.1 To add to this is the observation made by the seventh JNC (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) that each increment of 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in diastolic blood pressure (DBP) doubles the risk of cardiovascular disease (CVD) across the entire BP range from 115/75 to 185/115 mmHg in people aged 40–70 years.2 In the present scenario where the age, gender, and height need to be taken into account while interpreting blood pressure values, there is a dearth of similar data in children. However, all this does bring home the message that blood pressure control in children too needs to be much tighter than we have accepted in the past. Hypertension often begins in childhood, and children can inherit the tendency from one or both parents. According to many studies performed in adult populations, the effective treatment of hypertension reduces the risk of coronary heart disease, stroke, renal disease, and congestive heart failure. 3 It has been established beyond doubt that early detection of high blood pressure will improve health care of children. 30

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PREVALENCE OF PRIMARY AND SECONDARY HYPERTENSION IN CHILDREN The prevalence of hypertension in the pediatric age group is reported to be about 1–3%. The American Heart Association recommends yearly blood pressure measurements in children beyond 3 years of age. However, as this practice is rarely followed, these figures may be an underestimate. In recent years, the prevalence of hypertension in school-aged children appears to be increasing, perhaps as a result of the increased prevalence of obesity. A school-based BP screening and measurement of height and weight performed in 5102 children (mean age 13.5 years) in 2002 revealed that the prevalence of hypertension in childhood is 4.5%, which is higher than that reported earlier.4 Most of the children with hypertension have only a mild increase in A school-based BP screening and measurement of height and weight performed in 5102 children (mean age 13.5 years) in 2002 revealed that the prevalence of hypertension in childhood is 4.5%, which is higher than that reported earlier.

blood pressure and belong to the category of primary (essential) hypertension. In these children, the condition can be diagnosed and managed by pediatricians. However, there is a small group of children with much higher blood pressure, most of whom suffer from secondary hypertension. The prevalence of persistent secondary hypertension in children is about 0.1%, and renal disease predominates in this group. Education, anticipatory guidance, early detection, accurate diagnosis, and effective therapy may help to improve the long-term outcomes of children and adolescents affected by this “silent killer.”

CHILDHOOD HYPERTENSION: TECHNIQUES AND TERMS The ideal technique of measuring blood pressure in a child is by a standard mercury sphygmomanometer on the child’s right arm with the cuff size covering 80–100% of the circumference of the arm.5 Despite the 31

ECAB Clinical Update: Nephrology

availability of new fancy electronic monitors, the mercury instrument still remains the method of choice. The aneroid sphygmomanometer can also be used but it needs to be periodically calibrated with the mercury instrument. Automated oscillometric devices are useful but expensive and require significantly more maintenance and calibration. However, these automated devices can be very helpful in evaluating infants and small children in whom resting, quiet, auscultatory readings often are difficult to obtain. The cuff should encircle at least 80–100% of the arm and the bladder length should be >40% of the arm circumference.6 Inappropriately small cuffs will give aberrantly high readings, whereas inappropriately large cuffs will underestimate the true reading. Measurements should be taken after 3–5 minutes of resting. Children should have measurements taken while sitting, with the arm at the level of the heart, and infants should have measurements taken while supine. Ambulatory blood pressure monitoring (ABPM) is based on the Inappropriately small cuffs will give aberrantly high readings, whereas inappropriately large cuffs will underestimate the true reading. Measurements should be taken after 3–5 minutes of resting.

principle that repeated measurements of blood pressure throughout a 24-hour period provide a better approximation of a true blood pressure level than does a single measurement. Because ABPM values have not been precisely correlated with single or repeated conventional cuff measurements, cuff and ABPM measurements cannot be used interchangeably, either for clinical management or in trials of antihypertension agents. Both types of measurements should therefore be evaluated according to respective standard values.7 A definition of hypertension ideally is based on a threshold level of blood pressure that divides those at risk for adverse outcomes from those who have no increased risk. Unfortunately, an identifiable cutoff does not exist. Hence, arbitrary thresholds have been established based on epidemiologic data compiled from large number of children. The current normative values are based on the “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”.6 As per the current NHBPEP (National 32

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High Blood Pressure Education Program) guidelines, the various terms associated with increased blood pressure are as follows:

Hypertension It is defined as an average systolic BP and/or diastolic BP that is above the 95th percentile (Table 1) for respective gender, age, and height as measured on more than three distinct occasions. If the BP is >95th percentile, it should be staged into stage 1 or 2. Stage 1 includes those with BP in the range of 95th percentile to the 99th percentile plus 5 mmHg. In these cases, BP measurements should be repeated on two more occasions. If hypertension is confirmed, evaluation should proceed. If BP is stage 2 (>99th percentile plus 5 mmHg), prompt referral should be made for evaluation and therapy. If the patient is symptomatic, immediate referral and treatment are indicated.

Pre-hypertension In children pre-hypertension is defined as average SBP or DBP levels that are above the 90th percentile but below the 95th percentile of blood pressure measurements. These children should be observed carefully and evaluated for the presence of risk factors like obesity. The tracking data suggest that this subgroup is more likely to develop

Table 1. Percentile (Pc) Blood Pressure Readings for Children According to Age and Gender (all readings in mmHg) Age (y)

Girls

Boys

5th Pc

50th Pc

95th Pc

5th Pc

50th Pc

95th Pc

1

101/57

104/58

107/60

98/55

102/53

106/59

6

108/71

111/73

114/75

109/72

114/74

117/76

12

120/79

123/80

126/82

119/79

123/81

127/83

17

126/83

129/84

132/86

132/85

136/87

140/89

33

ECAB Clinical Update: Nephrology

overt hypertension over time than more normotensive children.8 In adolescents, as with adults, BP levels of more than 120/80 mmHg is considered pre-hypertensive.

Masked Hypertension This is seen when blood pressure is normal when the child or adolescent is in the doctor’s chamber, but the child or adolescent is actually hypertensive. It is especially important to identify masked hypertension in children with an underlying renal disease because the elevated blood pressures may contribute to the progression of the renal disease. Even in the absence of elevated blood pressure in hospital settings, a carefully elicited history can point out those at increased risk of hypertension. Children with a history of hypertension in family members, and those who are obese, have UTI and renal scars, or a Current consensus recommendations from the NHBPEP state that blood pressure should be measured in all children and adolescents 3 years or older at all medical encounters, as well as in selected children less than 3 years old at risk for hypertension.

gestational history of IUGR are more likely to have hypertension. Hence, this subgroup needs to be monitored more closely. Current consensus recommendations from the NHBPEP state that blood pressure should be measured in all children and adolescents 3 years or older at all medical encounters, as well as in selected children less than 3 years old at risk for hypertension.

White-Coat Hypertension A person is said to have white-coat hypertension in the BP levels that person is above the 95th percentile in a physician’s office or clinic, but is normal outside a clinical setting. Children with white-coat hypertension are detected when they have isolated office hypertension while their BP is repeatedly normal when measured at home, at work, or by ambulatory BP monitoring. The prevalence is reported to be 45–60%. It is higher when the office 34

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values reveal borderline or mild hypertension, and much lower with moderate or severe hypertension.9 These patients have a relatively benign outcome compared to those with sustained hypertension. They may be at increased risk for eventual sustained hypertension and cardiovascular disease, although the risk of cardiovascular complications appears to be low as long as the ambulatory pressure remains normal. It is possible that white-coat hypertension in children represents two populations: one with an exaggerated stress response destined to develop essential hypertension, and the other to have persistent white-coat hypertension or revert to normotension.

ETIOLOGY Hypertension is usually described as primary (or “essential”) or secondary, i.e., resulting from a definable cause. Although essential hypertension by far the most common cause of hypertension in the adult population, in the pediatric population, it is a significant cause more within the adolescent age group. In a younger patient with severe hypertension, it is more likely that the hypertension is secondary to an underlying cause. The astute pediatrician should tailor his or her evaluation appropriately to distinguish one from the other.

Table 2. Distribution of Common Causes of Hypertension in Different Age Groups Age group

Common causes

Newborns

Renal artery thrombosis, renal artery stenosis, congenital renal malformation, coarctation of aorta, bronchopulmonary dysplasia

Infancy–6 years

Renal parenchymal disease, coarctation of aorta, renal artery stenosis

6–10 years

Essential hypertension (including obesity), renal artery stenosis, renal parenchymal diseases

Adolescence

Essential hypertension (including obesity), renal parenchymal diseases

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ECAB Clinical Update: Nephrology

Most cases of acute hypertension in childhood are due to glomerulonephritis. Chronic hypertension is most commonly associated with renal parenchymal disease, and only a small proportion has renovascular hypertension, pheochromocytoma, or coarctation of the aorta (Table 2). Late in the first decade and into the second decade of life, primary hypertension begins to predominate as the prominent cause.10 Coarctation of the aorta accounts for up to one-third of the cases of hypertension in neonatal period and infancy. Renovascular causes are among the curable forms of hypertension.11 In the Asian continent, aortoarteritis is the commonest cause and accounts for the major portion of patients presenting with malignant hypertension.12 Endocrine etiologies like congenital adrenal hyperplasia, primary hyperaldosteronism, and Liddle’s syndrome are rare causes of hypertension in children.

COMORBID FACTORS Essential hypertension is often associated with a family history of hypertension. Children whose blood pressures are measured in the higher percentiles tend to remain in those higher percentiles even in adulthood. Obesity is a common cofactor in the development of essential hypertension, with approximately 50% of hypertensive teens qualifying as obese. Although poorly understood, obesity probably contributes to blood pressure through high sodium intake and insulin resistance among other factors. The so-called “syndrome X” of hypertension, obesity, hyperlipidemia, and diabetes mellitus is clearly a major cause of long-term cardiovascular morbidity and mortality. Sleep disorders including sleep apnea are associated with hypertension, coronary artery disease, heart failure, and stroke in adults. The limited data available on childhood hypertension points at an association between sleepdisordered breathing and higher BP in children. Approximately 15% of children snore, and at least 1–3% have sleep-disordered breathing. Because of the association with hypertension and the frequency of occurrence of sleep disorders, particularly among overweight children, a history of sleeping patterns should always be obtained in a child with hypertension.6

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CLINICAL PRESENTATION Young infants may present in acute distress with signs and symptoms of congestive heart failure. In contrast, after infancy hypertension is usually silent. For this reason, it is appropriate to measure blood pressure as a part of all routine medical examinations. Patients who have severe hypertension may complain of headache, vision changes, nose-bleeds, or nausea, and if a child present with any of these symptoms, the condition should be treated immediately. A more severe manifestation of the condition includes hypertensive emergencies. Hypertensive emergencies are defined as the presence of severe hypertension associated with lifethreatening or organ-threatening complications, such as encephalopathy (seizures, stroke, focal deficits), cardiopathies (acute heart failure, myocardial infarction), pulmonary edema, dissecting aortic aneurysm, acute renal failure, or eclampsia. Severe hypertension always should Young infants may present in acute distress with signs and symptoms of congestive heart failure. In contrast, after infancy hypertension is usually silent.

be considered in the differential diagnosis of congestive heart failure in childhood, even in the absence of other symptoms or diseases suggestive of high blood pressure. Due attention needs to be paid to physical examination and anthropometric measurements such as height, weight, and body mass index. A meticulous physical examination and anthropometry may reveal signs associated with the specific underlying cause of hypertension, e.g., weak pulses and blood pressure differences between the upper and lower limbs in coarctation of the aorta, café-au-lait skin patches, or other features of neurofibromatosis with renal artery disease, abdominal masses in polycystic kidney disease. Signs and symptoms of cardiomegaly, hypertensive retinopathy, or neurological involvement are particularly important, since they indicate long-standing hypertension.

EVALUATION The extent of evaluation depends on the age of the child, severity of hypertension, extent of end-organ damage, and the long-term 37

ECAB Clinical Update: Nephrology

risk factors for the individual patient. Children with blood pressure levels exceeding the 90th percentile have 2.4 times the risk of having hypertension in adulthood compared with children with levels below the 90th percentile13 Since blood pressure is known to be quite labile in childhood, and since there is a high prevalence of the “white coat” effect in the young, it is recommended that elevated blood pressure measurements be repeated before a child is identified as hypertensive and a diagnostic evaluation is undertaken.

Initial Evaluation This can be performed by the general pediatrician. A thorough personal and family history should be elicited. This should include specific questions regarding neonatal development course, urinary tract infections, other significant medical illnesses or traumas, medication use, and family history of hypertension, early cardiovascular or A meticulous physical examination and anthropometry may reveal signs associated with the specific underlying cause of hypertension.

cerebrovascular events, or end-stage renal disease. The physical examination includes evaluation of all four extremity pulses and blood pressure, bruits, and skin lesions in addition to the standard components. This should be followed up by urine dipstick examination and baseline chemistry (Table 3). The initial phases of evaluation should characterize the severity of hypertension and identify common causes that require additional evaluation.

Additional Evaluation All children with hypertension need a nephrology consult for additional evaluation as by definition, essential hypertension is a diagnosis of exclusion. Some form of renal imaging is mandatory, and a combination of abdominal ultrasound and 99Tc-dimercaptosuccinic acid (DMSA) static scanning is very useful. The 99Tc-dimercaptosuccinic acid static scan is more sensitive than conventional intravenous urography, and requires less exposure to radiation. Hence, DMSA scan is considered the gold standard for diagnosis of renal scarring. Abdominal 38

Childhood Hypertension

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Table 3. Diagnostic Evaluation of a Hypertensive Child Level I (Initial evaluation) Full blood count Serum electrolytes, uric acid and renal function tests, lipid profile Urinalysis Urine culture Renal ultrasound Level II (Additional tests as indicated) Echocardiography Nuclear scans—DMSA, captopril renography, DTPA Doppler ultrasound of renal arteries Serum T3, T4, TSH Urinary catecholamines Measurement of plasma aldosterone and plasma renin activity and urine steroids MIBG scan Renal arteriography/DSA (only after urinary catecholamines have excluded pheochromocytoma)

ultrasound detects tumors of the adrenal gland and the kidneys and is also very valuable in the diagnosis of cystic renal diseases, renal calculi, dilatation of the collecting system, and presence of duplex system, ureterocele, and thickened bladder wall. Since it does not give any functional information, it has to be combined with a Lasix DTPA (diethylene triamine pentacetic acid) scan if an obstructive uropathy is suspected (Table 3). An MCU (micturating cystourethrogram) may be done in children under 2 years of age to stage the degree of reflux and plan the further management.

Target End-Organ Damage Evaluation The evaluation of hypertensive children should include assessment for additional risk factors as well. These risk factors, in addition to high BP and overweight, include low plasma high-density lipoprotein cholesterol, elevated plasma triglyceride, and abnormal glucose tolerance. To identify other cardiovascular risk factors, a fasting lipid 39

ECAB Clinical Update: Nephrology

panel and fasting glucose level should be obtained in children who are overweight and have BP between the 90th and 94th percentile and in all children with BP >95th percentile with or without obesity. If there is a strong family history of type 2 diabetes, a hemoglobin A1c or glucose tolerance test may also be considered. An echocardiography is recommended to evaluate for evidence of LVH.6

MANAGEMENT OF PEDIATRIC HYPERTENSION The goal of treatment for pediatric hypertension is to decrease the short- and long-term risks of cardiovascular diseases and end-organ damage that result from high blood pressure. However, reducing the blood pressure alone is insufficient for this objective; the issues of obesity, hyperlipidemia, exposure to smoking, and glucose intolerance The evaluation of hypertensive children should include assessment for additional risk factors as well. These risk factors, in addition to high BP and overweight, include low plasma high-density lipoprotein cholesterol, elevated plasma triglyceride, and abnormal glucose tolerance.

also must be addressed. Most nephrologists agree that therapy is warranted in children who have persistent elevation of blood pressure above the 99th percentile. In young adults who were being followed up in the Bogalusa Heart Study but who died from accidental injuries, an autopsy series revealed significant and independent correlations between childhood hypertension and hypercholesterolemia and the early development of aortic and coronary atherosclerosis.14 Studies in adult patients have shown that the treatment of mild to moderate hypertension decreases the risk of stroke and coronary heart disease.15 These findings support the initiation of medical management for even persistent mild hypertension as soon as it is detected in a patient, whether in an adult or a child.

Non-pharmacologic: Lifestyle Modifications Currently, the initial treatment for hypertension in children usually involves lifestyle modifications such as weight reduction, exercise, 40

Childhood Hypertension

Gulati

and dietary intervention. Weight reduction has been shown to be an effective therapy for obese children with hypertension.16 However, weight reduction in children, as in adults, is a goal that is extremely difficult to achieve. Exercise is helpful in reducing weight and both systolic and diastolic blood pressure levels. It must be undertaken on a continuing basis to have lasting benefit in the treatment of hypertension. Combinations of aerobic and static exercise should be followed. Dietary salt restriction has a very important place in the control of blood pressure. The current recommendation for adequate daily sodium intake is only 1.2 g/day for 4- to 8-year-olds and 1.5 g/day for older children.5 Sodium reduction in children and adolescents has been associated with significant reductions in BP in the range of 1–3 mmHg. Currently, the initial treatment for hypertension in children usually involves lifestyle modifications such as weight reduction, exercise, and dietary intervention.

Pharmacologic Although conservative measures clearly can reduce blood pressure, these options are often insufficient for the treatment of hypertension because of patient and family compliance problems. The indications for anti-hypertensive therapy in children are depicted in Table 4. No particular class of anti-hypertensive drugs has been shown to be superior to another class in terms of their effects in children. The choice of anti-hypertensive agent depends on the underlying cause, e.g., in children with post streptococcal glomerulonephritis diuretics are the preferred anti-hypertensive agents since the hypertension is secondary to salt and water retention. When comparing and choosing from the available pharmacologic therapies, the clinician must also consider efficacy, dosing, availability, frequency, adverse effects, and cost. 17 It is easier to dose amlodipine in children, as it is water soluble and stable as a suspension as opposed to nifedipine PA. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have assumed increasing popularity in recent times in view of their advantages of reducing 41

ECAB Clinical Update: Nephrology

Table 4. Indications for Anti-hypertensive Medications in Hypertensive Children and Adolescents Stage 2 hypertension Symptomatic hypertension Secondary hypertension Hypertensive target-organ damage Diabetes (types 1 and 2) Persistent hypertension despite non-pharmacologic measures

proteinuria as well retarding the progression of renal disease, an effect independent of their anti-hypertensive mechanism. The most effective treatment is usually the one that the patient will be compliant to. Common medications used to treat hypertension in children are shown in Table 5. The target BP goal for children with uncomplicated primary hypertension and no hypertensive target-organ damage should be