Clinical Approach to Renal Diseases in Diabetes T Dhinakaran
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1 Clinical Approach to Renal Diseases in Diabetes2
3 Clinical Approach to Renal Diseases in Diabetes
T Dhinakaran MBBS MD (Gen Med) MNAMS (Gen Med) DM (Neph) Director and Chief Nephrologist Madurai Kidney Centre and Transplantation Research Institute Madurai Tamil Nadu India President Southern Chapter Indian Society of Nephrology India Founder Secretary Nephrology Association of Tamilnadu and Puducherry Tamil Nadu India Formerly Professor and Head Department of Nephrology Madurai Medical College and Government Rajaji Hospital Madurai Tamil Nadu India Formerly Professor Department of Nephrology Sri Ramachandra Medical College and Research Institute Chennai Tamil Nadu India FormerlyProfessor Department of Nephrology Sri Ramachandra Medical College and Research Institute Chennai Tamil Nadu India Foreword D Shantharam
4
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Clinical Approach to Renal Diseases in Diabetes
First Edition: 2015
9789351525721
Printed at
5Contributors
6
7
Foreword
It is a great pleasure to write a foreword to this book.
Diabetes mellitus, an emergency in slow motion with devastating complications, is a serious threat to mankind. It is high time, we get alerted on the exponential rise in its incidence and the alarming number of victims of diabetic complications.
Kidney is an important target organ of diabetic complication. Diabetic kidney disease culminating in end-stage renal failure accounting for more than 2/3rd of the patients on renal replacement therapy poses a formidable challenge on a ‘resource poor’ country like ours. Diabetes has to be fought on a ‘war footing’ with awe and zeal. There is an urgent need for initiatives on prevention of diabetes and diabetic complications including kidney disease. Imparting updated knowledge about diabetes and its complications among the medical fraternity would be a crucial step in realizing the mission of tackling it. That way, this book assumes greater significance.
This book provides a comprehensive and systematic review on all the components of the complex relationship between ‘diabetes’ and ‘kidney’. Diabetes can affect kidney not just by the classical diabetic nephropathy, but, also by multiple other mechanisms like infections, renovascular disease due to accelerated atherosclerosis, etc. Though proteinuria is the ‘hallmark’ and harbinger of diabetic nephropathy, recently there has been a rising incidence of ‘normoalbuminuric diabetic nephropathy’ too.
There is a wealth of information on pathophysiology, pathology of diabetic nephropathy, detailed discussion on treatment of diabetes, associated hypertension, dyslipidemia and antiproteinuric measures. Role of renin-angiotensin-aldosterone system (RAAS) inhibition is appropriately emphasized and lifestyle modification is adequately stressed. There is a brief but very pertinent description of renal replacement therapy.
Simple and vivid language, descriptive illustrations, tabulated information (wherever required), optimal mix of theoretical and practical8 information both evidence and experience, and extensive literature references add to the value of the book.
I would strongly recommend this book for all those who are taking care of patients with diabetes and I am certain that they will find it a valuable tool for updating their knowledge on diabetic kidney disease and its management.
I congratulate Professor T Dhinakaran and the co-authors for their commendable and successful effort!
D Shantharam
MD DDiab
Vice-Chancellor
The Tamil Nadu Dr MGR Medical University
Chennai, Tamil Nadu, India
9 Preface
Clinical Approach to Renal Diseases in Diabetes looks into its magnitude, presentation, course and clinical aspects of diagnosis and therapy. The book is aimed at the physicians, postgraduate students in medicine and nephrology, diabetologists, nephrologists and everyone concerned with the management of diabetes and its complications. The 12 chapters take the reader through diabetes mellitus and its renal afflictions in a stepwise manner, starting from the epidemiology of diabetes, diabetic nephropathy, causative factors, role of proteinuria, diagnostic steps in various steps, and the management from hyperglycemia therapy to renal replacement in severe disease, and emphasis has been laid on the practical approach based on clinical and therapeutic trials, which are extensively quoted.
The less discussed areas of therapy, such as diet, lifestyle changes, obesity management, anemia management, and dyslipidemia therapy, and the newer approaches that aim to control the pathophysiological mechanisms, such as advanced glycation endproducts, endothelins, protein kinase ‘C’, and inflammatory mediators, are presented in an interesting and clinically useful manner. The affections of the kidney in diabetes extends beyond the classical diabetic nephropathy and can range from the simple urinary tract infection (UTI) to emphysematous pyelonephritis, renovascular problems, effects of diabetic neuropathy, obstructive uropathy, acute kidney infection during diagnostic and therapeutic procedures, and many more. The burning issue today in diabetic kidney disease is the manifold increase in cardiovascular morbidity and mortality seen in them. Tackling these issues effectively have far-reaching implications towards saving of lives and improving their quality of life. End-stage renal disease management has come a long way and has multiple options that are complimentary and lifesaving. These are presented in as simple a manner as possible for the benefit of physicians and diabetologists, who will continue to care for their patients at all stages of the problem.
The unenviable task of presenting the vast amount of information, experimental data, upcoming evidences and the genetic and molecular background of both diabetes and its renal manifestations have been attempted with the sole aim of making it simple, understandable and interesting without compromising the details, depth and current information.
I hope and wish that the book will be useful as a text, guide and reference to one and all.
T Dhinakaran10
11Acknowledgments
I acknowledge with gratitude the support and strength provided by my wife Mrs Uma Dhinakaran, in seeing to it that this book sees the ‘Light of the Day’
I am thankful to the fellow contributors, for their timely and updated inputs.
I also acknowledge the encouragement given by my physician friends and students, who have repeatedly insisted on publishing the material, that I had presented to them as lectures and updates on many occasions over the past two decades.
I am thankful to Mr M Rajasekaran, for his immense help in preparing the manuscript, charts, diagrams, proofreading and editing on multiple occasions.
Heartfelt thanks to Shri Jitendar P Vij (Group Chairman), Mr Ankit Vij (Group President) and Mr Tarun Duneja (Director Publishing) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, for their continuous support and encouragement throughout the endeavor.12
17Abbreviations AACE
American Association of Clinical Endocrinologist
ACE
Angiotensin-converting enzyme
ACR
Albumin/creatinine ratio
ACTION
A clinical trial in overt nephropathy
ADA
American Diabetes Association
ADMA
Asymmetric dimethyl arginine
ADVANCE
"Action in diabetes and vascular disease: PreterAx and diamicron MR controlled evaluation study"
AER
Albumin excretion rate
AG
Anion gap
AGE
Advanced glycation endproduct
AKI
Acute kidney injury
ALLHAT
Antihypertensive and lipid lowering treatment to prevent heart attack trial
ALT
Alanine transaminase
ALTITUDE
Aliskiren trial in T2DM using cardiorenal disease endpoints
AMPK
AMP activated protein kinase
ARB
Angiotensin receptor blocker
ARIC
Atherosclerosis risk in communities
ARVD
Atherosclerotic renovascular disease
ASB
Asymptomatic bacteriuria
AUC
Area under the curve
AVOID
Aliskiren in the evaluation of proteinuria in diabetes trial
BENEDICT
Bergamo nephrologic diabetes complications trial
BMI
Body mass index
BP
Blood pressure
BUN
Blood urea nitrogen
CAD
Coronary artery disease
18CALM
Candesartan and lisinopril microalbuminuria study
CAPD
Continuous ambulatory peritoneal dialysis
CCB
Calcium channel blocker
CCF
Congestive cardiac failure
CCPD
Continuous cyclic peritoneal dialysis
CFU
Colony forming units
CHF
Chronic heart failure
CI
Confidence interval
CKD
Chronic kidney disease
CLEARED
"Cilnidipine vs I-type calcium channel blockers evaluation of antihypertensive renoprotective effects in diabetic patients"
CML
Carboxy methyl lysine
CMV
Cytomegalovirus
CNI
Calcineurin inhibitor
Cr CL
Creatinine clearance
CTGF
Connective tissue growth factor
CUPS
Chennai urban population study
CV
Cardiovascular
CVD
Cardiovascular disease
CYP
Cytochrome P
DAG
Diacyl glycerol
DAIS
Diabetes atherosclerosis intervention study
DBP
Diastolic blood pressure
DCCT
Diabetes control and complication trial
DD
Double deletion
DKD
Diabetes kidney disease
DM
Diabetes mellitus
DN
Diabetic nephropathy
DNA
Deoxyribonucleic acid
DPP
Diabetes prevention program
DPP-4
Di-peptidyl peptidase 4
DPS
Diabetes prevention study
DRI
Direct renin inhibitor
19eGFR
Estimated glomerular filtration rate
ECF
Extracellular fluid
ED
Erectile dysfunction
EDIC
Epidemiology of diabetes intervention and complications
ELMOI
Engulfment and cell motility gene
ENOS
Endothelial nitric oxide synthase
ERFD
Early renal function decline
ERK
Extracellular signal regulated kinase
ESRD
End-stage renal disease
ESRF
End-stage renal failure
ET
Endothelin
ETAR
Endothelial A receptor
EUCLID
EURODIAB controlled trial of lisinopril in insulin dependent diabetes
FOXO
Forkhead box O
GBM
Glomerular basement membrane
GDP
Glucose degradation product
GFAT
Glutamine fructose 6-phosphate aminotransferase
GFR
Glomerular filtration rate
GH
Growth hormone
GLP
Glucagon like peptide
GLUT4
Glucose transporter-4
GTT
Glucose tolerance test
HD
Hemodialysis
HDL
High density lipoprotein
HGF
Hepatocyte growth factor
HIF
Hypoxia inducible factor
HOPE TRIAL
Heart outcome prevention evaluation trial
HOT
Hypertension optimal treatment
HPT
Hypertension
HR
Hazard ratio
ICAM
Intercellular adhesion molecule
ICF
Intracellular fluid
IDDM
Insulin-dependent diabetes mellitus
20IDF
International Diabetic Federation
IDNT
Irbesartan in diabetic nephropathy trial
IFG
Impaired fasting glucose
IGF
Insulin-like growth factor
IGT
Impaired glucose tolerance
IGTT
Impaired glucose tolerance test
IL
Interleukin
IMT
Intima media thickness
INNOVATION
"In incipient to overt angiotensin-II blocker telmisartan investigation on type 2 diabetic nephropathy study"
IPD
Intermittent peritoneal dialysis
IRMA
Irbesartan in microalbuminuria study
IVU
Intravenous urography
JAK-STAT
Janus kinase signal transducer and activator of transcription
JNC
Joint national committee
KEEP
Kidney early evaluation program
KIM
Kidney injury molecule
LDL
Low density lipoprotein
LFABP
Liver fatty acid binding protein
LFT
Liver function test
LIFE
Losartan intervention for endpoint reduction in hypertension
LVH
Left ventricular hypertrophy
MA
Microalbuminuria
MAPK
Mitogen-activated protein kinase
MARVAL
Microalbuminuria reduction with valsartan
MCP1
Monocyte chemoattractant protein-1
MI
Myocardial infarction
MMP
Matrix metalloproteinase
MRI
Magnetic resonance imaging
NAC
N-acetyl glucosamine
NAG
N-acetyl β D-glucosaminidase
NESTOR
Natrilix SR vs enalapril in type 2 diabetic hypertensives with microalbuminuria
21NFKB
Nuclear factor kappa B
NGAL
Neutrophil gelatinase-associated lipocalin
NHANES
National health and nutrition examination survey
NICE
National institute for health and care excellence
NIDDM
Noninsulin-dependent diabetes mellitus
NODAT
New onset diabetes after kidney transplantation
NPH
Neutral protamine hagedorn
NPT
Nocturnal penile tumescence
NYHA
New York Heart Association
ORIENT
Olmesartan-reducing incidence of end-stage renal disease in diabetic nephropathy trial
PAI-1
Plasminogen activator inhibitor-1
PAK
Pancreas after kidney tranplantation
PARP
Poly-ADP ribose polymerase
PD
Peritoneal dialysis
PDGF
Platelet-derived growth factor
PGC
Proliferator-activated receptor gamma co-activator 1-alpha
PKC
Protein kinase C
PPAR γ
Peroxisome proliferator-activated receptor gamma
PVD
Peripheral vascular disease
QOL
Quality of life
RAAS
Renin-angiotensin-aldosterone system
RAGE
Receptor of advanced glycation endproducts
RAS
Renal artery stenosis/renin-angiotensin system
RCT
Randomized controlled trial
RENAAL TRIAL
Reduction in endpoints in NIDDM with A II antagonist losartan trial
RNA
Ribonucleic acid
ROADMAP
Randomized olmesartan and diabetes microalbuminuria prevention study
ROS
Reactive oxygen species
RPN
Renal papillary necrosis
RRT
Renal replacement therapy
22RTA
Renal tubular acidosis
SBP
Systolic blood pressure
SCr
Serum creatinine
SGLT2
Sodium glucose co-transporter 2
SPK
Simultaneous pancreas and kidney transplantation
STZ
Streptozocin
SU
Sulfonylurea
T1DM
Type 1 diabetes mellitus
T2DM
Type 2 diabetes mellitus
TDD
Total daily dose
TGFβ
Transforming growth factor β
TGL
Triglyceride
TLC
Therapeutic lifestyle change
TM
Thrombomodulin
TRANSCEND
"Telmisartan randomized assessment study in ace intolerant subjects with cardiovascular disease"
TZD
Thiazolidinediones
UAE
Urine albumin excretion
UAER
Urinary albumin excretion rate
UDP
Uridine diphosphate
UKPDS
United Kingdom Prospective Diabetes Study
ULN
Upper limit of normal
UTI
Urinary tract infection
VCAM
Vascular cell adhesion molecule
VDRA
Vitamin D receptor activator
VEGF
Vascular endothelial growth factor
VLDL
Very low density lipoprotein
WHO
World Health Organization
WHR
Waist-hip ratio