Diabetic Kidney Disease

Preface
Contents
Part I: Clinical Aspects
	Chapter 1: Clinical Epidemiology
		1.1 Definition of DKD
		1.2 Prevalence of Diabetes
		1.3 Incidence of DKD
		1.4 Incidence of ESRD in DKD Patients
		1.5 Prevalence of DKD
		1.6 DKD Without Albuminuria
		1.7 Conclusion
		References
	Chapter 2: The Japanese Registries of Diabetic Nephropathy/Diabetic Kidney Disease
		2.1 Introduction
		2.2 Analysis of the J-RBR/J-KDR
		2.3 Analysis of the JDNCS
			2.3.1 Clinical Characteristics at Enrollment
			2.3.2 Clinical Variables at Enrollment Associated with Outcomes
			2.3.3 Transition in eGFR and UACR Categories
			2.3.4 Percentage Changes in eGFR and ESRD
			2.3.5 Remission of Macroalbuminuria and ESRD
		2.4 Conclusion
		References
	Chapter 3: Diabetic Kidney Disease and Cardiovascular Disease
		3.1 Introduction
		3.2 Risk Factors and Mechanisms of CVD in DKD
		3.3 Manifestation of CVD in DKD
		3.4 Prevention and Management to Reduce CVD Risk
			3.4.1 Management of Hyperglycemia
			3.4.2 New Glucose-Lowering Therapies and CVD
			3.4.3 Management of Hypertension
			3.4.4 Management of Albuminuria
			3.4.5 Management of Dyslipidemia
			3.4.6 Multifactorial Therapy
			3.4.7 Lifestyle
			3.4.8 Management of CVD
		3.5 Conclusion
		References
	Chapter 4: Possible Biomarkers for Diabetic Kidney Disease
		4.1 Introduction
		4.2 Biomarkers Currently Established Through the Use of Previously Reported Analytical Methods
			4.2.1 Urine Biomarkers
				4.2.1.1 Urine Albumin
				4.2.1.2 Tubular Damage Biomarkers
					Urinary Neutrophil Gelatinase-Associated Lipocalin
					Urinary α-1-Microglobulin
					Urinary Kidney Injury Molecule-1
					Urinary L-Type Fatty Acid Binding Protein
					Urinary Angiotensinogen
					Urinary Cystatin C
					Urinary N-Acetyl-Glucosaminidase
				4.2.1.3 Glomerular Injury Biomarkers
					Urinary Type IV Collagen
					Urinary Ceruloplasmin
					Others
			4.2.2 Urinary and Serum Inflammatory Biomarkers
				4.2.2.1 Inflammatory Cytokines
				4.2.2.2 Growth Factors
				4.2.2.3 Adhesion Molecules
				4.2.2.4 Other Factors
			4.2.3 Serum and Urinary Oxidative Stress Biomarkers
			4.2.4 Development of Novel Biomarkers
				4.2.4.1 Integrated Omics Analysis in the Development of Comprehensive Biomarkers
					Analytical Methods Using Metabolomics
				4.2.4.2 Application of Omics Analysis to the Development of Urinary Biomarkers of DKD (Table 4.2)
					Proteomic Analysis
					Metabolomic Analysis
					miRNA
				4.2.4.3 Exploratory Biomarkers Identified by Research Performed by the Ministry of Health, Labour and Welfare (MHLW)/AMED Team (Representative: Takashi Wada)
		References
	Chapter 5: Blood Pressure Management in Diabetic Kidney Disease
		5.1 Introduction
		5.2 Basic Strategy for CKD Treatment
		5.3 Basic Pathophysiology of DKD
			5.3.1 Alterations in Microhemodynamics in the Kidney
			5.3.2 Vascular Endothelial Dysfunction
		5.4 BP Management in DKD
		5.5 First-Line Treatment for DKD
			5.5.1 Effectiveness of RA Inhibitors in Inhibiting Progression of DKD
			5.5.2 Preventive Effect of RA Inhibitors Against DKD
		5.6 Antihypertensive Drug Combination Therapy
			5.6.1 The Advantages of Combination Therapy with an RA Inhibitor and Diuretic
			5.6.2 The Advantages of Combination Therapy with Ca Antagonist
			5.6.3 Combination Therapy with RA Inhibitors
		5.7 Conclusion
		References
	Chapter 6: Glycemic Control and Future Perspectives for Treatment
		6.1 Glycemic Control
			6.1.1 Introduction
			6.1.2 Glycemic Control and Prevention of Development and Progression of DKD
			6.1.3 Relationship Between Strict Glycemic Control and Cardiovascular Events and Mortality
			6.1.4 Target Level of Glycemic Control and Points of Attention
			6.1.5 Glycemic Control in Patients with Renal Dysfunction
			6.1.6 Intensive Therapy
			6.1.7 Conclusion
		6.2 Future Perspectives for Treatment
			6.2.1 Introduction
			6.2.2 Pathogenetic Factors for DKD
				6.2.2.1 Glycation Reaction
				6.2.2.2 Activation of RAS and Changes in Glomerular Hemodynamics
				6.2.2.3 Abnormal Intracellular Metabolism
				6.2.2.4 Oxidative Stress
				6.2.2.5 Inflammation
			6.2.3 Therapeutics for DKD
				6.2.3.1 GLP-1 Receptor Antagonist
				6.2.3.2 SGLT2 Inhibitor
				6.2.3.3 Bardoxolone Methyl
				6.2.3.4 Mineralocorticoid Receptor Antagonist
			6.2.4 Conclusions
		References
	Chapter 7: Nutrition and Diet Therapy for DKD
		7.1 Introduction
		7.2 Diet Therapy for DKD
			7.2.1 Diet Therapy in Chronic Kidney Disease Stages G1A1-2 and G2A1-2
				7.2.1.1 Caloric Intake
				7.2.1.2 Protein Intake
				7.2.1.3 Salt Restriction
				7.2.1.4 Potassium Intake
			7.2.2 Diet Therapy in CKD Stages G1-2A3 and G3-4
				7.2.2.1 Caloric Intake
				7.2.2.2 Restriction of Protein Intake
				7.2.2.3 Issues of Performing Protein Restriction
				7.2.2.4 Restriction of Salt Intake
				7.2.2.5 Potassium Restriction
				7.2.2.6 Phosphorus Restriction
			7.2.3 Other Issues in Diet Therapy of Clinical DKD
			7.2.4 Mechanisms Behind Dietary Therapy-Related Renoprotection in Experimental Diabetic Kidney Disease and Vascular Damage
		7.3 Conclusion
		References
	Chapter 8: Renal Structural-Functional Relationships at the Early Stage of Diabetic Nephropathy Among Types 1 and 2 Diabetes: Similarity and Difference
		8.1 Renal Histological Changes and Clinical Manifestations of Diabetic Nephropathy in Type 1 and Type 2 Diabetes
		8.2 Renal Pathological Findings in Types 1 and 2 Patients
			8.2.1 Typical Renal Histological Findings as Diabetic Glomerulosclerosis
			8.2.2 Morphometric Analysis of Renal Biopsies
				8.2.2.1 Light Microscopic (LM) Morphometric Analysis
				8.2.2.2 Electron Microscopic (EM) Morphometry
		8.3 Renal Structural-Functional Relationships at the Early Stage of Diabetic Nephropathy in Types 1 and 2 Diabetic Patients
			8.3.1 Cross-Sectional Studies
				8.3.1.1 Renal Structure and Albuminuria
				8.3.1.2 Renal Structure and Glomerular Filtration Rate (GFR)
			8.3.2 Longitudinal Studies
				8.3.2.1 Renal Histological Findings as Predictors for Renal Functional Decline in Types 1 and 2 Diabetic Patients
				8.3.2.2 Renal Histological Heterogeneity and Renal Functional Changes
				8.3.2.3 Arteriolar Hyalinosis and Renal Functional Changes
		8.4 The Importance of Serial Renal Biopsy
		8.5 The Relationships Between Diabetic Nephropathy Lesions and Retinopathy
		8.6 Similarity or Difference of Diabetic Nephropathy Between Types 1 and 2 Diabetes
		References
	Chapter 9: Study at AMED Collecting 600 Biopsy-Proven Diabetic Nephropathies
		9.1 Clinical and Pathological Backgrounds of Diabetic Nephropathy
		9.2 Importance of Pathological Findings in Diabetic Nephropathy
		9.3 A Pathological Classification by the Renal Pathology Society of the United States for Diabetic Nephropathy
		9.4 A New Pathological Classification for Diabetic Nephropathy
		9.5 Definition of Each Pathological Finding and Score
		9.6 Pathological Findings Based on the Classification of Diabetic Nephropathy in Japan
			9.6.1 The Classification of Diabetic Nephropathy in Japan
			9.6.2 Kidney Biopsy Cohort in Japan
		9.7 Characteristic Pathological Findings Based on the Classification of Diabetic Nephropathy in Japan
		9.8 Impacts of Pathological Findings on Clinical Outcomes
		9.9 Summary
		9.10 Indication of Kidney Biopsy
		References
Part II: Pathological Aspects
	Chapter 10: Evaluation of Diabetic Kidney Lesions
		10.1 Patients Characteristics of Diabetic Nephropathy (DN): Clinical Perspectives
		10.2 Diagnosis of DN: Pathological Perspective
		10.3 Purposes of Renal Biopsy
		10.4 Pathological Changes in Early Stage of DN
		10.5 Typical Pathological Findings of DN
		10.6 Evaluation of DN by RPS and JRPS
		10.7 Renal Biopsy Findings and Renal Prognosis
		References
	Chapter 11: Nephrosclerosis and Diabetic Kidney Disease
		11.1 Nephrosclerosis
		11.2 Nephrosclerosis and Diabetic Nephropathy
		References
	Chapter 12: Nondiabetic Renal Disease (NDRD) and Diabetic Kidney Disease (DKD)
		12.1 NDRD Superimposed on DN
			12.1.1 Prevalence and the Most Common NDRD
			12.1.2 Renal Prognosis and Mortality Among DN, NDRD, and Mixed Forms
		12.2 Predictors for Differentiating Among DN Alone, Coexistence of NDRD, and NDRD Alone
			12.2.1 Duration of DM
			12.2.2 Diabetic Retinopathy
			12.2.3 Hematuria
		References
	Chapter 13: Experimental Animal Models of Diabetic Kidney Disease
		13.1 Pathological Lesions of Diabetic Nephropathy
		13.2 Animal Models of DKD
			13.2.1 Type 1 DM Models
				13.2.1.1 STZ-Injected Rodent Models
				13.2.1.2 STZ-Injected Rat Models
				13.2.1.3 STZ-Injected Mouse Models
				13.2.1.4 STZ-DBA/2 Mice
				13.2.1.5 STZ-eNOS KO Mice
				13.2.1.6 Akita (Ins2+/C96Y) Mice
				13.2.1.7 OVE26 Mice
			13.2.2 Type 2 Diabetes Models
				13.2.2.1 Ob/Ob (BTBR) Mice
				13.2.2.2 Db/Db Mice
				13.2.2.3 Db/Db eNOS KO Mice
				13.2.2.4 KK-Ay Mice
				13.2.2.5 ZDF Rats
				13.2.2.6 OLETF Rats
				13.2.2.7 Goto-Kakizaki (GK) Rats
				13.2.2.8 WBN/Kob-Leprfa Rats
		13.3 Conclusion
		References