General introduction of nephrology Xiaoqiang Ding M.D., Ph.D. Department of nephrology Zhongshan Hospital, Fudan University
Terminology Kidney,renal Nephrology
Scope of nephrology Kidney diseases and other problems of the urinary systems, no requirement for surgery intervention Glomerular disease:nephrotic syndrom, glomerulonephritis Urinary tract infection Interstitial nephritis Acute renal failure or chronic renal failure Blood purification: kidney disease or nonkindey disease
Kidney functions excreting metabolic waste products excreting redundant fluid and sodium ---hypertension eliminating dissoluable metabolic products, exogenous drugs and toxins ---uremia
Kidney functions Endocrine functions Erythropoiesis---erythropoietin Blood pressure---renin Bone and mineral metablism---vitd activation Internal Environment Homeostasis regulation fluid, acid-base homeostasis Acid excretion---metabolic acidosis Potassium excretion---hyperkalemia, hypokalemia
Endothelial fenestrae Foot processes
Mechanisms Celluar:calcium channels, NO, Kinins, RAS Myogenic: vascular wall tensioin Tubuloglomerular feedback (TGF) Metabolic: vasodilator metabolite as adenosine, ADP, ATP
Adaptation to renal injury Adaptation to renal injury ~ to nephron loss Response to Reduction in Numbers of Functioning Nephrons Common Mechanisms of Progressive Renal Disease Adaptation Maladaptation
Glomerular Changes in GFR during Progression of chronic renal injury
Mechanisms of renal progression
Adaptation to Nephron Loss Structural and Functional Adaptation of the Kidney to Nephron Loss Alterations in Glomerular Physiology Mediators of the Glomerular Hemodynamic Responses to Nephron Loss Renal Hypertrophic Responses to Nephron Loss Mechanisms of Renal Hypertrophy Adaptation of Specific Tubule Functions in Response to Nephron Loss Adaptation in Proximal Tubule Solute Handling Loop of Henle and Distal Nephron Glomerulotubular Balance Sodium Excretion and Extracellular Fluid Volume Regulation Urinary Concentration and Dilution Potassium Excretion Acid-Base Regulation Calcium and Phosphate
Structural and Functional Adaptation of the Kidney to Nephron Loss Alterations in Glomerular Physiology SNGFR (glomerular hyperfiltration glomerular hypertension) Mediators of the Glomerular Hemodynamic Responses to Nephron Loss AII, aldosterone, natriuretic peptides (NP), endothelins (ET) eicosanoids and bradykinin Renal Hypertrophic Responses to Nephron Loss Whole-Kidney Hypertrophic Responses/ Glomerular Enlargement Cell size-increasing Elasticity or growth of interstitial spaces Mechanisms of Renal Hypertrophy
Glomerulotubular balance Residual tubules alterated reabsorption or excretion of filtered water and solutes maintain homeostasis Compensatory adaption Maladaptation Tubular Size: hypertrophy Tubular Function: regulatory adjustments Further Tubule Injury
Adaptation of Specific Tubule Functions in Response to Nephron Loss Adaptation in Proximal Tubule Solute Handling tubule size surface area transport activity Loop of Henle and Distal Nephron a major adaptive increase in active solute transport Glomerulotubular Balance Sodium Excretion and Extracellular Fluid Volume Regulation Urinary Concentration and Dilution Potassium Excretion Acid-Base Regulation Calcium and Phosphate
Response to Reduction in Numbers of Functioning Nephrons Loss of nephrons vasoconstriction RAS Compensatory adaption Renal hypertrophy GFR persistent injury >80% of renal mass-lose tubuloglomerular feedback system Nephron: lose autoregulation intraglomerular hypertension Maladaptation Nephron: lose autoregulation Proteinuria progressive nephron destruction Glomerulosclerosis Tubular atroph and interstitial fibrosis
Long-Term Adverse Consequences of Adaptations to Nephron Loss Hemodynamic Factors Mechanisms of Hemodynamically Induced Injury Non-hemodynamic Factors in the Development of Nephron Injury Following Extensive Renal Mass Ablation
Diagnosis of kidney diseases symptome sign Laboratory tests and imageology urinalysis renal function ultrasound X-ray Magnetic resonance imaging, MRI
Clinical manifestation Proteinuria Qualitation test: urine protein positive Quantitation test: urine protein 150mg/d
Quantity of urine protein Mild proteinuria Moderate proteinuria Severe proteinuria < 1.5g/d 1.5-3.5g/d > 3.5g/d or 50mg/kg/d
Hematuria Fresh urine 10 ml centrifugate 1500rmp5min Microscopic hematuria urine sediment RBC >3/HP Macroscopic hematuria pink or red > 1ml blood/1l urine
Hematuria Glomerular hematuria PH and osmolality changes crushed when passing through GBM Dysmorphic RBC Phase contrast microscope Dysmorphic RBC > 50% suspected Dysmorphic RBC > 70% Definite diagnosis Red blood cell volume distribution curves Dissymmetrical curve MCV of RBC
Clinical classificatioin Glomerulonephropathy proteinuria as the chief complain, with or without hematuria Glomerulonephritis hematuria as the chief complain, with or without proteinuria
Nephrotic syndrome 1. grave proteinuria Upr > 3.5g/d 2. hypoproteinemia Serum Alb < 30g/L 3. Severe edema 4. hyperlipemia 1+2 are necessary for diagnosis
Patterns of Clinical Glomerulonephritis
Patterns of Clinical Glomerulonephritis
Definition of Chronic Kidney Disease (CKD)
Stages of chronic kidney disease
ESRD in U.S. high incidence,high medicare cost 美国终末期肾衰患者的发病率 2500000 2000000 1500000 1000000 500000 0 2,200,000 700,000 2010 年 2030 年 Coresh et al. Am J Kidney Dis, 2003:1-12 Real cost(billion) ESRD cost 6.4% 25.2 of the entire medicare budget 23.2 Annual medicare spending: 20-40 billion 2006 USRDS NIH budget(billion) USRDS Predicted: prevalent and incident of ESRD is expected to double in 2010 (700,000), up to 2,200,000 in 2030. Third National Health and Nutrition Examination Survey. The prevalence of CKD in the US adult population was 11% (19.2 million, 1988-1994) CKD in Chine > 100 million!
Acute Kidney Injury (AKI) common condition that precipitates critical illness General hospital 18% ICU 67% General population 1180/pmp High mortality 30%-80% Medical Cost increased by 2-10 times Half survived patients with incomplete recovery with residual damage Cost for kidney disease account for 6% of the entire medicare budget Clinical outcomes of AKI are poor and have not improved over the past 50 years
Prevention and Treatment of Kidney Disease Disease-specific treatments Glomerulonephritis Immunosuppressive therapy Diabetic nephropathy Blood glucose control Hypertensive nephropathy anti-hypertension therapy Non-specific treatments
Prevention and Treatment of Kidney Disease Non-specific treatments Resting Infection prevention Diet salt intake low salt diet: sodium 2-3g/d,NaCl 5-6g/d U Na or U Cl 80-100mmol/d Protein intake low protein diet: protein 0.5-0.6g/kg/d very low protein diet: protein 0.3-0.4g/kg/d
Prevention and Treatment of Kidney Disease Non-specific treatments RAAS inhibitor renin-angiotensin-aldosteron system Angiotensin II incrementally vasoconstricts the efferent arteriole intraglmerlar hypertension RASi decrease intraglomerular capillary pressure decrease proteinuria slow CKD progression
Mean arterial blood pressure (mmhg) Relationship between blood pressurereduction and urine protein reduction 120 110 100 90 80 Anti-hypertension dose Renal protection dose
Prevention and Treatment of Kidney Disease Non-specific treatments Lipids control Renal mesangial cell and arterial smooth muscle cells share similar biologic feathers Similar mechanism of glomerular sclerosis and artherosclerosis Correcting hyperuricemia 90% cases of hyperuricemia are secondary to kidney disease Hyperuricemia induce renal tubulointerstitial injury Avoiding renal toxic drugs aminoglycosieds, NSAIDs, renal toxic Chinese herb
Key Points Kidney functions Adaptation to renal injury Long-Term Adverse Consequences of Adaptations to Nephron Loss
Taking home question What is the Structural and Functional Adaptation of the Kidney to Nephron Loss