renal failure in children and adolescents在儿童和青少年慢性肾功能衰竭（ppt53）课件

Chronic Renal Failure in Children and Adolescents Dr Ian Ramage Consultant Paediatric Nephrologist Glasgow Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome Definition - Adults Definition - Adults Definition - Children (a) Kidney damage for 3 months, as defined by structural or functional abnormalities determined by kidney biopsy, imaging tests or composition of the blood or urine, with or without decreased GFR; AND (b) GFR GH Max growth from 25cm/yr at birth 18cm/yr age 1yr 10cm/yr age 2 yr Childhood GH and Thyroid hormone dependent Children grow along percentile achieved at the end of 2 years of life (Van Dyck M Pediatr Nephrol 1999) Pubertal Delayed peak height velocity of 2.5 years Growth spurt delayed & shortened with reduced growth velocity Only 65% of healthy children Loss of pulsatile hypothalamic release ofGnRH Growth Children with CKD fail to reach adult height potential (Haffner D N Eng J Med 2000) 36% of CKD patients have growth impairment Average Ht SDS at transplantation 1.85 Greatest in Males Greatest in Younger Patients Increased morbidity and mortality (Furth NL Pediatr Nephrol 2002) Each SDS decrease associated with a 14% increase in death (Wong CS A J Kid Dis 2000) Growth Dietician Nutrition Supplemental Feeding Gastro-oesophageal reflux NG/Gastrostomy Fundoplication Growth Hormone (Haffner D N Eng J Med 2000) Everything Else Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome Renal Osteodystrophy Nutrition Dietician Pharmacist Psychologist Nurse Specialist Doctor Renal Osteodystrophy CKD Mineral and Bone Disorder (Moe S Kidney Int 2006) Abnormalities of calcium, phosphorous, PTH and vitamin D metabolism Abnormalities in bone turnover, mineralisation, volume, linear growth or strength Vascular and other soft tissue calcification Renal Osteodystrophy Abnormalities of calcium, phosphorous, PTH and vitamin D metabolism (Wesseling K Pediatr Nephrol 2008) Kidneys hydroxylate vitamin D to calcitriol Reduction in calcitriol early in CKD Decreased intestinal Calcium absorption Increased PTH release Initially N or low PO4 Later GFR PO4 excretion with hydroxylation and PTH Renal and skeletal PTH resistance Increased PTH Antagonised by Vitamin D If unchecked Parathyroid hyperplasia Autonomous unregulated Parathyroid growth and hormone release Renal Osteodystrophy Abnormalities in bone turnover, mineralisation, volume, linear growth or strength (Wesseling K Pediatr Nephrol 2008) Bone Turnover Characteristically “High Turnover” Increased Osteoclastic and Osteoblastic Activity Can occur early in CKD “Low Turnover” Adynamic bone disease Only reported in dialysis patients Excess of Vitamin D and Calcium with PTH suppression Increased fractures and growth retardation Renal Osteodystrophy Abnormalities in bone turnover, mineralisation, volume, linear growth or strength (Wesseling K Pediatr Nephrol 2008) Bone Mineralisation Increased Osteoid (unmineralised bone) Defective mineralisation Increased Fractures Growth retardation Bone Abnormalities Bone Volume PTH is anabolic to trabecular bone Increased bone volume Steroid therapy Renal Osteodystrophy Abnormalities in bone turnover, mineralisation, volume, linear growth or strength (Wesseling K Pediatr Nephrol 2008) Linear Growth Target PTH level unclear GH Resistance IGF1 Bioactivity Strength Epiphyseal widening Slipped Epiphysis Genu Valgum Femoral and wrist abnormalities Avascular necrosis Pathological fractures 18- NKF K/DOQI 2005 Am J Kid Dis 41 Klaus G EWPDG 2006 Pediatr Nephrol Renal Osteodystrophy Vascular and other soft tissue calcification (Wesseling K Pediatr Nephrol 2008) Vascular calcification is present in children (Milliner DS 1990 Kidney Int, Goodman WG N Eng J Med 2000) Risk factors* (Russo D Am J Kid Dis 2004, Mitsnefes MM JASN 2005) Hypercalcaemia Hyperphosphataemia Increased Ca x Po4 product High dose vitamin D Pathophysiology Menchymal to osteoblast conversion Upregulation of Na dependent PO4 transporter Upregulation of pro mineralisation factors Calcium based PO4 binders PREVENTABLE (Chertow GM Kidney Int 2002, Block GA Kidney Int 2005) Renal Osteodystrophy - Treatment Dietician Phosphate Binders Calcium based binders used most commonly Aim to keep Ca intake double DRI If Ca stop binder Vitamin D Sevelamer Non calcium based Halts progression of vascular calcification (Block GA Kidney Int 2005) Lower mortality rates (Block GA Kidney Int 2007) Lanthanum Accumulation in liver, bone and growth plate (Spasovski GB Nephrol Dial Transpl 2006, Slatopolsky E Kidney Int 2005) Intensive Dialysis Renal Osteodystrophy - Treatment Secondary Hyperparathyroidism Vitamin D Ergocalciferol/Cholecalciferol Calcitriol Paracalcitriol* Calcimimetics Cinacalcet Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome CKD - Anaemia Adequately treated anaemia (Morris KP Arch Dis Child 1994, Morris KP Arch Dis Child 1993, Jabs K Pediatr Nephrol 1996, Warady BA Pediatr Nephrol 2003) Mortality Quality of life Exercise tolerance Growth Cardiovascular Function CKD - Anaemia Published success (Children v Adults) (Chavers BM Kidney Int 2004) Haemodialysis - 54% v 40% Peritoneal Dialysis 69% v 55% CKD 36.6% (Wong H Kidney Int 2006) CKD 1 31% CKD 4/5 93% CKD Anaemia (Hollowell JG 2005) Initiate anaemia work-up when Hb 5th percentile (NKF K/DOQI 2006 AM J Kid Dis) CKD Anaemia Erythropoeitin Deficiency Iron Deficiency Blood Loss Phlebotomy Haemodoalysis Menses GI Dietary insufficiency or poor absorption Depletion during EPO therapy Decreased RBC survival Bone Marrow suppression Inadequate dialysis Malnutrition Infection and Inflammation Hyperparathyroidism B12 or Folate Deficiency Carnitine Deficiency Medications CKD Anaemia Koshy SM & Geary DF Pediatr Nephrol 2008 CKD Anaemia Treatment Measure pre-dialysis ? Measurement Monthly if stable 1-2 weeks if changes made ? (Greenbaum LA, Comprehensive Pediatric Nephrology, Elsvier 2008) Iron Erythropoeitin Darbopoeitin Mircera CKD Anaemia Treatment Iron Monitoring Iron stores Ferritin Acute phase protein ESAs cause functional iron deficiency Normal or elevated level doesnt exclude deficiency TSAT Serum Iron/TIBC - 20% Iron therapy Oral IV Age specific Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome CKD - Hypertension Very common (Wong H Kidney In 2006) CKD I 63% CKD 4/5 80% ESDR 50% uncontrolled (Tcakzyk K 2006 Nephrol Dial Transplant, Mitsnefes MM J Am Soc Nephol 2005) Progression of CKD (Wingen AM Lancet 1997, Mitsnefes MM J Am Soc Nephol 2003) Cardiovascular mortality (Kroothoff JW Kidney Int 2002) Aetiology BP = CO X TPR Hadstein C & Schaefer F Ped Nephrol 2008 CKD Hypertension Aetiology BP = CO X TPR RAS Fluid Overload Sympathetic system Catecholamines & Renalase Nitrous Oxide NO synthetase ADMA (Zocalli C Lancet 2001, Fliser D 2002 J Am Soc Nephrol) Drugs Hadstein C & Schaefer F Ped Nephrol 2008 CKD Hypertension Surveillance CKD Hypertension Treatment Fluid management Dialysis prescription Lifestyle changes Salt Calories Exercise CKD Hypertension Treatment ACE ARB ACE/ARB Calcium Channel Blockers blockers Diuretics Others Escape Trial Group N Eng J Med 2009 CONCLUSIONS: Intensified blood-pressure control, with target 24-hour blood-pressure levels in the low range of normal, confers a substantial benefit with respect to renal function among children with chronic kidney disease. Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition. Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome CKD Cardiovascular Disease CKD Patient Survival 40-60 yrs less for dialysis 20-25 yrs less for transplants CV Disease 40-50% (Oh J Circulation 2002, Groothoff JW Kidney Int 2002, McDonald SP 2004 N Eng J Med) Sudden Cardiac Death Arrythmias Dilated Hypertrophic Cardiomyopathies LVH Ischaemic Heart Disease ? Mitsnefes MM 2008 Ped Nephrol CKD Cardiovascular Disease Treatment - Minimise Risk Factors Transplantation Cardiac Death by 80% Life expectancy by 20-25 years Hypertension, Hyperlipidaemia, CAN Hypertension Proteinuria Anaemia Dyslipidaemia Renal Osteodystrophy Therapeutic Lifestyle Changes (TLC) No evidence for hyperhomocysteinaemia or chronic inflammmation Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome CKD Neurodevelopment Neuroimaging 12-23% Cerebral atrophy Chronic Infarct lesions Electrophysiology EEG abnormalities 30-40% Predominantly slow wave increase Cognitive Function Variable Results Largest deficit in infants* Lower IQ particularly non-verbal Variable Improvement post transplantation CKD Neurodevelopment Specific Neurocognitive Functions (Hulstijn-Dirkmaat GM 1995 Ped Nephrol, Ledermann 2000 J Pediatr, Warady BA 1999 Ped Nephrol) Attention and executive functions Language Visual-spatial Memory Academic Achievement and School Performance Poorer Performance than peers (Brouhard PH 2000 Ped Transplant) Transplanted patients perform better (Gipson DS 2006 Child Neuropsychol) 15% Special Educational Needs 77% had CNS Infarcts (Qvist E 2002Ped Tansplant) Assessment and early intervention key Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome Chronic Renal Failure in Children and Adolescents Definition Epidemiology Aetiology Clinical Nutrition Growth Bones Anaemia Blood Pressure Cardiovascular Disease Neurodevelopment Psychosocial Pharmacy Treatment Outcome CKD - Progression Age of attainment of renal mass deficit Gender Underlying Disease & Genetic Pathology Polymorphic Genetic Variation Dyslipidaemia and Insulin Resistance Nutrition Anaemia Disorders of Calcium & Phosphate Proteinuria Hypertension Gonzalez Celedon C 2007 Pediatr Nephrol CKD Progression - Proteinuria REIN Study (Kramer BK 1997 Lancet) ItalKid Study (Ardissino G 2004 Ped Nephrol) Escape Study (2009 N Eng J Med) Summary 1G/day reduction in proteinuria reduces GFR decline by 2ml/