CKD IN CHILDREN DR GRK.pptx

chronic kidney disease in children

1. Case scenario A 4 year old Rahim from Kelambakkam came with complaints of polyuria, polydipsia for past 4 months, failure to thrive for past 3 months On further query he had irregular fever for 2 months, no H/O of contact with TB, no loss of appetite O/E moderately pale, hypertensive, growth retartded, No organomegaly Dr GRK CHRI 1

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3. Dr. G.Rajkumar MD Professor of Paediatrics CHRI Chronic Kidney Disease in Children

4. Outline CKD is a chronic progressive disease that can clog normal lifestyle & reduce lifespan Definition Etiopathogenesis Stages Clinical features Management Dr GRK CHRI 4

5. Criteria for definition of chronic kidney disease (NKF KDOQI Guidelines) Patient has CKD if either of the following criteria are present: 1. Kidney damage for ≥3 months as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by one or more of the following features: Abnormalities in composition of blood or urine Abnormalities in imaging Abnormalities in biopsy 2. GFR < 60ml/min/1.73m 2 ≥ 3 months with or without signs of kidney damage described above Dr GRK CHRI 5

6. 3 exceptions in Paediatrics 1. Criteria duration longer than 3 months does not apply for infant less than 3 months 2. GFR < 60ml/min/1.73m2 cannot be used for children < 2 years as this group has developmental immaturity leading to low GFR Urine protein can be used instead of urine albumin excretion in children Dr GRK CHRI 6

7. Risk factors for CKD VUR with recurrent UTI Obstructive uropathy Previous history of nephritis or NS Family history of PCKD Renal dysplasia or hypoplasia LBW DM/SHT SLE, Vasculitis, HSP Dr GRK CHRI 7

8. Stages of CKD Stage Description GFR 1 Kidney damage with normal or increased GFR ≥ 90 2 Kidney damage with mild decrease in GFR 60-89 3 Moderate decrease in GFR 30-59 4 Severe decrease in GFR 15-29 5 Kidney failure < 15 or on dialysis Dr GRK CHRI 8

9. Proteinuria categories applicable to children Category Protein: creatinine ratio (g/mmol) Terms P1 <0.02 Normal P2 >0.02 - <0.2 Moderate increase, non-nephrotic range P3 ≥0.2 Nephrotic range proteinuria Dr GRK CHRI 9

10. Epidemiology Prevalence of CKD in children is 18/10,00000 Childhood onset ESRD has significant morbidity and 30 fold increase risk od dying from cardiovascular & infective causes. Dr GRK CHRI 10

11. Etiology In children < 5 yrs. congenital anomalies of kidney & urinary tract ( renal hypoplasia/dysplasia or obstructive uropathy), RVT, Prune belly syndrome and is often diagnosed with perinatal USG In children older than 5 yrs. acquired or inherited causes of glomerulo-nephritis predominate Dr GRK CHRI 11

12. Non Glomerular Aplastic, dysplastic, hypoplastic kidneys Cystinosis Medullary kidney disease/ juvenile nephrolithiasis Obstructive uropathy ( PUV, cloaca, neurogenic bladder) Oxalosis AD & AR PCKD Pyelonephritis, interstitial nephritis, reflux nephropathy Renal infarct syndrome of agenesis of abdominal musculature (Eagle Barrett syndrome) Wilms tumour Dr GRK CHRI 12

13. Glomerular Chronic glomerulonephritis ( including FSGS) Congenital nephrotic syndrome (CNS) HUS HSP Idiopathic crescentic glomerulonephritis Ig A nephropathy MPGN Membranous nephropathy Sickle cell nephropathy SLE, Wegener Granulomatosis Hereditary nephritis- Alport Syndrome Dr GRK CHRI 13

14. Pathogenesis Hyperfiltration Injury : final common pathway of all causes of renal injury Nephron loss Rest of nephron undergo structural & functional hypertrophy Increased glomerular blood flow Hyperfiltration preserves renal function for a while Effect of elevated hydrostatic pressure on vessel wall Toxicity due to increased protein filtration Dr GRK CHRI 14

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16. Remaining nephrons suffer from increased excretory burden leading on to a vicious cycle of increased glomerular blood flow and hyperfiltration injury Dr GRK CHRI 16

17. B. Proteinuria Direct toxic effect of proteins on tubular cells Recruit monocytes & macrophages-glomerular sclerosis & tubule interstitial fibrosis C. Uncontrolled Hypertension-arterial nephrosclerosis & enhances hyperfiltration injury D. Hyperphosphatemia- calcium phosphate deposition in renal interstitium & blood vessels E. Hyperlipidemia- Oxidant-mediated injury Regardless of etiology, progression of interstitial fibrosis is the primary determinant of CKD Dr GRK CHRI 17

18. Pathophysiology 1. Accumulation of nitrogenous waste-d/t decreased GFR 2. Acidosis- decreased ammonia synthesis, decreased bicarbonate reabsorption, decreased net acid excretion 3. Sodium wasting- solute diuresis, tubular damage 4. Urinary concentrating defect- solute diuresis, tubular damage 5. Hyperkalemia- Reduced GFR, Metabolic acidosis, Excessive potassium intake, hyporeninemic hypoaldosteronism 6. Renal osteodystrophy- impaired renal production of 1,25 dihydroxycholecalciferol, hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism Dr GRK CHRI 18

19. 7. Growth retardation- inadequate calorie intake, metabolic acidosis, renal osteodystrophy, anemia, GH resistance 8. Anemia-decreased erythropoietin secretion, Iron, Folic acid and or Vitamin B12 deficiency, decreased erythrocyte survival 9. Bleeding tendency-defective platelet function 10. Infection- Defective granulocyte function, impaired cellular immunity, indwelling catheters 11. Decreased academic achievement, attention regulation or executive functioning- hypertension, LBW Dr GRK CHRI 19

20. 12. Gastrointestinal symptoms ( feed intolerance, abdominal pain)-GERD, decreased GI motility 13. Hypertension- volume over load, excessive renin production 14. Hyperlipidemia- decreased lipoprotein lipase activity, abnormal HDL-C 15. Cardiomyopathy-volume overload, hypertension, anemia 16. Glucose intolerance-tissue insulin resistance 17. Neurological Symptoms- fatigue, poor concentration, headache, memory loss, seizures, peripheral neuropathy-uremic factors, Aluminum toxicity, Hypertension Dr GRK CHRI 20

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23. Clinical features of CKD Appearance: Pallor secondary to anemia Hypertension Shortness of breath-volume overload, anemia, cardiomyopathy Kidneys- B/L small thinned cortices suggests intrinsic disease (Glomerulonephritis) U/L small kidney-renal artery disease Clubbed cortices & cortices scar-Chronic infection Enlarged cystic kidneys Itch & cramps Cognitive changes GI Symptoms-Anorexia, vomiting, taste disturbances, uremic odour Urinary changes- polyuria, proteinuria, poor concentrating ability Dr GRK CHRI 23

24. Hematuria- immune injury to glomerular capillary wall Proteinuria Tubular- low grade proteinuria (<2 g), Low MW Glomerular- selective proteinuria > 3.5 g, Peripheral edema- salt retention Dr GRK CHRI 24

25. ESRD Stage in which renal dysfunction has progressed in to a point at which the homeostasis & survival can no longer be sustained with native kidney function & medical management Mx Renal transplant at stage 4 CKD Birth to 5 years-Peritoneal dialysis > 12 yrs. Hemodialysis Dr GRK CHRI 25

26. Laboratory findings Elevations in BUN & creatinine Hyperkalemia Hyponatremia- renal salt wasting & volume overload Hypernatremia-water loss Acidosis Hypocalcemia Hyperphosphatemia Elevation of uric acid Hypoalbuminemia-d/t proteinuria CBC-N/N anemia Dyslipidemia AGN-Hematuria, proteinuria Congenital abnormalities- low specific gravity Dr GRK CHRI 26

27. Measurement of renal functions By measuring GFR Inulin clearance-gold standard- but no routinely available Iohexol or Radio isotopes (99m Tc-DTPA, 51 Cr- EDTA, 125 lothalamate) Estimating GFR by endogenous markers (creatinine and or cystatin c)- assess the severity GFR(ml/min/1.73m 2 )= k x0.43 x height(cm)/serum creatinine (mg/dl) k= 0.33 LBW < 1 yr, 0.45 term AGA, 0.55 children & adolescent female, 0.70 adolescent male Dr GRK CHRI 27

28. Management of CKD CKD treatment is supportive Replacing absent/ diminished renal function Slowing progression of renal dysfunction Dr GRK CHRI 28

29. Close monitoring of blood studies, urine studies(spot PCR, 24hrs urinary protein) Ambulatory blood pressure monitoring over 24 hrs Masked hypertension-Normal office blood pressure but abnormal ABPM Its seen up to 35% of Paediatric predialysis patients 4 fold increased risk of LVH Dr GRK CHRI 29

30. 1. Nutritional management Patient should receive 100% of estimated energy requirement for age, adjusted to physical activity & BMI, response to weight gain/loss Dietary protein restriction not suggested considering growth restriction (2.5 g/kg/d) MCT fat High biological value protein( fish, fowl, meat, egg) CKD stages 2-5 should receive 100% of daily requirement of vitamins& trace elements (Fe & Zn only if deficient) Water soluble vitamins Dr GRK CHRI 30

31. Growth Short stature is a long term squeal GH resistance( GH IGF ) Abnormality of IGF binding Protein Recombinant human GH (0.05 mg/kg/24 hr) Continue until 50 th percentile MPH or achieves full adult height or undergoes renal transplantation Dr GRK CHRI 31

32. 2. Fluid & Electrolyte management Most patients maintain normal sodium & water balance Polyuric urinary sodium loss: give high volume, high caloric density feeding with sodium supplements High BP, edema or heart failure: require sodium restriction & diuretic therapy Fluid restriction is rarely unnecessary until ESRD Hyperkalemia: restriction of dietary K+intake oral alkalysing agent kayexalate DOC in severe hyperkalemia- Calcium gluconate Dr GRK CHRI 32

33. 3. Acidosis Sodium bicarbonate tablet (650 mg= 8 mEq base) Bacitra ( 1 mEq sodium citrate/ml) Maintain serum Bicarbonate > 22 mEq/L Dr GRK CHRI 33

34. 4. Renal osteodystrophy Spectrum of bone disease in CKD High turnover bone disease Secondary hyperparathyroidism Osteitis fibrosa cystica Dr GRK CHRI 34

35. Pathophysiology When GFR declines to 50%of normal Decline in 1 α hydroxylase Decreased production of activated Vitamin D intestinal absorption of calcium Hypocalcemia Secondary hyperparathyroidism Increase bone resorption when GFR decline to 25% of normal Hyperphosphatemia Dr GRK CHRI 35

36. Clinical manifestations Muscle weakness Bone pain Fractures with trivial trauma Rickitic changes Ca Ph alkaline phosphatase PTH normal Subperiosteal resorption of bone with widening of metaphysis Dr GRK CHRI 36

37. Treatment of renal osteodystrophy Low phosphorus diet Phosphate binders Calcium carbonate & calcium acetate Sevelamer(Renagel)- calcium binder Avoid aluminum based binder Vitamin D therapy Maintain calcium/ phosphorus product <55 Dr GRK CHRI 37

38. 5. Anemia Keep Hb between 12-13g/dl Erythropoietin if Hb< 10g/dl-Dose 50-150 mg/kg SC 1-3 times/week Darbopoeitin alfa (long acting) Dose 0.45 µg/kg/week Dr GRK CHRI 38

39. 6. Hypertension Salt restriction Diuretic therapy Hydrochlorothizide-2 mg/kg/d Furosemide 1-2 mg/kg/dose ACE inhibitors-Angiotensin II blockers for proteinuric renal failure ( enalapril, lisinopril, losartan) Dr GRK CHRI 39

40. 7. Immunisation As per schedule Avoid live vaccine if on immunosuppressants Give live vaccine before transplant Yearly influenza vaccine Dr GRK CHRI 40

41. 8. Adjustment in drug dosage Drugs excreted by kidney may need dose adjustment to maximize effectiveness & reduce toxicity Dr GRK CHRI 41

42. Strategy to slow progression Optimal control of hypertension Maintain calcium/ phosphorus product <55 Prompt treatment of infection & dehydration Correction of anemia Correction of hyperlipidemia Prevent obesity Avoid NSAIDS Dietary protein restriction helpful but not recommended in children Dr GRK CHRI 42

43. Long term follow up Serum electrolytes BUN Creatinine Calcium Phosphorus Albumin Alkaline phosphatase Hb & Hct PTH Echo Dr GRK CHRI 43

44. Summary CKD is irreversible loss of renal function Glomerulonephritis, congenital Renal & urological anomalies, reflux nephropathy account for major chunk of CKD in children. Hypertension & proteinuria are major causes of disease progression Presenting complaints include anemia, growth retardation, hypertension, bone disease, acidosis, encephalopathy, malnutrition Adequate management of early stages halt progression Psychological & emotional support to patients & parents Renal replacement therapy initiated when GFR < 15 ml/min/ 1.73m 2 Dr GRK CHRI 44