1. Chronic renal Failure
Dr. Jumana Albaramki

2. Chronic renal failure
Plasma Cr does not rise until renal function has fallen to less than half normal levels Cr affected by muscle bulk GRF= height x k /creat in mg/dl ml/min/1.73 m2

4. Normal progression of GFR with age

5. Creatinine with age

7. presentation
Asymptomatic Anorexia,lethargy Polydipsia,polyuria Anemia,HTN FTT,bone osteodystrophy Causes: 1.Structural congenital malformations 2.Hereditary nephropathy 3.Glomerulonephritis

9. Management
Investigations:FBC,iron studies EUC, biocarbonte,Ca,PO4,ALP,PTH Urine protein,lipid profile Attention: Nutrition,fluid.growth,anemia,HTN,renal osteodystrophy

10. Prevention of progression of CRF
1.Proteinuria:due to hyperfilteration,ACEI,ARB dilate afferent art and reduce intraglomerular pressure ACEI cause anemia,high K,Cr, cough 2.HTN 3.Dyslipidemia

11. Bone disorders in CKD

12. Figure 50-1 Mean plasma intact PTH, 1,25(OH)2D3 (left y-axis), and FGF-23 concentrations (right Y axis) in patients with different degrees of CKD. Individual values may vary considerably, especially in patients with advanced renal failure. (Adapted from Reichel H, Deibert B, Schmidt-Gayk H, Ritz E: Calcium metabolism in early chronic renal failure: Implications for the pathogenesis of hyperparathyroidism, Nephrol Dial Transplant 6(3):162-69, 1991; and adapted from Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F, et al.: Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency, Am J Kidney Dis 44(2):250-56, 2004.)

13. PTH
Mobilizes Ca from bones Decrease renal tubular absorption of PO4 Increase renal tubular absorption of Ca Promote 1 alpha hydroxylase

15. Disorders of Bone Mineral Metabolism in CKD
Reduced 1,25 OH vit D impairs intestinal Ca absorption leads to low Ca and increase PTH stimulates 1hydroxylase increase Vit D,Ca. Calcemic response to PTH is reduced CKD Ca major regulator of parathyroids High PO4 increase FGF23 increase excretion High PO4 stimulte PTH,lowers Ca Acidosis impairs bone mineralization

16. Figure 50-3 Pathophysiology of secondary hyperparathyroidism.

17. Clinical Manifestations
Bone pain Myopathy due uremic toxins,carnitine def Skeletal deformities:bowing,genu valgum,ricket changes of widening of metaphyseal regions Slipped epiphyses,proximal femur,presents as limping,waddling gait Fractures Vascular calcification (maintain PO4 X Ca <65 mg2/dl2)

18. Biochemistry
Ca low or normal,high in low turn over,tertiary hyperparathyroidism, Tx with calcitriol,volume depletion PO4 high is age dependant PTH high,ALP high Xrays detect subperiostal resorption,

19. Treatment
Optimal control of PO4 by diet ,phosphate binders (Ca carbonate 40%elemental Ca),dialysis not enough,to be taken with meals.
Sevelamer HCL.:lower risk of hypercalcemia,lower lipids,same efficacy as CaCO3 in lowering PO4.
maintain PO4 X Ca <55mg2/dl2 in adults, <65mg2/dl2 in chidren
Vitamin D:10-60ng/kg/day,increase PO4,Ca,given daily or intermittent
Calimimetic,parathyroidectomy

20. Target PTH in children with CKD
Target PTH range
GFR (ml/min x1.73 m2)
CKD stage
35-70pg/ml
60-89 2
30-59 3
70-110pg/ml
15-29 4
pg/ml
<15
5 (PTH resistance

22. Histologic classification of renal osteodystrophy
Comments
Description
Etiology
TYPE
Common unTX,skeletal deformitis
High bone formation,resorption,woven bone,marrow fib
hyperparathyroidism
High turn over
Ostitis fibrosa
Fractures,calcifications
Low bone formatn,resorptn
Low osteoid
Low PTH,Ca,vit D,
Low turn over,adynamic
Osteoid,demineralized bone
AL,acidosis
osteomalacia

25. Anemia in CRD
Erythropoietin Deficiency Blood loss (HD lines,GIT losses due to impaired platelet function) Decreased RBC survival Hyperparathyroidism decrease BM production. Aluminum toxicity Iron deficiency Vitamin B12,folate deficiency Inflammation,infection

26. Clinical effects of anemia
Systemic symptoms of fatigue,loss of appetite,decrease exercise tolerance
CVD:LVH
Anemia increase mortality
Evaluation:FBC,ret,ferritin,iron,TIBC
TSAT:Iron/TIBC should be >20%
Target Hb levels based on KDOQI guidelines is between 11-13
Ferritin be above 100 in predialysis patients

27. ESA rHuEPO s.c. as 100 U/kg/week in two doses in predialysis,PD
rHuEPO i.v. as 150 U/kg/week in three doses in HD.
S.c. longer half life than iv
Complications:HTN,seizures,iron defiency,thrombosis,EPO antibodies
New darbepoetin-:longer T1/2, every 2 wk

28. Iron thearpy
iron not to be given with food,phosphate binders 3-5mg/kg elemental iron IV iron in HD as iron sucrose Various oral preparations as ferrous sulphate,ferrous gluconate

29. nutrition
Adequate nutrition to promote growth,prevent complications of uremia,bones. Protein intake 1.1 g/day 1-6 y Higher protein in dialysis Low phosphate,potassium diet Vitamin but vit A,minerals as folic acid Special formula low in K,PO4,increase energy by adding lipid,sugar Salt supplements in tubular losses

30. Growth and puberty in CKD

31. Causes of growth failure in CKD
Genetic factors:gender,parental height,syndromes
Age of onset of CKD
Residual renal function
Treatment modality
Energy malnutrition
Water and electrolyte disturbances:renal dysplasia needs salt.
Metabolic acidosis
Anemia,renal osteodystrophy

32. Gonadotropic hormone axis
Growth hormone levels are normal to high GH resistance due to low GH receptor expression or post-receptor signaling defect. IGF1 levels are high and there is resistance to its action

33. Treatement of growth failure
Adequate caloric intake to 100% of RDA Treatment with alkali,salt Calcitriol Growth hormone:benefit more in pre endsatge CKD,than dialysis Prepubertal start cause a marked pubertal growth spurt.

34. Figure 46-1 Typical growth pattern in congenital chronic renal failure
Figure 46-1 Typical growth pattern in congenital chronic renal failure. Relative loss during the nutrient-dependent infantile and gonadal hormone-dependent puberty phases and percentile-parallel growth during the mainly growth-hormone-dependent growth period during mid childhood are shown. The shaded area represents the normal range (3rd to 97th percentiles). (Reproduced from Mehls O, Schaefer F: Endocrine, metabolic and growth disorders—patterns of growth and maturation in chronic renal failure—impact of developmental stage. In Holliday MA, Barratt TM, Avner ED, editors: Pediatric nephrology, Baltimore, 1994, Williams & Wilkins, pp )

35. Treatment of ESRD Peritoneal dialysis:CAPD,NIPD
CCPD :Uses an automated machine with 7 night cycles with a long day time dwell
Acute intermittent hemodialysis:needs vacular acsess as AV fistula,permcath
Requires 3 X 5 hour sessions/week
Diffusion through a semipermeable membrane,ultrafilteration of fluids

36. Transplantation Living or cadervic donons,HLA matching
Needs long immunosuppression with steriods,CNI, mycophenolate acetate
Problems :rejection,hypertension,infection,obstruction,chronic allograft nephropathy
LRD 1 year graft survival of 91%,5 years of 74 %
CRD 1 year graft survival of 80%,5 years of 60 %

37. Dialysers