8-2. Management of chronic renal failure. Isidro Salusky (eng)

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8-2. Management of chronic renal failure. Isidro Salusky (eng)

  1. 1. Isidro B. Salusky, M.D. Distinguished Professor of Pediatrics Chief, Division of Pediatric Nephrology Director, Clinical Translational Research Center Associate Dean of Clinical Research David Geffen School of Medicine at UCLA
  2. 2. Mitsnefes MM JASN 23:578, 2012
  3. 3. % Annual mortality 100 Dialysis Population 10 1 GP Male GP Female GP Black GP White Dialysis Male Dialysis Female Dialysis Black Dialysis White 0.1 0.01 0 25-34 35-44 45-54 55-64 65-74 75-84 >85 Age (yr) NKF Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32(suppl 3):S115.Sarnak MJ, Levey AS. Am J Kidney Dis. 2000;35(suppl 1):S117-S131.
  4. 4. • • • • • • • Homozygous hypercholesterolemia Kawasaki disease Diabetes type I and II Chronic kidney disease Congenital heart disease/ Pediatric heart transplant Chronic inflammatory disease (SLE & RA) Childhood cancer Kavey REW et al. Circulation 114:2710, 2006
  5. 5. –Protein and Calorie Malnutrition –Acidosis/Electrolyte Abnormalities –Primary kidney disease –Anemia –Renal bone diseases –Hormonal Factors –Immunosuppressive Medications
  6. 6. GFR Description (mL/min/1.73 m2) 1 Kidney damage with normal or GFR 90 2 Kidney damage with mild GFR 60-89 3 Moderate 30-59 4 Severe 5 Kidney failure Stage GFR GFR 15-29 15 or dialysis K/DOQI: Evaluation, classification and stratification. AJKD 39: 2001
  7. 7. n=366 Wong H et al. KI 70:585, 2006
  8. 8. SAs s of Anemia in CKD Patients (1 of 3) • Renal insufficiency = EPO deficient state Kidney ency Decreased erythropoietin production production etin n of uremic Erythroid progenitor cells Inhibition of erythropoiesis Bone Bone marrow
  9. 9. • EPO resistance – Iron deficiency – Hyperparathyroidism – High dose ACE inhibition – Aluminum toxicity – Antibodies to ESA – – – – – – Inflammation Folate/B12 deficiency Hemoglobinopathies Hemolysis Chronic Blood Loss Chronic infection
  10. 10. • Erythropoietin Stimulating factors (ESA) • Iron • Diagnose and treat underlying cause of Epogen resistance
  11. 11. Borzych-Buzalka D et al. JASN 24:665, 2013
  12. 12. NAPRTCS 2011
  13. 13. • Loss of appetite-may manifest early in the course of kidney disease • Spontaneous food intake decreases with worsening kidney failure • Calorie Malnutrition-seen during the first years of life • Protein Malnutrition-not frequently seen in children with kidney failure
  14. 14. • Adequate caloric intake – Infants-growth rates during this period are correlated with calorie intake • Nasogastric (NG) or Gastrostomy (G) Tube Feeding – Older children- intake should not be less than 80% of the Recommended Daily Allowance (RDA) • Therapy with recombinant human growth hormone
  15. 15. Rees L et al. JASN 22:2302, 2011
  16. 16. (n=153) Rees L et al. JASN 22:2302, 2011
  17. 17. Rees L et al. JASN 22:2303, 2011
  18. 18. • North America: Oligo-anuric, high glucose exposure and treatment with RhGH • Europe: Biocompatible PD fluids • Turkish: Lower serum albumin levels, higher serum P levels and use of amino-acids containing solutions • Latin America: Persistent residual renal function, higher use of phosphate binders and lowest rate of NaCl supplementation Rees L et al. JASN 22:2302, 2011
  19. 19. • Many congenital kidney diseases lead to loss of electrolytes and decreased ability of the kidneys to concentrate urine • Infants with kidney failure due to renal dysplasia-high urinary losses of sodium • Metabolic acidosis- kidney function below 50% • The specific effect of bicarbonate therapy on growth in CKD remains to be defined • Correction prior to treatment with rhGH
  20. 20. • Effects on bone remodeling and modeling – Skeletal fracture and microfracture repair – Bone deformities – Growth retardation • Relationship to: – Osteopenia / osteoporosis – Changes in bone mass over time during long-term dialysis – Vascular calcifications • Bone loss after renal transplantation and cardiovascular disease
  21. 21. 100 Bone turnover % of Subjects 80 PTH 60 40 20 0 2 3 CKD Stage 4 Wesseling-Perry K CJASN (2012) 7:146
  22. 22. 1000 200 GH * 150 PTH (pg/ml) BFR (um3/um2/y) GH 100 50 GH GH 750 * 500 250 0 0 Low/nl BFR GH High BFR Low/nl BFR High BFR No GH Bacchetta J et al CJASN 2013
  23. 23. Height < -2 SD 153 (61.9%) Clinical manifestations of bone disease 91 (36.8%) Deformities 63 (25.5%) Pathological fractures 33 (13.4%) Aseptic bone necrosis 32 (13.0%) Mild disabling bone disease 26 (10.5%) Severe disabling bone disease 18 (7.3%) Invalidating bone disease (all) 44 (17.8%) Groothoff JW KI 63 (2003) 266–275
  24. 24. Lumen Intimal Atherosclerotic Plaque
  25. 25. From Passive Deposits to Active Processes
  26. 26. A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: – Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism – Abnormalities in bone turnover, mineralization, volume, linear growth, or strength – Vascular or other soft tissue calcification Moe et al Kidney International 2006
  27. 27. • Patients with Stage 5 CKD are at high risk for vascular calcification • Vascular calcifications are present in almost 50% of patients with stage 4 CKD and new dialysis patients • Vascular calcification can be quantified • Vascular calcification is associated with modifiable risk factors – Ca intake from calcium-based binders – S-P, S-Ca and Ca P product • Vascular calcification results in arterial stiffening and increased pulse pressure and adynamic bone disease
  28. 28. Therapeutic Options for the Treatment of CKD-MBD Phosphate Binders Calcitriol Paricalcitol D2-D3 1,25(OH)D Doxercalciferol Ca-Salts Sevelamer: Ca free – Metal Free Lanthanum Ca: Ca free - Metal + Ergocalciferol Calcimimetic Drugs Cinacalcet
  29. 29. Treatment Stage Treatment Target Range 3 KDIGO: Upper Limit of Normal* (2C) KDOQI: 35-70 pg/mL 4 KDIGO: Upper Limit of Normal* (2C) KDOQI: 70-110 pg/mL 5 KDIGO: Upper Limit of Normal* (2C) KDOQI: 150-300 pg/mL 5D KDIGO: 2 to 9 times Upper Limit of Normal (2C) KDOQI: 150-300 pg/mL Europe Children: 2 to 3 x upper Limit of Normal *In patients with CKD stages 3-5 not on dialysis, in whom serum PTH is progressively rising and remains persistently above the upper limit of normal for the assay despite correction of modifiable factors, treatment with calcitriol or vitamin D analogs is suggested. (2C) 1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) Kidney Int. 2009;76(suppl 113):S1-S130. 2. Adapted from National Kidney Foundation (NKF). KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.
  30. 30. (n=3409) (n= 4026) Favors Non-Ca Favors Ca Jamal SA et al. Lancet, 2013
  31. 31. Months on Dialysis 0 0 12 24 Months post Transplantation 0 24 48 72 -0.5 -1 -1.5 -2 -2.5 -3 NAPRTCS 2010/2011
  32. 32. GH/IGF System Optimize Growth and Survival Vascular Calcification Bone Health Vitamin D/PTH/ FGF23 Axis

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