Metabolic complications in patients ongoing pd

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ภาวะแทรกซ้อนทางเมตะบอลิกในผู้ป่วยล้างไตทางช่องท้อง

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Metabolic complications in patients ongoing pd

  1. 1. Metabolic Complications in Patients Ongoing Peritoneal dialysis Piti Niyomsirivanich, MD.
  2. 2. Outlines• Metabolic syndrome• Hyperglycemia• Dyslipidemia• Protein loss• Na• K• Mg and vascular calcification• PO4• Ca
  3. 3. Metabolic Syndrome• Central obesity• High blood pressure• High triglyceride• Low HDL-cholesterol• Insulin resistance
  4. 4. Metabolic Syndrome
  5. 5. WHR = Waist hip ratio
  6. 6. ระบาดวิทยาของโรคอ้วนและภาวะ ไตเสื่อม• Ejerblad et al. – BMI > 25 kg/m2  CKD 2-3 X – BMI > 35 kgm2 c diabetes  17.7 X• Hsu et al. – BMI 25-29.9 kg/m2  1.87 X – BMI 30-34.9 kg/m2  3.57 X – BMI 35-39.9 kg/m2  6.12 X – BMI > 40 kg/m2  7 X• Central adiposity Versus Peripheral adiposity
  7. 7. Metabolic syndrome & kidney disease• Chen et al. – Metabolic syndrome increase risks of kidney disease 2.6 X – 3 risk factors 3.38 X – 4 risk factors 4.23 X – 5 risk factor 5.85 X• Palaniappan et al. – Metabolic syndrome increased risk albuminurea
  8. 8. Mechanism of CKD in obesity with metabolic syndrome• Inflammation• Renin angiotensin system• Lipotoxicity• Hemodynamic factors
  9. 9. Cytokine
  10. 10. Cytokine from adipose tissue
  11. 11. Cytokines• 1. Leptin – 167 amino acid – Adipocyte-derived hormone – More fat more leptin – Pass Blood brain barrier – Inhibit neuropeptide Y  decrease appetide
  12. 12. Leptin and Energy balance
  13. 13. Mechanism of leptin Leptin secrete via kidney
  14. 14. IL-6 and CRP• Produced from visceral , peripheral tissue• decrease cytokine signal and leptin• Adiponectin• Increase TGF-b1  kidney fibrosis• Increased CRP from hepatocyte  metabolic syndrome visceral adiposity and atherosclerosis
  15. 15. TNF-a• 26-kDa• Macrophage• Increased in metabolic syndrome• Adipogenesis & lipogenesis
  16. 16. MCP-1• Pro-inflammatory cytokines  macrophage – Increased glucose uptake  insulin induced insulin receptor tyrosine phosphorylation insulin resistance
  17. 17. Adiponectin• 30 kDa• Produced from subcutaneous fat > visceral fat• Insulin sensitizing , anti inflammatory , anti- artherogenic• Increased in thinner person• Decreased in obesed person
  18. 18. RAS• Obesity  increase renin , angiotensinogen , ACE , Angiotensin II , aldosterone• Angiotensinogen , angiotensin II increase adipocyte growth –  lipogenesis , hepatic gluconeogenesis ,glycogenolysis – Inh. Lipolysis , insulin dependent glucose uptake•  metabolic syndrome
  19. 19. Conclusion
  20. 20. Metabolic syndrome in PD patient• Cardiovascular death • LANDMARK STUDY (Longtitudinal Assessment of Numerous Discrete Modification of Atherosclerosis Risk in Kidney Disease)
  21. 21. FBM & CD-163 (pro-inflammatory marker) Axelsson et al.
  22. 22. Treatment of metabolic syndrome• Low glucose in dialysate  icodextrin• Control blood sugar• Reduced peritonitis  inflammation• RAS blockage• PPAR agonists (thiazolidinedione)  insulin sensitizer• HMG-CoA reductase• Cardiovascular risks
  23. 23. Hyperglycemia
  24. 24. Insulin resistance in CAPD• 1/3 of insulin renal excretion• CKD  insulin resistance – increased insulin – Hyperparathyroidism – Animia – Malnutrition• Osmitic agent (glucose) absorption• Insulin resistance  decrease function of lipoprotein lipase
  25. 25. Glucose absorption• Osmotic agent – Glucose : cheap , stable , non toxic • Absorp across membrane • 60-80% of dialysate absorbed • Glucose absorption APD < CAPD (shorter duration) • Glucose 100-150 g per day absorbed – 500-800 kcal/day significant weight gain 5-10% – Increase insulin secretion  insulin resistance atherosclerosis – Required increase hypoglycemic drug – Amino acids – Polyglucose solution
  26. 26. Minimized glucose absorbtion• Appropriate salt and water management – Decrease need for hypertonic solutions• Non-glucose based solutions
  27. 27. Target of glucose control• FBS < 140 mg/dl• 1 hr post prandial glucose < 200 mg/dl• HbA1C 7-8 mg/dl• Uremia  increased measure HbA1C (Carbymylated hemoglobin) – Differentiate • borate-agarose affinity chromatography • Thiobarbituric acid
  28. 28. Hypoglycemia agent• Not recommend oral hypoglycemic drugs• May use Thiazolidinediones – Except CHF• Subcutaneous insulin
  29. 29. Subcutaneous insulin• No guidelines• Icodextrin – CPG  glucose dehydrogenase- pyrroloquinolinequinone , glucose dye oxidoreductase enzyme  over estimate due to maltose in blood • Accu-check , FreeStyle – Recommend  glucose dehydrogenase-nicotinamide adenine dinucleotide , glucose dehydrogenase flavin adenine dinucleotide ,glucose oxidase instead
  30. 30. IP insulin• adventage – Absorbed via lymphatic system  constant delivery 1 ml/min – Less variation among administration – Lower dosage than other route – Lesser Atheroscleosis risk• Disadventage – More expensive – Decrease HDL in some small studies – Infection – Subcapsular liver steatonecrosis  insulin induced triglyceride accumulation in liver – Malignant omentum syndrome  require more insulin
  31. 31. Insulin dosage• Mutiple subcutaneous injection• Total insulin per day• Divided – 10% at night time – 85-90% at day time /3• Added 1 ,2 ,3 unit/l for 1.5%D 2.5%D 4.25%D• FBS < 140 mg/dl , CBG tid pc 1 hr < 200 mg/dl• CCPD , NIPD for high transporter (rapid glucose absorption)•
  32. 32. • IP insulin – Stability – Peak concentration 90-120 min – 60% dose absorbed• Direct Via tenckhoff catheter – Peak concentration 15 min
  33. 33. TZDs• Insulin sensitizer – Troglitazone  withdrawed – Rosiglitazone – Pioglitazone – Ciglitazone  animal study – Englitazone  animal study• Excretedliver
  34. 34. Dyslipidemia
  35. 35. Lipoprotein
  36. 36. Lipoprotein• Chylomicrons – largest – GI lymphatic – A-I , A-II , A-IV , B-48 , C-I , C-II , C-III , E• Very low density lipoprotein – Liver  circulation – B-100 , C-I , C-II , C-III , E• IDL – VLDL Lipoprotein lipase  triglyceride >> IDL – B-100 , C-III , E• LDL – IDL Hepatic triglyceride lipase LDL – B-100 , C• HDL – A-I , A-II , C-I , C-II , C-III , D , E – return
  37. 37. Lipid metabolism : endogenous PW
  38. 38. Atherogenicity of lipoprotein• Esp. LDL , LP(a)• Small LDL > large LDL• Lipoprotein (a) increased in patients with proteinuria• HDL – Uremia  acute phase response (IL-6, CRP)  decreased HDL
  39. 39. Glomerular response to lipid• Nephron loss  renal adaptation (ขยายขนาด)•  increase single nephron GFR –  glomerulosclerosis and interstitial fibrosis in long term• Leakage of lipoprotein – Increase mesangial cell cytokine , increased macrophage – Macrophage  ROS – ECM  increased matrix glomerulosclerosis – Endothelial  NO + endothelin , thromboxane A2 – PTC  endocytosis , endothelin-1  cell death • Endothelin -1  peritubular capillary vasoconstriction , fibroblast ,monocyte – JG apparatus  renin  increase BP
  40. 40. Lipid metabolism abnormality due to kidney disease• Increase carbohydrate intake due to protein restriction• Lipoprotein lipase abnormality – Insulin resistance , – High PTH , uremic toxin – Low Erythopoietin (unknown mechanism)
  41. 41. Hypertriglyceridemia in patient w CKD w/wo dialysis
  42. 42. Treatment• Diet – Fat < 30% of total calories – Poly:mono:sat = <0.7 : 1 : 1-1.5 (Nephrotic Syndrome , post KT) – decreased calories , simple sugar (CKD) – High fiber – 35 kcal/kg/day in < 60 yo – 30-35 kcal/kg/day in > 60 yo• Exercise• Medication
  43. 43. HMG-CoA reductase inhibitor• Inhibit HMG-CoA reductase• Decreased cholesterol by 20-30%• CYP3A4 and CYP 2C9• Atorvastatin & pravastatin  decrease dose• Rosuvastatin90% excreted from kidney  avoid• Rhabdomyositis , hepatitis
  44. 44. Ezethimibe• Inhibit dietary & biliary cholesterol absorption• Decrease LDL 20% – Total cholesterol 15%
  45. 45. Bile acid binding resins• Not recommend in patients with uremia (increased VLDL)• Others – Fish oilhigh dose , expensive – ACTH  short term study long term?? – Sevalemer decrease P ,LDL, increase HDL – L-carnitine cofactor FA into mitochondria • Not recommend due to adverse effect to muscle ,blood – Heparin HD decreased TG , cholesterol – Dialysis membrane
  46. 46. Treatment for dyslipidemia in PD• LDL/apoB protein – The lower the better – Statins – No equivalent studies have been done in PD – NKF (National kidney foundation) ,KDOQI ,International Society for Peritoneal dialysis • Elevated LDL-c w/wo CAD • PD with dyslipidemia Rx as nonuremic pt. c CAD
  47. 47. Elevated triglycerides• Always found in association with other lipid and lipoprotein abnormalities• Carbohydrate loading from the dialysis solution  hypertriglyceridemia• Na and water Mx  minimize the use of hypertonic solutions• Alcohol increase triglycerides• Triglyceride > 350 mg/ml Rx• Fibrate – (benzofibrate ,fenofibrate ,gemfibrozil)dose reduced by 25% – Muscle enzyme
  48. 48. Low HDL-c• Fibrate class  raises HDL• Reducing cardiac morbidity and mortality has not been established
  49. 49. AntioxidantsVit E not proven to reduce CV eventsNo trials both PD and HD
  50. 50. Protein loss• Protein 0.5 g/L of dialysate drainage – May 10-20 g/day• Amino acid loss 2-3 g/day• Albumin• IgG 15%• Protein loss greatest in high and high-average transporters• Peritonitis• Nephrotic syndrome
  51. 51. Hyponatremia/hypernatremia• Hyponatremias –  excessive water drinker – Hyperglycemia  translocational hyponatremia – 1.3 mmol/L : 100 mg/dl of Na• Hypernatremia – Rapid UF more water than salt convects across membrane – Short dwell PD more likely hypernatremia – Esp. low transporters
  52. 52. Hypokalemia / Hyperkalemia• Hypokalemia  10%-30% of CAPD patients – Associate poor potassium intake – Diet – K < 3 mmol/L  K supplement• Hyperkalemia  non compliance , excessive K intake
  53. 53. Hypercalcemia / hypocalcemia• Ca 2.5 ,3.5 mEq/L• 3.5 mEq/L  positive calcium balance• 2.5 mEq/L  slightly negative balance of calcium• Concerns about vascular calcification  lower 2.5 mEqL• Hypercalcemia – Large doses of calcium based phosphate binders – Rx • Non-cacium based phosphate binder • Stop Vit-D • Ca 2.5mEq/L solution of dialysate• Hypocalcemia – Not common due to use of calcium base phosphate binder & Vit D – Rx • Cacium & vitamin D • Ca 3.5 mEq/L dialysate solution
  54. 54. Magnesium and vascular calcification• Mg depletion  increased risk of atherosclerosis and cardioevents• Excess > deficiency• Higher dialysate solution Mg  suppress PTH  adynamic bone disease• Optimum Mg in dialysate remain unknown
  55. 55. Hypophosphatemia/hyperphosphatemia• Calcium based Phosphate binder , Sevalemer –  fall in serum bicarbonate• Amino acid based dialysis solution has been reported to lower the serum bicarbonate level in some patients

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